The optimal preoperative bilirubin level before pancreaticoduodenectomy for distal cholangiocarcinoma

The optimal preoperative bilirubin level before pancreaticoduodenectomy for distal cholangiocarcinoma | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The optimal preoperative bilirubin level before pancreaticoduodenectomy for distal cholangiocarcinoma Ao Ren, Ling Zhao, Wei Li, Jiawei Li, Shiqiao Luo This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7746301/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Introduction It is currently unclear what the optimal level of preoperative bilirubin is for pancreaticoduodenectomy(PD) to reduce severe complications. The aim of this study is to identify the optimal bilirubin level of patients with hyperbilirubinemia undergoing PD. Methods Receiver operating characteristic (ROC) curve(AUC) based on the highest Youden index was used to determine cut-off value of the optimal preoperative bilirubin that were associated with increases in 90-day mortality. Subgroup comparisons analyses were performed for patients with preoperative bilirubin according to the cut-off value. Results Preoperative bilirubin > 163 µmol/L was associated with an increase in 90-day mortality rate(P = 0.001). Significantly more patients with preoperative bilirubin > 163 µmol/L had biliary leakage (16.39% vs 3.7%; p = 0.026). Although there were more infections, postoperative bleeding and transfusion, delayed gastric emptying, reoperation, ICU use and pancreatic fistula in patients with preoperative bilirubin > 163 µmol/L compared to ≤ 163 µmol/L, there was no statistically significant difference. Disease-free survival did not differ much between the two groups (p = 0.418). The 5-year overall survival rate was 23.4% in patients with preoperative bilirubin ≤ 163 µmol/L and 16.2% in patients with preoperative bilirubin > 163 µmol/L, overall survival was significantly better in patients with preoperative bilirubin ≤ 163 µmol/L (p < 0.05). Conclusions The cut-off value of preoperative bilirubin level of 163 µmol/L is recommended, as the study showed that preoperative bilirubin level ≤ 163 µmol/L significantly reduced the 90-day mortality, complications and got better survival after PD for distal cholangiocarcinoma. Malignant obstruction jaundice Preoperative bilirubin Pancreaticoduodenectomy Distal cholangiocarcinoma Postoperative complications Figures Figure 1 Figure 2 Introduction Distal cholangiocarcinoma (dCCA) is a rare malignancy arising from the epithelial cells of the distal biliary tract, with poor prognosis, surgical resection remains the only curative treatment strategy[ 1 ]. Pancreaticoduodenectomy (PD) has been widely applied in patients with dCCA, the scope of surgical resection includes distal part of the stomach, duodenum, distal common bile duct, head of pancreas and first jejunal loop, and three anastomoses need to be completed[ 2 ]. Although advancements in medical technology, postoperative complications after PD remain a major challenge[ 3 – 5 ]. Hyperbilirubinemia in patients has been associated with coagulopathy, decline in renal and myocardial function, immunological incompetence, and malnutrition[ 6 – 7 ]. Preoperative biliary drainage may reduce the postoperative risks associated with hyperbilirubinemia[ 8 ]. The methods for preoperative biliary drainage (PBD) mainly include endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic nasobiliary drainage (ENBD)[ 8 ]. However, the optimal preoperative bilirubin has not been quantified. Makuuchi et al[ 9 ] found that preoperative bilirubin more than 3 mg/dL(51 µmol/L) had negative impact on overall survival. And preoperative bilirubin more 10 mg/dL (171 µmol/L) might increase postoperative mortality rate[ 10 ]. Sauvanet et al[ 11 ] showed that the serum bilirubin level ≥ 300 µmol/L had negative impact on survival. The aim of study is to explore the optimal level of bilirubin before pancreaticoduodenectomy for distal cholangiocarcinoma in relation to postoperative complication and mortality. Methods Clinical data of distal cholangiocarcinoma patients at a single center (The First Affiliated Hospital of Chongqing Medical University) in the period from January 2013 to May 2022 were reviewed. This study only included patients with distal cholangiocarcinoma undergoing pancreaticoduodenectomy. Patients with unresectable distal cholangiocarcinoma during initial investigation or during operation, < 18 years old, and those without complete clinical data were excluded from the study. 115 patients were included in this study. The postoperative complications were graded according to the Clavien-Dindo descriptions[ 12 ]. Postoperative observation data included number of complications per patient, postoperative bleeding, infection, delayed gastric emptying, reoperation, ICU use, length of stay after operation, biliary leakage, pancreatic fistula, abdominal hemorrhage and gastrointestinal hemorrhage. The follow-up data included severe complications (grade III or above), 90-day mortality, tumor recurrence or death, and date of last follow-up. This study was approved by the clinical research ethics committee of The First Affiliated Hospital of Chongqing Medical University(No 2024-578-01). All patients agreed to participate in the study and the informed consent was verbal. And the study adheres to the Declaration of Helsinki. To assess the