{"paper_id":"04e51bd5-0d5e-42d9-9152-a1941a2a111f","body_text":"Preoperative factors predicting outcomes in patients with suspected perihilar cholangiocarcinoma referred for curative resection— a single-center 10-year experience | 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 Research Article Preoperative factors predicting outcomes in patients with suspected perihilar cholangiocarcinoma referred for curative resection— a single-center 10-year experience Hasan Ahmad Al-Saffar, Peter Nørrgaard Larsen, Nicolai Schultz, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5201960/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Dec, 2024 Read the published version in Langenbeck's Archives of Surgery → Version 1 posted 9 You are reading this latest preprint version Abstract Background Perihilar cholangiocarcinoma (pCCA) is a rare malignancy requiring resection of extrahepatic bile ducts with or without hepatectomy, for radicality. Prognostic models for post-operative outcomes in pCCA are unusable in pre-operative decision-making as most are based on post-operative variables. Additionally, no pre-operative model consider futile laparotomy or benign hilar stenosis (BHS) as an outcome, despite rates of up to 30 % and 15 % respectively. We investigated pre-operative predictive factors for non-resectability, disease-free survival (DFS), and overall survival (OS), in patients referred for resection of suspected pCCA. Method Patients with suspected pCCA evaluated at multidisciplinary team (MDT) conference and referred for curative resection at Rigshospitalet, from 2013-2023. All were identified from the Danish Liver Cancer Group (DLGCD). Patients were evaluated, starting from date of first MDT for suspected pCCA; and starting from date of surgery if proven pCCA. Outcomes were preoperative factors related to OS, DFS and non-resectability. Results Ninety-three patients with suspected pCCA were considered resectable at MDT, of which 74 (79.5 %) were resected. In resected patients 65 (87.8 %) had pCCA, 2 (2.1 %) had gallbladder cancer (GBC) and 7 (7.5 %) had BHS. Patients with futile lapartomy (n=19 [20.4%]) had higher pre-operative p-bilirubin and ECOG-performance status (ECOG-PS) score >0 compared to resected pCCA and BHS (p=0.02 and 0.01). Portal vein embolization (p<0.001, HR 2.99 [95 % CI 1.61-5.53]) and ECOG-PS >0 (p=0.003, HR 2.32 [95% CI 1.31-4.11]) had worse OS. No preoperative factors were independently associated with non-resectability or DFS. Conclusion ECOG-PS >0 and PVE had worse survival in patients with suspected pCCA. Patients with futile laparotomy had higher frequency of ECOG-PS >0 and elevated p-bilirubin compared to resected pCCA and BHS. Figures Figure 1 Figure 2 Figure 3 Introduction Biliary tract cancer (BTC) is a gastrointestinal malignancy with a reported incidence of 1–2 per 100,000/year 1 . It is subdivided into four groups, with perihilar cholangiocarcinoma (pCCA) accounting for 50–70% of all cases 2 . Previous data have shown a five-year survival ranging from 20–40% following hepatic resection 3 . Moreover, up to 30% of patients are non-resectable at the time of surgery 4 . To achieve curative resection with tumor free margins, extensive surgery including extrahepatic bile duct (EHBD) resection with or without liver resection is required. However, previous cohorts describe long-term recurrence rates of up to 75% despite radical resection 3 , 4 . Thus, prognostic models are needed to identify patients who may benefit from surgery. Despite development of several prognostic models for postoperative outcomes in pCCA, most are not usable in preoperative decision-making, as most are based on postoperative histopathological variables 6 – 8 . Also, no models consider non-resectability or benign hilar stenosis (BHS) as a possible outcomes, despite accounting for 30% and 15% of all patients referred to resection for suspected pCCA, respectively 9 , 10 . Additionally, most studies investigating preoperative predictors of survival stretch over extensive time periods, with changing preoperative work-up over time 8 , 11 . The purpose of this study was to investigate which preoperative predictive factors determine outcomes in terms of resectability, overall survival (OS), and disease-free survival (DFS) in patients planned for resection of pCCA. Methods Patient selection Patients were identified through the Danish Liver Cancer Group (DLGCD), provided by the Danish Clinical Quality Program (RKKP). Included patients were those with suspected pCCA evaluated at multidisciplinary team (MDT) conference and referred for curative resection from January 1, 2013, to January 1, 2023, at Rigshospitalet, Copenhagen, Denmark. Patients who at the first MDT conference presented with hilar lesions not suspected to be pCCA, patients undergoing liver transplant or referred to palliative surgery, and patients receiving only palliative chemotherapy, were excluded. Preoperative work-up and procedure Preoperative assessment of resectability was done using computed tomography (CT) of the chest and abdomen with magnetic resonance imaging (MRI) of the liver (including MRCP [Magnetic resonance cholangiopancreatography], diffusion weighted images and multiphasic contrast enhanced sequences). Vascular involvement was evaluated with MRI-angiography. In selected cases with small tumor burden, a CT-angiography was performed. Tumor classification was decided upon determination of Bismuth-Corlette type 14 . Assessment of operability was dependent upon Eastern Cooperative Oncology Group Performance Status scale (ECOG-PS), co-morbidities and presence of chronic liver disease. Resectability was primarily based on radiological presence of extrahepatic disease, extent of future liver remnant (FLR) vascular involvement and locoregional or distant lymph node metastases (LNM). Resection type with possible FLR side, was dependent on Bismuth-Corlette type and vascular FLR-involvement. Final resectability assessment was done by FLR measurement. If the FLR-ratio was less than 30%, patients were referred to portal vein embolization (PVE) with hypertrophy assessment by CT-scan after 4–6 weeks. If the left liver lobe was chosen as FLR (segment 2 and 3), right hepatic PVE (including liver segment 4 when possible), was routinely done regardless of FLR-ratio. A total of 4 patients underwent association liver partition and portal vein ligation for staged hepatectomy (ALPPS) to gain FLR hypertrophy. Patients with suspected pCCA routinely underwent preoperative biliary decompression with either percutaneous transhepatic cholangiography (PTC) or endoscopic retrograde cholangiopancreatography (ERCP). When possible, preoperative cytology was obtained in this procedure and considered a sign of potential malignancy if malignant or premalignant cells were present. Patients were resected after p-bilirubin fell below 50 µmol/L. Plasma bilirubin (p-bilirubin) was measured the day before surgery following biliary decompression. Also, serum carbohydrate antigen 19 − 9 (CA 19 − 9) was measured preoperatively after biliary decompression. In cases of locally advanced disease (radiological vascular FLR-invasion) or dissemination to regional lymph nodes, neoadjuvant chemotherapy was considered with reassessment of resectability at MDT conference following 3–6 months of treatment. Curative resection, depending on tumor extent, was defined as macroscopically radical resection of EHBD with (Bismuth-Corlette type 2–4) or without (Bismuth-Corlette type 1) hepatectomy or Whipple resection in combination with hepatectomy. Caudate lobe resection was done in all patients undergoing any liver resection. Also, simultaneous lymphadenectomy of the hilum and hepatoduodenal ligament was done routinely. Frozen section of the biliary resection margins was done routinely. Macroscopically suspected carcinosis or metastasis to lymph nodes outside the hepatoduodenal ligament were investigated with freeze sampling and patients were considered non-resectable if positive. This was also the case if macroscopic invasion of arterial supply to the FLR was noted during the surgical exploration. In these cases, patients were administered neoadjuvant chemotherapy with reassessment at MDT conference and attempted re-resection if a satisfactory radiological response was achieved. Histopathology was reported according to the 8th TNM classification 15 . Adjuvant chemotherapeutic regime varied over time and administration was dependent on nodular status or radicality in the early part of the study period. Patients were subsequently followed with clinical control, CA 19 − 9 and carcinoembryonic antigen (CEA). In case of clinical suspicion of recurrence, CT-scan was carried out. Variables Outcomes were OS, DFS (patients with confirmed pCCA), non-resectability, or advanced T- and N-status (patients with confirmed pCCA). Postoperative complications were registered 90 days following resection and reported according to the CD-Classification, with major complications defined as CD ≥ 3a. For time-to-event analyses in patients with suspected pCCA regardless of received treatment and histology, time (months) started from date of first MDT, whereas time started from date of surgery for analyses in patients with histologically proven pCCA. Patients were followed until the end of the study period (January 1, 2023). OS was defined as time to death from any cause. DFS was defined as time to date of recurrence or death from any cause. Definition of recurrence was radiological evidence of recurrence with or without pathological confirmation. Nineteen preoperative variables were assessed: Gender, age (years) at first MDT conference, weight loss (kg), ECOG-PS, p-CA 19 − 9, p-bilirubin, primary sclerosing cholangitis (PSC), positive preoperative histology or cytology, Bismuth-Corlette type, presence of hilar radiological mass, enlarged hilar/portal lymph nodes on CT/MRI at presentation, arterial invasion contra- or ipsilateral to FLR, venous invasion contra- or ipsilateral to FLR, neoadjuvant chemotherapy, PVE, preoperative biliary drainage, previous resection attempt, malignant- and benign histology (BHS). Statistical analysis Categorical variables were described as frequencies and percentages of subjects within each category. Continuous data were reported as medians and interquartile ranges (IQRs). P-values were calculated using Chi-Squared test for categorical data. Based on decision on the first MDT-conference, operative findings and histology, all treatment-naïve patients with suspected pCCA who are deemed resectable were divided into non-resected, resected and BHS. Patients planned for neoadjuvant treatment on the first MDT conference were considered in these groups based on whether they underwent subsequent surgical exploration/resection or not. None of the patients planned for neoadjuvant treatment had BHS. Thus, patients initially deemed resectable at MDT where intended surgical exploration was not carried out on due e.g ., progression, inadequate growth or insufficient neoadjuvant treatment were also included in the analysis along with patients, who were unresectable at laparotomy (non-resected group). Preoperative prognostic factors of patients with suspected pCCA deemed resectable at MDT, were evaluated with OS, non-resectability, BHS and CD-score as outcomes. Patient resected for histologically confirmed pCCA were evaluated with DFS, T3 and N1 as outcomes. Logistic regression estimated odds ratio (OR) with 95% confidence intervals (95% CI) of preoperative factors that influenced occurrence of non-resectability and advanced T-/N-stage for patients with confirmed pCCA. Cox proportional hazards regression evaluated correlation (hazard ratio (HR) with 95% CI between preoperative risk factors and OS in patients with suspected pCCA, and DFS in patients who were resected for histologically confirmed pCCA, respectively. Subsequent Kaplan-Meyer survival estimators and log-rank test presented differences in survival probability between groups. The assumptions governing Cox proportional hazards were graphically assessed and tested using scaled Schoenfeld residuals. A p value of < 0.05 was considered statistically significant. Approval was obtained from The Danish Data Protection Agency (P-2022-510) and Danish Health Authority in The Capital Region of Denmark (R-23057752). Results Patient characteristics Ninety-three patients had suspected resectable pCCA at MDT. Four patients (4.3 %) with confirmed pCCA were not operated due to preoperative complications or disease progression. Eighty-nine (95.6%) underwent exploration, of which 15 (16.1 %) were unresectable. Of all patients resected for suspected pCCA (n=74), 26 (35.1 %) underwent extended right hepatectomy (ERH) and 36 (48.6 %) underwent left hepatectomy (LH) in addition to EHBD resection. Twelve patients (16.2 %) underwent EHBD resection. Sixty-five (87.8 %) of all resected patients had histologically confirmed pCCA, 2 (2.7 %) had gallbladder carcinoma (GBC) and 7 (9.4 %) had BHS. In BHS, 5 patients presented IgG4-related disease, 1 patient was reported with low grade dysplasia and 1 had unspecific inflammation. Four patients (5.4 %) died due to postoperative complications within 90 days (CD 5). Baseline characteristics of the study population are displayed in Table 1 . From the entire cohort, 91 patients had either BHS or histologically confirmed pCCA. Age distribution was even between patients with BHS, resection, and non-resection (69.9 vs 64.9 vs 68.2 years respectively, p=0.23). Patients with BHS and those resected for pCCA had a significantly lower incidence of ECOG-PS >0 compared with non-resected patients with pCCA (42.0 vs 23.0 vs 57.8 %, p=0.01). As for p-bilirubin, patients with BHS and those resected for pCCA had significantly lower p-bilirubin after decompression compared to non-resected patients with pCCA (0.0 vs 24.6 vs 42.2 %, p=0.02). Radiological characteristics Distribution of Bismuth type and patients with radiological hilar mass were even between patients with BHS, resection, and non-resection (p=0.79 and p=0.27, respectively). Patients with BHS had a non-significantly lower distribution of radiological arterial as well as venous invasion on preoperative scanning compared with resected and non-resected patients with pCCA (0.0 vs 33.8 vs 31.5%, p=0.06 and 14.2 vs 40.0 vs 31.5 %, p=0.15, respectively). This was also the case regarding enlarged lymph nodes on preoperative radiology (14.2 vs 36.8 vs 33.8 %, p=0.26) ( Table 1 ). Preoperative interventions Twenty patients (21.9 %) with suspected pCCA underwent PVE, with equal distribution between BHS, resection and non-resection (28.5 vs 21.5 vs 21.0 %, p=0.43). No pre-malignant or malignant preoperative cytology was obtained in patients with BHS, compared with resected and non-resected patients (0.0 vs 32.3 vs 51.6 %, p=0.01). No patients with BHS underwent neoadjuvant chemotherapy. However, 13 patients (14.2 %) with confirmed pCCA received neoadjuvant chemotherapy with an equal distribution between resected and non-resected patients (0.0 vs 15.3 vs 15.7 %, p=0.26). Time from first MDT to surgery was longer, however non-significant, in patients with BHS compared to resected and non-resected patients, respectively (75 vs 54 vs 54 days, p=0.54). T- and N-status High age and low p-bilirubin were significantly associated with T-stage>2 ( Table 2 ). In case of N1-status ( Table 2 ), rate of arterial invasion and earlier resection attempt were significantly higher (p=0.01 and 0.04, respectively). Correlation between N1 and arterial invasion had an OR of 3.55 (95% CI 1.25-10.91, p=0.02). Risk factors for non-resectability, OS and DFS Non-resectability was significantly associated with shorter OS compared to resected with a 5-year survival of 0.0 and 39.2 %, respectively (p <0.001). Median survival for resected and non-resected patients was 38.3 (IQR 24.3-50.6) and 16.6 (IQR 6.3-26.2) months, respectively. ECOG-PS >0 was the only significant risk factor associated with resectability for all patients with suspected pCCA (OR 0.23 (95% CI 0.07-0.66), p=0.006) (Table 3) . Only ECOG-PS >0 (HR 2.32 (95% CI 1.31-4.11), p=0.003) and PVE (HR 2.99 (95 % CI 1.61-5.53) , p <0.001) remained significantly associated with poorer OS in the multivariable analysis, for patients with suspected pCCA ( Table 4 ). Kaplan-Meier estimates (Figure 1 and 2) showed a 5-year survival for patients with ECOG-PS >0 of 14.3 % compared to 38.3 % for patients with ECOG-PS 0 (p=0.002), and 12.0 % for patients undergoing PVE compared to 37.2 % in patients not undergoing PVE (p=0.02). PVE was a risk factor for reduced DFS among resected patients with an HR of 2.89 (95 % CI 1.46- 5.71) ( Table 5 ). All patients in our cohort with PVE (n= 16) had undergone ERH (69 %). A sub-analysis in our study showed that patients with ERH compared with LH and EHBD resection, had a significantly higher frequency of progressive N-stage (43 vs 33 vs 0 % (p=0.02) respectively).This association was not observed in regard to progressive T-stage (26 vs 15 vs 40 % (p=0.23)) Discussion This study investigated preoperative factors affecting outcomes in patients with suspected pCCA who were deemed resectable at the first MDT conference. Our results showed that ECOG-PS > 0, preoperative elevated p-bilirubin and PVE were associated with non-resectability and worse long-term survival outcomes for patients referred to resection for suspected pCCA. We also observed that factors such as advanced age, radiological arterial invasion and earlier resection attempt were associated with advanced tumor stages. We showed that ECOG-PS > 0 was associated with a significantly higher frequency of non-resectability and was an independent predictor for reduced OS. The associations with ECOG-PS > 0 may be explained by a general physiological effect of more progressive tumor stages that has been observed in previous studies in patients with advanced non-resectable biliary tract carcinoma (BTC) 16 . Yet, in our sub-analysis for T- and N-stage, no association between ECOG-PS > 0 and progressive tumor stages were observed. One explanation may be the high number of non-resected patients with elevated ECOG-PS in our cohort (11%), where pathological assessment of tumor stage was not possible. The association between elevated ECOG-PS and poor OS has previously been shown in one western cohort investigating patients resected for BTC in general. However, that study also included patients who were deemed non-resectable at the MDT (49%) and treated with palliative chemotherapy or best supportive care, potentially overestimating the correlation between elevated ECOG-PS and OS 17 . Our results demonstrated that non-resectable patients had a significantly higher frequency of post-decompression elevated p-bilirubin, compared to patients resected for pCCA and with BHS. Additionally, no patient with BHS had elevated post-decompression p-bilirubin. Although elevated p-bilirubin was not independently associated with worse OS, our results may still add to current evidence that elevated post-decompression p-bilirubin is associated with advanced tumor stage, reflecting extensive hilar stricture even after biliary decompression. This is in line with two previous eastern and western studies that demonstrated the incidence of elevated p-bilirubin in non-resectable and locally advanced resected pCCA 9 , 11 . Our study also adds to the current evidence in the field by including patients with BHS who did not have any case of elevated p-bilirubin after biliary decompression. Our data may be generalizable to a preoperative setting, as it also included patients with BHS (n = 7) or other BTC (n = 2) in the final pathology, together accounting for 9.6% of suspected pCCA referred to resection. Is important to note that p-bilirubin due to liver insufficiency may also have been a confounder in our cohort. Nevertheless, no patient undergoing liver resection in our cohort had any pre-operative sign of cirrhosis as it was an absolute contraindication. Nevertheless, studying correlation between elevated p-bilirubin and OS in the future, may be aided by estimating and adjusting for liver function through measurement of indocyanine green (ICG) clearance test 18 . One additional confounder that may have hampered our results is resection prior to complete normalization of the p-bilirubin following biliary decompression. Interestingly, our results indicated an association between PVE and worse DFS and OS. This is contrary to previous studies showing that PVE is associated with lower 90-day morbidity and mortality due to reduced incidence of post-operative liver failure 19 , 20 . However, the association between worse survival and PVE may be due to confounding in that patients who underwent PVE had more advanced and complex tumors. The association between PVE and non-resectability in pCCA has been observed in one recent study investigating preoperative prognostic factors 4 . No significant association between PVE and progressive T- or N-stage was observed in our cohort. However, all patients with PVE had undergone ERH which in turn was significantly associated with progressive N-stage, a well-known factor for worse OS 21 – 23 . Tumor progression following PVE has been reported for other liver malignancies in both the embolized and non-embolized lobe due to neovascularization 30 . No study has investigated predictive variables for T-stage and two studies have only recently described predictive models for LNM in pCCA 21 – 23 . Our results showed that older patients had a higher frequency of advanced T-stage. In pCCA, association between age and clinically aggressive malignancy is yet to be investigated. Although biologically different, one recent cohort likewise showed that advanced T-stage in intrahepatic cholangiocarcinoma, was associated with late disease onset 24 . However, in contrary to that study, we showed no association between age and worse OS or DFS. LNM was associated with radiological arterial invasion as well as earlier resection attempt. Both factors may reflect advanced disease and, thus, the association. We add to the field of predicting LNM as previous models have not included radiological variables 22 . The main strength of this study was a detailed analysis of patients referred to surgery for suspected pCCA from the MDT, regardless of final pathological or surgical outcome. This may be more reflective of the clinical reality in the context of an MDT conference. Moreover, patients with suspected pCCA were followed-up from the time of the initial MDT conference. Furthermore, the short study period of 10 years resulted in homogenous pre- and perioperative clinical management with less variations over time. However, our study should be viewed with caution as it is a single-center design with a limited number of patients with some cases of missing variables and risk of false negative findings. Therefore, future studies should include larger patient cohorts with a multicenter design. Also, more patients will increase power to the analysis with an opportunity to design a validated preoperative predictive model. Moreover, we were not able to assess the prognostic impact of PSC, as some resectable patients undergo liver transplantation according to the Mayo protocol 29 . Conclusively, ECOG-PS > 0 and PVE affected OS in suspected pCCA if deemed resectable at MDT. Additionally, ECOG-PS > 0 and elevated p-bilirubin were associated with higher frequency of non-resectability in pCCA. We also showed that high age and arterial invasion were associated with advanced tumor- and lymph node stage. These findings may aid selection of suitable candidates for surgery at the MDT where only preoperative variables are available. However, larger studies with subsequent validation are needed. Declarations Conflicts of interest Authors stated no conflict of interest. Financial declaration Authors received no reported funding in this study. Author Contribution HAA wrote the first version of the manuscript and conducted statistical analysis. TS, LK, DR, PN, NS and HCP contributed to editing the manuscript. 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J Clin Med 10(7):1345 Rosen CB, Heimbach JK, Gores GJ (2008) Surgery for cholangiocarcinoma: the role of liver transplantation. HPB (Oxford) 10(3):186–189 Simoneau E, Hassanain M, Shaheen M et al (2015) Portal vein embolization and its effect on tumour progression for colorectal cancer liver metastases. Br J Surg 102(10):1240–1249 Tables Table 1. Characteristics for patients with pCCA and BHS (n= 91) Patients with BHS, n = 7 Resected patients with pCCA, n = 65 Non-resected patients with pCCA, n=19 P OS (Time from first MDT), median (IQR)a 35.0 (17.4-41.7) 38.3 (24.3-52.4) 15.6 (3.7-26.2) 0.52 Age, median (IQR) 69.9 (65.8-73.0) 64.9 (54.4-70.4) 68.2 (59.5-72.1) 0.23 Sex, male, n (%) 5 (71.4) 36 (55.3) 10 (52.6) 0.67 Patient ECOG-PSb>0, n (%) 3 (42.8) 15 (23.0) 11 (57.8) 0.01 Preoperative weight loss, Median (IQR) 2.0 (0.0-10.0) 4.0 (0.0-8.0) 5.0 (0.0-7.5) 0.99 Preoperative P-Bilirubin >25, n (%) 0 (0.0) 16 (24.6) 8 (42.2) 0.02 Preoperative CA 19-9 >37, n (%) 2 (28.5) 29 (44.6) 9 (47.3) 0.77 PSC, n (%)c 0 (0.0) 7 (10.7) 1 (5.2) 0.25 Previous resection attempt, n (%) 0 (0) 7 (10.7) 1 (5.2) 0.25 Bismuth type: I, n (%) II, n (%) IIIa, n (%) IIIb, n (%) IV, n (%) I: 1 (14.2) II: 1 (14.2) IIIa: 2 (28.5) IIIb: 2 (28.5) IV:1 (14.2) I: 11 (16.9) II: 8 (13.3) IIIa: 16 (24.6) IIIb: 15 (23.0) IV: 15 (23.0) I: 3 (15.7) II: 5 (26.3) IIIa: 2 (5.2) IIIb: 3 (15.7) IV: 6 (31.5) 0.79 Hilar mass on radiology, n (%) 5 (71.4) 54 (83.7) 14 (73.6) 0.27 Enlarged local lymph nodes on radiology, n (%) 1 (14.2) 22 (33.8) 7 (36.8) 0.26 Arterial invasion on pre-operative radiology, n (%) 0 (0.0) 22 (33.8) 6 (31.5) 0.06 Venous invasion on pre-operative radiology, n (%) 1 (14.2) 26 (40.0) 6 (31.5) 0.15 FLR >30 %, n (%)d 7 (100.0) 63 (96.9) 17 (89.4) 0.31 Preoperative biliary drainage, n (%) 7 (100.0) 62 (95.3) 19 (100) 0.54 Preoperative malignant histo-/cytology, n (%) 0 (0.0) 21 (32.3) 10 (52.6) 0.01 Pre-operative neoadjuvant therapy, n (%) 0 (0.0) 10 (15.3) 3 (15.7) 0.26 Portal vein embolization, n (%) 2 (28.5) 14 (21.5) 4 (21.0) 0.43 Time from MDTc to surgery (days), median (IQR) 75 (58-92) 54 (33-80) 54 (40-107) 0.54 a: Overall survival; b: ECOG-Performance status; c: Primary sclerotizing cholangitis; d: Future liver remnant CA 19-9 Missing n (%): 28 (30) Table 2. Preoperative characteristics for patients according to T- and N-status in patients resected with confirmed pCCA (n=65) T-stage >2, n= 12 T-stage ≤2, n= 53 P N 1, n=24 N 0, n=41 P Age >70, n (%) 6 (50.0) 11 (20.7) 0.03 7 (29.1) 10 (24.3) 0.67 Sex, male, n (%) 6 (50.0) 22 (41.5) 0.59 10 (41.6) 18 (43.9) 0.86 Patient ECOG-PSa>0; n (%) 1 (8.3) 14 (26.4) 0.17 6 (25.0) 9 (21.9) 0.07 CA 19-9 high, n (%) 5 (41.6) 24 (45.2) 0.051 14 (58.3) 15 (36.5) 0.08 Bilirubin high, n (%) 1 (8.3) 24 (45.2) 0.01 8 (33.3) 8 (19.5) 0.21 PSCb, n (%) 0 (0.0) 7 (13.2) >1.00 3 (12.5) 4 (9.75) 0.11 Preoperative downstaging, n (%) 2 (16.6) 8 (15.0) 0.89 5 (20.8) 5 (12.1) 0.25 Portal vein embolization, n (%) 4 (33.3) 10 (18.8) 0.27 7 (29.1) 7 (17.0) 0.21 Bismuth type, n (%) I II IIIa IIIb IV I: 3 (25.0) II: 0 (0.0) IIIa: 3 (25.0) IIIb: 3 (25.0) IV: 3 (25.0) I: 8 (15.0) II: 8 (15.0) IIIa: 13 (24.5) IIIb: 12 (23.0) IV: 12 (23.0) 0.81 I: 5 (20.8) II: 1 (4.1) IIIa: 5 (20.8) IIIb: 7 (29.1) IV: 6 (25.0) I: 6 (14.6) II: 7 (17.0) IIIa: 11 (26.8) IIIb: 8 (19.5) IV: 9 (21.9) 0.51 Hilar mass, n (%) 9 (75.0) 45 (84.9) 0.40 19 (79.1) 35 (85.3) 0.52 Enlarged local lymph nodes on radiology, n (%) 5 (41.6) 17 (32.0) 0.52 11 (45.8) 11 (26.8) 0.11 Arterial invasion on pre-operative radiology, n (%) 4 (33.3) 17 (32.0) 0.93 12 (50.0 ) 9 (20.9) 0.01 Venous invasion on pre-operative radiology, n (%) 4 (33.3) 22 (41.5) 0.60 10 (41.6) 16 (39.0) 0.83 Earlier resection attempt, n (%) 1 (8.3) 6 (11.3) 0.76 5 (20.8) 2 (4.8) 0.04 Chi-square analysis for preoperative predictive variables for a T- and N-status. a: ECOG-Performance status; b: Primary sclerotizing cholangitis; CA 19-9 Missing n (%): 28 (30) Table 3. Preoperative factors for resectability after referral in pCCA (n=93) Univariable OR (95% CI) P Age >70, (yes) 0.63 (0.22, 1.91) 0.40 Sex, female (yes) 0.80 (0.28, 2.23) 0.66 Patient ECOG-PSa >0, (no) 0.23 (0.07, 0.66) 0.006 Preoperative bilirubin >25 (yes) 0.35 (0.12, 1.02) 0.05 CA 19-9 >37 (yes) 0.62 (0.15, 2.13) 0.46 PSCb, (yes) 1.88 (0.30, 36.33) 0.56 Bismuth type I II IIIa IIIb IV I: (ref) II: 0.46 (0.07, 2.34) IIIa: 2.07 (0.30, 17.53) IIIb: 1.30 (0.21, 8.11) IV: 0.61 (0.11, 2.82) I: (ref) II: 0.35 IIIa: 0.45 IIIb: 0.76 IV: 0.54 Hilar radiological mass (yes) 1.53 (0.43, 4.78) 0.47 Enlarged local lymph nodes on radiology, (yes) 0.77 (0.27, 2.31) 0.63 Arterial invasion on pre-operative radiology, (yes) 1.16 (0.36, 3.37) 0.87 Venous invasion on pre-operative radiology, (yes) 0.80 (0.25, 2.28) 0.69 Preoperative biliary drainage (yes) n/a 0.99 Portal vein embolization (yes) 1.03 (0.32, 4.01) 0.95 Neoadjuvant chemotherapy (yes) 0.83 (0.22, 4.03) 0.79 Time to surgery from MDTc-date (days) 0.99 (0.99, 1.00) 0.98 Univariable logistical regression analysis for patients not undergoing resection. a: ECOG-Performance status; b: Primary sclerotizing cholangitis; CA 19-9 Missing n (%): 28 (30) Table 4. R isk factors affecting OS for all patients with suspected PHCC deemed resectable at MDT (n=93) Univariable HR (95% CI) P Multivariable HR (95% CI) P Age >70 (yes) 0.88 (0.48, 1.61) 0.68 Sex, female 0.87 (0.52, 1.47) 0.62 ECOG-PSa >0 (yes) 1.92 (1.11, 3.32) 0.01 2.32 (1.31, 4.11) 0.003 Preoperative bilirubin >25 (yes) 1.70 (0.99, 2.90) 0.05 CA 19-9 >37 (yes) 1.17 (0.61, 2.24) 0.62 PSCb (yes) 1.33 (0.60, 2.97) 0.47 Bismuth type I II IIIa IIIb IV I: (ref) II: 0.89 (0.32, 2.47) IIIa: 1.54 (0.64, 3.73) IIIb: 1.00 (0.41, 2.46) IV: 1.57 (0.68, 3.63) I: (ref) II: 0.82 IIIa: 0.34 IIIb: 0.99 IV: 0.27 Hilar radiological mass 0.88 (0.48, 1.60) 0.67 Enlarged local lymph nodes on radiology, (yes) 1.30 (0.77, 2.19) 0.32 Arterial invasion on pre-operative radiology, (yes) 0.80 (0.47, 1.37) 0.42 Venous invasion on pre-operative radiology, (yes) 1.12 (0.66, 1.90) 0.66 FLR >30 % (yes) 0.98 (0.13, 7.25) 1.01 Preoperative biliary drainage (yes) 1.18 (0.36, 3.79) 0.77 Portal vein embolization (yes) 2.47 (1.37, 4.46) 0.002 2.99 (1.61, 5.53) <0.001 Neoadjuvant chemotherapy (yes) 1.01 (0.49, 2.06) 0.96 Time from MDT (days) 2.71 (2.69, 2.71) 0.24 Earlier resection attempt (yes) 1.64 (0.80, 3.34) 0.12 Uni- and multivariable Cox regression analysis with Overall Survival. a: ECOG-Performance status; b: Primary sclerotizing cholangitis; CA 19-9 Missing n (%): 28 (30) Table 5. Preoperative risk factors affecting Disease Free Survival (DFS) for all patients resected with PHCC in final histology (n=65) Univariable HR (95% CI) P Age >70 (yes) 0.66 (0.32, 1.33) 0.24 Sex (female) 1.14 (0.63, 2.06) 0.64 Patient PSa>0, (yes) 1.10 (0.54, 2.24) 0.78 Weightloss (kg) 1.00 (0.95, 1.07) 0.81 Bilirubin >25 (yes) 1.69 (0.89, 3.20) 0.10 CA 19-9 >37 (yes) 1.55 (0.71, 3.39) 0.27 PSCb (yes) 1.98 (0.87, 4.47) 0.10 Bismuth type I, (yes) II, (yes) IIIa, (yes) IIIb, (yes) IV, (yes) I: (ref) II: 0.14 (0.01, 1.16) IIIa: 1.87 (0.73, 4.79) IIIb: 1.27 (0.49, 3.26) IV: 2.20 (0.87, 5.56) I: (ref) II: 0.06 IIIa: 0.19 IIIb: 0.60 IV: 0.09 Hilar mass (Yes) 1.54 (0.68, 3.46) 0.29 Enlarged local lymph nodes on radiology, (yes) 1.63 (0.89, 2.96) 0.10 Arterial invasion on pre-operative radiology, (yes) 0.60 (0.33, 1.09) 0.09 Venous invasion on pre-operative radiology, (yes) 0.82 (0.45, 1.49) 0.53 Portal vein embolization, (yes) 2.89 ( 1.46 , 5.71 ) 0.002 Biliary decompression 1.26 (0.30, 5.24) 0.74 Neoadjuvant chemotherapy, (yes) 1.59 (0.76, 3.32) 0.21 Time to surgery (days) 1.00 (0.99, 1.09) 0.26 Earlier resection attempt (yes) 2.25 (0.99, 5.08) 0.05 Univariable Cox regression analysis with Disease Free Survival. a: ECOG-Performance status; b: Primary sclerotizing cholangitis; CA 19-9 Missing n (%): 28 (30), CA 19-9 Missing n (%): 28 (30) Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 21 Dec, 2024 Read the published version in Langenbeck's Archives of Surgery → Version 1 posted Editorial decision: Revision requested 25 Nov, 2024 Reviews received at journal 18 Nov, 2024 Reviews received at journal 12 Nov, 2024 Reviewers agreed at journal 02 Nov, 2024 Reviewers agreed at journal 02 Nov, 2024 Reviewers invited by journal 02 Nov, 2024 Editor assigned by journal 10 Oct, 2024 Submission checks completed at journal 08 Oct, 2024 First submitted to journal 04 Oct, 2024 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-5201960\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":382640840,\"identity\":\"f2e9c5df-f7de-406d-9165-93bd328ff152\",\"order_by\":0,\"name\":\"Hasan Ahmad 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legend\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5201960/v1/6974f171a97bc7392cecbfc3.png\"},{\"id\":71805649,\"identity\":\"5f40ee2a-4885-45fc-a99a-1e2306ae282b\",\"added_by\":\"auto\",\"created_at\":\"2024-12-18 17:30:23\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":64469,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eSee image above for figure legend\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5201960/v1/e51a570b62eb3fe4d9b91596.png\"},{\"id\":71804765,\"identity\":\"a29d1ab5-5262-4da6-8ce3-9473bcd1ac62\",\"added_by\":\"auto\",\"created_at\":\"2024-12-18 17:22:23\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 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referred for curative resection— a single-center 10-year experience\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eBiliary tract cancer (BTC) is a gastrointestinal malignancy with a reported incidence of\\u003c/p\\u003e \\u003cp\\u003e1\\u0026ndash;2 per 100,000/year\\u003csup\\u003e1\\u003c/sup\\u003e. It is subdivided into four groups, with perihilar cholangiocarcinoma (pCCA) accounting for 50\\u0026ndash;70% of all cases\\u003csup\\u003e\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e\\u003c/sup\\u003e. Previous data have shown a five-year survival ranging from 20\\u0026ndash;40% following hepatic resection\\u003csup\\u003e\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e\\u003c/sup\\u003e. Moreover, up to 30% of patients are non-resectable at the time of surgery\\u003csup\\u003e\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e\\u003c/sup\\u003e. To achieve curative resection with tumor free margins, extensive surgery including extrahepatic bile duct (EHBD) resection with or without liver resection is required. However, previous cohorts describe long-term recurrence rates of up to 75% despite radical resection\\u003csup\\u003e\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e\\u003c/sup\\u003e. Thus, prognostic models are needed to identify patients who may benefit from surgery.\\u003c/p\\u003e \\u003cp\\u003eDespite development of several prognostic models for postoperative outcomes in pCCA, most are not usable in preoperative decision-making, as most are based on postoperative histopathological variables\\u003csup\\u003e\\u003cspan additionalcitationids=\\\"CR7\\\" citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e\\u003c/sup\\u003e. Also, no models consider non-resectability or benign hilar stenosis (BHS) as a possible outcomes, despite accounting for 30% and 15% of all patients referred to resection for suspected pCCA, respectively\\u003csup\\u003e\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e\\u003c/sup\\u003e. Additionally, most studies investigating preoperative predictors of survival stretch over extensive time periods, with changing preoperative work-up over time\\u003csup\\u003e\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eThe purpose of this study was to investigate which preoperative predictive factors determine outcomes in terms of resectability, overall survival (OS), and disease-free survival (DFS) in patients planned for resection of pCCA.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003ePatient selection\\u003c/h2\\u003e \\u003cp\\u003ePatients were identified through the Danish Liver Cancer Group (DLGCD), provided by the Danish Clinical Quality Program (RKKP). Included patients were those with suspected pCCA evaluated at multidisciplinary team (MDT) conference and referred for curative resection from January 1, 2013, to January 1, 2023, at Rigshospitalet, Copenhagen, Denmark. Patients who at the first MDT conference presented with hilar lesions not suspected to be pCCA, patients undergoing liver transplant or referred to palliative surgery, and patients receiving only palliative chemotherapy, were excluded.\\u003c/p\\u003e \\u003c/div\\u003e\\n\\u003ch3\\u003ePreoperative work-up and procedure\\u003c/h3\\u003e\\n\\u003cp\\u003ePreoperative assessment of resectability was done using computed tomography (CT) of the chest and abdomen with magnetic resonance imaging (MRI) of the liver (including MRCP [Magnetic resonance cholangiopancreatography], diffusion weighted images and multiphasic contrast enhanced sequences). Vascular involvement was evaluated with MRI-angiography. In selected cases with small tumor burden, a CT-angiography was performed. Tumor classification was decided upon determination of Bismuth-Corlette type\\u003csup\\u003e\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e\\u003c/sup\\u003e. Assessment of operability was dependent upon Eastern Cooperative Oncology Group Performance Status scale (ECOG-PS), co-morbidities and presence of chronic liver disease. Resectability was primarily based on radiological presence of extrahepatic disease, extent of future liver remnant (FLR) vascular involvement and locoregional or distant lymph node metastases (LNM). Resection type with possible FLR side, was dependent on Bismuth-Corlette type and vascular FLR-involvement. Final resectability assessment was done by FLR measurement. If the FLR-ratio was less than 30%, patients were referred to portal vein embolization (PVE) with hypertrophy assessment by CT-scan after 4\\u0026ndash;6 weeks. If the left liver lobe was chosen as FLR (segment 2 and 3), right hepatic PVE (including liver segment 4 when possible), was routinely done regardless of FLR-ratio. A total of 4 patients underwent association liver partition and portal vein ligation for staged hepatectomy (ALPPS) to gain FLR hypertrophy. Patients with suspected pCCA routinely underwent preoperative biliary decompression with either percutaneous transhepatic cholangiography (PTC) or endoscopic retrograde cholangiopancreatography (ERCP). When possible, preoperative cytology was obtained in this procedure and considered a sign of potential malignancy if malignant or premalignant cells were present. Patients were resected after p-bilirubin fell below 50 \\u0026micro;mol/L. Plasma bilirubin (p-bilirubin) was measured the day before surgery following biliary decompression. Also, serum carbohydrate antigen 19\\u0026thinsp;\\u0026minus;\\u0026thinsp;9 (CA 19\\u0026thinsp;\\u0026minus;\\u0026thinsp;9) was measured preoperatively after biliary decompression.\\u003c/p\\u003e \\u003cp\\u003eIn cases of locally advanced disease (radiological vascular FLR-invasion) or dissemination to regional lymph nodes, neoadjuvant chemotherapy was considered with reassessment of resectability at MDT conference following 3\\u0026ndash;6 months of treatment. Curative resection, depending on tumor extent, was defined as macroscopically radical resection of EHBD with (Bismuth-Corlette type 2\\u0026ndash;4) or without (Bismuth-Corlette type 1) hepatectomy or Whipple resection in combination with hepatectomy. Caudate lobe resection was done in all patients undergoing any liver resection. Also, simultaneous lymphadenectomy of the hilum and hepatoduodenal ligament was done routinely. Frozen section of the biliary resection margins was done routinely. Macroscopically suspected carcinosis or metastasis to lymph nodes outside the hepatoduodenal ligament were investigated with freeze sampling and patients were considered non-resectable if positive. This was also the case if macroscopic invasion of arterial supply to the FLR was noted during the surgical exploration. In these cases, patients were administered neoadjuvant chemotherapy with reassessment at MDT conference and attempted re-resection if a satisfactory radiological response was achieved. Histopathology was reported according to the 8th TNM classification\\u003csup\\u003e\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e\\u003c/sup\\u003e. Adjuvant chemotherapeutic regime varied over time and administration was dependent on nodular status or radicality in the early part of the study period. Patients were subsequently followed with clinical control, CA 19\\u0026thinsp;\\u0026minus;\\u0026thinsp;9 and carcinoembryonic antigen (CEA). In case of clinical suspicion of recurrence, CT-scan was carried out.\\u003c/p\\u003e\\n\\u003ch3\\u003eVariables\\u003c/h3\\u003e\\n\\u003cp\\u003eOutcomes were OS, DFS (patients with confirmed pCCA), non-resectability, or advanced T- and N-status (patients with confirmed pCCA). Postoperative complications were registered 90 days following resection and reported according to the CD-Classification, with major complications defined as CD\\u0026thinsp;\\u0026ge;\\u0026thinsp;3a. For time-to-event analyses in patients with suspected pCCA regardless of received treatment and histology, time (months) started from date of first MDT, whereas time started from date of surgery for analyses in patients with histologically proven pCCA. Patients were followed until the end of the study period (January 1, 2023). OS was defined as time to death from any cause. DFS was defined as time to date of recurrence or death from any cause. Definition of recurrence was radiological evidence of recurrence with or without pathological confirmation.\\u003c/p\\u003e \\u003cp\\u003eNineteen preoperative variables were assessed: Gender, age (years) at first MDT conference, weight loss (kg), ECOG-PS, p-CA 19\\u0026thinsp;\\u0026minus;\\u0026thinsp;9, p-bilirubin, primary sclerosing cholangitis (PSC), positive preoperative histology or cytology, Bismuth-Corlette type, presence of hilar radiological mass, enlarged hilar/portal lymph nodes on CT/MRI at presentation, arterial invasion contra- or ipsilateral to FLR, venous invasion contra- or ipsilateral to FLR, neoadjuvant chemotherapy, PVE, preoperative biliary drainage, previous resection attempt, malignant- and benign histology (BHS).\\u003c/p\\u003e \\u003cdiv id=\\\"Sec6\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical analysis\\u003c/h2\\u003e \\u003cp\\u003eCategorical variables were described as frequencies and percentages of subjects within each category. Continuous data were reported as medians and interquartile ranges (IQRs). P-values were calculated using Chi-Squared test for categorical data. Based on decision on the first MDT-conference, operative findings and histology, all treatment-na\\u0026iuml;ve patients with suspected pCCA who are deemed resectable were divided into non-resected, resected and BHS. Patients planned for neoadjuvant treatment on the first MDT conference were considered in these groups based on whether they underwent subsequent surgical exploration/resection or not. None of the patients planned for neoadjuvant treatment had BHS. Thus, patients initially deemed resectable at MDT where intended surgical exploration was not carried out on due \\u003cem\\u003ee.g\\u003c/em\\u003e., progression, inadequate growth or insufficient neoadjuvant treatment were also included in the analysis along with patients, who were unresectable at laparotomy (non-resected group).\\u003c/p\\u003e \\u003cp\\u003ePreoperative prognostic factors of patients with suspected pCCA deemed resectable at MDT, were evaluated with OS, non-resectability, BHS and CD-score as outcomes. Patient resected for histologically confirmed pCCA were evaluated with DFS, T3 and N1 as outcomes.\\u003c/p\\u003e \\u003cp\\u003eLogistic regression estimated odds ratio (OR) with 95% confidence intervals (95% CI) of preoperative factors that influenced occurrence of non-resectability and advanced T-/N-stage for patients with confirmed pCCA.\\u003c/p\\u003e \\u003cp\\u003eCox proportional hazards regression evaluated correlation (hazard ratio (HR) with 95% CI between preoperative risk factors and OS in patients with suspected pCCA, and DFS in patients who were resected for histologically confirmed pCCA, respectively. Subsequent Kaplan-Meyer survival estimators and log-rank test presented differences in survival probability between groups. The assumptions governing Cox proportional hazards were graphically assessed and tested using scaled Schoenfeld residuals. A p value of \\u0026lt;\\u0026thinsp;0.05 was considered statistically significant.\\u003c/p\\u003e \\u003cp\\u003e Approval was obtained from The Danish Data Protection Agency (P-2022-510) and Danish Health Authority in The Capital Region of Denmark (R-23057752).\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cp\\u003e\\u003cem\\u003ePatient characteristics\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNinety-three patients had suspected resectable pCCA at MDT. Four patients (4.3 %) with confirmed pCCA were not operated due to preoperative complications or disease progression. Eighty-nine (95.6%) underwent exploration, of which 15 (16.1 %) were unresectable. Of all patients resected for suspected pCCA (n=74), 26 (35.1 %) underwent extended right hepatectomy (ERH) and 36 (48.6 %) underwent left hepatectomy (LH) in addition to EHBD resection. Twelve patients (16.2 %) underwent EHBD resection. Sixty-five (87.8 %) of all resected patients had histologically confirmed pCCA, 2 (2.7 %) had gallbladder carcinoma (GBC) and 7 (9.4 %) had BHS. In BHS, 5 patients presented IgG4-related disease, 1 patient was reported with low grade dysplasia and 1 had unspecific inflammation. Four patients (5.4 %) died due to postoperative complications within 90 days (CD 5).\\u003c/p\\u003e\\n\\u003cp\\u003eBaseline characteristics of the study population are displayed in \\u003cem\\u003eTable 1\\u003c/em\\u003e. From the entire cohort, 91 patients had either BHS or histologically confirmed pCCA. Age distribution was even between patients with BHS, resection, and non-resection (69.9 vs 64.9 vs 68.2 years respectively, p=0.23). Patients with BHS and those resected for pCCA had a significantly lower incidence of ECOG-PS \\u0026gt;0 compared with non-resected patients with pCCA (42.0 vs 23.0 vs 57.8 %, p=0.01). As for p-bilirubin, patients with BHS and those resected for pCCA had significantly lower p-bilirubin after decompression compared to non-resected patients with pCCA (0.0 vs 24.6 vs 42.2 %, p=0.02).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eRadiological characteristics\\u0026nbsp;\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eDistribution of Bismuth type and patients with radiological hilar mass were even between patients with BHS, resection, and non-resection (p=0.79 and p=0.27, respectively). Patients with BHS had a non-significantly lower distribution of radiological arterial as well as venous invasion on preoperative scanning compared with resected and non-resected patients with\\u0026nbsp;pCCA (0.0 vs 33.8 vs 31.5%, p=0.06 and 14.2 vs 40.0 vs 31.5 %, p=0.15, respectively). This was also the case regarding enlarged lymph nodes on preoperative radiology (14.2 vs 36.8 vs 33.8 %, p=0.26)\\u003cem\\u003e\\u0026nbsp;\\u003c/em\\u003e(\\u003cem\\u003eTable 1\\u003c/em\\u003e).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003ePreoperative interventions\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eTwenty patients (21.9 %) with suspected pCCA underwent PVE, with equal distribution between BHS, resection and non-resection (28.5 vs 21.5 vs 21.0 %, p=0.43). No pre-malignant or malignant preoperative cytology was obtained in patients with BHS, compared with resected and non-resected patients (0.0 vs 32.3 vs 51.6 %, p=0.01). No patients with BHS underwent neoadjuvant chemotherapy. However, 13 patients (14.2 %) with confirmed pCCA received neoadjuvant chemotherapy with an equal distribution between resected and non-resected patients (0.0 vs 15.3 vs 15.7 %, p=0.26). Time from first MDT to surgery was longer, however non-significant, in patients with BHS compared to resected and non-resected patients, respectively (75 vs 54 vs 54 days, p=0.54).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eT- and N-status\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eHigh age and low p-bilirubin were significantly associated with T-stage\\u0026gt;2 (\\u003cem\\u003eTable 2\\u003c/em\\u003e).\\u003c/p\\u003e\\n\\u003cp\\u003eIn case of N1-status (\\u003cem\\u003eTable 2\\u003c/em\\u003e), rate of arterial invasion and earlier resection attempt were\\u003c/p\\u003e\\n\\u003cp\\u003esignificantly higher (p=0.01 and 0.04, respectively). Correlation between N1 and arterial invasion\\u003c/p\\u003e\\n\\u003cp\\u003ehad an OR of 3.55 (95% CI 1.25-10.91, p=0.02). \\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eRisk factors for non-resectability, OS and DFS\\u0026nbsp;\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNon-resectability was significantly associated with shorter OS compared to resected with a 5-year survival of 0.0 and 39.2 %, respectively (p \\u0026lt;0.001). Median survival for resected and non-resected patients was 38.3 (IQR 24.3-50.6) and 16.6 (IQR 6.3-26.2) months, respectively.\\u003c/p\\u003e\\n\\u003cp\\u003eECOG-PS \\u0026gt;0 was the only significant risk factor associated with resectability for all patients with suspected pCCA (OR 0.23 (95% CI 0.07-0.66), p=0.006) \\u003cem\\u003e(Table 3)\\u003c/em\\u003e.\\u003c/p\\u003e\\n\\u003cp\\u003eOnly ECOG-PS \\u0026gt;0 (HR 2.32 (95% CI 1.31-4.11), p=0.003) and PVE (HR 2.99 (95 % CI 1.61-5.53)\\u003cstrong\\u003e,\\u0026nbsp;\\u003c/strong\\u003ep \\u0026lt;0.001) remained significantly associated with poorer OS in the multivariable analysis, for patients with suspected pCCA (\\u003cem\\u003eTable 4\\u003c/em\\u003e).\\u003c/p\\u003e\\n\\u003cp\\u003eKaplan-Meier estimates \\u003cem\\u003e(Figure 1 and 2)\\u003c/em\\u003e showed a 5-year survival for patients with ECOG-PS \\u0026gt;0\\u003c/p\\u003e\\n\\u003cp skip=\\\"true\\\"\\u003eof 14.3 % compared to 38.3 % for patients with ECOG-PS 0 (p=0.002), and 12.0 % for patients \\u003c/p\\u003e\\n\\u003cp skip=\\\"true\\\"\\u003eundergoing PVE compared to 37.2 % in patients not undergoing PVE (p=0.02). \\u003c/p\\u003e\\n\\u003cp skip=\\\"true\\\"\\u003ePVE was a risk factor for reduced DFS among resected patients with an HR of 2.89 (95 % CI 1.46- 5.71) (\\u003cem\\u003eTable 5\\u003c/em\\u003e). All patients in our cohort with PVE (n= 16) had undergone ERH (69 %).\\u003c/p\\u003e\\n\\u003cp skip=\\\"true\\\"\\u003eA sub-analysis in our study showed that patients with ERH compared with LH and EHBD resection, had a significantly higher frequency of progressive N-stage (43 vs 33 vs 0 % (p=0.02) respectively).This association was not observed in regard to progressive T-stage (26 vs 15 vs 40 % (p=0.23)) \\u0026nbsp; \\u0026nbsp;\\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eThis study investigated preoperative factors affecting outcomes in patients with suspected pCCA who were deemed resectable at the first MDT conference. Our results showed that ECOG-PS\\u0026thinsp;\\u0026gt;\\u0026thinsp;0, preoperative elevated p-bilirubin and PVE were associated with non-resectability and worse long-term survival outcomes for patients referred to resection for suspected pCCA. We also observed that factors such as advanced age, radiological arterial invasion and earlier resection attempt were associated with advanced tumor stages.\\u003c/p\\u003e \\u003cp\\u003eWe showed that ECOG-PS\\u0026thinsp;\\u0026gt;\\u0026thinsp;0 was associated with a significantly higher frequency of non-resectability and was an independent predictor for reduced OS. The associations with ECOG-PS\\u0026thinsp;\\u0026gt;\\u0026thinsp;0 may be explained by a general physiological effect of more progressive tumor stages that has been observed in previous studies in patients with advanced non-resectable biliary tract carcinoma (BTC)\\u003csup\\u003e\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e\\u003c/sup\\u003e. Yet, in our sub-analysis for T- and N-stage, no association between ECOG-PS\\u0026thinsp;\\u0026gt;\\u0026thinsp;0 and progressive tumor stages were observed. One explanation may be the high number of non-resected patients with elevated ECOG-PS in our cohort (11%), where pathological assessment of tumor stage was not possible. The association between elevated ECOG-PS and poor OS has previously been shown in one western cohort investigating patients resected for BTC in general. However, that study also included patients who were deemed non-resectable at the MDT (49%) and treated with palliative chemotherapy or best supportive care, potentially overestimating the correlation between elevated ECOG-PS and OS\\u003csup\\u003e\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eOur results demonstrated that non-resectable patients had a significantly higher frequency of post-decompression elevated p-bilirubin, compared to patients resected for pCCA and with BHS. Additionally, no patient with BHS had elevated post-decompression p-bilirubin. Although elevated p-bilirubin was not independently associated with worse OS, our results may still add to current evidence that elevated post-decompression p-bilirubin is associated with advanced tumor stage, reflecting extensive hilar stricture even after biliary decompression. This is in line with two previous eastern and western studies that demonstrated the incidence of elevated p-bilirubin in non-resectable and locally advanced resected pCCA \\u003csup\\u003e\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e\\u003c/sup\\u003e. Our study also adds to the current evidence in the field by including patients with BHS who did not have any case of elevated p-bilirubin after biliary decompression. Our data may be generalizable to a preoperative setting, as it also included patients with BHS (n\\u0026thinsp;=\\u0026thinsp;7) or other BTC (n\\u0026thinsp;=\\u0026thinsp;2) in the final pathology, together accounting for 9.6% of suspected pCCA referred to resection. Is important to note that p-bilirubin due to liver insufficiency may also have been a confounder in our cohort. Nevertheless, no patient undergoing liver resection in our cohort had any pre-operative sign of cirrhosis as it was an absolute contraindication. Nevertheless, studying correlation between elevated p-bilirubin and OS in the future, may be aided by estimating and adjusting for liver function through measurement of indocyanine green (ICG) clearance test\\u003csup\\u003e\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e\\u003c/sup\\u003e. One additional confounder that may have hampered our results is resection prior to complete normalization of the p-bilirubin following biliary decompression.\\u003c/p\\u003e \\u003cp\\u003eInterestingly, our results indicated an association between PVE and worse DFS and OS. This is contrary to previous studies showing that PVE is associated with lower 90-day morbidity and mortality due to reduced incidence of post-operative liver failure\\u003csup\\u003e\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e\\u003c/sup\\u003e. However, the association between worse survival and PVE may be due to confounding in that patients who underwent PVE had more advanced and complex tumors. The association between PVE and non-resectability in pCCA has been observed in one recent study investigating preoperative prognostic factors\\u003csup\\u003e\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e\\u003c/sup\\u003e. No significant association between PVE and progressive T- or N-stage was observed in our cohort. However, all patients with PVE had undergone ERH which in turn was significantly associated with progressive N-stage, a well-known factor for worse OS\\u003csup\\u003e\\u003cspan additionalcitationids=\\\"CR22\\\" citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e\\u003c/sup\\u003e. Tumor progression following PVE has been reported for other liver malignancies in both the embolized and non-embolized lobe due to neovascularization\\u003csup\\u003e\\u003cspan citationid=\\\"CR30\\\" class=\\\"CitationRef\\\"\\u003e30\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eNo study has investigated predictive variables for T-stage and two studies have only recently described predictive models for LNM in pCCA \\u003csup\\u003e\\u003cspan additionalcitationids=\\\"CR22\\\" citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e\\u003c/sup\\u003e. Our results showed that older patients had a higher frequency of advanced T-stage. In pCCA, association between age and clinically aggressive malignancy is yet to be investigated. Although biologically different, one recent cohort likewise showed that advanced T-stage in intrahepatic cholangiocarcinoma, was associated with late disease onset \\u003csup\\u003e\\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e\\u003c/sup\\u003e. However, in contrary to that study, we showed no association between age and worse OS or DFS.\\u003c/p\\u003e \\u003cp\\u003eLNM was associated with radiological arterial invasion as well as earlier resection attempt. Both factors may reflect advanced disease and, thus, the association. We add to the field of predicting LNM as previous models have not included radiological variables\\u003csup\\u003e\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eThe main strength of this study was a detailed analysis of patients referred to surgery for suspected pCCA from the MDT, regardless of final pathological or surgical outcome. This may be more reflective of the clinical reality in the context of an MDT conference. Moreover, patients with suspected pCCA were followed-up from the time of the initial MDT conference. Furthermore, the short study period of 10 years resulted in homogenous pre- and perioperative clinical management with less variations over time.\\u003c/p\\u003e \\u003cp\\u003eHowever, our study should be viewed with caution as it is a single-center design with a limited number of patients with some cases of missing variables and risk of false negative findings. Therefore, future studies should include larger patient cohorts with a multicenter design. Also, more patients will increase power to the analysis with an opportunity to design a validated preoperative predictive model. Moreover, we were not able to assess the prognostic impact of PSC, as some resectable patients undergo liver transplantation according to the Mayo protocol\\u003csup\\u003e\\u003cspan citationid=\\\"CR29\\\" class=\\\"CitationRef\\\"\\u003e29\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eConclusively, ECOG-PS\\u0026thinsp;\\u0026gt;\\u0026thinsp;0 and PVE affected OS in suspected pCCA if deemed resectable at MDT. Additionally, ECOG-PS\\u0026thinsp;\\u0026gt;\\u0026thinsp;0 and elevated p-bilirubin were associated with higher frequency of non-resectability in pCCA. We also showed that high age and arterial invasion were associated with advanced tumor- and lymph node stage. These findings may aid selection of suitable candidates for surgery at the MDT where only preoperative variables are available. However, larger studies with subsequent validation are needed.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003ch2\\u003eConflicts of interest\\u003c/h2\\u003e \\u003cp\\u003eAuthors stated no conflict of interest.\\u003c/p\\u003e \\u003ch2\\u003eFinancial declaration\\u003c/h2\\u003e \\u003cp\\u003eAuthors received no reported funding in this study.\\u003c/p\\u003e\\u003ch2\\u003eAuthor Contribution\\u003c/h2\\u003e\\u003cp\\u003eHAA wrote the first version of the manuscript and conducted statistical analysis. TS, LK, DR, PN, NS and HCP contributed to editing the manuscript. HCP was main supervisor\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eBanales JM, Marin JJG, Lamarca A et al (2020) Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol 17(9):557\\u0026ndash;588\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eDeOliveira ML, Cunningham SC, Cameron JL et al (2007) Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Ann Surg 245:755\\u0026ndash;762\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eRoos E, Strijker M, Franken LC et al (2020) Comparison of short- and long-term outcomes between anatomical subtypes of resected biliary tract cancer in a Western high-volume center. HPB (Oxford) 22(3):405\\u0026ndash;414\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eOtto CC, Mantas A, Heij LR et al (2024) Preoperative predictors for non-resectability in perihilar cholangiocarcinoma. World J Surg Onc 22:48\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eWiggers JK, Koerkamp BG, Cieslak KP et al (2016) Postoperative mortality after liver resection for perihilar cholangiocarcinoma: development of a risk score and importance of biliary drainage of the future liver remnant. J Am Coll Surg 223:321\\u0026ndash;331\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eKoerkamp BG, Wiggers JK, Gonen M et al (2015) Survival after resection of perihilar cholangiocarcinoma\\u0026mdash; Development and external validation of a prognostic normogram. Ann Oncol 26:1930\\u0026ndash;1935\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eGaspersz MP, Buettner S, Roos E et al (2018) A preoperative prognostic model to predict surgical success in patients with perihilar cholangiocarcinoma. J Surg Oncol 118:469\\u0026ndash;476\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003evan Keulen AM, Buettner S, Erdmann JI et al (2023) Multivariable prediction model for both 90-day mortality and long-term survival for individual patients with perihilar cholangiocarcinoma: does the predicted survival justify the surgical risk? Br J Surg 110(5):599\\u0026ndash;605\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eWiggers JK, Groot Koerkamp B et al (2018) Preoperative Risk Score to Predict Occult Metastatic or Locally Advanced Disease in Patients with Resectable Perihilar Cholangiocarcinoma on Imaging. J Am Coll Surg 227(2):238\\u0026ndash;246e2\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePeng D, Lu J, Hu H, Li B et al (2020) Lymphocyte to Monocyte Ratio Predicts Resectability and Early Recurrence of Bismuth-Corlette Type IV Hilar Cholangiocarcinoma. J Gastrointest Surg 24(2):330\\u0026ndash;340\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLi CX, Zhang H, Wang K et al (2019) Preoperative Bilirubin Level Predicts Overall Survival and Tumor Recurrence After Resection for Perihilar Cholangiocarcinoma Patients. Cancer Manag Res 11:10157\\u0026ndash;10165\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eTirotta F, Giovinazzo F, Hodson J et al (2020) Risk factors to differentiate between benign proximal biliary strictures and perihilar cholangiocarcinoma. HPB (Oxford) 22(12):1753\\u0026ndash;1758\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSoares K, Kamel I, Cosgrove D et al (2014) Holar cholangiocarcinoma: Diagnosis, treatment options, and management. Hepatobiliary Surg Nutr 3(1):18\\u0026ndash;34\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eRassam F, Roos E, van Lienden KP et al (2018) Modern work-up and extended resection in perihilar cholangiocarcinoma: the AMC experience. Langenbecks Arch Surg 403:289\\u0026ndash;307\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLee JW, Lee JH, Park Y et al (2020) Prognostic Predictability of American Joint Committee on Cancer 8th Staging System for Perihilar Cholangiocarcinoma: Limited Improvement Compared with th 7th Staging System. Cancer Rs Treat 52(3):886\\u0026ndash;895\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePeixoto RD, Renouf D, Lim H et al (2014) A population based analysis of prognostic factors in advanced biliary tract cancer. J Gastrointest Oncol 5(6):428\\u0026ndash;432\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eIzquierdo-Sanchez L, Lamarca A, La Casta A et al (2022) Cholangiocarcinoma landscape in Europe: Diagnostic, prognostic and therapeutic insights from the ENSCCA Registry. J Hepatol 76(5):1109\\u0026ndash;1121\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eDe Gasperi A, Mazza E, Prosperi M et al (2016) Indocyanine green kinetics to assess liver function: Ready for a clinical dynamic assessment in major liver surgery? World J Hepatol 8(7):355\\u0026ndash;367\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003evan Keulen AM, Olthof PB, Cescon M et al (2021) Actual 10-Year Survival after Resection of Perihilar Cholangiocarcinoma: What Factors Preclude a Chance for Cure? Cancers (Basel) 13(24):6260\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eOlthof PB, Erdmann JI, Alikhanov R et al (2024 Mar) Higher Postoperative Mortality and Inferior Survival After Right-Sided Liver Resection for Perihilar Cholangiocarcinoma: Left-Sided Resection is Preferred When Possible. Ann Surg Oncol 12. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1245/s10434-024-15115-0\\u003c/span\\u003e\\u003cspan address=\\\"10.1245/s10434-024-15115-0\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eZhan P, Yang T, Zhang Y et al (2024) Radiomics using CT images for preoperative prediction of lymph node metastasis in perihilar cholangiocarcinoma: a multi-centric study. Eur Radiol 34:1280\\u0026ndash;1291\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMao S, Shan Y, Yu X et al (2024) Development and validation of a novel preoperative clinical model for predicting lymph node metastasis in perihilar cholangiocarcinoma. BMC Cancer 24:297\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMatsuo K, Rocha FG, Ito K et al (2012) The Blumgart preoperative staging system for hilar cholangiocarcinoma: analysis of resectability and outcomes in 380 patients. J Am Coll Surg 215(3):343\\u0026ndash;355\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eTsilimigras DI, Han X, Guglielmi A, Aldrighetti L et al (2024) Early Onset Intrahepatic Cholangiocarcinoma: Clinical Characteristics, Oncological Outcomes, and Genomic/Transcriptomic Features. Ann Surg Oncol 31(5):3087\\u0026ndash;3097\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eToyoda J, Sahara K, Takahashi T et al (2023) Neoadjuvant Therapy for Extrahepatic Biliary Tract Cancer: A Propensity Score-Matched Survival Analysis. J Clin Med 12(7):2654\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eErcolani G, Dazzi A, Giovinazzo F et al (2015) Intrahepatic, peri-hilar and distal cholangiocarcinoma: Three different locations of the same tumor or three different tumors? Eur J Surg Oncol 41(9):1162\\u0026ndash;1169\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLi B, Couris CM, Fushimi K et al (2011) Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol 173(6):676\\u0026ndash;682\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLee JW, Lee JH, Park Y et al (2021) Prognostic Impact of Perioperative CA19-9 Levels in Patients with Resected Perihilar Cholangiocarcinoma. J Clin Med 10(7):1345\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eRosen CB, Heimbach JK, Gores GJ (2008) Surgery for cholangiocarcinoma: the role of liver transplantation. HPB (Oxford) 10(3):186\\u0026ndash;189\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSimoneau E, Hassanain M, Shaheen M et al (2015) Portal vein embolization and its effect on tumour progression for colorectal cancer liver metastases. Br J Surg 102(10):1240\\u0026ndash;1249\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"},{\"header\":\"Tables\",\"content\":\"\\u003ctable border=\\\"1\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"746\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"4\\\" valign=\\\"top\\\" style=\\\"width: 708px;\\\"\\u003e\\u003cstrong\\u003eTable 1. \\u0026nbsp;Characteristics for patients\\u0026nbsp;\\u003c/strong\\u003e\\u003cstrong\\u003ewith pCCA\\u003c/strong\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003cstrong\\u003eand BHS\\u0026nbsp;\\u003c/strong\\u003e\\u003cstrong\\u003e(n= 91)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003ePatients with BHS, n = 7\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003eResected patients with pCCA, n = 65\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003eNon-resected patients with pCCA, n=19\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003eP\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003eOS (Time from first MDT), median (IQR)a\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003e35.0 (17.4-41.7)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e38.3 (24.3-52.4)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e15.6 (3.7-26.2)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e0.52\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003eAge, median (IQR)\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003e69.9 (65.8-73.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e64.9 (54.4-70.4)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e68.2 (59.5-72.1)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e0.23\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003eSex, male, n (%)\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003e5 (71.4)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e36 (55.3)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e10 (52.6)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e0.67\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003ePatient ECOG-PSb\\u0026gt;0, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003e\\u003cstrong\\u003e3 (42.8)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\u003cstrong\\u003e15 (23.0)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u003cstrong\\u003e11 (57.8)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e\\u003cstrong\\u003e0.01\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003ePreoperative weight loss, Median (IQR)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003e2.0 (0.0-10.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e4.0 (0.0-8.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e5.0 (0.0-7.5)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e0.99\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003ePreoperative P-Bilirubin \\u0026gt;25, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003e\\u003cstrong\\u003e0 (0.0)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\u003cstrong\\u003e16 (24.6)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u003cstrong\\u003e8 (42.2)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e\\u003cstrong\\u003e0.02\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003ePreoperative CA 19-9 \\u0026gt;37, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003e2 (28.5)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e29 (44.6)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e9 (47.3)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e0.77\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003ePSC, n (%)c\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003e0 (0.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e7 (10.7)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e1 (5.2)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e0.25\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003ePrevious resection attempt, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003e0 (0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e7 (10.7)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e1 (5.2)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e0.25\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003eBismuth type:\\u0026nbsp;\\u003cbr\\u003eI, n (%)\\u003cbr\\u003eII, n (%)\\u003cbr\\u003eIIIa, n (%)\\u003cbr\\u003eIIIb, n (%)\\u003cbr\\u003eIV, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003eI: 1 (14.2)\\u003cbr\\u003eII: 1 (14.2)\\u003cbr\\u003eIIIa: 2 (28.5)\\u003cbr\\u003eIIIb: 2 (28.5)\\u003cbr\\u003eIV:1 (14.2)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003eI: 11 (16.9)\\u003cbr\\u003eII: 8 (13.3)\\u003cbr\\u003eIIIa: 16 (24.6)\\u003cbr\\u003eIIIb: 15 (23.0)\\u003cbr\\u003eIV: 15 (23.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003eI: 3 (15.7)\\u003cbr\\u003eII: 5 (26.3)\\u003cbr\\u003eIIIa: 2 (5.2)\\u003cbr\\u003eIIIb: 3 (15.7)\\u003cbr\\u003eIV: 6 (31.5)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e0.79\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003eHilar mass on radiology, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003e5 (71.4)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e54 (83.7)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e14 (73.6)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e0.27\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003eEnlarged local lymph nodes on radiology, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003e1 (14.2)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e22 (33.8)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e7 (36.8)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e0.26\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003eArterial invasion on pre-operative radiology, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003e0 (0.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e22 (33.8)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e6 (31.5)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e0.06\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003eVenous invasion on pre-operative radiology, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003e1 (14.2)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e26 (40.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e6 (31.5)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e0.15\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003eFLR \\u0026gt;30 %, n (%)d\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003e7 (100.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e63 (96.9)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e17 (89.4)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e0.31\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003ePreoperative biliary drainage, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003e7 (100.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\u0026nbsp;62 (95.3)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e19 (100)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e0.54\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003ePreoperative malignant histo-/cytology, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003e\\u003cstrong\\u003e0 (0.0)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e\\u003cstrong\\u003e21 (32.3)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u003cstrong\\u003e10 (52.6)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e\\u003cstrong\\u003e0.01\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003ePre-operative neoadjuvant therapy, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003e0 (0.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e10 (15.3)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e3 (15.7)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e0.26\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003ePortal vein embolization, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003e2 (28.5)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e14 (21.5)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e4 (21.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e0.43\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 360px;\\\"\\u003eTime from MDTc to surgery (days), median (IQR)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 122px;\\\"\\u003e75 (58-92)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 123px;\\\"\\u003e54 (33-80)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e54 (40-107)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 38px;\\\"\\u003e0.54\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003ea: Overall survival; b: ECOG-Performance status; c: Primary sclerotizing cholangitis; d: Future liver remnant CA 19-9 Missing n (%): 28 (30)\\u003c/p\\u003e\\n\\u003ctable border=\\\"1\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" align=\\\"left\\\" width=\\\"842\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"7\\\" valign=\\\"top\\\" style=\\\"width: 842px;\\\"\\u003e\\u003cstrong\\u003eTable 2.\\u0026nbsp;\\u003c/strong\\u003e\\u003cstrong\\u003ePreoperative characteristics for patients according to T- and N-status in patients resected with confirmed pCCA (n=65)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 291px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 115px;\\\"\\u003eT-stage \\u0026gt;2, n= 12\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003eT-stage \\u0026le;2, n= 53\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 47px;\\\"\\u003eP\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003eN 1, n=24\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 118px;\\\"\\u003eN 0, n=41\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44px;\\\"\\u003eP\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 291px;\\\"\\u003eAge \\u0026gt;70, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 115px;\\\"\\u003e\\u003cstrong\\u003e\\u0026nbsp;6 (50.0)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e\\u003cstrong\\u003e11 (20.7)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 47px;\\\"\\u003e\\u003cstrong\\u003e0.03\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e7 (29.1)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 118px;\\\"\\u003e10 (24.3)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44px;\\\"\\u003e0.67\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 291px;\\\"\\u003eSex, male, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 115px;\\\"\\u003e\\u0026nbsp;6 (50.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e22 (41.5)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 47px;\\\"\\u003e0.59\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e10 (41.6)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 118px;\\\"\\u003e18 (43.9)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44px;\\\"\\u003e0.86\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 291px;\\\"\\u003ePatient ECOG-PSa\\u0026gt;0; n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 115px;\\\"\\u003e\\u0026nbsp;1 (8.3)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e14 (26.4)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 47px;\\\"\\u003e0.17\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e6 (25.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 118px;\\\"\\u003e9 (21.9)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44px;\\\"\\u003e0.07\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 291px;\\\"\\u003eCA 19-9 high, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 115px;\\\"\\u003e\\u0026nbsp;5 (41.6)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e24 (45.2)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 47px;\\\"\\u003e0.051\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e14 (58.3)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 118px;\\\"\\u003e15 (36.5)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44px;\\\"\\u003e0.08\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 291px;\\\"\\u003eBilirubin high, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 115px;\\\"\\u003e\\u003cstrong\\u003e\\u0026nbsp;1 (8.3)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e\\u003cstrong\\u003e24 (45.2)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 47px;\\\"\\u003e\\u003cstrong\\u003e0.01\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e8 (33.3)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 118px;\\\"\\u003e8 (19.5)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44px;\\\"\\u003e0.21\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 291px;\\\"\\u003ePSCb, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 115px;\\\"\\u003e0 (0.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e7 (13.2)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 47px;\\\"\\u003e\\u0026gt;1.00\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e3 (12.5)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 118px;\\\"\\u003e4 (9.75)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44px;\\\"\\u003e0.11\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 291px;\\\"\\u003ePreoperative downstaging, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 115px;\\\"\\u003e\\u0026nbsp;2 (16.6)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e8 (15.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 47px;\\\"\\u003e0.89\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e5 (20.8)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 118px;\\\"\\u003e5 (12.1)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44px;\\\"\\u003e0.25\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 291px;\\\"\\u003ePortal vein embolization, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 115px;\\\"\\u003e\\u0026nbsp;4 (33.3)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e10 (18.8)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 47px;\\\"\\u003e0.27\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e7 (29.1)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 118px;\\\"\\u003e7 (17.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44px;\\\"\\u003e0.21\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 291px;\\\"\\u003eBismuth type, n (%)\\u003cbr\\u003e\\n \\u003cul\\u003e\\n \\u003cli\\u003eI\\u003c/li\\u003e\\n \\u003cli\\u003eII\\u0026nbsp;\\u003c/li\\u003e\\n \\u003cli\\u003eIIIa\\u0026nbsp;\\u003c/li\\u003e\\n \\u003cli\\u003eIIIb\\u0026nbsp;\\u003c/li\\u003e\\n \\u003cli\\u003eIV\\u0026nbsp;\\u003c/li\\u003e\\n \\u003c/ul\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 115px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003eI: 3 (25.0)\\u003cbr\\u003eII: 0 (0.0) \\u0026nbsp;\\u003cbr\\u003eIIIa: 3 (25.0)\\u0026nbsp;\\u003cbr\\u003eIIIb: 3 (25.0)\\u003cbr\\u003eIV: 3 (25.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003eI: 8 (15.0)\\u003cbr\\u003eII: 8 (15.0)\\u003cbr\\u003eIIIa: 13 (24.5)\\u003cbr\\u003eIIIb: 12 (23.0)\\u003cbr\\u003eIV: 12 (23.0)\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 47px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e0.81\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003eI: 5 (20.8)\\u003cbr\\u003eII: 1 (4.1)\\u003cbr\\u003eIIIa: 5 (20.8)\\u0026nbsp;\\u003cbr\\u003eIIIb: 7 (29.1)\\u003cbr\\u003eIV: 6 (25.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 118px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003eI: 6 (14.6)\\u003cbr\\u003eII: 7 (17.0)\\u003cbr\\u003eIIIa: 11 (26.8)\\u003cbr\\u003eIIIb: 8 (19.5)\\u003cbr\\u003eIV: 9 (21.9)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e0.51\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 291px;\\\"\\u003eHilar mass, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 115px;\\\"\\u003e9 (75.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e45 (84.9)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 47px;\\\"\\u003e0.40\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e19 (79.1)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 118px;\\\"\\u003e35 (85.3)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44px;\\\"\\u003e0.52\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 291px;\\\"\\u003eEnlarged local lymph nodes on radiology, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 115px;\\\"\\u003e\\u0026nbsp;5 (41.6)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e\\u0026nbsp;17 (32.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 47px;\\\"\\u003e0.52\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e11 (45.8)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 118px;\\\"\\u003e11 (26.8)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44px;\\\"\\u003e0.11\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 291px;\\\"\\u003eArterial invasion on pre-operative radiology, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 115px;\\\"\\u003e\\u0026nbsp;4 (33.3)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e\\u0026nbsp;17 (32.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 47px;\\\"\\u003e0.93\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e\\u003cstrong\\u003e12 (50.0 )\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 118px;\\\"\\u003e\\u003cstrong\\u003e9 (20.9)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44px;\\\"\\u003e\\u003cstrong\\u003e0.01\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 291px;\\\"\\u003eVenous invasion on pre-operative radiology, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 115px;\\\"\\u003e\\u0026nbsp;4 (33.3)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e\\u0026nbsp;22 (41.5)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 47px;\\\"\\u003e0.60\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e10 (41.6)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 118px;\\\"\\u003e16 (39.0)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44px;\\\"\\u003e0.83\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 291px;\\\"\\u003eEarlier resection attempt, n (%)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 115px;\\\"\\u003e1 (8.3)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e6 (11.3)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 47px;\\\"\\u003e0.76\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 113px;\\\"\\u003e\\u003cstrong\\u003e\\u0026nbsp;5 (20.8)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 118px;\\\"\\u003e\\u003cstrong\\u003e\\u0026nbsp;2 (4.8)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 44px;\\\"\\u003e\\u003cstrong\\u003e0.04\\u0026nbsp;\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003e\\u003cbr\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eChi-square analysis for preoperative predictive variables for a T- and N-status. a: ECOG-Performance status; b: Primary sclerotizing cholangitis; CA 19-9 Missing n (%): 28 (30)\\u003c/p\\u003e\\n\\u003ctable border=\\\"1\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"624\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"3\\\" valign=\\\"top\\\" style=\\\"width: 624px;\\\"\\u003e\\u003cstrong\\u003eTable 3. Preoperative factors for resectability after referral in pCCA (n=93)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 293px;\\\"\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003eUnivariable\\u003cbr\\u003eOR (95% CI)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003eP\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 293px;\\\"\\u003eAge \\u0026gt;70, (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003e0.63 (0.22, 1.91)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e0.40\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 293px;\\\"\\u003eSex, female (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003e0.80 (0.28, 2.23)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e0.66\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 293px;\\\"\\u003ePatient ECOG-PSa \\u0026gt;0, (no)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003e\\u003cstrong\\u003e0.23 (0.07, 0.66)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e\\u003cstrong\\u003e0.006\\u003c/strong\\u003e\\u003cbr\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 293px;\\\"\\u003ePreoperative bilirubin \\u0026gt;25 (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003e0.35 (0.12, 1.02)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e0.05\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 293px;\\\"\\u003eCA 19-9 \\u0026gt;37 (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003e0.62 (0.15, 2.13)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e0.46\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 293px;\\\"\\u003ePSCb, (yes)\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003e1.88 (0.30, 36.33)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e0.56\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 293px;\\\"\\u003eBismuth type\\u003cbr\\u003e\\n \\u003cul\\u003e\\n \\u003cli\\u003eI\\u0026nbsp;\\u003c/li\\u003e\\n \\u003cli\\u003eII\\u0026nbsp;\\u003c/li\\u003e\\n \\u003cli\\u003eIIIa\\u003c/li\\u003e\\n \\u003cli\\u003eIIIb\\u003c/li\\u003e\\n \\u003cli\\u003eIV\\u003c/li\\u003e\\n \\u003c/ul\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003eI: (ref)\\u003cbr\\u003eII: 0.46 (0.07, 2.34)\\u003cbr\\u003eIIIa: 2.07 (0.30, 17.53)\\u003cbr\\u003eIIIb: 1.30 (0.21, 8.11)\\u003cbr\\u003eIV: 0.61 (0.11, 2.82)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003eI: (ref)\\u003cbr\\u003eII: 0.35\\u003cbr\\u003eIIIa: 0.45\\u0026nbsp;\\u0026nbsp;\\u003cbr\\u003eIIIb: 0.76\\u003cbr\\u003eIV: 0.54\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 293px;\\\"\\u003eHilar radiological mass (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003e1.53 (0.43, 4.78)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e0.47\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 293px;\\\"\\u003eEnlarged local lymph nodes on radiology, (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003e0.77 (0.27, 2.31)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e0.63\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 293px;\\\"\\u003eArterial invasion on pre-operative radiology, (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003e1.16 (0.36, 3.37)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e0.87\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 293px;\\\"\\u003eVenous invasion on pre-operative radiology, (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003e0.80 (0.25, 2.28)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e0.69\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 293px;\\\"\\u003ePreoperative biliary drainage (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003en/a\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e0.99\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 293px;\\\"\\u003ePortal vein embolization\\u0026nbsp;(yes)\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003e1.03 (0.32, 4.01)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e0.95\\u0026nbsp;\\u0026nbsp;\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 293px;\\\"\\u003eNeoadjuvant chemotherapy (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003e0.83 (0.22, 4.03)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e0.79\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 293px;\\\"\\u003eTime to surgery from MDTc-date (days)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 180px;\\\"\\u003e0.99 (0.99, 1.00)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 151px;\\\"\\u003e0.98\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003eUnivariable logistical regression analysis for patients not undergoing resection. a: ECOG-Performance status; b: Primary sclerotizing cholangitis; CA 19-9 Missing n (%): 28 (30)\\u003c/p\\u003e\\n\\u003ctable border=\\\"1\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"662\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"5\\\" valign=\\\"top\\\" style=\\\"width: 662px;\\\"\\u003e\\u003cstrong\\u003eTable\\u0026nbsp;\\u003c/strong\\u003e\\u003cstrong\\u003e4.\\u003c/strong\\u003e\\u003cstrong\\u003e\\u0026nbsp;R\\u003c/strong\\u003e\\u003cstrong\\u003eisk factors affecting OS for all patients with suspected PHCC deemed resectable at MDT (n=93)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 284px;\\\"\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 142px;\\\"\\u003eUnivariable\\u003cbr\\u003eHR (95% CI)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 76px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003eP\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u0026nbsp;Multivariable\\u003cbr\\u003eHR (95% CI)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003eP\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 284px;\\\"\\u003eAge \\u0026gt;70 (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 142px;\\\"\\u003e0.88 (0.48, 1.61)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 76px;\\\"\\u003e0.68\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 284px;\\\"\\u003eSex, female\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 142px;\\\"\\u003e0.87 (0.52, 1.47)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 76px;\\\"\\u003e0.62\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 284px;\\\"\\u003eECOG-PSa \\u0026gt;0 (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 142px;\\\"\\u003e\\u003cstrong\\u003e1.92 (1.11, 3.32)\\u0026nbsp;\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 76px;\\\"\\u003e\\u003cstrong\\u003e0.01\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u003cstrong\\u003e2.32 (1.31, 4.11)\\u0026nbsp;\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\u003cstrong\\u003e0.003\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 284px;\\\"\\u003ePreoperative bilirubin \\u0026gt;25 (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 142px;\\\"\\u003e1.70 (0.99, 2.90)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 76px;\\\"\\u003e0.05\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u0026nbsp;\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 284px;\\\"\\u003eCA 19-9 \\u0026gt;37 (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 142px;\\\"\\u003e1.17 (0.61, 2.24)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 76px;\\\"\\u003e0.62\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 284px;\\\"\\u003ePSCb (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 142px;\\\"\\u003e1.33 (0.60, 2.97)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 76px;\\\"\\u003e0.47\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 284px;\\\"\\u003eBismuth type\\u003cbr\\u003e\\n \\u003cul\\u003e\\n \\u003cli\\u003eI\\u0026nbsp;\\u003c/li\\u003e\\n \\u003cli\\u003eII\\u0026nbsp;\\u003c/li\\u003e\\n \\u003cli\\u003eIIIa\\u003c/li\\u003e\\n \\u003cli\\u003eIIIb\\u003c/li\\u003e\\n \\u003cli\\u003eIV\\u003c/li\\u003e\\n \\u003c/ul\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 142px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003eI: (ref)\\u003cbr\\u003eII: 0.89 (0.32, 2.47)\\u003cbr\\u003eIIIa: 1.54 (0.64, 3.73)\\u003cbr\\u003eIIIb: 1.00 (0.41, 2.46)\\u003cbr\\u003eIV: 1.57 (0.68, 3.63) \\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 76px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003eI: (ref)\\u003cbr\\u003eII: 0.82\\u003cbr\\u003eIIIa: 0.34\\u003cbr\\u003eIIIb: 0.99\\u003cbr\\u003eIV: 0.27\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 284px;\\\"\\u003eHilar radiological mass\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 142px;\\\"\\u003e0.88 (0.48, 1.60)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 76px;\\\"\\u003e0.67\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 284px;\\\"\\u003eEnlarged local lymph nodes on radiology, (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 142px;\\\"\\u003e1.30 (0.77, 2.19)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 76px;\\\"\\u003e0.32\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 284px;\\\"\\u003eArterial invasion on pre-operative radiology, (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 142px;\\\"\\u003e0.80 (0.47, 1.37)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 76px;\\\"\\u003e0.42\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 284px;\\\"\\u003eVenous invasion on pre-operative radiology, (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 142px;\\\"\\u003e1.12 (0.66, 1.90)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 76px;\\\"\\u003e0.66\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 284px;\\\"\\u003eFLR \\u0026gt;30 % (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 142px;\\\"\\u003e0.98 (0.13, 7.25)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 76px;\\\"\\u003e1.01\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 284px;\\\"\\u003ePreoperative biliary drainage\\u0026nbsp;(yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 142px;\\\"\\u003e1.18 (0.36, 3.79)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 76px;\\\"\\u003e0.77\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 284px;\\\"\\u003ePortal vein embolization\\u0026nbsp;(yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 142px;\\\"\\u003e\\u003cstrong\\u003e2.47 (1.37, 4.46)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 76px;\\\"\\u003e\\u003cstrong\\u003e0.002\\u0026nbsp;\\u003c/strong\\u003e\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u003cstrong\\u003e2.99 (1.61, 5.53)\\u0026nbsp;\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\u003cstrong\\u003e\\u0026lt;0.001\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 284px;\\\"\\u003eNeoadjuvant chemotherapy (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 142px;\\\"\\u003e1.01 (0.49, 2.06)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 76px;\\\"\\u003e0.96\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 284px;\\\"\\u003eTime from MDT (days)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 142px;\\\"\\u003e2.71 (2.69, 2.71)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 76px;\\\"\\u003e0.24\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 284px;\\\"\\u003eEarlier resection attempt (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 142px;\\\"\\u003e1.64 (0.80, 3.34)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 76px;\\\"\\u003e0.12\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 104px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 57px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003eUni- and multivariable Cox regression analysis with Overall Survival. a: ECOG-Performance status; b: Primary sclerotizing cholangitis; CA 19-9 Missing n (%): 28 (30)\\u003c/p\\u003e\\n\\u003ctable border=\\\"1\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"576\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"3\\\" valign=\\\"top\\\" style=\\\"width: 576px;\\\"\\u003e\\u0026nbsp;\\u003cstrong\\u003eTable 5. Preoperative risk factors affecting Disease Free Survival (DFS) for all patients resected with PHCC in final histology (n=65)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 283px;\\\"\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 198px;\\\"\\u003eUnivariable\\u003cbr\\u003eHR (95% CI)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 94px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003eP\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 283px;\\\"\\u003eAge \\u0026gt;70 (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 198px;\\\"\\u003e0.66 (0.32, 1.33)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 94px;\\\"\\u003e0.24\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 283px;\\\"\\u003eSex (female)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 198px;\\\"\\u003e1.14 (0.63, 2.06)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 94px;\\\"\\u003e0.64\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 283px;\\\"\\u003ePatient PSa\\u0026gt;0,\\u0026nbsp;(yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 198px;\\\"\\u003e1.10 (0.54, 2.24)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 94px;\\\"\\u003e0.78\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 283px;\\\"\\u003eWeightloss (kg)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 198px;\\\"\\u003e1.00 (0.95, 1.07)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 94px;\\\"\\u003e0.81\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 283px;\\\"\\u003eBilirubin \\u0026gt;25 (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 198px;\\\"\\u003e1.69 (0.89, 3.20)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 94px;\\\"\\u003e0.10\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 283px;\\\"\\u003eCA 19-9 \\u0026gt;37 (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 198px;\\\"\\u003e1.55 (0.71, 3.39)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 94px;\\\"\\u003e0.27\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 283px;\\\"\\u003ePSCb\\u0026nbsp;(yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 198px;\\\"\\u003e1.98 (0.87, 4.47)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 94px;\\\"\\u003e0.10\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 283px;\\\"\\u003eBismuth type\\u003cbr\\u003e\\n \\u003cul\\u003e\\n \\u003cli\\u003eI, (yes)\\u003c/li\\u003e\\n \\u003cli\\u003eII, (yes)\\u003c/li\\u003e\\n \\u003cli\\u003eIIIa, (yes)\\u003c/li\\u003e\\n \\u003cli\\u003eIIIb, (yes)\\u003c/li\\u003e\\n \\u003cli\\u003eIV, (yes)\\u003c/li\\u003e\\n \\u003c/ul\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 198px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003eI: (ref)\\u003cbr\\u003eII: 0.14 (0.01, 1.16)\\u003cbr\\u003eIIIa: 1.87 (0.73, 4.79)\\u003cbr\\u003eIIIb: 1.27 (0.49, 3.26)\\u003cbr\\u003eIV: 2.20 (0.87, 5.56)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 94px;\\\"\\u003e\\u0026nbsp;\\u003cbr\\u003e\\u0026nbsp;\\u003cbr\\u003eI: (ref)\\u003cbr\\u003eII: 0.06\\u003cbr\\u003eIIIa: 0.19\\u003cbr\\u003eIIIb: 0.60\\u003cbr\\u003eIV: 0.09\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 283px;\\\"\\u003eHilar mass (Yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 198px;\\\"\\u003e1.54 (0.68, 3.46)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 94px;\\\"\\u003e0.29\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 283px;\\\"\\u003eEnlarged local lymph nodes on radiology, (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 198px;\\\"\\u003e1.63 (0.89, 2.96)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 94px;\\\"\\u003e0.10\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 283px;\\\"\\u003eArterial invasion on pre-operative radiology, (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 198px;\\\"\\u003e0.60 (0.33, 1.09)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 94px;\\\"\\u003e0.09\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 283px;\\\"\\u003eVenous invasion on pre-operative radiology, (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 198px;\\\"\\u003e0.82 (0.45, 1.49)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 94px;\\\"\\u003e0.53\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 283px;\\\"\\u003ePortal vein embolization,\\u0026nbsp;(yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 198px;\\\"\\u003e\\u003cstrong\\u003e2.89\\u0026nbsp;\\u003c/strong\\u003e\\u003cstrong\\u003e(\\u003c/strong\\u003e\\u003cstrong\\u003e1.46\\u003c/strong\\u003e\\u003cstrong\\u003e,\\u0026nbsp;\\u003c/strong\\u003e\\u003cstrong\\u003e5.71\\u003c/strong\\u003e\\u003cstrong\\u003e)\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 94px;\\\"\\u003e\\u003cstrong\\u003e0.002\\u003c/strong\\u003e\\u003cbr\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 283px;\\\"\\u003eBiliary decompression\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 198px;\\\"\\u003e1.26 (0.30, 5.24)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 94px;\\\"\\u003e0.74\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 283px;\\\"\\u003eNeoadjuvant chemotherapy, (yes)\\u0026nbsp;\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 198px;\\\"\\u003e1.59 (0.76, 3.32)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 94px;\\\"\\u003e0.21\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 283px;\\\"\\u003eTime to surgery (days)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 198px;\\\"\\u003e1.00 (0.99, 1.09)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 94px;\\\"\\u003e0.26\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 283px;\\\"\\u003eEarlier resection attempt (yes)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"bottom\\\" style=\\\"width: 198px;\\\"\\u003e2.25 (0.99, 5.08)\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 94px;\\\"\\u003e0.05\\u003cbr\\u003e\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003eUnivariable Cox regression analysis with Disease Free Survival. a: ECOG-Performance status; b: Primary sclerotizing cholangitis; CA 19-9 Missing n (%): 28 (30), CA 19-9 Missing n (%): 28 (30)\\u003c/p\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"langenbecks-archives-of-surgery\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"laos\",\"sideBox\":\"Learn more about [Langenbeck's Archives of Surgery](http://link.springer.com/journal/423)\",\"snPcode\":\"423\",\"submissionUrl\":\"https://submission.nature.com/new-submission/423/3\",\"title\":\"Langenbeck's Archives of Surgery\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"Springer Hybrid\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":false},\"keywords\":\"\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-5201960/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-5201960/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cem\\u003eBackground\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003ePerihilar cholangiocarcinoma (pCCA) is a rare malignancy requiring resection of extrahepatic bile ducts with or without hepatectomy, for radicality. Prognostic models for post-operative outcomes in pCCA are unusable in pre-operative decision-making as most are based on post-operative variables. Additionally, no pre-operative model consider futile laparotomy or benign hilar stenosis (BHS) as an outcome, despite rates of up to 30 % and 15 % respectively. We investigated pre-operative predictive factors for non-resectability, disease-free survival (DFS), and overall survival (OS), in patients referred for resection of suspected pCCA.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eMethod\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003ePatients with suspected pCCA evaluated at multidisciplinary team (MDT) conference and referred for curative resection at Rigshospitalet, from 2013-2023. All were identified from the Danish Liver Cancer Group (DLGCD). Patients were evaluated, starting from date of first MDT for suspected pCCA; and starting from date of surgery if proven pCCA. Outcomes were preoperative factors related to OS, DFS and non-resectability.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eResults\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNinety-three patients with suspected pCCA were considered resectable at MDT, of which\\u003c/p\\u003e\\n\\u003cp\\u003e74 (79.5 %) were resected. In resected patients 65 (87.8 %) had pCCA, 2 (2.1 %) had gallbladder cancer (GBC) and 7 (7.5 %) had BHS.\\u003c/p\\u003e\\n\\u003cp\\u003ePatients with futile lapartomy (n=19 [20.4%]) had higher pre-operative p-bilirubin and ECOG-performance status (ECOG-PS) score \\u0026gt;0 compared to resected pCCA and BHS (p=0.02 and 0.01). Portal vein embolization (p\\u0026lt;0.001, HR 2.99 [95 % CI 1.61-5.53]) and ECOG-PS \\u0026gt;0 (p=0.003, HR 2.32 [95% CI 1.31-4.11]) had worse OS. No preoperative factors were independently associated with non-resectability or DFS.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cem\\u003eConclusion\\u003c/em\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eECOG-PS \\u0026gt;0 and PVE had worse survival in patients with suspected pCCA. Patients with futile laparotomy had higher frequency of ECOG-PS \\u0026gt;0 and elevated p-bilirubin compared to resected pCCA and BHS.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Preoperative factors predicting outcomes in patients with suspected perihilar cholangiocarcinoma referred for curative resection— a single-center 10-year experience\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-12-18 17:22:18\",\"doi\":\"10.21203/rs.3.rs-5201960/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Revision requested\",\"date\":\"2024-11-26T04:12:05+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2024-11-18T05:37:51+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2024-11-12T22:04:43+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"12456988592027281806380121401304115952\",\"date\":\"2024-11-02T17:45:06+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"66442380249548320159291917535598870853\",\"date\":\"2024-11-02T11:32:40+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2024-11-02T11:13:04+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2024-10-10T06:29:36+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2024-10-08T13:50:10+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"Langenbeck's Archives of Surgery\",\"date\":\"2024-10-04T06:38:32+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"langenbecks-archives-of-surgery\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"laos\",\"sideBox\":\"Learn more about [Langenbeck's Archives of Surgery](http://link.springer.com/journal/423)\",\"snPcode\":\"423\",\"submissionUrl\":\"https://submission.nature.com/new-submission/423/3\",\"title\":\"Langenbeck's Archives of Surgery\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"Springer Hybrid\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":false}}],\"origin\":\"\",\"ownerIdentity\":\"80051648-1aff-409e-8986-240d0f64dc24\",\"owner\":[],\"postedDate\":\"December 18th, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"published-in-journal\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2024-12-23T16:06:43+00:00\",\"versionOfRecord\":{\"articleIdentity\":\"rs-5201960\",\"link\":\"https://doi.org/10.1007/s00423-024-03583-7\",\"journal\":{\"identity\":\"langenbecks-archives-of-surgery\",\"isVorOnly\":false,\"title\":\"Langenbeck's Archives of Surgery\"},\"publishedOn\":\"2024-12-21 15:57:25\",\"publishedOnDateReadable\":\"December 21st, 2024\"},\"versionCreatedAt\":\"2024-12-18 17:22:18\",\"video\":\"\",\"vorDoi\":\"10.1007/s00423-024-03583-7\",\"vorDoiUrl\":\"https://doi.org/10.1007/s00423-024-03583-7\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-5201960\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-5201960\",\"identity\":\"rs-5201960\",\"version\":[\"v1\"]},\"buildId\":\"_2-kVJe1T_tPrBINL-cwx\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}