Preoperative serum CA19-9 predicts postoperative pancreatic fistula in PDAC patients: retrospective analysis at a single institution.

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Hiroki Sugita, Hirohisa Okabe, Daisuke Ogawa, Hiroki Hirao, Daisuke Kuroda, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1935530/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background: Postoperative pancreatic fistula (POPF) is a critical complication of pancreatectomy in patients with pancreatic ductal adenocarcinoma (PDAC). Recent papers reported that serum carbohydrate antigen (CA)19 − 9 levels predicted long-term prognosis. We investigated whether preoperative serum CA19-9 levels were associated with POPF in PDAC patients. Methods: This cohort study was conducted at a single institution retrospectively. Clinicopathologic features were determined using medical records. Results: Among of 196 consecutive patients who underwent pancreatectomy against PDAC, 180 patients whose CA19-9 levels were above the measurement sensitivity, were registered in this study. The patients consisted of 122 patients who underwent pancreaticoduodenectomy and 58 patients who underwent distal pancreatectomy. Several clinicopathological factors, including CA 19 − 9 level, as well as surgical factors were determined retrospectively based on the medical records. Patients with high CA19-9 levels had a significantly higher incidence of POPF than those with low levels (43.9% vs. 13.0%, P < 0.0001). The receiver operating characteristic curves calculated that the cutoff CA19-9 value to predict POPF was 428 U/mL. CA19-9, BMI, curability, and histology were statistically significant risk factors for POPF by univariate analysis. Multivariate analysis showed that CA19-9 and BMI levels were statistically significant independent risk factors for POPF. CA19-9 levels were correlated with both histology and curability. Disease free survival and overall survival of patients with higher levels of CA19-9 were significantly shorter than that of patients with lower levels of preoperative serum CA19-9. Conclusions: In patients undergoing pancreatectomy for PDAC, higher preoperative CA19-9 levels are a significant predictor for POPF. Body mass index Postoperative complication Postoperative pancreatic fistula CA19-9 Long-term outcome Figures Figure 1 Figure 2 Figure 3 Introduction Pancreatic ductal adenocarcinoma (PDAC) is prone to recurrence and the long-term prognosis is poor 1 – 3 . Pancreatectomy is the most effective treatment available for resectable PDAC. Pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) is selected by tumor location. Papers reported that the morbidity and mortality after pancreaticoduodenectomy were 20–50% and 1–8%, respectively 4 – 6 . In contrast to this, the morbidity and mortality after distal pancreatectomy were 25–64% and 0–3%, respectively 7 . Pancreatic fistula (PF) as a postoperative complication occurred in 12–27% of the patients who underwent PD, in 16–51% of the patients who underwent DP and sometimes led to severe conditions in patients 7 – 11 . The effects of adjuvant chemotherapy on long-term prognosis of PDAC have been confirmed by several randomized control studies 2 , 12 , 13 . However, it is difficult to perform immediate adjuvant chemotherapy in the cases with post-operative pancreatic fistula (POPF). Therefore, recognizing the risk for POPF before pancreatectomy is critical. Serum carbohydrate antigen (CA)19 − 9 levels are elevated in 69–92% of PDAC patients 14 . Papers had reported that elevated preoperative CA19-9 levels predicted long-term prognosis 15 , 16 . On the other hand, there is no report that adequately examine the relationship between preoperative CA 19 − 9 levels and postoperative complication in PDAC patients. We investigated whether preoperative CA19-9 levels were associated with postoperative complications such as POPF. Patients And Methods This study was conducted at Kumamoto Regional Medical Center, Kumamoto, Japan. This study has been approved by the institutional ethics committee (#19–019). The informed consent was obtained from all enrollees. The cohort consisted of consecutive 196 patients who underwent PD or DP for PDAC between December 2002 and August 2020. The clinicopathological findings of 180 patients whose preoperative CA19-9 levels were more than measurement sensitivity, were determined retrospectively based on the medical record. Cancer staging was performed according to the International Union Against Cancer (UICC, 8th edition) classification. Residual cancer status was defined using the standard R-classification (R0, R1, and R2). Histological classification was determined using international classification of diseases for oncology (ICD-O) code. PF was determined using the International Study Group of Pancreatic Fistula (ISGPF) 2005 classification, and grade B and C were defined as PF 6 , 9 . Post-operative complication was determined by Clavien Dindo criteria and grade 2 and over was defined as post-operative complication 17 . The International Study Group of Pancreatic Surgery (ISGPS) classification was used to define delayed gastric emptying (DGE), and grade B and C were defined as DGE 18 . Operative risk was determined using the American Society of Anesthesiologists Physical Status classification system (ASA-PS) 19 Several clinicopathological factors such as gender, age, body mass index (BMI), ASA-PS, histological types, tumor size, tumor factor (T1-T4), lymph node metastases, pathological stage, neoadjuvant chemotherapy, and CA19-9 level were retrospectively determined as the risk factors for POPF, along with surgical factors such as operation time, amount of bleeding, and curability (R 0 / R1/ R2) based on the medical record. Surgical site infection, length of hospital stay, hospital mortality and adjuvant chemotherapy also were determined. Furthermore, long-term postoperative follow-up and prognostic studies were conducted. Statistical analysis Data were analyzed using JMP® 15.0 (SAS Institute Inc., Cary, NC, USA). The Wilcoxon and Kruskal-Wallis tests were used to compare between-group differences in the continuous variables. Proportions were analyzed with the Chi-squared test. Risk factors with p-values < 0.05 on univariate analysis were subjected to multivariate logistic regression. Disease free survival (DFS) and overall survival (OS) curves were plotted using the Kaplan-Meier method, and these comparisons were made using the log-rank test. All p-values less than 0.05 were considered statistically significant. Results Among of one hundred ninety-six patients undergoing pancreatectomy for PDAC, 16 patients were excluded from the analysis, because their CA19-9 levels were below the measurement sensitivity threshold (< 1 U/mL). Finally, 180 patients, including 122 patients undergoing PD and 58 patients who underwent DP for PDAC, were registered. Clinicopathologic features in the cohort of 180 patients (96 men, 84 women; mean age, 68.9 ± 0.7 years) are summarized in Table 1. Median CA19-9 was 148 U/mLand; mean BMI was 22.0; mean tumor size was 3.34 cm.; the T-factor with the highest number of patients is T3 (n = 165, 91.7%); the most numerous cancer stage was IIB (n = 77, 42.8%). Portal vein resection was performed in 50 of the 122 patients who underwent PD and 3 of the 58 patients who underwent DP. Table 1 Clinicopathologic features in the cohort of 180 patients enrolled in this study Variables Gender (male/female) 96/84 Age 68.9 ± 0.7 BMI 22.0 ± 0.2 ASA-PS 1 40 (22.2%) ≥ 2 140 (77.8%) Histology: well-differentiated 72 (40%) Mean CA19-9 (U/mL) 1065 ± 319 Median CA 19-9 (U/mL) 148 Tumor size (cm) 3.34 ± 0.11 pT(UICC) 1 5 (2.8%) 2 5 (2.8%) 3 165 (91.7%) 4 5 (2.8%) pN(UICC) 0 57 (31.7%) 1 78 (43.3%) 2 45 (25.0%) pStage(UICC) IA 5 (2.8%) IB 3 (1.7%) IIA 50 (27.8%) IIB 77 (42.8%) III 45 (25.0%) R0 145 (80.6%) Surgery PD 122 DP 58 Neoadjuvant chemotherapy 28 (15.6%) Postoperative complications 83 (46.1%) Short-term outcomes of pancreatectomy for PDAC Surgery-related death occurred in 3 patients (1.7%); the cause of death was postoperative bleeding in all patients (one patient was complicated with POPF). Pathologic curability (R0) was achieved in 145 patients (80.6%). Eighty-three patients (46.1%) had complications after pancreatectomy. Postoperative complications included DGE in 49 patients (27.2%), PF in 41 patients (22.8%), and surgical site infection in 13 patients (7.2%). Preoperative serum CA19-9 levels were significantly elevated in patients with postoperative complications than in patients without postoperative complications (Fig. 1 ). The receiver operating characteristic (ROC) curve resulted in a CA19-9 cutoff value of 398 U/mL and the area under the curve (AUC) of 0.596, predicting postoperative complications. The frequency of postoperative complications was also found to be significantly