degree of biliary obstruction in patients and to alleviate obstructive jaundice through PTCD or ERCP before pancreaticoduodenectomy. Pancreaticoduodenectomy included laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD). With the development of time, laparoscopic technology is becoming more mature, and there are more choices for laparoscopic surgery. The receiver operating characteristic (ROC) curve was used to detect the optimal preoperative level of bilirubin. We determined the best cut-off value by the highest Youden index. Survival was analysed by the Kaplan–Meier method, and compared with the log-rank test. All data were analyzed using SPSS version 19.0 (SPSS, Chicago, IL, USA). P value < 0.05 was considered statistically significant. Results Preoperative bilirubin level correlated more strongly with 90-day mortality, and an optimal cut-off value of 163µmol/L was determined by to the maximum Youden index. The AUC of the model for predicting 90-day mortality was 0.758 [95% CI: 0.644–0.872, p = 0.001]. The 115 patients were divided into two groups according to the optimal cut-off value: bilirubin ≤ 163 µmol/L (Group A: n = 54) and bilirubin > 163 µmol/L (Group B: n = 61). There were 11 (9.57%) 90-day mortalities, and the 90-day mortality was shown to be statistically different between two groups (3.70% VS.14.75%, p = 0.044) (Table 1 ). Table 1 Preoperative bilirubin level of 163 µmol/L on 90-day mortality 90-day mortality ≤ 163 µmol/L (n = 54) > 163 µmol/L (n = 61) P value Yes 2(3.70%) 9(14.75%) 0.044 No 52(96.30%) 52(85.25%) Table 2 showed the demographic and preoperative characteristics of the patients. The median preoperative bilirubin level was 110.1 µmol/L (range, 37.23–143.2 µmol/L) in Group A and 227.1 µmol/L (range, 199.7–273.9 µmol/L) in Group B(p = 0.047). As for the drainage procedure, 20.37% of patients received drainage procedure in Group A and 37.70% in Group B(p = 0.042). And more people choose ERCP than PTCD in Group A(16.67% VS.3.70%), otherwise in Group B(21.31% VS.16.39%). Table 2 Comparison of the two groups of patients in terms of demographic and preoperative characteristics Variable ≤ 163 µmol/L (n = 54) > 163 µmol/L (n = 61) P value Age (years) 66(59–70) 64(58–69) 0.753 Male: Female 38:16 37:24 0.275 Albumin (g/L) 37.5(34.25-41) 37(34–40) 0.550 Preoperative bilirubin level(µmol/L) 110.1(37.23–143.2) 227.1(199.7-273.9) 0.047 BMI,kg/m 2 22.77(20.20-24.22) 22.31(20.20-24.22) 0.865 CA199(ng/mL) 72.30(23.98–181.9) 134.9(47.7-381.6) 0.092 CEA(ng/mL) 2.9(1.77,4.2) 2.75(2.13,4.59) 0.667 ALT(U/L) 173(100.8–257) 183(108.8-298.5) 0.733 AST(U/L) 104(81.3–186) 129(82.5–200) 0.931 Drainage procedure 11(20.37%) 23(37.70%) 0.042 ERCP 9(16.67%) 13(21.31%) PTCD 2(3.70%) 10(16.39%) Type of Surgery 0.857 PD 31(57.41%) 34(55.74%) LPD 23(42.59%) 27(44.26%) Table 3 showed the postoperative results. Group B had significantly more 90-day mortality (14.75% vs 3.7%; p = 0.044) and biliary leakage (16.39% vs 3.7%; p = 0.026). Although there were more infections, postoperative bleeding, severe complications, delayed gastric emptying, reoperation, ICU use, postoperative transfusion and pancreatic fistula in Group B compared to Group A, there was no statistically significant difference. Table 3 Comparison of the two groups of patients in terms of postoperative results Variable ≤ 163 µmol/L (n = 54) > 163 µmol/L (n = 61) P value Number of complications per patient 1.39 ± 1.46 1.49 ± 1.3 0.360 Severe complication(accordion grade3-5) 23(42.59%) 30(49.18%) 0.479 90-day Mortality 2(3.7%) 9(14.75%) 0.044 Infection 18(33.33%) 28(45.90%) 0.170 Delayed gastric emptying 1(1.85%) 3(4.92%) 0.370 Reoperation 2(3.70%) 3(4.92%) 0.750 ICU use 9(16.67%) 12(19.67%) 0.677 Postoperative transfusion 7(12.96%) 16(26.23%) 0.076 Length of stay 27(20–36) 29(24–35) 0.928 Biliary leakage 2(3.70%) 10(16.39%) 0.026 Pancreatic fistula 9(16.67%) 13(21.31%) 0.527 Postoperative bleeding 11(20.37%) 14(22.95%) 0.738 Gastrointestinal hemorrhage 5(9.26%) 7(11.48%) 0.698 Abdominal hemorrhage 6(11.11%) 7(11.48%) 0.951 The median follow-up time was 24 months(Group A:31 months vs Group B:18 months). The median disease-free survival was 16 months(Group A:18 months vs Group B:14 months). There was not much difference in disease-free survival rates between the two groups (p = 0.418). Compared to Group B, The 5-year overall survival rate was significantly better in Group A (p < 0.05)(Fig. 1 ). And Group A had better 5-year disease-free survival rate than Group B(14.8% vs 8.4%) (Fig. 2 ). DISCUSSION The most common symptom of distal cholangiocarcinoma caused by invasion or blockage of the common bile duct is obstructive jaundice, and the more severe the course of the disease, the higher the level of bilirubin[ 13 , 14 ]. Therefore, malignant jaundice may led to more postoperative complications, it is necessary to fully preoperative evaluate and biliary drainage[ 15 , 16 ]. Preoperative reduction of jaundice can reduce postoperative complications, and prolong survival[ 17 ]. According to the method of bile drainage, preoperative biliary drainage can be divided into endoscopic nasobiliary drainage (ENBD) and percutaneous transhepatic biliary drainage (PTBD)[ 18 , 19 ]. However, there is still controversy over the selection of preoperative biliary drainage methods in terms of complications such as surgical trauma, pancreatitis, and cholangitis[ 20 ]. However, the optimal preoperative bilirubin level has not been defined. The timing of surgery usually relies mainly on the professional knowledge of the surgeon. Therefore, establish a clinically relevant critical cut-off value for preoperative bilirubin can reduce adverse postoperative events. Patients in this study with bilirubin > 163 µmol/L had greater postoperative 90-day mortality and biliary leakage, Although there were more infections, postoperative bleeding, severe complications, delayed gastric emptying, reoperation, ICU use, postoperative transfusion and pancreatic fistula in patients with bilirubin > 163 µmol/L, there was no statistically significant difference. As for the disease-free survival and overall survival, overall survival was significantly better in patients with bilirubin ≤ 163 µmol/L (p 163 µmol/L. However, disease-free survival did not differ much between the two groups (p = 0.418). Thus, both of these findings corroborate current literature. The obstructive jaundice in cholangiocarcinoma patients was associated with 90-day mortality and survival time after surgery[ 21 , 22 ]. And the patients with higher level of bilirubin has a higher risk of postoperative complications, including biliary leakage, bleeding, pancreatic fistula, etc[ 23 , 24 ]. The postoperative complications may be related to the systemic inflammation caused by jaundice, which can lead to multiple organ dysfunction, killing or damaging Kupffer cells in the liver[ 25 ]. The question of whether there is a degree of severe jaundice for which preoperative biliary drainage would reduce the occurrence of complications and provide a mortality-reduction benefit, still remains. De Pastena et al[ 26 ] showed that patients with bilirubin more than 7.5 mg/dL had more complications than patients who received biliary drainage. And Sauvenet et al[ 11 ] found the cutoff value was 17.54 mg/dL. However, these studies did not study potential impact of jaundice on mortality. Our study indicates that bilirubin > 163 µmol/L increases the 90-day mortality. There are also some limitations to this study. Firstly, the series is small, only 115 patients were included in this study. Secondly, it is a retrospective study from one center. Therefore, Therefore, selection bias is unavoidable. Therefore, prospective, multicenter, and large sample studies are needed for further validation. Preoperative bilirubin of 163 µmol/L is a cut-off value associated with increased 90-day mortality after PD for distal cholangiocarcinoma. Direct surgery could be considered if preoperative bilirubin ≤ 163 µmol/L, which may reduce death and severe complications. Therefore, in the case of a patient with preoperative bilirubin above 163 µmol/L, reduction of biliary drainage to reducing bilirubin is recommended. These results may provide guidance for surgeons to choose the optimal surgical timing for patients with jaundice before pancreaticoduodenectomy for distal cholangiocarcinoma. Declarations Competing interests The authors declare that they have no competing interests. Funding This work is supported by the National Natural Science Foundation of China (30972789), Medical Cultivation Fund from the First Affiliated Hospital of Chongqing Medical University(PYJJ2021-01). Author Contribution AR and SQL designed the study. AR and SQL developed the methodology of study. AR, LZ, WL,JWL participated in the acquisition of data. AR, LZ, WL analyzed and interpreted the data. AR wrote the manuscript. All authors reviewed and revised the manuscript. Data Availability The data that support the findings of this study are available from the corresponding author, [AR], upon reasonable request. References Gorji L, Beal EW. Surgical Treatment of Distal Cholangiocarcinoma. Curr Oncol. 2022;29(9):6674–87. Skalicky P, Urban O, Ehrmann J, et al. The short- and long-term outcomes of pancreaticoduodenectomy for distal cholangiocarcinoma. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2022;166(4):386–92. Yu ZH, Du MM, Zhang X, et al. The impact of preoperative biliary drainage on postoperative healthcare-associated infections and clinical outcomes following pancreaticoduodenectomy: a ten-year retrospective analysis. BMC Infect Dis. 2024;24(1):361. Kokkinakis S, Kritsotakis EI, Maliotis N, et al. 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Preoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma: a preliminary report. Surgery. 1990;107(5):521–7. Su CH, Tsay SH, Wu CC, et al. Factors influencing postoperative morbidity, mortality, and survival after resection for hilar cholangiocarcinoma. Ann Surg. 1996;223(4):384–94. Sauvanet A, Boher JM, Paye F, et al. Severe Jaundice Increases Early Severe Morbidity and Decreases Long-Term Survival after Pancreaticoduodenectomy for Pancreatic Adenocarcinoma. J Am Coll Surg. 2015;221(2):380–9. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13. Stupin V, Abramov I, Gahramanov T, et al. Comparative Study of the Results of Operations in Patients with Tumor and Non-Tumor Obstructive Jaundice Who Received and Did Not Receive Antioxidant Therapy for the Correction of Endotoxemia, Glycolysis, and Oxidative Stress. Antioxid (Basel). 2022;11:1203. Zhu L, Yang Y, Cheng H, et al. The role of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy in patients with obstructive jaundice. Gland Surg. 2023;12(5):593–608. Pavlidis ET, Pavlidis TE. Pathophysiological consequences of obstructive jaundice and perioperative management. Hepatobiliary Pancreat Dis Int. 2018;17:17–21. Wang L, Yu WF. Obstructive jaundice and perioperative management. Acta Anaesthesiol Taiwan. 2014;52:22–9. Hucl T. Malignant biliary obstruction. Cas Lek Cesk. 2016;155:30–7. Yang G, Xiong Y, Sun J, et al. Effects of different preoperative biliary drainage methods for resected malignant obstruction jaundice on the incidence rate of implantation metastasis: A meta-analysis. Oncol Lett. 2020;20(3):2217–24. Hameed A, Pang T, Chiou J, et al. Percutaneous vs. endoscopic pre-operative biliary drainage in hilar cholangiocarcinoma-A systematic review and meta-analysis. HPB (Oxford). 2016;18:400–10. She WH, Cheung TT, Ma KW, et al. Impact of preoperative biliary drainage on postoperative outcomes in hilar cholangiocarcinoma. Asian J Surg. 2022;45(4):993–1000. Liu Y, Wang Y, Yu Y, et al. Comparison of clinical characteristics and mortality risk between patients with cholangiocarcinoma: A retrospective cohort study. Front Surg. 2023;9:1037310. Termsinsuk P, Charatcharoenwitthaya P, Pausawasdi N. Development and validation of a 90-day mortality prediction model following endobiliary drainage in patients with unresectable malignant biliary obstruction. Front Oncol. 2022;12:922386. Pattarapuntakul T, Charoenrit T, Netinatsunton N, et al. Postoperative outcomes of resectable periampullary cancer accompanied by obstructive jaundice with and without preoperative endoscopic biliary drainage. Front Oncol. 2022;12:1040508. Mostafa A, Habeeb TA, Neri V, et al. Risk factors for postoperative pancreatic fistula following non-traumatic, pancreatic surgery. Retrospective observational study. Ann Ital Chir. 2023;94:435–42. Yang R, Zhu S, Pischke SE, et al. Bile and circulating HMGB1 contributes to systemic inflammation in obstructive jaundice. J Surg Res. 2018;228:14–9. De Pastena M, Marchegiani G, Paiella S, et al. Impact of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy: an analysis of 1500 consecutive cases. Dig Endosc. 2018;30(6):777–84. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 12 Nov, 2025 Reviewers agreed at journal 04 Nov, 2025 Reviewers agreed at journal 02 Nov, 2025 Reviewers invited by journal 24 Oct, 2025 Editor invited by journal 30 Sep, 2025 Editor assigned by journal 30 Sep, 2025 Submission checks completed at journal 30 Sep, 2025 First submitted to journal 29 Sep, 2025 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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1","display":"","copyAsset":false,"role":"figure","size":197397,"visible":true,"origin":"","legend":"\u003cp\u003eOverall survival of distal cholangiocarcinoma patients undergoing pancreaticoduodenectomy according to the cut-off value of preoperative bilirubin level of 163 μmol/L.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7746301/v1/bc3cd03c57d82f2d5009645f.jpeg"},{"id":95263159,"identity":"b3bdd644-a852-49df-8e88-c9e3efc4e411","added_by":"auto","created_at":"2025-11-06 05:20:55","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":205506,"visible":true,"origin":"","legend":"\u003cp\u003eProgression free survival of distal cholangiocarcinoma patients undergoing pancreaticoduodenectomy according to the cut-off value of preoperative bilirubin level of 163 μmol/L.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7746301/v1/aa7e825cc91538205446655b.jpeg"},{"id":95315679,"identity":"d1bb28ff-adc0-401f-849e-8b8779258785","added_by":"auto","created_at":"2025-11-06 15:56:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":858808,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7746301/v1/6f1427d1-6d23-4624-8a2e-84cc26c78143.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The optimal preoperative bilirubin level before pancreaticoduodenectomy for distal cholangiocarcinoma","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDistal cholangiocarcinoma (dCCA) is a rare malignancy arising from the epithelial cells of the distal biliary tract, with poor prognosis, surgical resection remains the only curative treatment strategy[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Pancreaticoduodenectomy (PD) has been widely applied in patients with dCCA, the scope of surgical resection includes distal part of the stomach, duodenum, distal common bile duct, head of pancreas and first jejunal loop, and three anastomoses need to be completed[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Although advancements in medical technology, postoperative complications after PD remain a major challenge[\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Hyperbilirubinemia in patients has been associated with coagulopathy, decline in renal and myocardial function, immunological incompetence, and malnutrition[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePreoperative biliary drainage may reduce the postoperative risks associated with hyperbilirubinemia[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The methods for preoperative biliary drainage (PBD) mainly include endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic nasobiliary drainage (ENBD)[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, the optimal preoperative bilirubin has not been quantified. Makuuchi et al[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] found that preoperative bilirubin more than 3 mg/dL(51 \u0026micro;mol/L) had negative impact on overall survival. And preoperative bilirubin more 10 mg/dL (171 \u0026micro;mol/L) might increase postoperative mortality rate[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Sauvanet et al[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] showed that the serum bilirubin level\u0026thinsp;\u0026ge;\u0026thinsp;300 \u0026micro;mol/L\u003c/p\u003e\u003cp\u003ehad negative impact on survival. The aim of study is to explore the optimal level of bilirubin before pancreaticoduodenectomy for distal cholangiocarcinoma in relation to postoperative complication and mortality.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e Clinical data of distal cholangiocarcinoma patients at a single center (The First Affiliated Hospital of Chongqing Medical University) in the period from January 2013 to May 2022 were reviewed. This study only included patients with distal cholangiocarcinoma undergoing pancreaticoduodenectomy. Patients with unresectable distal cholangiocarcinoma during initial investigation or during operation, \u0026lt;\u0026thinsp;18 years old, and those without complete clinical data were excluded from the study. 115 patients were included in this study. The postoperative complications were graded according to the Clavien-Dindo descriptions[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Postoperative observation data included number of complications per patient, postoperative bleeding, infection, delayed gastric emptying, reoperation, ICU use, length of stay after operation, biliary leakage, pancreatic fistula, abdominal hemorrhage and gastrointestinal hemorrhage. The follow-up data included severe complications (grade III or above), 90-day mortality, tumor recurrence or death, and date of last follow-up. This study was approved by the clinical research ethics committee of The First Affiliated Hospital of Chongqing Medical University(No 2024-578-01). All patients agreed to participate in the study and the informed consent was verbal. And the study adheres to the Declaration of Helsinki.\u003c/p\u003e\u003cp\u003eTo assess the degree of biliary obstruction in patients and to alleviate obstructive jaundice through PTCD or ERCP before pancreaticoduodenectomy. Pancreaticoduodenectomy included laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD). With the development of time, laparoscopic technology is becoming more mature, and there are more choices for laparoscopic surgery.\u003c/p\u003e\u003cp\u003eThe receiver operating characteristic (ROC) curve was used to detect the optimal preoperative level of bilirubin. We determined the best cut-off value by the highest Youden index. Survival was analysed by the Kaplan\u0026ndash;Meier method, and compared with the log-rank test. All data were analyzed using SPSS version 19.0 (SPSS, Chicago, IL, USA). P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003ePreoperative bilirubin level correlated more strongly with 90-day mortality, and an optimal cut-off value of 163\u0026micro;mol/L was determined by to the maximum Youden index. The AUC of the model for predicting 90-day mortality was 0.758 [95% CI: 0.644\u0026ndash;0.872, p\u0026thinsp;=\u0026thinsp;0.001]. The 115 patients were divided into two groups according to the optimal cut-off value: bilirubin\u0026thinsp;\u0026le;\u0026thinsp;163 \u0026micro;mol/L (Group A: n\u0026thinsp;=\u0026thinsp;54) and bilirubin\u0026thinsp;\u0026gt;\u0026thinsp;163 \u0026micro;mol/L (Group B: n\u0026thinsp;=\u0026thinsp;61).\u003c/p\u003e\u003cp\u003eThere were 11 (9.57%) 90-day mortalities, and the 90-day mortality was shown to be statistically different between two groups (3.70% VS.14.75%, p\u0026thinsp;=\u0026thinsp;0.044) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePreoperative bilirubin level of 163 \u0026micro;mol/L on 90-day mortality\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003e90-day mortality\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;163 \u0026micro;mol/L (n\u0026thinsp;=\u0026thinsp;54)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;163 \u0026micro;mol/L (n\u0026thinsp;=\u0026thinsp;61)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2(3.70%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9(14.75%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.044\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e52(96.30%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e52(85.25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e showed the demographic and preoperative characteristics of the patients. The median preoperative bilirubin level was 110.1 \u0026micro;mol/L (range, 37.23\u0026ndash;143.2 \u0026micro;mol/L) in Group A and 227.1 \u0026micro;mol/L (range, 199.7\u0026ndash;273.9 \u0026micro;mol/L) in Group B(p\u0026thinsp;=\u0026thinsp;0.047). As for the drainage procedure, 20.37% of patients received drainage procedure in Group A and 37.70% in Group B(p\u0026thinsp;=\u0026thinsp;0.042). And more people choose ERCP than PTCD in Group A(16.67% VS.3.70%), otherwise in Group B(21.31% VS.16.39%).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of the two groups of patients in terms of demographic and preoperative characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;163 \u0026micro;mol/L (n\u0026thinsp;=\u0026thinsp;54)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;163 \u0026micro;mol/L (n\u0026thinsp;=\u0026thinsp;61)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e66(59\u0026ndash;70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64(58\u0026ndash;69)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.753\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale: Female\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38:16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37:24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.275\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin (g/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37.5(34.25-41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37(34\u0026ndash;40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.550\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreoperative bilirubin level(\u0026micro;mol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e110.1(37.23\u0026ndash;143.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e227.1(199.7-273.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.047\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI,kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22.77(20.20-24.22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22.31(20.20-24.22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.865\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCA199(ng/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e72.30(23.98\u0026ndash;181.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e134.9(47.7-381.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.092\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCEA(ng/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.9(1.77,4.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.75(2.13,4.59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.667\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALT(U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e173(100.8\u0026ndash;257)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e183(108.8-298.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.733\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAST(U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e104(81.3\u0026ndash;186)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e129(82.5\u0026ndash;200)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.931\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDrainage procedure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11(20.37%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23(37.70%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.042\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eERCP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9(16.67%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13(21.31%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePTCD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2(3.70%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10(16.39%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eType of Surgery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.857\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31(57.41%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e34(55.74%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLPD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23(42.59%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27(44.26%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e showed the postoperative results. Group B had significantly more 90-day mortality (14.75% vs 3.7%; p\u0026thinsp;=\u0026thinsp;0.044) and biliary leakage (16.39% vs 3.7%; p\u0026thinsp;=\u0026thinsp;0.026). Although there were more infections, postoperative bleeding, severe complications, delayed gastric emptying, reoperation, ICU use, postoperative transfusion and pancreatic fistula in Group B compared to Group A, there was no statistically significant difference.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of the two groups of patients in terms of postoperative results\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;163 \u0026micro;mol/L (n\u0026thinsp;=\u0026thinsp;54)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;163 \u0026micro;mol/L (n\u0026thinsp;=\u0026thinsp;61)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of complications per patient\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.39\u0026thinsp;\u0026plusmn;\u0026thinsp;1.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.49\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.360\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSevere complication(accordion grade3-5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23(42.59%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30(49.18%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.479\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e90-day Mortality\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2(3.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9(14.75%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.044\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInfection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18(33.33%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28(45.90%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.170\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDelayed gastric emptying\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1(1.85%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3(4.92%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.370\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReoperation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2(3.70%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3(4.92%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.750\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eICU use\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9(16.67%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12(19.67%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.677\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePostoperative transfusion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7(12.96%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16(26.23%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.076\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLength of stay\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27(20\u0026ndash;36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29(24\u0026ndash;35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.928\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBiliary leakage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2(3.70%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10(16.39%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.026\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePancreatic fistula\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9(16.67%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13(21.31%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.527\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePostoperative bleeding\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11(20.37%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14(22.95%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.738\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGastrointestinal hemorrhage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5(9.26%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7(11.48%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.698\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbdominal hemorrhage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6(11.11%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7(11.48%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.951\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe median follow-up time was 24 months(Group A:31 months vs Group B:18 months). The median disease-free survival was 16 months(Group A:18 months vs Group B:14 months). There was not much difference in disease-free survival rates between the two groups (p\u0026thinsp;=\u0026thinsp;0.418). Compared to Group B, The 5-year overall survival rate was significantly better in Group A (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05)(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). And Group A had better 5-year disease-free survival rate than Group B(14.8% vs 8.4%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe most common symptom of distal cholangiocarcinoma caused by invasion or blockage of the common bile duct is obstructive jaundice, and the more severe the course of the disease, the higher the level of bilirubin[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Therefore, malignant jaundice may led to more postoperative complications, it is necessary to fully preoperative evaluate and biliary drainage[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Preoperative reduction of jaundice can reduce postoperative complications, and prolong survival[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. According to the method of bile drainage, preoperative biliary drainage can be divided into endoscopic nasobiliary drainage (ENBD) and percutaneous transhepatic biliary drainage (PTBD)[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. However, there is still controversy over the selection of preoperative biliary drainage methods in terms of complications such as surgical trauma, pancreatitis, and cholangitis[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. However, the optimal preoperative bilirubin level has not been defined. The timing of surgery usually relies mainly on the professional knowledge of the surgeon. Therefore, establish a clinically relevant critical cut-off value for preoperative bilirubin can reduce adverse postoperative events.\u003c/p\u003e\u003cp\u003ePatients in this study with bilirubin\u0026thinsp;\u0026gt;\u0026thinsp;163 \u0026micro;mol/L had greater postoperative 90-day mortality and biliary leakage, Although there were more infections, postoperative bleeding, severe complications, delayed gastric emptying, reoperation, ICU use, postoperative transfusion and pancreatic fistula in patients with bilirubin\u0026thinsp;\u0026gt;\u0026thinsp;163 \u0026micro;mol/L, there was no statistically significant difference. As for the disease-free survival and overall survival, overall survival was significantly better in patients with bilirubin\u0026thinsp;\u0026le;\u0026thinsp;163 \u0026micro;mol/L (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), The 5-year overall survival rate was 23.4% in patients with bilirubin\u0026thinsp;\u0026le;\u0026thinsp;163 \u0026micro;mol/L and 16.2% in patients with bilirubin\u0026thinsp;\u0026gt;\u0026thinsp;163 \u0026micro;mol/L. However, disease-free survival did not differ much between the two groups (p\u0026thinsp;=\u0026thinsp;0.418). Thus, both of these findings corroborate current literature. The obstructive jaundice in cholangiocarcinoma patients was associated with 90-day mortality and survival time after surgery[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. And the patients with higher level of bilirubin has a higher risk of postoperative complications, including biliary leakage, bleeding, pancreatic fistula, etc[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe postoperative complications may be related to the systemic inflammation caused by jaundice, which can lead to multiple organ dysfunction, killing or damaging Kupffer cells in the liver[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The question of whether there is a degree of severe jaundice for which preoperative biliary drainage would reduce the occurrence of complications and provide a mortality-reduction benefit, still remains. De Pastena et al[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] showed that patients with bilirubin more than 7.5 mg/dL had more complications than patients who received biliary drainage. And Sauvenet et al[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] found the cutoff value was 17.54 mg/dL. However, these studies did not study potential impact of jaundice on mortality. Our study indicates that bilirubin\u0026thinsp;\u0026gt;\u0026thinsp;163 \u0026micro;mol/L increases the 90-day mortality.\u003c/p\u003e\u003cp\u003eThere are also some limitations to this study. Firstly, the series is small, only 115 patients were included in this study. Secondly, it is a retrospective study from one center. Therefore, Therefore, selection bias is unavoidable. Therefore, prospective, multicenter, and large sample studies are needed for further validation.\u003c/p\u003e\u003cp\u003ePreoperative bilirubin of 163 \u0026micro;mol/L is a cut-off value associated with increased 90-day mortality after PD for distal cholangiocarcinoma. Direct surgery could be considered if preoperative bilirubin\u0026thinsp;\u0026le;\u0026thinsp;163 \u0026micro;mol/L, which may reduce death and severe complications. Therefore, in the case of a patient with preoperative bilirubin above 163 \u0026micro;mol/L, reduction of biliary drainage to reducing bilirubin is recommended. These results may provide guidance for surgeons to choose the optimal surgical timing for patients with jaundice before pancreaticoduodenectomy for distal cholangiocarcinoma.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eCompeting interests\u003c/h2\u003e\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis work is supported by the National Natural Science Foundation of China (30972789), Medical Cultivation Fund from the First Affiliated Hospital of Chongqing Medical University(PYJJ2021-01).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAR and SQL designed the study. AR and SQL developed the methodology of study. AR, LZ, WL,JWL participated in the acquisition of data. AR, LZ, WL analyzed and interpreted the data. AR wrote the manuscript. All authors reviewed and revised the manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data that support the findings of this study are available from the corresponding author, [AR], upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGorji L, Beal EW. Surgical Treatment of Distal Cholangiocarcinoma. Curr Oncol. 2022;29(9):6674\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSkalicky P, Urban O, Ehrmann J, et al. The short- and long-term outcomes of pancreaticoduodenectomy for distal cholangiocarcinoma. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2022;166(4):386\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYu ZH, Du MM, Zhang X, et al. The impact of preoperative biliary drainage on postoperative healthcare-associated infections and clinical outcomes following pancreaticoduodenectomy: a ten-year retrospective analysis. BMC Infect Dis. 2024;24(1):361.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKokkinakis S, Kritsotakis EI, Maliotis N, et al. Complications of modern pancreaticoduodenectomy: a systematic review and meta-analysis. Hepatobiliary Pancreat Dis Int. 2022;21(6):527\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSmits FJ, Verweij ME, Daamen LA, et al. Impact of Complications after Pancreatoduodenectomy on mortality, organ failure, hospital stay, and readmission: analysis of a Nationwide audit. Ann Surg. 2022;275(1):e222\u0026ndash;ee28.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen B, Trudeau MT, Maggino L, et al. Defining the Safety Profile for Performing Pancreatoduodenectomy in the Setting of Hyperbilirubinemia. Ann Surg Oncol. 2020;27(5):1595\u0026ndash;605.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLe Zarzavadjian A, Fuks D, Dalla Valle R, et al. Effectiveness and risk of biliary drainage prior to pancreatoduodenectomy: review of current status. Surg Today. 2018;48(4):371\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShe WH, Cheung TT, Ma KW, et al. Defining the optimal bilirubin level before hepatectomy for hilar cholangiocarcinoma. BMC Cancer. 2020;20(1):914.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMakuuchi M, Thai BL, Takayasu K, et al. Preoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma: a preliminary report. