Mutation Rate of IDH1 and the Impact of Pathological Features on Survival in Intrahepatic Cholangiocarcinoma

Mutation Rate of IDH1 and the Impact of Pathological Features on Survival in Intrahepatic Cholangiocarcinoma | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Mutation Rate of IDH1 and the Impact of Pathological Features on Survival in Intrahepatic Cholangiocarcinoma Muge Buyukaksoy, Selin Akturk Esen, Nesrin Turhan, Enes Seyda Sahiner, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8449961/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive malignancy with limited therapeutic options and poor survival outcomes. Recent advances in molecular oncology have highlighted the significance of isocitrate dehydrogenase 1 (IDH1) mutations as potential therapeutic targets. However, data regarding the prevalence and prognostic implications of IDH1 mutations in patients with iCCA are scarce. This study aimed to retrospectively investigate the IDH1 mutation rate, histopathological features, and survival outcomes of patients with iCCA. A total of 88 patients diagnosed and treated between 2005 and 2025 at two tertiary oncology centers were retrospectively analyzed. Clinical, pathological, and survival data were obtained from institutional oncology archives and national population databases. IDH1 mutation status was evaluated using polymerase chain reaction and next-generation sequencing on paraffin-embedded tissue samples. The median follow-up duration was 3.4 years and the median age at diagnosis was 62 years. IDH1 mutation was identified in 2.3% of cases, while 85.2% were wild-type. Curative surgery was performed for 71.6% of patients and 28.4% received noncurative or palliative treatment. Significant prognostic factors for overall survival included perineural invasion, microvascular invasion, histological subtype, albumin-bilirubin (ALBI) score, surgical margin status, and advanced disease stage. In multivariate analysis, the ALBI score remained independently associated with survival (p = 0.025). The median overall survival was 19.1 months. This study provides the first comprehensive multicenter evaluation of IDH1 mutations and clinicopathological features in iCCA patients. The findings underscore the potential role of molecular profiling in guiding personalized treatment strategies and may serve as a reference for future subtype-specific investigations. Biological sciences/Cancer Health sciences/Gastroenterology Health sciences/Oncology Intrahepatic cholangiocarcinoma isocitrate dehydrogenase 1 (IDH1) mutation ALBI score pathological prognostic factors survival Figures Figure 1 Figure 2 Figure 3 Introduction Cholangiocarcinoma (CCA) is an aggressive epithelial cancer arising from the bile ducts. Intrahepatic CCA (iCCA) ranks as the second most common primary liver cancer after hepatocellular carcinoma and represents about 3% of all gastrointestinal malignancies. The incidence of iCCA is increasing and its prognosis remains poor due to the absence of distinct symptoms, often resulting in diagnosis at advanced stages. The 5-year overall survival rate for iCCA is generally low, ranging between 5% and 20%. Molecular profiling has identified potentially targetable genomic alterations in approximately 40% of CCA patients. Among these, mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) are notable, occurring in about 14% of iCCA cases but rarely in extrahepatic CCA. Clinically, the prognostic implications of IDH1 mutation are still debated. Some studies have demonstrated long-term progression-free survival for mutation carriers (1), while other studies of advanced disease have reported a negative impact of IDH1 on survival after progression (2). One study associated IDH1/2 mutations in iCCA with longer overall survival and a longer time to recurrence after resection (3). Taken together, these findings highlight the need for integrative analyses combining mutation status and histopathological features to decipher the prognostic value of IDH1 in iCCA. This study aims to retrospectively analyze pathological tissue samples from iCCA patients treated at two centers in Türkiye. The primary objectives are to determine the prevalence of IDH1 mutations and to evaluate the effects of other clinicopathological features on survival. The results are expected to provide important insights that can guide future clinical decisions and improve outcomes for patients with this challenging cancer. Materials and Methods Study Design This retrospective, cross-sectional study was conducted between October 1, 2023, and February 1, 2025, at two tertiary centers: the University of Health Sciences Ankara Bilkent City Hospital and the Gazi University Faculty of Medicine Hospital. The study included patients diagnosed with iCCA between 2005 and 2025; their records were obtained from the archives of the Medical Oncology Department of Ankara Bilkent City Hospital and the Medical Oncology Department of Gazi University’s Faculty of Medicine. Population and Participants A total of 88 patients with histologically confirmed iCCA were included. Eligible participants were men or women aged ≥18 years, under follow-up with a confirmed iCCA diagnosis, and with accessible pathology blocks and complete clinical data from the oncology archives. Data Collection Clinical, laboratory, and survival data were retrospectively retrieved from the medical records of the Department of Medical Oncology of Ankara Bilkent City Hospital and the Gazi University Faculty of Medicine Hospital. Histopathological prognostic factors were assessed by experienced pathologists from both participating institutions. Survival data were obtained from the Turkish National Population Registry System. Laboratory Analysis Formalin-fixed paraffin-embedded (FFPE) tumor blocks, obtained either by Tru-Cut biopsy or surgical resection, were retrieved from the pathology archives for IDH1 mutation testing. Histological sections of 3–5 µm in thickness were prepared and examined under light microscopy. DNA extraction was performed using the QIAamp DNA FFPE Tissue Kit (Qiagen Inc., USA) according to the manufacturer’s protocol, with isolates stored at –20 °C until polymerase chain reaction (PCR) amplification. Primers were designed to target exon 4 of the IDH1 gene (NM_05896), encompassing codon 132, with amplification extending from codon 54 to the C-terminal end of the exon. PCR amplification was performed and the resulting amplicons were pooled in approximately equal ratios based on reaction yield. DNA quantification and standardization were carried out using a Nanodrop N1000 spectrophotometer (Thermo Inc., USA), adjusting the DNA concentration to 0.2 ng/µL. Library preparation for next-generation sequencing (NGS) was performed using the NexteraXT kit (Illumina Inc., USA) and sequencing was conducted on the Illumina MiSeq platform. Read alignment was performed with MiSeq Reporter software and mutation analysis was carried out using IGV 2.9.5 (Broad Institute, USA). The coverage allele fraction threshold was set to 0.03 to enable the detection of low-frequency somatic mutations, and only regions with read depths of ≥200× were analyzed. Codon 132 corresponded to chr2:208248387–208248389 (hg38 reference genome), resulting in an R132 protein variant when mutated. Each sequencing result was independently reviewed by two molecular biologists to confirm mutation status. Survival Analysis Progression-free survival (PFS) was defined as the interval from initiation of first-line chemotherapy to radiologically confirmed disease progression or death from any cause. Overall survival (OS) was defined as the interval from histopathological diagnosis to death from any cause or last follow-up. Ethical Approval This study was approved by the Institutional Ethics Committee of Ankara Bilkent City Hospital (protocol number E1-23-3976, dated September 6, 2023) and was conducted in accordance with good clinical practice, applicable laws, and the Declaration of Helsinki. In accordance with the decision of the Institutional Ethics Committee of Ankara Bilkent City Hospital, informed consent was not required due to the retrospective design of the study and the use of fully anonymized data with no possibility of identifying individual participants. Statistical Analyses All statistical analyses were performed using IBM SPSS Statistics 26.0 for Windows (IBM Corp., USA). The normality of the data distribution was assessed using the Kolmogorov–Smirnov test. Continuous variables were summarized as median, minimum, and maximum values, while categorical variables were expressed as counts and percentages. Survival analyses were performed using the Kaplan–Meier method and survival curves were compared using the log-rank test. Multivariate analysis was conducted using the Cox proportional hazards regression model, including variables with statistical significance in univariate analysis. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated, and values of p<0.05 were considered statistically significant. Results This study included 88 patients diagnosed with iCCA who were followed at two different centers. The median age at diagnosis was 62 (range: 31–79) years. The study group consisted of 55 men (62.5%) and 33 women (37.5%) , reflecting a male predominance. Among the presenting symptoms, abdominal pain was the most common, observed in 67% (n=59) of patients. Regarding disease staging, Stage IB and Stage IIIB were the most frequent stages, each accounting for 22.7% (n=15) of cases. In the evaluation of distant metastasis sites, liver metastasis and nonregional lymph node metastasis were detected at equal frequencies, each observed in 5.7% (n=4) of patients. The baseline demographic and clinicopathological characteristics of patients diagnosed with iCCA are presented in Table 1. Table 1. Baseline Demographic and Clinicopathological Characteristics of Patients with Intrahepatic Cholangiocarcinoma Variables Group Median (min – max) n (%) 88 (100) Age at diagnosis, years 62 (31–79) Sex Female 33 (37.5) Male 55 (62.5) ECOG PS 0 4 (4.5) 1 74 (84.1) 2 7 (8) 3 3 (3.4) Smoking history None 43 (48.9) Active smoker 12 (13.6) Ex-smoker 16 (18.2) Unknown 17 (19.3) Alcohol consumption No 66 (75) Yes 5 (5.7) Unknown 17 (19.3) Family history of CCA Absent 71 (80.7) Unknown 17 (19.3) HBV infection Absent 74 (84.1) Inactive chronic HBV 6 (6.8) Immunoactive, HBeAg-negative 6 (6.8) Occult HBV 2 (2.3) HCV infection Absent 88 (100) Cholelithiasis Absent 58 (65.9) Present 18 (20.5) Unknown 12 (13.6) Incidental diagnosis Absent 75 (85.2) Present 13 (14.8) Abdominal pain Absent 29 (33) Present 59 (67) Weight loss Absent 82 (93.2) Present 6 (6.8) Jaundice Absent 67 (76.1) Present 21 (23.9) Pruritus Absent 77 (87.5) Present 11 (12.5) Nausea Absent 80 (90.9) Present 8 (9.1) Stage Stage IA 8 (9.1) Stage IB 20 (22.7) Stage II 13 (14.8) Stage IIIA 3 (3.4) Stage IV 14 (15.9) Unknown 10 (11.4) T T1 43 (48.9) T2 28 (31.8) T3 7 (8) T4 9 (10.2) Unknown 1 (1.1) N N0 60 (68.2) N1 24 (27.3) Unknown 4 (4.5) M M0 65 (73.9) M1 14 (15.9) Unknown 9 (10.2) Liver metastasis Absent 74 (84.1) Present 5 (5.7) Unknown 9 (10.2) Omentum metastasis Absent 77 (87.5) Present 2 (2.3) Unknown 9 (10.2) Peritoneal metastasis Absent 77 (87.5) Present 2 (2.3) Unknown 9 (10.2) Nonregional lymph node metastasis Absent 74 (84.1) Present 5 (5.7) Unknown 9 (10.2) Lung metastasis Absent 78 (88.6) Present 1 (1.1) Unknown 9 (10.2) Bone metastasis Absent 76 (86.4) Present 3 (3.4) Unknown 9 (10.2) Adrenal metastasis Absent 78 (88.6) Present 1 (1.1) Unknown 9 (10.2) Tumor diameter (mm) 60 (17–174) CCA: Cholangiocarcinoma, ECOG PS: Eastern Cooperative Oncology Group performance status, HBV: hepatitis B virus, HCV: hepatitis C virus PCR-based analysis revealed an IDH1 wild-type profile in 85.2% (n=75) of patients and an IDH1 mutation in 2.3% (n=2). Mutation status was indeterminate in 12.5% (n=11) due to inadequate tumor tissue. According to the histopathological subtype, the small-duct type was most prevalent, observed in 55.7% (n=49) of cases. Morphologically, the nodular form was the most frequent pattern, identified in 67% (n=59) of patients. Regarding tumor growth patterns, infiltrative growth was observed in 45.5% (n=40) of cases. Solitary tumors were present in 79.5% (n=70) of the patients. Histopathological assessment of the nontumorous liver parenchyma demonstrated that hepatocellular cholestasis (19.3%, n=17) and mild portal fibrosis with inflammation (17%, n=15) were the most frequently observed background lesions. In terms of tumor grade, Grade 2 differentiation was the most frequent, identified in 70.5% (n=62) of patients. Capsular invasion was absent in 68.2% (n=60) and adjacent structure invasion was not observed in 65.9% (n=58) of cases. According to tumor budding, Grade 1 was the most common, accounting for 45.5% (n=40). Lymphovascular invasion and perineural invasion were detected in 55.7% (n=49) and 47.7% (n=42) of patients, respectively, whereas microvascular invasion was observed in 9.1% (n=8). Assessment of the surgical margins demonstrated that negative margins were achieved in 58% (n=51) of cases. Regarding the albumin-bilirubin (ALBI) score, Grade 1 was the most frequent classification, observed in 39.8% (n=35) of patients. The pathological, molecular, and biochemical characteristics of patients diagnosed with iCCA are presented in Table 2. Table 2. Pathological, Molecular, and Biochemical Characteristics of Patients with Intrahepatic Cholangiocarcinoma Variables n (%) 88 (100) IDH1 mutation Negative 75 (85.2) Positive 2 (2.3) Insufficient material for analysis 11 (12.5) Histopathological subtype Small-duct type 49 (55.7) Large-duct type 27 (30.7) Unknown 12 (13.6) Morphology Nodular 59 (67) Sclerosing 11 (12.5) Papillary 4 (4.5) Unknown 14 (15.9) Solitary/multiple Solitary 70 (79.5) Multiple 8 (9.1) Unknown 10 (11.4) Nontumorous liver parenchyma Unremarkable pathology 12 (13.6) HBV-related liver cirrhosis 2 (2.3) MASH-related liver cirrhosis 1 (1.1) Cryptogenic liver cirrhosis 2 (2.3) Primary sclerosing cholangitis 2 (2.3) MASH 11 (12.5) Arising in the background of intraductal tubulopapillary neoplasm 2 (2.3) Hepatocellular cholestasis 17 (19.3) Incomplete cirrhosis 1 (1.1) Hepatocanalicular cholestasis 10 (11.4) Mild portal fibrosis and inflammation 15 (17) Cholangitis 1 (1.1) Foreign body-type granulomatous reaction 2 (2.3) Unknown 10 (11.4) Grade Grade X 10 (11.4) Grade 1 15 (17) Grade 2 62 (70.5) Grade 3 1 (1.1) Liver capsule invasion Absent 60 (68.2) Present 19 (21.6) Unknown 9 (10.2) Tumor growth pattern Expansile 36 (40.9) Infiltrative 40 (45.5) Unknown 12 (13.6) Adjacent structure invasion Absent 58 (65.9) Present 20 (22.7) Unknown 10 (11.4) Tumor budding Absent 6 (6.8) Grade 1 40 (45.5) Grade 2 13 (14.8) Grade 3 16 (18.2) Unknown 13 (14.8) Necrosis Absent 41 (46.6) <30% 24 (27.3) 30%–60% 9 (10.2) 60%–90% 1 (1.1) Unknown 13 (14.8) Lymphovascular invasion Absent 27 Present 49 (55.7) Unknown 12 (13.6) Perineural invasion Absent 33 (37.5) Present 42 (47.7) Unknown 13 (14.8) Microvascular invasion Absent 70 (79.5) Present 8 (9.1) Unknown 10 (11.4) Surgical margin Negative 51 (58) Positive 23 (26.1) Unknown 14 (15.9) ALBI score Grade 1 35 (39.8) Grade 2 29 (33) Grade 3 12 (13.6) Unknown 12 (13.6) CA 19-9 (U/mL) 58.1 (0.8–67838.6) CEA (ng/mL) 1.7 (0.05–1901) AFP (µg/L) 2.7 (0.05–133.2) Biochemical parameters at diagnosis AST (U/L) 51.5 (10–617) ALT (U/L) 49.5 (14–828) ALP (U/L) 169 (38–1941) GGT (U/L) 143 (18–1434) Total bilirubin (mg/dL) 1.2 (0.2–30.6) Direct bilirubin (mg/dL) 0.4 (0.1–20.9) LDH (U/L) 241 (120–862) Albumin (g/dL) 39.3 (12–50) AFP: Alpha-fetoprotein, ALBI: albumin-bilirubin score, ALP: alkaline phosphatase, ALT: alanine aminotransferase, AST: aspartate aminotransferase, CA 19-9: carbohydrate antigen 19-9, CEA: carcinoembryonic antigen, GGT: gamma-glutamyl transferase, IDH1: isocitrate dehydrogenase 1, LDH: lactate dehydrogenase, MASH: metabolic dysfunction-associated steatohepatitis A total of 87 patients were evaluated according to the intent of treatment. Among them, 68 patients (78.2%) underwent curative surgery , while 19 patients (21.8%) were managed noncuratively with a palliative or nonsurgical approach. We could not access surgical information for 14 patients. As shown in Table 3, most patients who underwent curative surgery were diagnosed at an early stage. Specifically, curative surgery was performed for 41.2% (n=28) of patients with stage I disease, 19.1% (n=13) of those with stage II disease, 30.9% (n=21) of those with stage III disease, and only 1.5% (n=1) of those with stage IV disease. In contrast, among patients who did not undergo curative surgery, the majority were stage IV, accounting for 68.4% (n=13) of cases. Analysis of treatment regimens revealed that 42.6% (n=29) of patients who underwent curative surgery received adjuvant chemotherapy, 10.3% (n=7) received radiotherapy following adjuvant chemotherapy, and 13.2% (n=9) were treated with adjuvant chemoradiotherapy. In the nonsurgical group, 63.2% (n=12) received palliative chemotherapy due to metastatic disease (Table 3). Regarding adjuvant chemotherapy regimens, the gemcitabine-capecitabine combination was the most commonly administered treatment (32.4%; n=22), followed by capecitabine monotherapy (17.6%; n=12). Among patients receiving palliative chemotherapy, the most frequently used regimen was gemcitabine-cisplatin, which was administered in 47.4% (n=9) of the cases (Table 3). Table 3. Treatment Regimens in Patients with Intrahepatic Cholangiocarcinoma Variables Curative surgery Yes No n (%) 68 (100) n (%) 19 (100) Stage Stage 1 28 (41.2) 0 (0) Stage 2 13 (19.1) 0 (0) Stage 3 21 (30.9) 1 (5.3) Stage 4 1 (1.5) 13 (68.4) Unknown 5 (7.4) 5 (26.3) Treatment regimen Treatment refusal 2 (2.9) 0 (0) Surgery + adjuvant CT 29 (42.6) 0 (0) Surgery + adjuvant CT followed by adjuvant RT 7 (10.3) 0 (0) Metastatic (palliative) CT 0 (0) 12 (63.2) Neoadjuvant CT + surgery + adjuvant CT/RT 2 (2.9) 0 (0) Surveillance after surgery without therapy 1 (1.5) 0 (0) Patients who died before receiving treatment 14 (20.6) 5 (26.3) Unknown 13 (19.1) 2 (10.5) Adjuvant CT Gemcitabine 2 (2.9) Gemcitabine + capecitabine 22 (32.4) Capecitabine 12 (17.6) Gemcitabine + oxaliplatin 1 (1.5) Unknown 14 (20.6) Treatment refusal 3 (4.4) Patients who died before receiving treatment 14 (20.6) Palliative CT Gemcitabine 1 (5.3) Gemcitabine + cisplatin 9 (47.4) Gemcitabine + carboplatin 1 (5.3) Unknown 3 (15.8) Patients who died before receiving treatment 5 (26.3) CRT None 32 (47.1) 12 (63.2) Adjuvant 9 (13.2) 0 (0) Unknown 13 (19.1) 2 (10.5) Patients who died before receiving treatment 14 (20.6) 5 (26.3) CT: Chemotherapy, CRT: chemoradiotherapy, RT: radiotherapy The median OS of all analyzed patients was 19.1 months (95% CI: 9.7–28.5) (Figure 2). Stratification by ALBI score revealed striking differences in OS, with rates of 40.1 months (95% CI: 26.6–53.7) for Grade 1, 11.1 months (95% CI: 4.1–18.1) for Grade 2, and 4.4 months (95% CI: 0.02–10.4) for Grade 3 (p<0.001). Pairwise comparisons confirmed significant survival differences across all grades (Grade 1 vs. 2, p<0.001; Grade 1 vs. 3, p<0.001; Grade 2 vs. 3, p=0.017) (Figure 3). As shown in Table 4, univariate and multivariate analyses for OS identified several significant prognostic factors. Univariate Analysis When tumor growth patterns were evaluated, using the expansive pattern as the reference, the infiltrative growth pattern was associated with a 2.39-fold increased risk of death (OR: 2.39; 95% CI: 1.33–4.28), and this finding was statistically significant (p=0.005). The presence of adjacent structure invasion was similarly associated with worse OS (OR: 2.49; 95% CI: 1.33–4.67; p=0.004). Positive surgical margins conferred a 2.83-fold higher risk of mortality compared to negative margins (OR: 2.83; 95% CI: 1.54–5.20; p=0.002). With respect to the ALBI score, Grade 2 (OR: 3.55; 95% CI: 1.75–7.17) and Grade 3 (OR: 11.05; 95% CI: 4.38–27.84) were both associated with significantly increased mortality risk compared to Grade 1 (p<0.001 for both). Additional parameters found to be significant in univariate analysis included CEA (OR: 1.00; 95% CI: 1.00–1.00; p=0.017), total bilirubin (OR: 1.06; 95% CI: 1.03–1.09; p<0.001), direct bilirubin (OR: 1.09; 95% CI: 1.04–1.14; p<0.001), and albumin (OR: 0.94; 95% CI: 0.90–0.98; p=0.005) (Table 4). Multivariate Analysis In multivariate analysis, histopathological subtype, perineural invasion, positive surgical margin, and ALBI score remained independent prognostic factors for OS. Compared to the small-duct subtype, patients with the large-duct subtype had a significantly higher risk of mortality (OR: 35.37; 95% CI: 5.11–244.38; p<0.001), confirming the large-duct subtype as a strong independent prognostic factor. Perineural invasion was also found to be a powerful predictor of poor survival (OR: 70.48; 95% CI: 7.21–688.30; p=0.001). Positive surgical margins increased the risk of death by 7.09-fold compared to negative margins (OR: 7.09; 95% CI: 0.11–427.78; p=0.046). Finally, the ALBI score remained statistically significant in the multivariate model (p=0.025), further supporting its value as an independent prognostic factor for OS (Table 4). Table 4. Univariate and Multivariate Analyses for OS Univariate analysis Multivariate analysis Variables OR (95% CI) p-value OR (95% CI) p-value Sex Female 1 0.249 Male 1.42 (0.78–2.61) Smoking history None 1 0.105 Active smoker 0.36 (0.13–0.99) Ex-smoker 0.82 (0.37–1.81) Alcohol consumption No 1 0.230 Yes 1.03 (0.31–3.40) HBV infection Absent 1 0.625 Inactive chronic HBV 2.11 (0.65–6.86) Immunoactive, HBeAg-negative 0.83 (0.25–2.69) Occult HBV 0.83 (0.11–6.06) Cholelithiasis Absent 1 0.365 Present 1.22 (0.59–2.52) Tumor grade Grade X 1 0.222 Grade 1 0.22 (0.02–1.85) Grade 2 0.21 (0.28–1.61) Grade 3 1.07 (0.60–17.3) LVI Absent 1 0.094 Present 1.42 (0.76–2.65) PNI Absent 1 <0.001* 1 0.001* Present 6.25 (3.05–12.79) 70.48 (7.21–688.30) Microvascular invasion Absent 1 0.001* Present 3.97 (1.77–8.89) Histopathological subtype Small duct 1 0.001* 1 <0.001* Large duct 2.5 (1.43–4.39) 35.37 (5.11–244.38) Morphology Nodular 1 0.003* Sclerosing 3.63 (1.75–7.52) Papillary 0.54 (0.17–1.72) Tumor focality Solitary 1 0.620 Multifocal 0.77 (0.27–2.15) T T1 1 0.005* T2 1.45 (0.73–2.89) T3 3.78 (1.47–9.72) T4 4.12 (1.80–9.43) N N0 1 <0.001* N1 3.95 (2.11–7.38) Metastasis Absent 1 0.030* Present 2.74 (1.27–5.91) Stage Stage 1 1 <0.001* Stage 2 0.75 (0.24–2.30) Stage 3 5.55 (2.45–12.55) Stage 4 5.81 (2.21–15.28) Liver capsule invasion Absent 11 0.483 Present 1.25 (0.66–2.34) Tumor growth pattern Expansive 1 0.005* Infiltrative 2.39 (1.33–4.28) Adjacent structure invasion Absent 1 0.004* Present 2.49 (1.33–4.67) Tumor budding Absent 1 0.122 Grade 1 1.68 (0.39–7.14) Grade 2 2.23 (0.48–10.27) Grade 3 3.50 (0.78–15.62) Necrosis None 1 0.381 <30% 0.92 (0.49–1.72) 30%-60% 1.40 (0.60–3.27) 60%-90% 3.39 (0.44–25.82) Surgical margin Negative 1 0.002* 1 0.046* Positive 2.83 (1.54-5.20) 7.09 (0.11–427.78) ALBI score Grade 1 1 <0.001* 1 0.025* Grade 2 3.55 (1.75–7.17) 0.46 (0.04–5.49) Grade 3 11.05 (4.38–27.84) 21.13 (0.23–192.46) CA 19-9 (U/mL) 1.00 (1.00–1.00) 0.328 CEA (ng/mL) 1.00 (1.00–1.00) 0.017* AFP (µg/L) 1.00 (0.98–1.01) 0.887 Tumor size 0.99 (0.98–1.00) 0.311 AST (U/L) 1.00 (0.99–1.00) 0.740 ALT (U/L) 1.00 (0.99–1.00) 0.942 ALP (U/L) 1.00 (1.00–1.00) 0.059 GGT (U/L) 1.00 (1.00–1.00) 0.080 Total bilirubin (U/L) 1.06 (1.03–1.09) <0.001* Direct bilirubin (U/L) 1.09 (1.04–1.14) <0.001* LDH (U/L) 1.00 (0.99–1.00) 0.577 Albumin (g/dL) 0.94 (0.90–0.98) 0.005* ALBI: Albumin-bilirubin score, AFP: alpha-fetoprotein, ALT: alanine aminotransferase, AST: aspartate aminotransferase, ALP: alkaline phosphatase, CA 19-9: cancer antigen 19-9, CEA: carcinoembryonic antigen, GGT: gamma-glutamyl transferase, LDH: lactate dehydrogenase, LVI: lymphovascular invasion, IDH1: isocitrate dehydrogenase-1, PNI: perineural invasion Discussion Although iCCA is considered a rare and aggressive gastrointestinal malignancy, its incidence has been observed to increase over the past decade (4). In the treatment of malignancies, detailed analyses of the tumor’s genetic profile and evaluation of prognostic factors are becoming increasingly important in designing targeted and individualized therapeutic strategies. Recent advances in genomic profiling have enabled the identification of targetable alterations such as variations in IDH1, FGFR2, BRAF V600E, HER2, and NTRK (5), leading to the integration of NGS-based panels into clinical practice as recommended by the European Society for Medical Oncology for detecting ESCAT tier I alterations including IDH1 mutations, FGFR2 and NTRK fusions, and MSI-high status (6). In our study, IDH1 mutation was retrospectively analyzed using DNA extracted from pathological tissue samples, with a mutation rate of 2.3%. In contrast, pooled analyses from the literature indicate an overall prevalence of approximately 13.1% in iCCA (7). The lower frequency observed in our study may reflect ethnic differences, as well as technical limitations, since IDH1 testing could not be performed for 11 patients (12.5%) in our study. Moreover, only tissue blocks were analyzed; liquid biopsy might provide different detection rates. Our findings showed no statistically significant association between IDH1 mutation and OS. While one retrospective multicenter study reported longer median OS in patients with IDH1 mutation (8), another identified IDH1 mutation as an independent negative prognostic factor following first-line therapy in iCCA (2). These conflicting results may be explained by heterogeneity in patient populations, molecular subgroups, and methodological differences. Additionally, the relatively small sample size in our study likely limited the statistical power of survival analyses. In this study, we investigated the histopathological background of iCCA by evaluating liver biopsy and resection specimens. Our findings suggest a multifactorial etiology for iCCA development. We observed histopathological features associated with fibrosis and cirrhosis, as well as MASH, in 12.5% of patients. This points to a potential link among metabolic syndrome, fatty liver disease, and iCCA, a finding consistent with the results of De Lorenzo et al. (9), who reported a MASH prevalence of 22.5% in patients without classic iCCA risk factors. Furthermore, the presence of hepatocellular and hepatocanalicular cholestasis indicates that impaired bile drainage may contribute to carcinogenesis. Other features such as intraductal tubulopapillary neoplasms, chronic cholangitis, and foreign body-type granulomas suggest that premalignant changes, chronic inflammation, and immune responses also contribute to tumor progression. Analysis of stage distribution revealed that most patients were diagnosed at stage IB or IIIB, indicating that the patients in our study generally presented with locally advanced or advanced disease. This finding is consistent with the well-recognized challenge of early diagnosis in iCCA, as the majority of cases are identified only after the onset of symptoms (6, 10, 11). Regarding metastatic patterns, distant metastases were observed in 15.9% of patients, most commonly to the liver, followed by nonregional lymph nodes and bone. These results align with previously reported dissemination patterns (12), confirming that nonregional lymph nodes and bone are frequent sites of extrahepatic spread in iCCA. In our study, 68 patients underwent curative surgery. Notably, the proportion of patients who underwent curative resection in our study (68 out of 88, or 77.3%) was significantly higher than the rates of 20%–30% reported in the literature (13). This observed difference may be attributable to specific institutional selection criteria, comprehensive multidisciplinary evaluation processes, or unique characteristics of our patient population. However, these findings warrant confirmation through larger-scale studies. The most frequent adjuvant chemotherapy regimens were gemcitabine-capecitabine and capecitabine, while gemcitabine-cisplatin and gemcitabine-carboplatin were predominant in palliative settings. According to the literature, the standard first-line systemic therapy for patients with unresectable or advanced iCCA is gemcitabine-cisplatin-durvalumab or pembrolizumab, with FOLFOX recently accepted as the standard second-line treatment (14, 15). In multivariate analysis, histopathological subtype, perineural invasion, positive surgical margin, and ALBI score remained independent prognostic factors for OS. In addition, our histopathological analysis revealed that the large-duct iCCA subtype was associated with a 2.5-fold higher risk of worse survival compared to the small-duct subtype. Notably, this remained an independent prognostic factor in multivariate analysis, corroborating findings from previous studies (10, 16, 17). Similarly, a German study including 116 surgically resected iCCA patients reported median OS of 54.4 months for the small-duct subtype and 25.4 months for the large-duct subtype. While the large-duct subtype was a significant risk factor in that study’s univariate analysis, it was not significant in the multivariate model (1). We evaluated ALBI scores in our cohort, with 39.8% of patients classified as Grade 1, 33% as Grade 2, and 13.6% as Grade 3. Survival declined markedly with increasing grade, consistent with previous research linking higher ALBI grades to poorer prognosis (18). Thus, our results further corroborate the observations in the literature. While some studies have reported a significant impact of perineural invasion on both OS and recurrence-free survival (19), others have found no significant effect in univariate or multivariate analyses (20, 21). Perineural invasion is not recognized as a prognostic factor in the 8th edition of the guidelines of the American Joint Committee on Cancer or other guidelines (22). Larger studies and meta-analyses are needed to clarify whether it can be considered an independent prognostic factor. In our study, the impact of positive surgical margins on OS was assessed, and patients with positive margins were found to experience a statistically significant reduction in median OS, highlighting its adverse prognostic effect. Consistent with the literature, the presence of an R1 surgical margin was associated with shorter recurrence-free survival (23-25). Regarding tumor necrosis, patients with 60%–90% necrosis exhibited a 3.39-fold higher risk of unfavorable survival outcomes compared to those with less than 30% necrosis, although this difference did not reach statistical significance. Nevertheless, this trend is consistent with previous reports linking extensive necrosis to hypoxia-driven tumor aggressiveness, as demonstrated by Tsilimigras et al . (26). Similarly, the infiltrative growth pattern was associated with a 2.39-fold increased risk of poor survival. This observation aligns with updated guidelines designating the periductal-infiltrative subtype of iCCA as an unfavorable morphological variant (22). We also explored the prognostic significance of tumor budding in iCCA, a feature that has been established as a strong predictor of poor prognosis in other malignancies, particularly colorectal cancer (27). Our findings showed that patients had tumor budding classified as Grade 1 in 45.5% of cases, Grade 2 in 14.8%, and Grade 3 in 18.2%. While we observed a numerical difference in median OS across these grades, it did not reach the level of statistical significance. This outcome suggests that the prognostic impact of tumor budding may be less pronounced in iCCA than in colorectal cancer, or that a larger-scale study is needed to detect a statistically significant effect. Further research is warranted to clarify the role of tumor budding as a potential prognostic marker in iCCA. This study has several limitations, primarily due to its retrospective design and incomplete data, which restricted the scope of our analyses. Our molecular profiling was based solely on tissue samples, as we did not perform cell-free DNA analysis via liquid biopsy. This may have led to an underestimation of the true prevalence of IDH1 mutation. Additional technical factors, such as tissue adequacy, DNA primers, and laboratory conditions, could have further limited our ability to detect mutations. The observed IDH1 mutation rate of 2.3% was notably lower than the rate of approximately 13% reported in the literature (7), which may reflect ethnic differences. However, the small sample size and limited population diversity of our cohort necessitate larger studies to clarify the true mutation prevalence among Turkish iCCA patients. Despite these limitations, our study has made a significant contribution as the first in Türkiye to perform IDH1 mutation analysis and a detailed evaluation of histopathological features for iCCA as a rare malignancy. Conclusion Our findings indicate that perineural invasion, large-duct histopathology, positive surgical margins, and ALBI score are independent prognostic factors that significantly worsen survival in cases of iCCA. In our study, the IDH1 mutation rate was found to be 2.3%. Due to the small sample size and the percentage of patients for whom mutation analysis could not be performed, no definitive conclusion can be drawn regarding the prognostic significance of the IDH1 mutation in iCCA patients. However, the data obtained in this study highlight the importance of other prognostic factors that may play roles in understanding tumor biology. Furthermore, advanced-stage disease, infiltrative tumor growth pattern, invasion of adjacent structures, and biochemical markers (bilirubin/albumin levels) emerged as important determinants of survival. Future large-scale studies could further elucidate the impact of the IDH1 mutation on treatment approaches and contribute to the development of personalized therapeutic strategies. In this context, more detailed evaluation of the IDH1 mutation and other histopathological factors is warranted in planning individualized patient management and follow-up, as well as in investigating the efficacy of targeted treatment strategies. Declarations Author contributions All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work. M.B.: conceptualized and designed the study, supervised the project, and wrote the original draft of the manuscript. S.A.E.: and U.O: assisted in data acquisition, clinical interpretation, and manuscript revision. N.T. , A.S. and O.E.: performed pathological evaluation and preparation assessment of tissue samples. E.S. , D.H. , O.B. , E.A. and S.Y.: contributed to data curation, database management, and statistical analysis, and prepared Tables 1–4 and Figures 1–3. I.E. and N.O.: provided patient data acquisition, interpretation of clinical findings, and support in methodological planning. D.U.: provided clinical oversight, critical review of the data, and substantial contributions to manuscript revision. All authors reviewed and approved the final version of the manuscript and agree to be accountable for all aspects of the work. All authors have read and agreed to the published version of the manuscript. Funding The authors declare that no funds, grants, or other support were received during the preparation of this study. Data availability All data generated or analysed during this study are included in this published article. The genomic mutation analysis data have been deposited in the European Genome-phenome Archive (EGA) under accession number EGAS50000001638 (Direct link: https://ega-archive.org/studies/EGAS50000001638). Due to the sensitive nature of human genomic data, these datasets are available under controlled access. Researchers wishing to access the raw data must submit a request to the corresponding Data Access Committee (DAC) as outlined in the EGA repository. Additional inquiries may be directed to the corresponding author ( [email protected] ). Acknowledgements The authors acknowledge Onko Koçsel Pharmaceuticals for assistance with genetic mutation analysis. Competing interests The authors declare no competing interests. This study was approved by the Institutional Ethics Committee of Ankara Bilkent City Hospital (protocol number E1-23-3976, dated September 6, 2023) and was conducted according to good clinical practice, applicable laws, and the Declaration of Helsinki. References Kinzler MN, Schulze F, Bankov K, Gretser S, Becker N, Leichner R, et al. Impact of small duct- and large duct type on survival in patients with intrahepatic cholangiocarcinoma: Results from a German tertiary center. Pathology - Research and Practice. 2022;238:154126. Rimini M, Fabregat-Franco C, Persano M, Burgio V, Bergamo F, Niger M, et al. Clinical Outcomes After Progression on First-Line Therapies in IDH1 Mutated Versus Wild-Type Intrahepatic Cholangiocarcinoma Patients. Targeted Oncology. 2023;18(1):139-45. Wang P, Dong Q, Zhang C, Kuan PF, Liu Y, Jeck WR, et al. Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas. Oncogene. 2013;32(25):3091-100. Global Burden of Disease Cancer C, Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, et al. The Global Burden of Cancer 2013. JAMA Oncol. 2015;1(4):505-27. Mahmood U, Abbass A, Khan K. Optimizing outcomes and personalizing care with targeted agents in advanced cholangiocarcinoma. Cancer Treat Rev. 2024;131:102851. Vogel A, Bridgewater J, Edeline J, Kelley RK, Klumpen HJ, Malka D, et al. Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(2):127-40. Boscoe AN, Rolland C, Kelley RK. Frequency and prognostic significance of isocitrate dehydrogenase 1 mutations in cholangiocarcinoma: a systematic literature review. Journal of Gastrointestinal Oncology. 2019;10(4):751-65. Wintheiser G, Zemla T, Shi Q, Tran N, Prasai K, Tella SH, et al. Isocitrate Dehydrogenase-Mutated Cholangiocarcinoma: Natural History and Clinical Outcomes. JCO Precis Oncol. 2022;6:e2100156. De Lorenzo S, Tovoli F, Mazzotta A, Vasuri F, Edeline J, Malvi D, et al. Non-Alcoholic Steatohepatitis as a Risk Factor for Intrahepatic Cholangiocarcinoma and Its Prognostic Role. Cancers (Basel). 2020;12(11). Banales JM, Marin JJG, Lamarca A, Rodrigues PM, Khan SA, Roberts LR, et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol. 2020;17(9):557-88. Rimini M, Puzzoni M, Pedica F, Silvestris N, Fornaro L, Aprile G, et al. Cholangiocarcinoma: new perspectives for new horizons. Expert Rev Gastroenterol Hepatol. 2021;15(12):1367-83. Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet. 2014;383(9935):2168-79. Suzuki S, Sakaguchi T, Yokoi Y, Okamoto K, Kurachi K, Tsuchiya Y, et al. Clinicopathological prognostic factors and impact of surgical treatment of mass-forming intrahepatic cholangiocarcinoma. World J Surg. 2002;26(6):687-93. Nakamura H, Arai Y, Totoki Y, Shirota T, Elzawahry A, Kato M, et al. Genomic spectra of biliary tract cancer. Nat Genet. 2015;47(9):1003-10. Zhang K, Yu J, Yu X, Han Z, Cheng Z, Liu F, et al. Clinical and survival outcomes of percutaneous microwave ablation for intrahepatic cholangiocarcinoma. Int J Hyperthermia. 2018;34(3):292-7. Komuta M, Govaere O, Vandecaveye V, Akiba J, Van Steenbergen W, Verslype C, et al. Histological diversity in cholangiocellular carcinoma reflects the different cholangiocyte phenotypes. Hepatology. 2012;55(6):1876-88. Park S, Lee Y, Kim H, Yu MH, Lee ES, Yoon JH, et al. Subtype Classification of Intrahepatic Cholangiocarcinoma Using Liver MR Imaging Features and Its Prognostic Value. Liver Cancer. 2022;11(3):233-46. Kaneko S, Kurosaki M, Tsuchiya K, Yasui Y, Inada K, Kirino S, et al. Prognosis of intrahepatic cholangiocarcinoma stratified by albumin-bilirubin grade. Hepatol Res. 2021;51(8):902-8. Shirai K, Ebata T, Oda K, Nishio H, Nagasaka T, Nimura Y, et al. Perineural invasion is a prognostic factor in intrahepatic cholangiocarcinoma. World J Surg. 2008;32(11):2395-402. Kang SH, Hwang S, Lee YJ, Kim KH, Ahn CS, Moon DB, et al. Prognostic comparison of the 7th and 8th editions of the American Joint Committee on Cancer staging system for intrahepatic cholangiocarcinoma. J Hepatobiliary Pancreat Sci. 2018;25(4):240-8. Chan KM, Tsai CY, Yeh CN, Yeh TS, Lee WC, Jan YY, et al. Characterization of intrahepatic cholangiocarcinoma after curative resection: outcome, prognostic factor, and recurrence. BMC Gastroenterol. 2018;18(1):180. Lee AJ, Chun YS. Intrahepatic cholangiocarcinoma: the AJCC/UICC 8th edition updates. Chinese Clinical Oncology. 2018;7(5):52. Farges O, Fuks D, Boleslawski E, Le Treut YP, Castaing D, Laurent A, et al. Influence of surgical margins on outcome in patients with intrahepatic cholangiocarcinoma: a multicenter study by the AFC-IHCC-2009 study group. Ann Surg. 2011;254(5):824-29; discussion 30. Moris D, Palta M, Kim C, Allen PJ, Morse MA, Lidsky ME. Advances in the treatment of intrahepatic cholangiocarcinoma: An overview of the current and future therapeutic landscape for clinicians. CA Cancer J Clin. 2023;73(2):198-222. Spolverato G, Yakoob MY, Kim Y, Alexandrescu S, Marques HP, Lamelas J, et al. The Impact of Surgical Margin Status on Long-Term Outcome After Resection for Intrahepatic Cholangiocarcinoma. Ann Surg Oncol. 2015;22(12):4020-8. Tsilimigras DI, Ejaz A, Cloyd J, Guglielmi A, Aldrighetti L, Weiss M, et al. Tumor Necrosis Impacts Prognosis of Patients Undergoing Resection for T1 Intrahepatic Cholangiocarcinoma. Annals of Surgical Oncology. 2022;29(7):4326-34. Zlobec I, Lugli A. Epithelial mesenchymal transition and tumor budding in aggressive colorectal cancer: tumor budding as oncotarget. Oncotarget. 2010;1(7):651-61. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8449961","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":604280756,"identity":"c9dfb390-a54d-47f0-ae6c-9c646b2fcea0","order_by":0,"name":"Muge 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15:38:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8449961/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8449961/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104782106,"identity":"6f475df5-378f-4360-a2da-02a3c3cc9901","added_by":"auto","created_at":"2026-03-17 07:56:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":600401,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eRepresentative histopathological features of intrahepatic cholangiocarcinoma subtypes. (1a) Large duct–type. (1b) Small duct–type (hematoxylin and eosin staining, scale bar = 500 µm).\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8449961/v1/d60c5a213751eb1207d9bbe0.png"},{"id":104593545,"identity":"cd41bfdd-f882-489f-b822-a308f5f791f8","added_by":"auto","created_at":"2026-03-13 17:41:52","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":33224,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan–Meier curve for median overall survival in patients with intrahepatic cholangiocarcinoma\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8449961/v1/2ec4887eeaa8b75edfab5135.png"},{"id":104593543,"identity":"2a215d66-174d-43d9-b656-6322187026d0","added_by":"auto","created_at":"2026-03-13 17:41:52","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":36545,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan–Meier curves for median overall survival according to albumin-bilirubin (ALBI) scores in patients with intrahepatic cholangiocarcinoma\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8449961/v1/67783c6cdbaa9a873127af3b.png"},{"id":105383007,"identity":"f03a235b-7008-49fe-9be5-270f2b7d6b5e","added_by":"auto","created_at":"2026-03-25 11:42:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3774663,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8449961/v1/65e81646-f194-4e22-bda2-47004e73a3b2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Mutation Rate of IDH1 and the Impact of Pathological Features on Survival in Intrahepatic Cholangiocarcinoma","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCholangiocarcinoma (CCA) is an aggressive epithelial cancer arising from the bile ducts. Intrahepatic CCA (iCCA) ranks as the second most common primary liver cancer after hepatocellular carcinoma and represents about 3% of all gastrointestinal malignancies. The incidence of iCCA is increasing and its prognosis remains poor due to the absence of distinct symptoms, often resulting in diagnosis at advanced stages. The 5-year overall survival rate for iCCA is generally low, ranging between 5% and 20%.\u003c/p\u003e \u003cp\u003eMolecular profiling has identified potentially targetable genomic alterations in approximately 40% of CCA patients. Among these, mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) are notable, occurring in about 14% of iCCA cases but rarely in extrahepatic CCA.\u003c/p\u003e \u003cp\u003eClinically, the prognostic implications of IDH1 mutation are still debated. Some studies have demonstrated long-term progression-free survival for mutation carriers (1), while other studies of advanced disease have reported a negative impact of IDH1 on survival after progression (2). One study associated IDH1/2 mutations in iCCA with longer overall survival and a longer time to recurrence after resection (3). Taken together, these findings highlight the need for integrative analyses combining mutation status and histopathological features to decipher the prognostic value of IDH1 in iCCA.\u003c/p\u003e \u003cp\u003eThis study aims to retrospectively analyze pathological tissue samples from iCCA patients treated at two centers in T\u0026uuml;rkiye. The primary objectives are to determine the prevalence of IDH1 mutations and to evaluate the effects of other clinicopathological features on survival. The results are expected to provide important insights that can guide future clinical decisions and improve outcomes for patients with this challenging cancer.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy Design\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective, cross-sectional study was conducted between October 1, 2023, and February 1, 2025, at two tertiary centers: the University of Health Sciences Ankara Bilkent City Hospital and the Gazi University Faculty of Medicine Hospital. The study included patients diagnosed with iCCA between 2005 and 2025; their records were obtained from the archives of the Medical Oncology Department of Ankara Bilkent City Hospital and the Medical Oncology Department of Gazi University’s Faculty of Medicine.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePopulation and Participants\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 88 patients with histologically confirmed iCCA were included. Eligible participants were men or women aged ≥18 years, under follow-up with a confirmed iCCA diagnosis, and with accessible pathology blocks and complete clinical data from the oncology archives.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eData Collection\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical, laboratory, and survival data were retrospectively retrieved from the medical records of the Department of Medical Oncology of Ankara Bilkent City Hospital and the Gazi University Faculty of Medicine Hospital. Histopathological prognostic factors were assessed by experienced pathologists from both participating institutions. Survival data were obtained from the Turkish National Population Registry System.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eLaboratory Analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFormalin-fixed paraffin-embedded (FFPE) tumor blocks, obtained either by Tru-Cut biopsy or surgical resection, were retrieved from the pathology archives for IDH1 mutation testing. Histological sections of 3–5 µm in thickness were prepared and examined under light microscopy. DNA extraction was performed using the QIAamp DNA FFPE Tissue Kit (Qiagen Inc., USA) according to the manufacturer’s protocol, with isolates stored at –20 °C until polymerase chain reaction (PCR) amplification.\u003c/p\u003e\n\u003cp\u003ePrimers were designed to target exon 4 of the IDH1 gene (NM_05896), encompassing codon 132, with amplification extending from codon 54 to the C-terminal end of the exon. PCR amplification was performed and the resulting amplicons were pooled in approximately equal ratios based on reaction yield. DNA quantification and standardization were carried out using a Nanodrop N1000 spectrophotometer (Thermo Inc., USA), adjusting the DNA concentration to 0.2 ng/µL.\u003c/p\u003e\n\u003cp\u003eLibrary preparation for next-generation sequencing (NGS) was performed using the NexteraXT kit (Illumina Inc., USA) and sequencing was conducted on the Illumina MiSeq platform. Read alignment was performed with MiSeq Reporter software and mutation analysis was carried out using IGV 2.9.5 (Broad Institute, USA). The coverage allele fraction threshold was set to 0.03 to enable the detection of low-frequency somatic mutations, and only regions with read depths of ≥200× were analyzed. Codon 132 corresponded to chr2:208248387–208248389 (hg38 reference genome), resulting in an R132 protein variant when mutated. Each sequencing result was independently reviewed by two molecular biologists to confirm mutation status.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eSurvival Analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eProgression-free survival (PFS) was defined as the interval from initiation of first-line chemotherapy to radiologically confirmed disease progression or death from any cause. Overall survival (OS) was defined as the interval from histopathological diagnosis to death from any cause or last follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthical Approval\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Institutional Ethics Committee of Ankara Bilkent City Hospital (protocol number E1-23-3976, dated September 6, 2023) and was conducted in accordance with good clinical practice, applicable laws, and the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003eIn accordance with the decision of the Institutional Ethics Committee of Ankara Bilkent City Hospital, informed consent was not required due to the retrospective design of the study and the use of fully anonymized data with no possibility of identifying individual participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStatistical Analyses\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll statistical analyses were performed using IBM SPSS Statistics 26.0 for Windows (IBM Corp., USA). The normality of the data distribution was assessed using the Kolmogorov–Smirnov test. Continuous variables were summarized as median, minimum, and maximum values, while categorical variables were expressed as counts and percentages. Survival analyses were performed using the Kaplan–Meier method and survival curves were compared using the log-rank test. Multivariate analysis was conducted using the Cox proportional hazards regression model, including variables with statistical significance in univariate analysis. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated, and values of p\u0026lt;0.05 were considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThis study included 88 patients diagnosed with iCCA who were followed at two different centers. The \u003cstrong\u003emedian age at diagnosis\u003c/strong\u003e was \u003cstrong\u003e62\u0026nbsp;\u003c/strong\u003e(range: 31\u0026ndash;79) years. The study group consisted of \u003cstrong\u003e55 men (62.5%)\u003c/strong\u003e and \u003cstrong\u003e33 women (37.5%)\u003c/strong\u003e, reflecting a male predominance.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong the presenting symptoms, abdominal pain was the most common, observed in 67% (n=59) of patients. Regarding disease staging, Stage IB and Stage IIIB were the most frequent stages, each accounting for 22.7% (n=15) of cases.\u003c/p\u003e\n\u003cp\u003eIn the evaluation of distant metastasis sites, liver metastasis and nonregional lymph node metastasis were detected at equal frequencies, each observed in 5.7% (n=4) of patients.\u003c/p\u003e\n\u003cp\u003eThe baseline demographic and clinicopathological characteristics of patients diagnosed with iCCA are presented in Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;Baseline Demographic and Clinicopathological Characteristics of Patients with Intrahepatic Cholangiocarcinoma\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"576\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"bottom\" style=\"width: 354px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (min\u003c/strong\u003e\u0026ndash;\u003cstrong\u003emax)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e88 (100)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 354px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at diagnosis, years\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e62 (31\u0026ndash;79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e33 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e55 (62.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"4\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eECOG PS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e4 (4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e74 (84.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e7 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e3 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"4\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSmoking history\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNone\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e43 (48.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eActive smoker\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e12 (13.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEx-smoker\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e16 (18.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e17 (19.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"3\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlcohol consumption\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e66 (75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e5 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e17 (19.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFamily history of CCA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e71 (80.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e17 (19.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"4\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHBV infection\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e74 (84.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInactive chronic HBV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e6 (6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eImmunoactive, HBeAg-negative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e6 (6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOccult HBV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e2 (2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHCV infection\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e88 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"3\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCholelithiasis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e58 (65.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e18 (20.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e12 (13.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIncidental diagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e75 (85.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e13 (14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbdominal pain\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e29 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e59 (67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeight loss\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e82 (93.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e6 (6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eJaundice\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e67 (76.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e21 (23.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePruritus\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e77 (87.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e11 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNausea\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e80 (90.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e8 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage IA \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e8 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage IB\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e20 (22.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage II\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e13 (14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage IIIA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e3 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage IV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e14 (15.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e10 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e43 (48.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e28 (31.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e7 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e9 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e1 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e60 (68.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e24 (27.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e4 (4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eM\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eM0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e65 (73.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eM1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e14 (15.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e9 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLiver metastasis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e74 (84.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e5 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e9 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOmentum metastasis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e77 (87.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e2 (2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e9 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePeritoneal metastasis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e77 (87.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e2 (2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e9 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNonregional lymph node metastasis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e74 (84.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e5 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e9 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLung metastasis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e78 (88.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e1 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e9 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBone metastasis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e76 (86.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e3 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e9 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdrenal metastasis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e78 (88.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e1 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e9 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumor diameter (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e60 (17\u0026ndash;174)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eCCA: Cholangiocarcinoma, ECOG PS: Eastern Cooperative Oncology Group performance status, HBV: hepatitis B virus, HCV: hepatitis C virus\u003c/p\u003e\n\u003cp\u003ePCR-based analysis revealed an IDH1 wild-type profile in 85.2% (n=75) of patients and an IDH1 mutation in 2.3% (n=2). Mutation status was indeterminate in 12.5% (n=11) due to inadequate tumor tissue.\u003c/p\u003e\n\u003cp\u003eAccording to the histopathological subtype, the small-duct type was most prevalent, observed in 55.7% (n=49) of cases. Morphologically, the nodular form was the most frequent pattern, identified in 67% (n=59) of patients. Regarding tumor growth patterns, infiltrative growth was observed in 45.5% (n=40) of cases. Solitary tumors were present in 79.5% (n=70) of the patients.\u003c/p\u003e\n\u003cp\u003eHistopathological assessment of the nontumorous liver parenchyma demonstrated that hepatocellular cholestasis (19.3%, n=17) and mild portal fibrosis with inflammation (17%, n=15) were the most frequently observed background lesions.\u003c/p\u003e\n\u003cp\u003eIn terms of tumor grade, Grade 2 differentiation was the most frequent, identified in 70.5% (n=62) of patients. Capsular invasion was absent in 68.2% (n=60) and adjacent structure invasion was not observed in 65.9% (n=58) of cases.\u003c/p\u003e\n\u003cp\u003eAccording to tumor budding, Grade 1 was the most common, accounting for 45.5% (n=40).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLymphovascular invasion and perineural invasion were detected in 55.7% (n=49) and 47.7% (n=42) of patients, respectively, whereas microvascular invasion was observed in 9.1% (n=8).\u003c/p\u003e\n\u003cp\u003eAssessment of the surgical margins demonstrated that negative margins were achieved in 58% (n=51) of cases. Regarding the albumin-bilirubin (ALBI) score, Grade 1 was the most frequent classification, observed in 39.8% (n=35) of patients.\u003c/p\u003e\n\u003cp\u003eThe pathological, molecular, and biochemical characteristics of patients diagnosed with iCCA are presented in Table 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ePathological, Molecular, and Biochemical Characteristics of Patients with Intrahepatic Cholangiocarcinoma\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"605\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e88 (100)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIDH1 mutation\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNegative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e75 (85.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePositive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e2 (2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInsufficient material for analysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e11 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistopathological subtype\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSmall-duct type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e49 (55.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLarge-duct type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e27 (30.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e12 (13.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMorphology\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNodular\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e59 (67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSclerosing\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e11 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePapillary\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e4 (4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e14 (15.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSolitary/multiple\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSolitary\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e70 (79.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultiple\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e8 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e10 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNontumorous\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eliver parenchyma\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnremarkable pathology\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e12 (13.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHBV-related liver cirrhosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e2 (2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMASH-related liver cirrhosis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e1 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCryptogenic liver cirrhosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e2 (2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrimary sclerosing cholangitis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e2 (2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMASH\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e11 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eArising in the background of intraductal tubulopapillary neoplasm\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e2 (2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHepatocellular cholestasis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e17 (19.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIncomplete cirrhosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e1 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHepatocanalicular cholestasis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e10 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMild portal fibrosis and inflammation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e15 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCholangitis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e1 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eForeign body-type granulomatous reaction\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e2 (2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e10 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade X\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e10 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e15 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e62 (70.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e1 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLiver capsule invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e60 (68.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e19 (21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e9 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumor growth\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003epattern\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eExpansile\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e36 (40.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInfiltrative\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e40 (45.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e12 (13.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjacent structure invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e58 (65.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e20 (22.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e10 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumor budding\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e6 (6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e40 (45.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade \u0026nbsp;2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e13 (14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e16 (18.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e13 (14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNecrosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e41 (46.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;30%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e24 (27.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e30%\u0026ndash;60%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e9 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e60%\u0026ndash;90%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e1 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e13 (14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLymphovascular invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e49 (55.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e12 (13.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePerineural \u0026nbsp;invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e33 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e42 (47.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e13 (14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMicrovascular invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e70 (79.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e8 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e10 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgical margin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNegative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e51 (58)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePositive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e23 (26.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e14 (15.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eALBI score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e35 (39.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e29 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e12 (13.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e12 (13.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCA 19-9 (U/mL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e58.1 (0.8\u0026ndash;67838.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCEA (ng/mL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e1.7 (0.05\u0026ndash;1901)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAFP (\u0026micro;g/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e2.7 (0.05\u0026ndash;133.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 267px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBiochemical parameters at diagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAST (U/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e51.5 (10\u0026ndash;617)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eALT (U/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e49.5 (14\u0026ndash;828)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eALP (U/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e169 (38\u0026ndash;1941)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGGT (U/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e143 (18\u0026ndash;1434)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal bilirubin (mg/dL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e1.2 (0.2\u0026ndash;30.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDirect bilirubin (mg/dL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e0.4 (0.1\u0026ndash;20.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLDH (U/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp;241 (120\u0026ndash;862)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlbumin (g/dL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 216px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;39.3 (12\u0026ndash;50)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAFP: Alpha-fetoprotein, ALBI: albumin-bilirubin score, ALP: alkaline phosphatase, ALT: alanine aminotransferase, AST: aspartate aminotransferase, CA 19-9: carbohydrate antigen 19-9, CEA: carcinoembryonic antigen, GGT: gamma-glutamyl transferase, IDH1: isocitrate dehydrogenase 1, LDH: lactate dehydrogenase, MASH: metabolic dysfunction-associated steatohepatitis\u003c/p\u003e\n\u003cp\u003eA total of \u003cstrong\u003e87 patients\u003c/strong\u003e were evaluated according to the intent of treatment. Among them, \u003cstrong\u003e68 patients (78.2%)\u003c/strong\u003e underwent \u003cstrong\u003ecurative surgery\u003c/strong\u003e, while \u003cstrong\u003e19 patients (21.8%)\u003c/strong\u003e were managed noncuratively with a palliative or nonsurgical approach. We could not access surgical information for 14 patients. As shown in Table 3, most patients who underwent curative surgery were diagnosed at an early stage. Specifically, curative surgery was performed for 41.2% (n=28) of patients with stage I disease, 19.1% (n=13) of those with stage II disease, 30.9% (n=21) of those with stage III disease, and only 1.5% (n=1) of those with stage IV disease. In contrast, among patients who did not undergo curative surgery, the majority were stage IV, accounting for 68.4% (n=13) of cases.\u003c/p\u003e\n\u003cp\u003eAnalysis of treatment regimens revealed that 42.6% (n=29) of patients who underwent curative surgery received adjuvant chemotherapy, 10.3% (n=7) received radiotherapy following adjuvant chemotherapy, and 13.2% (n=9) were treated with adjuvant chemoradiotherapy. In the nonsurgical group, 63.2% (n=12) received palliative chemotherapy due to metastatic disease (Table 3).\u003c/p\u003e\n\u003cp\u003eRegarding adjuvant chemotherapy regimens, the gemcitabine-capecitabine combination was the most commonly administered treatment (32.4%; n=22), followed by capecitabine monotherapy (17.6%; n=12). Among patients receiving palliative chemotherapy, the most frequently used regimen was gemcitabine-cisplatin, which was administered in 47.4% (n=9) of the cases (Table 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Treatment Regimens in Patients with Intrahepatic Cholangiocarcinoma\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"552\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"3\" valign=\"bottom\" style=\"width: 441px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCurative surgery\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e68 (100)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e19 (100)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e28 (41.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e13 (19.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage \u0026nbsp;3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e21 (30.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e1 (5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage \u0026nbsp;4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e1 (1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e13 (68.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e5 (7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e5 (26.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"8\" valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment regimen\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment refusal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e2 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery + adjuvant CT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e29 (42.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery + adjuvant CT followed by adjuvant RT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e7 (10.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMetastatic (palliative) CT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e12 (63.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNeoadjuvant CT + surgery + adjuvant CT/RT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e2 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurveillance after surgery without therapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e1 (1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients who died before receiving treatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e14 (20.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e5 (26.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e13 (19.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e2 (10.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\" valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjuvant CT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGemcitabine\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e2 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"7\" valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGemcitabine + capecitabine\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e22 (32.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCapecitabine\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e12 (17.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGemcitabine + oxaliplatin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e1 (1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e14 (20.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment refusal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e3 (4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients who died before receiving treatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e14 (20.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePalliative CT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGemcitabine\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"5\" valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e1 (5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGemcitabine + cisplatin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e9 (47.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGemcitabine + carboplatin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e1 (5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e3 (15.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients who died before receiving treatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e5 (26.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCRT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNone\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e32 (47.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e12 (63.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjuvant\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e9 (13.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnknown\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e13 (19.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e2 (10.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 314px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients who died before receiving treatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e14 (20.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e5 (26.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eCT: Chemotherapy, CRT: chemoradiotherapy, RT: radiotherapy\u003c/p\u003e\n\u003cp\u003eThe median OS of all analyzed patients was 19.1 months (95% CI: 9.7\u0026ndash;28.5) (Figure 2).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;Stratification by ALBI score revealed striking differences in OS, with rates of 40.1 months (95% CI: 26.6\u0026ndash;53.7) for Grade 1, 11.1 months (95% CI: 4.1\u0026ndash;18.1) for Grade 2, and 4.4 months (95% CI: 0.02\u0026ndash;10.4) for Grade 3 (p\u0026lt;0.001). Pairwise comparisons confirmed significant survival differences across all grades (Grade 1 vs. 2, p\u0026lt;0.001; Grade 1 vs. 3, p\u0026lt;0.001; Grade 2 vs. 3, p=0.017) (Figure 3).\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAs shown in Table 4, univariate and multivariate analyses for OS identified several significant prognostic factors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eUnivariate Analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWhen tumor growth patterns were evaluated, using the expansive pattern as the reference, the infiltrative growth pattern was associated with a 2.39-fold increased risk of death (OR: 2.39; 95% CI: 1.33\u0026ndash;4.28), and this finding was statistically significant (p=0.005). The presence of adjacent structure invasion was similarly associated with worse OS (OR: 2.49; 95% CI: 1.33\u0026ndash;4.67; p=0.004). Positive surgical margins conferred a 2.83-fold higher risk of mortality compared to negative margins (OR: 2.83; 95% CI: 1.54\u0026ndash;5.20; p=0.002). With respect to the ALBI score, Grade 2 (OR: 3.55; 95% CI: 1.75\u0026ndash;7.17)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;and Grade 3 (OR: 11.05; 95% CI: 4.38\u0026ndash;27.84) were both associated with significantly increased mortality risk compared to Grade 1 (p\u0026lt;0.001 for both). Additional parameters found to be significant in univariate analysis included CEA (OR: 1.00; 95% CI: 1.00\u0026ndash;1.00; p=0.017), total bilirubin (OR: 1.06; 95% CI: 1.03\u0026ndash;1.09; p\u0026lt;0.001), direct bilirubin (OR: 1.09; 95% CI: 1.04\u0026ndash;1.14; p\u0026lt;0.001), and albumin (OR: 0.94; 95% CI: 0.90\u0026ndash;0.98; p=0.005) (Table 4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eMultivariate Analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn multivariate analysis, histopathological subtype, perineural invasion, positive surgical margin, and ALBI score remained independent prognostic factors for OS. Compared to the small-duct subtype, patients with the large-duct subtype had a significantly higher risk of mortality (OR: 35.37; 95% CI: 5.11\u0026ndash;244.38; p\u0026lt;0.001), confirming the large-duct subtype as a strong independent prognostic factor. Perineural invasion was also found to be a powerful predictor of poor survival (OR: 70.48; 95% CI: 7.21\u0026ndash;688.30; p=0.001). Positive surgical margins increased the risk of death by 7.09-fold compared to negative margins (OR: 7.09; 95% CI: 0.11\u0026ndash;427.78; p=0.046). Finally, the ALBI score remained statistically significant in the multivariate model (p=0.025), further supporting its value as an independent prognostic factor for OS (Table 4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4. Univariate and Multivariate Analyses for OS\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"624\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 146px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariate analysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 146px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariate\u003c/strong\u003e \u003cstrong\u003eanalysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.249\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1.42 (0.78\u0026ndash;2.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSmoking history\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNone\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"3\" valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eActive smoker\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.36 (0.13\u0026ndash;0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEx-smoker\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.82 (0.37\u0026ndash;1.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlcohol consumption\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.230\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1.03 (0.31\u0026ndash;3.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHBV infection\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"4\" valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInactive chronic HBV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e2.11 (0.65\u0026ndash;6.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eImmunoactive,\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHBeAg-negative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.83 (0.25\u0026ndash;2.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOccult HBV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.83 (0.11\u0026ndash;6.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCholelithiasis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.365\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1.22 (0.59\u0026ndash;2.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumor grade\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade X\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.222\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"4\" valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.22 (0.02\u0026ndash;1.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.21 (0.28\u0026ndash;1.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1.07 (0.60\u0026ndash;17.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLVI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.094\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1.42 (0.76\u0026ndash;2.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePNI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e6.25 (3.05\u0026ndash;12.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e70.48 (7.21\u0026ndash;688.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMicrovascular invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e3.97 (1.77\u0026ndash;8.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistopathological subtype\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSmall duct\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLarge duct\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e2.5 (1.43\u0026ndash;4.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e35.37 (5.11\u0026ndash;244.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMorphology\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNodular\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.003*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"3\" valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSclerosing\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e3.63 (1.75\u0026ndash;7.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePapillary\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.54 (0.17\u0026ndash;1.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumor focality\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSolitary\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.620\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultifocal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.77 (0.27\u0026ndash;2.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.005*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"4\" valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1.45 (0.73\u0026ndash;2.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e3.78 (1.47\u0026ndash;9.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e4.12 (1.80\u0026ndash;9.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 191px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e3.95 (2.11\u0026ndash;7.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMetastasis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.030*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e2.74 (1.27\u0026ndash;5.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"4\" valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e0.75 (0.24\u0026ndash;2.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage 3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e5.55 (2.45\u0026ndash;12.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage 4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e5.81 (2.21\u0026ndash;15.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLiver capsule invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.483\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1.25 (0.66\u0026ndash;2.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumor growth pattern\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eExpansive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.005*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInfiltrative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e2.39 (1.33\u0026ndash;4.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjacent structure invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e2.49 (1.33\u0026ndash;4.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumor budding\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbsent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.122\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"4\" valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1.68 (0.39\u0026ndash;7.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e2.23 (0.48\u0026ndash;10.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e3.50 (0.78\u0026ndash;15.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNecrosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNone\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.381\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"4\" valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;30%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e0.92 (0.49\u0026ndash;1.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e30%-60%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1.40 (0.60\u0026ndash;3.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e60%-90%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e3.39 (0.44\u0026ndash;25.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgical margin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNegative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.046*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePositive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e2.83 (1.54-5.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e7.09 (0.11\u0026ndash;427.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eALBI score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.025*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e3.55 (1.75\u0026ndash;7.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e0.46 (0.04\u0026ndash;5.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e11.05 (4.38\u0026ndash;27.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e21.13 (0.23\u0026ndash;192.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCA 19-9 (U/mL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1.00 (1.00\u0026ndash;1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.328\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCEA (ng/mL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1.00 (1.00\u0026ndash;1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.017*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAFP (\u0026micro;g/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1.00 (0.98\u0026ndash;1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.887\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumor size\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e0.99 (0.98\u0026ndash;1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.311\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAST (U/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1.00 (0.99\u0026ndash;1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.740\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eALT (U/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1.00 (0.99\u0026ndash;1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.942\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eALP (U/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1.00 (1.00\u0026ndash;1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.059\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGGT (U/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1.00 (1.00\u0026ndash;1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.080\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ebilirubin (U/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1.06 (1.03\u0026ndash;1.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDirect\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ebilirubin (U/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1.09 (1.04\u0026ndash;1.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLDH (U/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e1.00 (0.99\u0026ndash;1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.577\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlbumin\u0026nbsp;(g/dL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e0.94 (0.90\u0026ndash;0.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.005*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eALBI: Albumin-bilirubin score, AFP: alpha-fetoprotein, ALT: alanine aminotransferase, AST: aspartate aminotransferase, ALP: alkaline phosphatase, CA 19-9: cancer antigen 19-9, CEA: carcinoembryonic antigen, GGT: gamma-glutamyl\u0026nbsp;transferase, LDH: lactate dehydrogenase, LVI: lymphovascular invasion, IDH1: isocitrate dehydrogenase-1,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ePNI: perineural invasion\u003c/p\u003e"},{"header":"Discussion ","content":"\u003cp\u003eAlthough iCCA is considered a rare and aggressive gastrointestinal malignancy, its incidence has been observed to increase over the past decade\u0026nbsp;(4). In the treatment of malignancies, detailed analyses of the tumor’s genetic profile and evaluation of prognostic factors are becoming increasingly important in designing targeted and individualized therapeutic strategies. Recent advances in genomic profiling have enabled the identification of targetable alterations such as variations in IDH1, FGFR2, BRAF V600E, HER2, and NTRK (5), leading to the integration of NGS-based panels into clinical practice as recommended by the European Society for Medical Oncology for detecting ESCAT tier I alterations including IDH1 mutations, FGFR2 and NTRK fusions, and MSI-high status (6). In our study, IDH1 mutation was retrospectively analyzed using DNA extracted from pathological tissue samples, with a mutation rate of 2.3%. In contrast, pooled analyses from the literature indicate an overall prevalence of approximately 13.1% in iCCA (7). The lower frequency observed in our study may reflect ethnic differences, as well as technical limitations, since IDH1 testing could not be performed for 11 patients (12.5%) in our study. Moreover, only tissue blocks were analyzed; liquid biopsy might provide different detection rates.\u003c/p\u003e\n\u003cp\u003eOur findings showed no statistically significant association between IDH1 mutation and OS. While one retrospective multicenter study reported longer median OS in patients with IDH1 mutation\u0026nbsp;(8), another identified IDH1 mutation as an independent negative prognostic factor following first-line therapy in iCCA (2). These conflicting results may be explained by heterogeneity in patient populations, molecular subgroups, and methodological differences. Additionally, the relatively small sample size in our study likely limited the statistical power of survival analyses.\u003c/p\u003e\n\u003cp\u003eIn this study, we investigated the histopathological background of iCCA by evaluating liver biopsy and resection specimens. Our findings suggest a multifactorial etiology for iCCA development. We observed histopathological features associated with fibrosis and cirrhosis, as well as MASH, in 12.5% of patients. This points to a potential link among metabolic syndrome, fatty liver disease, and iCCA, a finding consistent with the results of De Lorenzo et al. (9), who reported a MASH prevalence of 22.5% in patients without classic iCCA risk factors. Furthermore, the presence of hepatocellular and hepatocanalicular cholestasis indicates that impaired bile drainage may contribute to carcinogenesis. Other features such as intraductal tubulopapillary neoplasms, chronic cholangitis, and foreign body-type granulomas suggest that premalignant changes, chronic inflammation, and immune responses also contribute to tumor progression.\u003c/p\u003e\n\u003cp\u003eAnalysis of stage distribution revealed that most patients were diagnosed at stage IB or IIIB, indicating that the patients in our study generally presented with locally advanced or advanced disease. This finding is consistent with the well-recognized challenge of early diagnosis in iCCA, as the majority of cases are identified only after the onset of symptoms (6, 10, 11). Regarding metastatic patterns, distant metastases were observed in 15.9% of patients, most commonly to the liver, followed by nonregional lymph nodes and bone. These results align with previously reported dissemination patterns\u0026nbsp;(12), confirming that nonregional lymph nodes and bone are frequent sites of extrahepatic spread in iCCA.\u003c/p\u003e\n\u003cp\u003eIn our study, 68 patients underwent curative surgery. Notably, the proportion of patients who underwent curative resection in our study (68 out of 88, or 77.3%) was significantly higher than the rates of 20%–30% reported in the literature\u0026nbsp;(13). This observed difference may be attributable to specific institutional selection criteria, comprehensive multidisciplinary evaluation processes, or unique characteristics of our patient population. However, these findings warrant confirmation through larger-scale studies. The most frequent adjuvant chemotherapy regimens were gemcitabine-capecitabine and capecitabine, while gemcitabine-cisplatin and gemcitabine-carboplatin were predominant in palliative settings. According to the literature, the standard first-line systemic therapy for patients with unresectable or advanced iCCA is gemcitabine-cisplatin-durvalumab or pembrolizumab, with FOLFOX recently accepted as the standard second-line treatment (14, 15).\u003c/p\u003e\n\u003cp\u003eIn multivariate analysis,\u0026nbsp;histopathological subtype, perineural invasion, positive surgical margin, and ALBI score remained independent prognostic factors for OS. In addition, our histopathological analysis revealed that the large-duct iCCA subtype was associated with a 2.5-fold higher risk of worse survival compared to the small-duct subtype. Notably, this remained an independent prognostic factor in multivariate analysis, corroborating findings from previous studies (10, 16, 17). Similarly, a German study including 116 surgically resected iCCA patients reported median OS of 54.4 months for the small-duct subtype and 25.4 months for the large-duct subtype. While the large-duct subtype was a significant risk factor in that study’s univariate analysis, it was not significant in the multivariate model (1).\u003c/p\u003e\n\u003cp\u003eWe evaluated ALBI scores in our cohort, with 39.8% of patients classified as Grade 1, 33% as Grade 2, and 13.6% as Grade 3. Survival declined markedly with increasing grade, consistent with previous research linking higher ALBI grades to poorer prognosis\u0026nbsp;(18). Thus, our results further corroborate the observations in the literature.\u003c/p\u003e\n\u003cp\u003eWhile some studies have reported a significant impact of perineural invasion on both OS and recurrence-free survival (19), others have found no significant effect in univariate or multivariate analyses (20, 21). Perineural invasion is not recognized as a prognostic factor in the 8th edition of the guidelines of the American Joint Committee on Cancer or other guidelines (22). Larger studies and meta-analyses are needed to clarify whether it can be considered an independent prognostic factor.\u003c/p\u003e\n\u003cp\u003eIn our study, the impact of positive surgical margins on OS was assessed, and patients with positive margins were found to experience a statistically significant reduction in median OS, highlighting its adverse prognostic effect. Consistent with the literature, the presence of an R1 surgical margin was associated with shorter recurrence-free survival (23-25).\u003c/p\u003e\n\u003cp\u003eRegarding tumor necrosis, patients with 60%–90% necrosis exhibited a 3.39-fold higher risk of unfavorable survival outcomes compared to those with less than 30% necrosis, although this difference did not reach statistical significance. Nevertheless, this trend is consistent with previous reports linking extensive necrosis to hypoxia-driven tumor aggressiveness, as demonstrated by Tsilimigras et al . (26). Similarly, the infiltrative growth pattern was associated with a 2.39-fold increased risk of poor survival. This observation aligns with updated guidelines designating the periductal-infiltrative subtype of iCCA as an unfavorable morphological variant\u0026nbsp;(22).\u003c/p\u003e\n\u003cp\u003eWe also explored the prognostic significance of tumor budding in iCCA, a feature that has been established as a strong predictor of poor prognosis in other malignancies, particularly colorectal cancer\u0026nbsp;(27).\u0026nbsp;Our findings showed that patients had tumor budding classified as Grade 1 in 45.5% of cases, Grade 2 in 14.8%, and Grade 3 in 18.2%. While we observed a numerical difference in median OS across these grades, it did not reach the level of statistical significance. This outcome suggests that the prognostic impact of tumor budding may be less pronounced in iCCA than in colorectal cancer, or that a larger-scale study is needed to detect a statistically significant effect. Further research is warranted to clarify the role of tumor budding as a potential prognostic marker in iCCA.\u003c/p\u003e\n\u003cp\u003eThis study has several limitations, primarily due to its retrospective design and incomplete data, which restricted the scope of our analyses. Our molecular profiling was based solely on tissue samples, as we did not perform cell-free DNA analysis via liquid biopsy. This may have led to an underestimation of the true prevalence of IDH1 mutation. Additional technical factors, such as tissue adequacy, DNA primers, and laboratory conditions, could have further limited our ability to detect mutations. The observed IDH1 mutation rate of 2.3% was notably lower than the rate of approximately 13% reported in the literature (7), which may reflect ethnic differences. However, the small sample size and limited population diversity of our cohort necessitate larger studies to clarify the true mutation prevalence among Turkish iCCA patients. Despite these limitations, our study has made a significant contribution as the first in Türkiye to perform IDH1 mutation analysis and a detailed evaluation of histopathological features for iCCA as a rare malignancy.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur findings indicate that perineural invasion, large-duct histopathology, positive surgical margins, and ALBI score are independent prognostic factors that significantly worsen survival in cases of iCCA.\u003c/p\u003e\n\u003cp\u003eIn our study, the IDH1 mutation rate was found to be 2.3%. Due to the small sample size and the percentage of patients for whom mutation analysis could not be performed, no definitive conclusion can be drawn regarding the prognostic significance of the IDH1 mutation in iCCA patients. However, the data obtained in this study highlight the importance of other prognostic factors that may play roles in understanding tumor biology. Furthermore, advanced-stage disease, infiltrative tumor growth pattern, invasion of adjacent structures, and biochemical markers (bilirubin/albumin levels) emerged as important determinants of survival. Future large-scale studies could further elucidate the impact of the IDH1 mutation on treatment approaches and contribute to the development of personalized therapeutic strategies. In this context, more detailed evaluation of the IDH1 mutation and other histopathological factors is warranted in planning individualized patient management and follow-up, as well as in investigating the efficacy of targeted treatment strategies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eM.B.: conceptualized and designed the study, supervised the project, and wrote the original draft of the manuscript. \u0026nbsp;\u003cbr\u003e\u0026nbsp;S.A.E.: and U.O: assisted in data acquisition, clinical interpretation, and manuscript revision. \u0026nbsp;\u003cbr\u003e\u0026nbsp; N.T. , A.S. \u0026nbsp;and O.E.: performed pathological evaluation and preparation assessment of tissue samples. \u0026nbsp; E.S. , D.H. , O.B. , E.A. and S.Y.: contributed to data curation, database management, and statistical analysis, and prepared Tables 1–4 and Figures 1–3.\u003c/p\u003e\n\u003cp\u003eI.E. and N.O.: provided patient data acquisition, interpretation of clinical findings, and support in methodological planning. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eD.U.: provided clinical oversight, critical review of the data, and substantial contributions to manuscript revision. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll authors reviewed and approved the final version of the manuscript and agree to be accountable for all aspects of the work. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article. The genomic mutation analysis data have been deposited in the European Genome-phenome Archive (EGA) under accession number EGAS50000001638 (Direct link: https://ega-archive.org/studies/EGAS50000001638). Due to the sensitive nature of human genomic data, these datasets are available under controlled access. Researchers wishing to access the raw data must submit a request to the corresponding Data Access Committee (DAC) as outlined in the EGA repository. Additional inquiries may be directed to the corresponding author ([email protected]).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors acknowledge Onko Koçsel Pharmaceuticals for assistance with genetic mutation analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Institutional Ethics Committee of Ankara Bilkent City Hospital (protocol number E1-23-3976, dated September 6, 2023) and was conducted according to good clinical practice, applicable laws, and the Declaration of Helsinki.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKinzler MN, Schulze F, Bankov K, Gretser S, Becker N, Leichner R, et al. 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Liver Cancer. 2022;11(3):233-46.\u003c/li\u003e\n\u003cli\u003eKaneko S, Kurosaki M, Tsuchiya K, Yasui Y, Inada K, Kirino S, et al. Prognosis of intrahepatic cholangiocarcinoma stratified by albumin-bilirubin grade. Hepatol Res. 2021;51(8):902-8.\u003c/li\u003e\n\u003cli\u003eShirai K, Ebata T, Oda K, Nishio H, Nagasaka T, Nimura Y, et al. Perineural invasion is a prognostic factor in intrahepatic cholangiocarcinoma. World J Surg. 2008;32(11):2395-402.\u003c/li\u003e\n\u003cli\u003eKang SH, Hwang S, Lee YJ, Kim KH, Ahn CS, Moon DB, et al. Prognostic comparison of the 7th and 8th editions of the American Joint Committee on Cancer staging system for intrahepatic cholangiocarcinoma. J Hepatobiliary Pancreat Sci. 2018;25(4):240-8.\u003c/li\u003e\n\u003cli\u003eChan KM, Tsai CY, Yeh CN, Yeh TS, Lee WC, Jan YY, et al. Characterization of intrahepatic cholangiocarcinoma after curative resection: outcome, prognostic factor, and recurrence. BMC Gastroenterol. 2018;18(1):180.\u003c/li\u003e\n\u003cli\u003eLee AJ, Chun YS. Intrahepatic cholangiocarcinoma: the AJCC/UICC 8th edition updates. Chinese Clinical Oncology. 2018;7(5):52.\u003c/li\u003e\n\u003cli\u003eFarges O, Fuks D, Boleslawski E, Le Treut YP, Castaing D, Laurent A, et al. Influence of surgical margins on outcome in patients with intrahepatic cholangiocarcinoma: a multicenter study by the AFC-IHCC-2009 study group. Ann Surg. 2011;254(5):824-29; discussion 30.\u003c/li\u003e\n\u003cli\u003eMoris D, Palta M, Kim C, Allen PJ, Morse MA, Lidsky ME. Advances in the treatment of intrahepatic cholangiocarcinoma: An overview of the current and future therapeutic landscape for clinicians. CA Cancer J Clin. 2023;73(2):198-222.\u003c/li\u003e\n\u003cli\u003eSpolverato G, Yakoob MY, Kim Y, Alexandrescu S, Marques HP, Lamelas J, et al. The Impact of Surgical Margin Status on Long-Term Outcome After Resection for Intrahepatic Cholangiocarcinoma. Ann Surg Oncol. 2015;22(12):4020-8.\u003c/li\u003e\n\u003cli\u003eTsilimigras DI, Ejaz A, Cloyd J, Guglielmi A, Aldrighetti L, Weiss M, et al. Tumor Necrosis Impacts Prognosis of Patients Undergoing Resection for T1 Intrahepatic Cholangiocarcinoma. Annals of Surgical Oncology. 2022;29(7):4326-34.\u003c/li\u003e\n\u003cli\u003eZlobec I, Lugli A. Epithelial mesenchymal transition and tumor budding in aggressive colorectal cancer: tumor budding as oncotarget. Oncotarget. 2010;1(7):651-61.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Intrahepatic cholangiocarcinoma, isocitrate dehydrogenase 1 (IDH1) mutation, ALBI score, pathological prognostic factors, survival","lastPublishedDoi":"10.21203/rs.3.rs-8449961/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8449961/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIntrahepatic cholangiocarcinoma (iCCA) is a highly aggressive malignancy with limited therapeutic options and poor survival outcomes. Recent advances in molecular oncology have highlighted the significance of isocitrate dehydrogenase 1 (IDH1) mutations as potential therapeutic targets. However, data regarding the prevalence and prognostic implications of IDH1 mutations in patients with iCCA are scarce. This study aimed to retrospectively investigate the IDH1 mutation rate, histopathological features, and survival outcomes of patients with iCCA. A total of 88 patients diagnosed and treated between 2005 and 2025 at two tertiary oncology centers were retrospectively analyzed. Clinical, pathological, and survival data were obtained from institutional oncology archives and national population databases. IDH1 mutation status was evaluated using polymerase chain reaction and next-generation sequencing on paraffin-embedded tissue samples. The median follow-up duration was 3.4 years and the median age at diagnosis was 62 years. IDH1 mutation was identified in 2.3% of cases, while 85.2% were wild-type. Curative surgery was performed for 71.6% of patients and 28.4% received noncurative or palliative treatment. Significant prognostic factors for overall survival included perineural invasion, microvascular invasion, histological subtype, albumin-bilirubin (ALBI) score, surgical margin status, and advanced disease stage. In multivariate analysis, the ALBI score remained independently associated with survival (p\u0026thinsp;=\u0026thinsp;0.025). The median overall survival was 19.1 months. This study provides the first comprehensive multicenter evaluation of IDH1 mutations and clinicopathological features in iCCA patients. The findings underscore the potential role of molecular profiling in guiding personalized treatment strategies and may serve as a reference for future subtype-specific investigations.\u003c/p\u003e","manuscriptTitle":"Mutation Rate of IDH1 and the Impact of Pathological Features on Survival in Intrahepatic Cholangiocarcinoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-13 17:41:47","doi":"10.21203/rs.3.rs-8449961/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"35e89c50-42a7-4079-938b-f4f7281e6cea","owner":[],"postedDate":"March 13th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":64301364,"name":"Biological sciences/Cancer"},{"id":64301365,"name":"Health sciences/Gastroenterology"},{"id":64301366,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2026-03-25T11:42:33+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-13 17:41:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8449961","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8449961","identity":"rs-8449961","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}