higher in patients with high CA19-9 compared to those with low levels (64.4% vs. 37.2%, P < 0.001). CA19-9 levels were significantly higher in patients with POPF than in patients without POPF (P < 0.005) (Fig. 1 ). ROC curve resulted in a CA19-9 cutoff value of 428 U/mL and an AUC of 0.65, predicting POPF (Fig. 2 A). Patients with high CA19-9 levels had a significantly higher frequency of POPF than those with low levels (43.9% vs. 13.0%, P < 0.0001) (Table 2 ). Table 2 Risk factors for POPF in the cohort of 180 patients enrolled in this study non-PF (n = 139) PF (n = 41) P- value Gender (male/female) 76/63 20/21 0.44 Age 69.2 ± 0.8 67.9 ± 1.8 0.45 BMI 21.6 ± 0.3 23.6 ± 0.5 0.001 BMI ≥ 21.7 59 (42.4%) 31 (75.6%) 0.0001 ASA-PS 0.230 1 28 (20.1%) 12 (29.3%) ≥ 2 111 (79.9%) 29 (70.7%) Preoperative biliary drainage 47 (33.8%) 12 (29.3%) 0.706 Histology: well-differentiated 61 (43.9%) 11 (26.8%) 0.046 Mean CA 19 − 9 (U/mL) 925 ± 380 1540 ± 556 0.0037 Median CA 19 − 9 (U/mL) 123 643 CA19-9 ≥ 428 U/mL 32 (23.0%) 25 (61.0%) < 0.0001 Tumor size (cm) 3.31 ± 0.13 3.41 ± 0.23 0.67 pT (UICC) 0.16 1 3 (2.2%) 2 (4.9%) 2 3 (2.2%) 2 (4.9%) 3 131 (94.2%) 34 (82.9%) 4 2 (1.4%) 3 (7.3%) pN (UICC) 0.320 0 40 (28.8%) 17 (41.5%) 1 63 (45.3%) 15 (36.6%) 2 36 (25.9%) 9 (22.0%) pStage (UICC) 0.67 IA 3 (2.2%) 2 (4.9%) IB 2 (1.4%) 1 (2.4%) IIA 36 (25.9%) 14 (34.2%) IIB 62 (44.6%) 15 (36.6%) III 36 (25.9%) 9 (22.0%) Curability (R0) 117 (84.2%) 28 (68.3%) 0.03 Surgery 0.073 PD (n = 122) 99 23 DP (n = 58) 40 18 Operative time (min) 521 ± 41 492 ± 33 0.980 Bleeding (g) 1870 ± 133 2105 ± 298 0.50 Neoadjuvant chemotherapy 21 (15.1%) 7 (17.1%) 0.76 Other factors predicting POPF were investigated. BMI levels were significantly higher in the patients with POPF than in those without POPF (P = 0.001). ROC curve resulted in a BMI cutoff value of 21.7 and AUC of 0.67, predicting POPF (Fig. 2 B). The frequency of POPF was also found to be significantly higher in patients with higher BMI values than in those with lower values (34.4% vs. 11.1%, P = 0.0001) (Table 2 ). The frequency of POPF was also significantly higher in patients with not well differentiated adenocarcinoma than in patients with well-differentiated adenocarcinoma (P = 0.046) (Table 2 ). We also found that CA19-9 was significantly higher in patients with not well differentiated adenocarcinomas than in those with well differentiated adenocarcinomas (P < 0.01) (Table 3 ). The frequency of POPF in patients with R1 or R2 was also significantly higher than in patients with R0 (P < 0.05) (Table 2 ). CA19-9 levels in R1 or R2 patients were significantly higher than in R0 patients (P < 0.05) (Table 3 ). Table 3 Relationship between CA19-9 levels and histology or curability CA19-9 (U/mL) CA19-9 ≥ 428 (n = 57) Histology not well-differentiated (n = 108) 1431 ± 520 42 (38.9%) well-differentiated (n = 72) 517 ± 158 15 (20.8%) P-value P < 0.01 P < 0.005 Curability R0 (n = 145) 496 ± 87 42 (29.0%) R1 or R2 (n = 35) 3456 ± 1558 15 (42.9%) P-value P = 0.084 P < 0.05 However, age, sex, ASA-PS, preoperative biliary drainage, tumor size, T-factor, lymph node metastases, surgical method, pathological stage, surgical blood loss, operative time and neoadjuvant chemotherapy were not associated with POPF (Table 2 ). Multivariate analysis demonstrated that preoperative serum CA19-9 ≧ 428 U/mL (odds ratio [OR]: 4.36, 95%, confidence interval [CI]: 1.96–9.68) and BMI ≧ 21.7 (OR: 4.06, CI: 1.76–9.37) were statistically significant independent risk factors for POPF (Table 4 ). Table 4 Multivariate analysis of risk factors for POPF Risk factor Odds ratio 95% CI P-value CA19-9 ≥ 428 U/mL 4.36 1.96 9.68 0.0003 BMI ≥ 21.7 4.06 1.76 9.37 0.001 Curability (R0) 1.99 0.79 5 0.145 Histology (well-differentiated) 0.66 0.28 1.53 0.33 We investigated whether the significance of CA19-9 levels for POPF differs by operative method. In 122 patients who underwent pancreaticoduodenectomy, CA19-9 levels were significantly higher in patients with POPF than in those without, and patients with higher CA19-9 levels had a significantly higher incidence of POPF than those with lower levels (35.9% vs. 10.8%, P < 0.005) (Table 5 ). In 122 patients who underwent pancreaticoduodenectomy, 58 patients underwent preoperative biliary drainage. Serum CA19-9 levels were higher in patients with preoperative biliary drainage than in those without. However, preoperative biliary drainage was not correlated with POPF (supplemental data). In 58 patients who underwent distal pancreatectomy, CA19-9 levels were higher in patients with POPF than in patients without POPF, and the frequency of POPF was significantly higher in patients with high CA19-9 levels than in patients with low CA19-9 levels (61.1% vs. 17.5%, P < 0.005) (Table 5 ). Table 5 Relationship between CA19-9 and POPF by operative method CA19-9 (U/mL) CA19-9 < 428 (n = 123) CA19-9 ≥ 428 (n = 57) PD (n = 122) 83 39 non-PF (n = 99) 1109 ± 523 74 (89.2%) 25 (64.1%) PF (n = 23) 1808 ± 917 9 (10.8%) 14 (35.9%) P-value P = 0.024 P = 0.0014 DP (n = 58) 40 18 non-PF (n = 40) 469 ± 255 33 (82.5%) 7 (38.9%) PF (n = 18) 1199 ± 503 7 (17.5%) 11 (61.1%) P-value P = 0.054 P = 0.0011 Postoperative course in the patients who underwent pancreatectomy Length of hospital stay for patients with POPF was significantly longer than for patients without POPF (P < 0.0001). Patients with elevated CA19-9 had longer hospital stays than those with low levels (P = 0.07) (Table 6 ). A total of 147 (81.7%) patients underwent adjuvant chemotherapy. Patients with POPF received postoperative adjuvant chemotherapy less frequently than patients without POPF (73.2% vs. 84.2%, not significantly, P = 0.12). Table 6 Short- and long-term outcomes CA19-9 < 428 (n = 123) CA19-9 ≥ 428 (n = 57) P- value Postoperative complications 47 (38.2%) 36 (63.2%) < 0.005 POPF 16 (13.0%) 25 (43.9%) < 0.0001 Hospital stay (days) 40.6 ± 2.1 44.7 ± 3.0 0.07 In-hospital mortality 3 0 Adjuvant chemotherapy 101 (82.1%) 46 (80.7%) 0.82 Median DFS (m) 23 8 < 0.0001 5-year DFS 36.50% 13% Median OS (m) 56 18 < 0.0001 5-year OS 43.40% 15.40% Long-term outcomes of pancreatectomy for PDAC Figure 3 shows Kaplan-Meier survival curves by CA19-9 level in patients who underwent pancreatectomy. Patients with higher CA19-9 levels had significantly shorter DFS and OS than those with lower CA19-9 levels (P < 0.0001). Table 6 shows a summary of short- and long-term outcomes after pancreatectomy by CA19-9 levels. Discussion We investigated whether elevation of preoperative CA19-9 levels is associated with short- and long-term outcomes after pancreatectomy for PDAC. Multivariate analysis shows that high levels of CA19-9 and BMI were statistically significant independent risk factors for PF after pancreatectomy. DFS and OS of patients with higher levels of CA19-9 were significantly shorter than those with lower levels of preoperative serum CA19-9. CA19-9 is a tumor marker which is known to be a Sialyl Lewis-a antigen. This antigen is normally present in salivary mucus and in exocrine pancreatic secretions. Elevated serum CA19-9 levels are found in 69–92% of patients with pancreatic cancer 14 . CA19-9 is not detectable in the patients with Le a−b− phenotype. Approximately 5% of the population belong to this group. Thus, 16 patients (8.1%), whose CA19-9 were not detected, were eliminated in analysis. Elevation of CA19-9 levels is useful for diagnosis of pancreatic cancer 14 . Also, previous reports have demonstrated that elevation of CA19-9 levels is a long-term prognostic factor 20 . CA19-9 is produced in pancreatic cancers and expressed on cancer cell surfaces, induces cancer cells to attach to vascular endothelial cells by E-selectin and results in metastasis. This is the first paper reporting significance of higher preoperative serum CA19-9 as an independent risk factor for PF in patients who undergo pancreatectomy for PDAC. Sufficient investigation of the relationship between CA19-9 levels and POPF has not been reported, because most of papers had investigated the risk factors in cohorts including the patients who had pancreatic diseases other than PDAC. We can formulate some hypothesis to why elevation of CA19-9 levels is an independent risk factor for PF after pancreatectomy. CA19-9 levels are elevated in the patients with advanced and aggressive cancer generally, in which surgical stress is greater. Therefore, the patients experienced hypercatabolic conditions after surgery compared to the patients with not-elevated CA19-9 levels. This study demonstrated that curability was associated with CA19-9, and both of them were associated with POPF. These results support this hypothesis. However, this hypothesis conflicts with the results that cancer stage, bleeding or operative time were not related to PF after pancreatectomy in this study. Main pancreatic duct (MPD) stenosis or obstruction results in elevation of serum CA19-9 levels 21 . High serum CA19-9 levels may be one of the results of pancreatitis that causes delayed pancreatic tissue repair 22 . Serum CA19-9 elevation in chronic pancreatitis is not so high compared to pancreatic cancer related CA19-9 elevation. Serum CA19-9 elevation is associated with cancer aggressiveness and may be associated with tumor growing speed. Previous papers reported that POPF was associated with hard pancreatic texture contributes to suppression of pancreatic fistula development. Hard of pancreatic tissue means fibrosis of the pancreatic tissue. In patients with higher CA19-9 levels, fibrosis of pancreatic tissue has not yet occurred. because there may not be enough time for inflammation and fibrosis to development. These may be the reason why pancreatic fistulas are more likely to occur in patients with higher CA19-9. In this study, CA19-9 was associated with histology. The results support this hypothesis. Note that the texture of pancreatic tissue was not investigated in this study because an appropriate method for measuring the hardness of pancreatic tissue has not been established. BMI was an independent risk factor for POPF in this study. These results are consistent with previous reports 23 , 24 . Higher CA19-9 l is an independent risk factor. On the other hand, curability and histology were significant risk factors in univariate analysis, but not independent risk factors in multivariate analysis. The reason for this may be that the curability and histology correlated with CA19-9 levels. POPF is a critical complication of pancreatectomy and sometimes induces arterial wall breakdown followed by major bleeding into the peritoneal cavity. Therefore, it is important to know the risk of POPF before surgery. Recent papers reported that DFS and OS of the patients with high levels of CA19-9 were shorter compared to the patients with low levels 15 , 16 . Higher CA19-9 was a significant long-term prognostic factor in this study. CA19-9 was produced by pancreatic cancer cells and may be associated with aggressiveness of the tumor. On the other hand, POPF may be involved in poor long-term prognosis, because the rate of patients with post-operative adjuvant chemotherapy was lower in the patients with POPF compared to the patients without POPF (P = 0.12). The importance of neoadjuvant chemotherapy and decreased CA19-9 levels before surgery for improvement of the long-term prognosis had been reported 25 , 26 .Therefore, preoperative CA19-9 may be important for the management of PDAC. This is retrospective analysis at a single institution, therefore large-scale prospective cohort studies are necessary in the future. Conclusion Preoperative serum CA19-9 levels are a significant predictor of POPF in PDAC patients undergoing pancreatectomy. Abbreviations CA 19-9: carbohydrate antigen 19-9 PDAC: pancreatic ductal adenocarcinoma POPF: postoperative pancreatic fistula PD: pancreaticoduodenectomy DP: distal pancreatectomy DGE: delayed gastric emptying ROC curve: receiver operating characteristic curve DFS: disease free survival OS: overall survival Declarations Ethics approval and consent to participate: This study has been approved by Kumamoto Regional Medical Center Institutional Ethics Committee (approval #. 19-019). All methods were carried out in accordance with Helsinki Declaration and followed Japanese law. The informed consent was obtained from all enrollees. Consent for publication: Not applicable Availability of data and materials: All data generated or analyzed during this study are included in this published article [and its supplementary information files]. Competing interests: The author reports no ownership or commercial interest in the products or concepts mentioned in this article. Funding: This research was not specifically funded by any funding agency in the public, for-profit, or non-profit sectors. Authors’ contributions: Hiroki Sugita MD, PhD created this study design and summarized data and wrote the manuscript. Hirohisa Okabe MD, PhD discussed the significance of this study with first author and supported data analysis. Daisuke Ogawa MD performed data collection and analysis. Hiroki Hirao MD performed data collection and analysis. Daisuke Kuroda MD, PhD performed data collection and analysis and discussed the significance of this study with first author. Katsunobu Taki MD, PhD performed data analysis. Shinjiro Tomiyasu MD, PhD performed data collection and discussed the significance of this study with first author. Masahiko Hirota MD, PhD supervised these works. Acknowledgment: We would like to thank Kazumi Isechi for data collection and supporting this works. References Hidalgo M. Pancreatic cancer. N Engl J Med. 2010;362:1605–17. 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Supplementary Files supplementaldata1BMCsubmit.docx SupplementalDatatable12submit.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 25 Aug, 2022 Reviewers agreed at journal 23 Aug, 2022 Reviews received at journal 22 Aug, 2022 Reviewers agreed at journal 20 Aug, 2022 Reviewers invited by journal 20 Aug, 2022 Editor assigned by journal 18 Aug, 2022 Editor invited by journal 10 Aug, 2022 Submission checks completed at journal 10 Aug, 2022 First submitted to journal 06 Aug, 2022 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-1935530","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":127887054,"identity":"88bf3461-89e6-48ab-9fe8-2d4fa06796d1","order_by":0,"name":"Hiroki Sugita","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABD0lEQVRIie2Sv0vDQBTHvyFwWaJdW4TmX3glg//OHQ5Z2ip0ydAhIMSl6Jo/I5t08kngpoq4ZWwRnBziIhWKenGQDl5wFLzP+LjPu/cLcDj+KAwMhwSf94OiW2HEMUHI/cfdivkmViVC+k1+ICqSh6qZU3IdMHnbFNNelIl1g8OpTaF6fMasabJcSOmHK8wGOYJRATGzKv2xZBa7ScmSfS//UKWGOAohVGYtrFXeKaH7Tea95VA3rbLrUFAnzLc5SapPgAOjlMIo6FBo9Qy+u6TRsnhCZXpRhVb5YEH2XqKL5LFJXyk67p2+bMzE1NV5pfvbVFsnhu914OsMWjxTEmlpV4L1j+F5h+JwOBz/jE/d4lsw7r+K4AAAAABJRU5ErkJggg==","orcid":"","institution":"Kumamoto Regional Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Hiroki","middleName":"","lastName":"Sugita","suffix":""},{"id":127887055,"identity":"a2fc13ac-221c-46b6-a023-0b9137de9bde","order_by":1,"name":"Hirohisa Okabe","email":"","orcid":"","institution":"Kumamoto Regional Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Hirohisa","middleName":"","lastName":"Okabe","suffix":""},{"id":127887057,"identity":"8e3dc2c6-10fe-477b-9aa1-9524fb672630","order_by":2,"name":"Daisuke Ogawa","email":"","orcid":"","institution":"Kumamoto Regional Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Daisuke","middleName":"","lastName":"Ogawa","suffix":""},{"id":127887058,"identity":"bf96cf12-f0e7-4d6d-a281-871752d8f77c","order_by":3,"name":"Hiroki Hirao","email":"","orcid":"","institution":"Kumamoto Regional Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Hiroki","middleName":"","lastName":"Hirao","suffix":""},{"id":127887060,"identity":"c58c8aaa-e2ba-49eb-a11d-cbfea0f17987","order_by":4,"name":"Daisuke Kuroda","email":"","orcid":"","institution":"Kumamoto Regional Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Daisuke","middleName":"","lastName":"Kuroda","suffix":""},{"id":127887062,"identity":"942ef680-86ac-48cf-b8cb-e62698a490a3","order_by":5,"name":"Katsunobu Taki","email":"","orcid":"","institution":"Kumamoto Regional Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Katsunobu","middleName":"","lastName":"Taki","suffix":""},{"id":127887064,"identity":"f4cbec09-3d3a-4b78-ab01-399ede00c3ea","order_by":6,"name":"Shinjiro Tomiyasu","email":"","orcid":"","institution":"Kumamoto Regional Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Shinjiro","middleName":"","lastName":"Tomiyasu","suffix":""},{"id":127887066,"identity":"df171d82-8b73-4d12-aa45-bb8313830999","order_by":7,"name":"Masahiko Hirota","email":"","orcid":"","institution":"Kumamoto Regional Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Masahiko","middleName":"","lastName":"Hirota","suffix":""}],"badges":[],"createdAt":"2022-08-06 10:14:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1935530/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1935530/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":25150702,"identity":"cffb0c76-93c8-45be-817c-466b1d2dd5f6","added_by":"auto","created_at":"2022-08-12 16:37:40","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":966735,"visible":true,"origin":"","legend":"\u003cp\u003ePreoperative serum CA19-9 levels in patients with various postoperative complications were compared with those of patients without various postoperative complications. A: any complication, B: postoperative pancreatic fistula (POPF), C: delayed gastric emptying, D: surgical site infection, E: others. * p\u0026lt; 0.05 vs. the patients without any postoperative complications; **p\u0026lt;0.005 vs. the patients without POPF.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1935530/v1/402deefb3d553ae6b90f33cc.jpg"},{"id":25150701,"identity":"118e8fdd-4474-4323-9f2c-1e73b8fbaa14","added_by":"auto","created_at":"2022-08-12 16:37:40","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":922197,"visible":true,"origin":"","legend":"\u003cp\u003eA.\u0026nbsp;The receiver operating characteristic (ROC) curve showed that the cutoff value of preoperative CA19-9 levels predicting POPF was 428 U/mL and the area under the curve (AUC) was 0.65 in patients undergoing pancreatectomy \u003c/p\u003e\u003cp\u003eB.\u0026nbsp;ROC curve showed that the cutoff BMI value predicting POPF was 21.7, and the AUC was 0.67 in patients undergoing pancreatectomy.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1935530/v1/3504811dae4ce0490bdc8387.jpg"},{"id":25151030,"identity":"2dc126df-352a-4cd3-bdee-9c8b2ab9f357","added_by":"auto","created_at":"2022-08-12 16:42:40","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":956013,"visible":true,"origin":"","legend":"\u003cp\u003eA. Disease-free survival curves for high and low preoperative serum CA 19-9 levels in patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). Significant differences in survival rates were observed between patients with high and low CA19-9 levels (log-rank test, P \u0026lt; 0.0001).\u003c/p\u003e\u003cp\u003eB. Overall survival curves for high and low preoperative serum CA19-9 levels in patients undergoing pancreatectomy for PDAC. Significant differences in survival rates were observed between patients with high and low CA19-9 levels (log-rank test, P \u0026lt; 0.0001).\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1935530/v1/9ccddd80d626c5d8d0b6d205.jpg"},{"id":25151031,"identity":"a84753bb-fe6c-4444-afb2-befcbd6275ea","added_by":"auto","created_at":"2022-08-12 16:42:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":540222,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1935530/v1/d2235f4a-e272-41ae-9a8c-7a5d1301fa62.pdf"},{"id":25150699,"identity":"1b985bff-1b8d-48b9-95e6-0de34ab638f6","added_by":"auto","created_at":"2022-08-12 16:37:40","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":13158,"visible":true,"origin":"","legend":"","description":"","filename":"supplementaldata1BMCsubmit.docx","url":"https://assets-eu.researchsquare.com/files/rs-1935530/v1/adae1f215d8129ff3e7509ee.docx"},{"id":25150698,"identity":"b0fd6378-75f2-41a7-9f58-ae400eddea79","added_by":"auto","created_at":"2022-08-12 16:37:40","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":16503,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalDatatable12submit.docx","url":"https://assets-eu.researchsquare.com/files/rs-1935530/v1/075172b7938196324888b850.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Preoperative serum CA19-9 predicts postoperative pancreatic fistula in PDAC patients: retrospective analysis at a single institution.","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePancreatic ductal adenocarcinoma (PDAC) is prone to recurrence and the long-term prognosis is poor \u003csup\u003e\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Pancreatectomy is the most effective treatment available for resectable PDAC. Pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) is selected by tumor location. Papers reported that the morbidity and mortality after pancreaticoduodenectomy were 20\u0026ndash;50% and 1\u0026ndash;8%, respectively \u003csup\u003e\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. In contrast to this, the morbidity and mortality after distal pancreatectomy were 25\u0026ndash;64% and 0\u0026ndash;3%, respectively \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Pancreatic fistula (PF) as a postoperative complication occurred in 12\u0026ndash;27% of the patients who underwent PD, in 16\u0026ndash;51% of the patients who underwent DP and sometimes led to severe conditions in patients \u003csup\u003e\u003cspan additionalcitationids=\"CR8 CR9 CR10\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe effects of adjuvant chemotherapy on long-term prognosis of PDAC have been confirmed by several randomized control studies \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. However, it is difficult to perform immediate adjuvant chemotherapy in the cases with post-operative pancreatic fistula (POPF). Therefore, recognizing the risk for POPF before pancreatectomy is critical.\u003c/p\u003e \u003cp\u003eSerum carbohydrate antigen (CA)19\u0026thinsp;\u0026minus;\u0026thinsp;9 levels are elevated in 69\u0026ndash;92% of PDAC patients \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Papers had reported that elevated preoperative CA19-9 levels predicted long-term prognosis \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. On the other hand, there is no report that adequately examine the relationship between preoperative CA 19\u0026thinsp;\u0026minus;\u0026thinsp;9 levels and postoperative complication in PDAC patients. We investigated whether preoperative CA19-9 levels were associated with postoperative complications such as POPF.\u003c/p\u003e"},{"header":"Patients And Methods","content":"\u003cp\u003e This study was conducted at Kumamoto Regional Medical Center, Kumamoto, Japan. This study has been approved by the institutional ethics committee (#19\u0026ndash;019). The informed consent was obtained from all enrollees. The cohort consisted of consecutive 196 patients who underwent PD or DP for PDAC between December 2002 and August 2020. The clinicopathological findings of 180 patients whose preoperative CA19-9 levels were more than measurement sensitivity, were determined retrospectively based on the medical record. Cancer staging was performed according to the International Union Against Cancer (UICC, 8th edition) classification. Residual cancer status was defined using the standard R-classification (R0, R1, and R2). Histological classification was determined using international classification of diseases for oncology (ICD-O) code. PF was determined using the International Study Group of Pancreatic Fistula (ISGPF) 2005 classification, and grade B and C were defined as PF \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Post-operative complication was determined by Clavien Dindo criteria and grade 2 and over was defined as post-operative complication \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. The International Study Group of Pancreatic Surgery (ISGPS) classification was used to define delayed gastric emptying (DGE), and grade B and C were defined as DGE \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Operative risk was determined using the American Society of Anesthesiologists Physical Status classification system (ASA-PS) \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eSeveral clinicopathological factors such as gender, age, body mass index (BMI), ASA-PS, histological types, tumor size, tumor factor (T1-T4), lymph node metastases, pathological stage, neoadjuvant chemotherapy, and CA19-9 level were retrospectively determined as the risk factors for POPF, along with surgical factors such as operation time, amount of bleeding, and curability (R 0 / R1/ R2) based on the medical record. Surgical site infection, length of hospital stay, hospital mortality and adjuvant chemotherapy also were determined. Furthermore, long-term postoperative follow-up and prognostic studies were conducted.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData were analyzed using JMP\u0026reg; 15.0 (SAS Institute Inc., Cary, NC, USA). The Wilcoxon and Kruskal-Wallis tests were used to compare between-group differences in the continuous variables. Proportions were analyzed with the Chi-squared test. Risk factors with p-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 on univariate analysis were subjected to multivariate logistic regression. Disease free survival (DFS) and overall survival (OS) curves were plotted using the Kaplan-Meier method, and these comparisons were made using the log-rank test. All p-values less than 0.05 were considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eAmong of one hundred ninety-six patients undergoing pancreatectomy for PDAC, 16 patients were excluded from the analysis, because their CA19-9 levels were below the measurement sensitivity threshold (\u0026lt;\u0026thinsp;1 U/mL). Finally, 180 patients, including 122 patients undergoing PD and 58 patients who underwent DP for PDAC, were registered. Clinicopathologic features in the cohort of 180 patients (96 men, 84 women; mean age, 68.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7 years) are summarized in Table\u0026nbsp;1. Median CA19-9 was 148 U/mLand; mean BMI was 22.0; mean tumor size was 3.34 cm.; the T-factor with the highest number of patients is T3 (n\u0026thinsp;=\u0026thinsp;165, 91.7%); the most numerous cancer stage was IIB (n\u0026thinsp;=\u0026thinsp;77, 42.8%). Portal vein resection was performed in 50 of the 122 patients who underwent PD and 3 of the 58 patients who underwent DP.\u003c/p\u003e\n\u003ctable border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cp\u003eTable 1\u003c/p\u003e\n \u003cp\u003eClinicopathologic features in the cohort of 180 patients enrolled in this study\u003c/p\u003e\n \u003c/caption\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender (male/female)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e96/84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e68.9 \u0026plusmn; 0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e22.0 \u0026plusmn; 0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003eASA-PS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e40 (22.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026ge;\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e140 (77.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistology: well-differentiated\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e72 (40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean CA19-9 (U/mL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e1065 \u0026plusmn; 319\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian CA 19-9 (U/mL) \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e148\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumor size (cm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e3.34 \u0026plusmn; 0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003epT(UICC)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e5 (2.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e5 (2.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e165 (91.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e5 (2.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003epN(UICC)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e57 (31.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e78 (43.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e45 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003epStage(UICC)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003eIA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e5 (2.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003eIB\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e3 (1.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003eIIA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e50 (27.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003eIIB\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e77 (42.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003eIII\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e45 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003eR0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e145 (80.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003ePD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e122\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003eDP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003eNeoadjuvant chemotherapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e28 (15.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"196\"\u003e\n \u003cp\u003e\u003cstrong\u003ePostoperative complications\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"85\"\u003e\n \u003cp\u003e83 (46.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cdiv class=\"Section2\" id=\"Sec5\"\u003e\n \u003ch2\u003eShort-term outcomes of pancreatectomy for PDAC\u003c/h2\u003e\n \u003cp\u003eSurgery-related death occurred in 3 patients (1.7%); the cause of death was postoperative bleeding in all patients (one patient was complicated with POPF). Pathologic curability (R0) was achieved in 145 patients (80.6%). Eighty-three patients (46.1%) had complications after pancreatectomy. Postoperative complications included DGE in 49 patients (27.2%), PF in 41 patients (22.8%), and surgical site infection in 13 patients (7.2%).\u003c/p\u003e\n \u003cp\u003ePreoperative serum CA19-9 levels were significantly elevated in patients with postoperative complications than in patients without postoperative complications (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The receiver operating characteristic (ROC) curve resulted in a CA19-9 cutoff value of 398 U/mL and the area under the curve (AUC) of 0.596, predicting postoperative complications. The frequency of postoperative complications was also found to be significantly higher in patients with high CA19-9 compared to those with low levels (64.4% vs. 37.2%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\n \u003cp\u003eCA19-9 levels were significantly higher in patients with POPF than in patients without POPF (P\u0026thinsp;\u0026lt;\u0026thinsp;0.005) (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). ROC curve resulted in a CA19-9 cutoff value of 428 U/mL and an AUC of 0.65, predicting POPF (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA). Patients with high CA19-9 levels had a significantly higher frequency of POPF than those with low levels (43.9% vs. 13.0%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eRisk factors for POPF in the cohort of 180 patients enrolled in this study\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003enon-PF (n\u0026thinsp;=\u0026thinsp;139)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePF (n\u0026thinsp;=\u0026thinsp;41)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP- value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGender (male/female)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76/63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20/21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cem\u003e0.001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI\u0026thinsp;\u0026ge;\u0026thinsp;21.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59 (42.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31 (75.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cem\u003e0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eASA-PS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.230\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28 (20.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (29.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e111 (79.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29 (70.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePreoperative biliary drainage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47 (33.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (29.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.706\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHistology: well-differentiated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61 (43.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (26.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cem\u003e0.046\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean CA 19\u0026thinsp;\u0026minus;\u0026thinsp;9 (U/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e925\u0026thinsp;\u0026plusmn;\u0026thinsp;380\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1540\u0026thinsp;\u0026plusmn;\u0026thinsp;556\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cem\u003e0.0037\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian CA 19\u0026thinsp;\u0026minus;\u0026thinsp;9 (U/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e643\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCA19-9\u0026thinsp;\u0026ge;\u0026thinsp;428 U/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32 (23.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25 (61.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;\u0026thinsp;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTumor size (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003epT (UICC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (2.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (4.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (2.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (4.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e131 (94.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34 (82.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (1.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (7.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003epN (UICC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.320\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40 (28.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 (41.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63 (45.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (36.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36 (25.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (22.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003epStage (UICC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (2.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (4.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (1.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (2.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIIA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36 (25.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (34.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIIB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62 (44.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (36.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36 (25.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (22.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCurability (R0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e117 (84.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28 (68.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cem\u003e0.03\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSurgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePD (n\u0026thinsp;=\u0026thinsp;122)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDP (n\u0026thinsp;=\u0026thinsp;58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOperative time (min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e521\u0026thinsp;\u0026plusmn;\u0026thinsp;41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e492\u0026thinsp;\u0026plusmn;\u0026thinsp;33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.980\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBleeding (g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1870\u0026thinsp;\u0026plusmn;\u0026thinsp;133\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2105\u0026thinsp;\u0026plusmn;\u0026thinsp;298\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNeoadjuvant chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (15.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (17.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/div\u003e\n \u003cp\u003eOther factors predicting POPF were investigated. BMI levels were significantly higher in the patients with POPF than in those without POPF (P\u0026thinsp;=\u0026thinsp;0.001). ROC curve resulted in a BMI cutoff value of 21.7 and AUC of 0.67, predicting POPF (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eB). The frequency of POPF was also found to be significantly higher in patients with higher BMI values than in those with lower values (34.4% vs. 11.1%, P\u0026thinsp;=\u0026thinsp;0.0001) (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). The frequency of POPF was also significantly higher in patients with not well differentiated adenocarcinoma than in patients with well-differentiated adenocarcinoma (P\u0026thinsp;=\u0026thinsp;0.046) (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). We also found that CA19-9 was significantly higher in patients with not well differentiated adenocarcinomas than in those with well differentiated adenocarcinomas (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01) (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). The frequency of POPF in patients with R1 or R2 was also significantly higher than in patients with R0 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). CA19-9 levels in R1 or R2 patients were significantly higher than in R0 patients (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eRelationship between CA19-9 levels and histology or curability\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCA19-9 (U/mL)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCA19-9\u0026thinsp;\u0026ge;\u0026thinsp;428 (n\u0026thinsp;=\u0026thinsp;57)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHistology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enot well-differentiated (n\u0026thinsp;=\u0026thinsp;108)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1431\u0026thinsp;\u0026plusmn;\u0026thinsp;520\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42 (38.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ewell-differentiated (n\u0026thinsp;=\u0026thinsp;72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e517\u0026thinsp;\u0026plusmn;\u0026thinsp;158\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (20.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.01\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.005\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCurability\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eR0 (n\u0026thinsp;=\u0026thinsp;145)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e496\u0026thinsp;\u0026plusmn;\u0026thinsp;87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42 (29.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eR1 or R2 (n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3456\u0026thinsp;\u0026plusmn;\u0026thinsp;1558\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (42.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.084\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/div\u003e\n \u003cp\u003eHowever, age, sex, ASA-PS, preoperative biliary drainage, tumor size, T-factor, lymph node metastases, surgical method, pathological stage, surgical blood loss, operative time and neoadjuvant chemotherapy were not associated with POPF (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eMultivariate analysis demonstrated that preoperative serum CA19-9\u0026thinsp;≧\u0026thinsp;428 U/mL (odds ratio [OR]: 4.36, 95%, confidence interval [CI]: 1.96\u0026ndash;9.68) and BMI\u0026thinsp;≧\u0026thinsp;21.7 (OR: 4.06, CI: 1.76\u0026ndash;9.37) were statistically significant independent risk factors for POPF (Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab3\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMultivariate analysis of risk factors for POPF\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRisk factor\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOdds ratio\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCA19-9\u0026thinsp;\u0026ge;\u0026thinsp;428 U/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cem\u003e0.0003\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI\u0026thinsp;\u0026ge;\u0026thinsp;21.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cem\u003e0.001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCurability (R0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.145\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHistology (well-differentiated)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/div\u003e\n \u003cp\u003eWe investigated whether the significance of CA19-9 levels for POPF differs by operative method. In 122 patients who underwent pancreaticoduodenectomy, CA19-9 levels were significantly higher in patients with POPF than in those without, and patients with higher CA19-9 levels had a significantly higher incidence of POPF than those with lower levels (35.9% vs. 10.8%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.005) (Table \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e). In 122 patients who underwent pancreaticoduodenectomy, 58 patients underwent preoperative biliary drainage. Serum CA19-9 levels were higher in patients with preoperative biliary drainage than in those without. However, preoperative biliary drainage was not correlated with POPF (supplemental data). In 58 patients who underwent distal pancreatectomy, CA19-9 levels were higher in patients with POPF than in patients without POPF, and the frequency of POPF was significantly higher in patients with high CA19-9 levels than in patients with low CA19-9 levels (61.1% vs. 17.5%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.005) (Table \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab4\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eRelationship between CA19-9 and POPF by operative method\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCA19-9 (U/mL)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCA19-9\u0026thinsp;\u0026lt;\u0026thinsp;428 (n\u0026thinsp;=\u0026thinsp;123)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCA19-9\u0026thinsp;\u0026ge;\u0026thinsp;428 (n\u0026thinsp;=\u0026thinsp;57)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePD (n\u0026thinsp;=\u0026thinsp;122)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enon-PF (n\u0026thinsp;=\u0026thinsp;99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1109\u0026thinsp;\u0026plusmn;\u0026thinsp;523\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74 (89.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25 (64.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePF (n\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1808\u0026thinsp;\u0026plusmn;\u0026thinsp;917\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (10.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (35.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026thinsp;=\u0026thinsp;0.024\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026thinsp;=\u0026thinsp;0.0014\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDP (n\u0026thinsp;=\u0026thinsp;58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enon-PF (n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e469\u0026thinsp;\u0026plusmn;\u0026thinsp;255\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33 (82.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (38.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePF (n\u0026thinsp;=\u0026thinsp;18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1199\u0026thinsp;\u0026plusmn;\u0026thinsp;503\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (17.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (61.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.054\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026thinsp;=\u0026thinsp;0.0011\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec6\"\u003e\n \u003ch2\u003ePostoperative course in the patients who underwent pancreatectomy\u003c/h2\u003e\n \u003cp\u003eLength of hospital stay for patients with POPF was significantly longer than for patients without POPF (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Patients with elevated CA19-9 had longer hospital stays than those with low levels (P\u0026thinsp;=\u0026thinsp;0.07) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e). A total of 147 (81.7%) patients underwent adjuvant chemotherapy. Patients with POPF received postoperative adjuvant chemotherapy less frequently than patients without POPF (73.2% vs. 84.2%, not significantly, P\u0026thinsp;=\u0026thinsp;0.12).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab5\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eShort- and long-term outcomes\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCA19-9\u0026thinsp;\u0026lt;\u0026thinsp;428 (n\u0026thinsp;=\u0026thinsp;123)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCA19-9\u0026thinsp;\u0026ge;\u0026thinsp;428 (n\u0026thinsp;=\u0026thinsp;57)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP- value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePostoperative complications\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47 (38.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36 (63.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePOPF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16 (13.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25 (43.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;\u0026thinsp;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHospital stay (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIn-hospital mortality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAdjuvant chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e101 (82.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46 (80.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian DFS (m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;\u0026thinsp;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5-year DFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.50%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian OS (m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026lt;\u0026thinsp;0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5-year OS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.40%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.40%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec7\"\u003e\n \u003ch2\u003eLong-term outcomes of pancreatectomy for PDAC\u003c/h2\u003e\n \u003cp\u003eFigure \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e shows Kaplan-Meier survival curves by CA19-9 level in patients who underwent pancreatectomy. Patients with higher CA19-9 levels had significantly shorter DFS and OS than those with lower CA19-9 levels (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e shows a summary of short- and long-term outcomes after pancreatectomy by CA19-9 levels.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe investigated whether elevation of preoperative CA19-9 levels is associated with short- and long-term outcomes after pancreatectomy for PDAC. Multivariate analysis shows that high levels of CA19-9 and BMI were statistically significant independent risk factors for PF after pancreatectomy. DFS and OS of patients with higher levels of CA19-9 were significantly shorter than those with lower levels of preoperative serum CA19-9.\u003c/p\u003e \u003cp\u003eCA19-9 is a tumor marker which is known to be a Sialyl Lewis-a antigen. This antigen is normally present in salivary mucus and in exocrine pancreatic secretions. Elevated serum CA19-9 levels are found in 69\u0026ndash;92% of patients with pancreatic cancer \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. CA19-9 is not detectable in the patients with Le\u003csup\u003ea\u0026minus;b\u0026minus;\u003c/sup\u003e phenotype. Approximately 5% of the population belong to this group. Thus, 16 patients (8.1%), whose CA19-9 were not detected, were eliminated in analysis.\u003c/p\u003e \u003cp\u003eElevation of CA19-9 levels is useful for diagnosis of pancreatic cancer \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Also, previous reports have demonstrated that elevation of CA19-9 levels is a long-term prognostic factor\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. CA19-9 is produced in pancreatic cancers and expressed on cancer cell surfaces, induces cancer cells to attach to vascular endothelial cells by E-selectin and results in metastasis.\u003c/p\u003e \u003cp\u003eThis is the first paper reporting significance of higher preoperative serum CA19-9 as an independent risk factor for PF in patients who undergo pancreatectomy for PDAC. Sufficient investigation of the relationship between CA19-9 levels and POPF has not been reported, because most of papers had investigated the risk factors in cohorts including the patients who had pancreatic diseases other than PDAC. We can formulate some hypothesis to why elevation of CA19-9 levels is an independent risk factor for PF after pancreatectomy. CA19-9 levels are elevated in the patients with advanced and aggressive cancer generally, in which surgical stress is greater. Therefore, the patients experienced hypercatabolic conditions after surgery compared to the patients with not-elevated CA19-9 levels. This study demonstrated that curability was associated with CA19-9, and both of them were associated with POPF. These results support this hypothesis. However, this hypothesis conflicts with the results that cancer stage, bleeding or operative time were not related to PF after pancreatectomy in this study. Main pancreatic duct (MPD) stenosis or obstruction results in elevation of serum CA19-9 levels \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. High serum CA19-9 levels may be one of the results of pancreatitis that causes delayed pancreatic tissue repair \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Serum CA19-9 elevation in chronic pancreatitis is not so high compared to pancreatic cancer related CA19-9 elevation. Serum CA19-9 elevation is associated with cancer aggressiveness and may be associated with tumor growing speed. Previous papers reported that POPF was associated with hard pancreatic texture contributes to suppression of pancreatic fistula development. Hard of pancreatic tissue means fibrosis of the pancreatic tissue. In patients with higher CA19-9 levels, fibrosis of pancreatic tissue has not yet occurred. because there may not be enough time for inflammation and fibrosis to development. These may be the reason why pancreatic fistulas are more likely to occur in patients with higher CA19-9. In this study, CA19-9 was associated with histology. The results support this hypothesis. Note that the texture of pancreatic tissue was not investigated in this study because an appropriate method for measuring the hardness of pancreatic tissue has not been established.\u003c/p\u003e \u003cp\u003eBMI was an independent risk factor for POPF in this study. These results are consistent with previous reports \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. Higher CA19-9 l is an independent risk factor. On the other hand, curability and histology were significant risk factors in univariate analysis, but not independent risk factors in multivariate analysis. The reason for this may be that the curability and histology correlated with CA19-9 levels.\u003c/p\u003e \u003cp\u003ePOPF is a critical complication of pancreatectomy and sometimes induces arterial wall breakdown followed by major bleeding into the peritoneal cavity. Therefore, it is important to know the risk of POPF before surgery. Recent papers reported that DFS and OS of the patients with high levels of CA19-9 were shorter compared to the patients with low levels \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Higher CA19-9 was a significant long-term prognostic factor in this study. CA19-9 was produced by pancreatic cancer cells and may be associated with aggressiveness of the tumor. On the other hand, POPF may be involved in poor long-term prognosis, because the rate of patients with post-operative adjuvant chemotherapy was lower in the patients with POPF compared to the patients without POPF (P\u0026thinsp;=\u0026thinsp;0.12). The importance of neoadjuvant chemotherapy and decreased CA19-9 levels before surgery for improvement of the long-term prognosis had been reported \u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e.Therefore, preoperative CA19-9 may be important for the management of PDAC. This is retrospective analysis at a single institution, therefore large-scale prospective cohort studies are necessary in the future.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePreoperative serum CA19-9 levels are a significant predictor of POPF in PDAC patients undergoing pancreatectomy.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCA 19-9: carbohydrate antigen 19-9\u003c/p\u003e\n\u003cp\u003ePDAC: pancreatic ductal adenocarcinoma\u003c/p\u003e\n\u003cp\u003ePOPF: postoperative pancreatic fistula\u003c/p\u003e\n\u003cp\u003ePD: pancreaticoduodenectomy\u003c/p\u003e\n\u003cp\u003eDP: distal pancreatectomy\u003c/p\u003e\n\u003cp\u003eDGE: delayed gastric emptying\u003c/p\u003e\n\u003cp\u003eROC curve: receiver operating characteristic curve\u003c/p\u003e\n\u003cp\u003eDFS: disease free survival\u003c/p\u003e\n\u003cp\u003eOS: overall survival\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study has been approved by Kumamoto Regional Medical Center Institutional Ethics Committee (approval #. 19-019). All methods were carried out in accordance with Helsinki Declaration and followed Japanese law. The informed consent was obtained from all enrollees.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article [and its supplementary information files].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author reports no ownership or commercial interest in the products or concepts mentioned in this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was not specifically funded by any funding agency in the public, for-profit, or non-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHiroki Sugita MD, PhD created this study design and summarized data and wrote the manuscript. Hirohisa Okabe MD, PhD discussed the significance of this study with first author and supported data analysis. Daisuke Ogawa MD performed data collection and analysis. Hiroki Hirao MD performed data collection and analysis. Daisuke Kuroda MD, PhD performed data collection and analysis and discussed the significance of this study with first author. Katsunobu Taki MD, PhD performed data analysis. Shinjiro Tomiyasu MD, PhD performed data collection and discussed the significance of this study with first author. Masahiko Hirota MD, PhD supervised these works.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Kazumi Isechi for data collection and supporting this works.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHidalgo M. Pancreatic cancer. 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J Hepatobiliary Pancreat Sci. 2018;25:55\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGroot VP, Gemenetzis G, Blair AB, Rivero-Soto RJ, Yu J, Javed AA, et al. Defining and Predicting Early Recurrence in 957 Patients With Resected Pancreatic Ductal Adenocarcinoma. Ann Surg. 2019;269:1154\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFuruya N, Kawa S, Hasebe O, Tokoo M, Mukawa K, Maejima S, et al. Comparative study of CA242 and CA19-9 in chronic pancreatitis. Br J Cancer. 1996;73:372\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDistler M, Kersting S, Ruckert F, Kross P, Saeger HD, Weitz J, et al. Chronic pancreatitis of the pancreatic remnant is an independent risk factor for pancreatic fistula after distal pancreatectomy. BMC Surg. 2014;14:54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoberts KJ, Sutcliffe RP, Marudanayagam R, Hodson J, Isaac J, Muiesan P, et al. Scoring System to Predict Pancreatic Fistula After Pancreaticoduodenectomy: A UK Multicenter Study. Ann Surg. 2015;261:1191\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen CB, McCall NS, Pucci MJ, Leiby B, Dabbish N, Winter JM, et al. The Combination of Pancreas Texture and Postoperative Serum Amylase in Predicting Pancreatic Fistula Risk. Am Surg. 2018;84:889\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsai S, George B, Wittmann D, Ritch PS, Krepline AN, Aldakkak M, et al. Importance of Normalization of CA19-9 Levels Following Neoadjuvant Therapy in Patients With Localized Pancreatic Cancer. Ann Surg. 2020;271:740\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMotoi F, Unno M. Adjuvant and neoadjuvant treatment for pancreatic adenocarcinoma. Jpn J Clin Oncol. 2020;50:483\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003c/ol\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":"[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Body mass index, Postoperative complication, Postoperative pancreatic fistula, CA19-9, Long-term outcome","lastPublishedDoi":"10.21203/rs.3.rs-1935530/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1935530/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e \u003cp\u003ePostoperative pancreatic fistula (POPF) is a critical complication of pancreatectomy in patients with pancreatic ductal adenocarcinoma (PDAC). Recent papers reported that serum carbohydrate antigen (CA)19\u0026thinsp;\u0026minus;\u0026thinsp;9 levels predicted long-term prognosis. We investigated whether preoperative serum CA19-9 levels were associated with POPF in PDAC patients.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eThis cohort study was conducted at a single institution retrospectively. Clinicopathologic features were determined using medical records.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eAmong of 196 consecutive patients who underwent pancreatectomy against PDAC, 180 patients whose CA19-9 levels were above the measurement sensitivity, were registered in this study. The patients consisted of 122 patients who underwent pancreaticoduodenectomy and 58 patients who underwent distal pancreatectomy. Several clinicopathological factors, including CA 19\u0026thinsp;\u0026minus;\u0026thinsp;9 level, as well as surgical factors were determined retrospectively based on the medical records. Patients with high CA19-9 levels had a significantly higher incidence of POPF than those with low levels (43.9% vs. 13.0%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). The receiver operating characteristic curves calculated that the cutoff CA19-9 value to predict POPF was 428 U/mL. CA19-9, BMI, curability, and histology were statistically significant risk factors for POPF by univariate analysis. Multivariate analysis showed that CA19-9 and BMI levels were statistically significant independent risk factors for POPF. CA19-9 levels were correlated with both histology and curability. Disease free survival and overall survival of patients with higher levels of CA19-9 were significantly shorter than that of patients with lower levels of preoperative serum CA19-9.\u003c/p\u003e\u003ch2\u003eConclusions:\u003c/h2\u003e \u003cp\u003eIn patients undergoing pancreatectomy for PDAC, higher preoperative CA19-9 levels are a significant predictor for POPF.\u003c/p\u003e","manuscriptTitle":"Preoperative serum CA19-9 predicts postoperative pancreatic fistula in PDAC patients: retrospective analysis at a single institution.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-08-12 16:37:38","doi":"10.21203/rs.3.rs-1935530/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-08-25T13:01:02+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"c9012f5c-7661-4adb-abbf-7c2c1147a0c1","date":"2022-08-23T20:21:44+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-08-23T01:23:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"1dcd3121-50db-4d89-a105-821860e77a6c","date":"2022-08-21T03:09:33+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-08-20T10:42:26+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-08-18T10:52:48+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2022-08-10T09:14:31+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-08-10T09:12:19+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Surgery","date":"2022-08-06T10:06:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d4eb4ea3-5ca3-4925-854e-dd022bd5870e","owner":[],"postedDate":"August 12th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-10-20T12:29:29+00:00","versionOfRecord":[],"versionCreatedAt":"2022-08-12 16:37:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1935530","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1935530","identity":"rs-1935530","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}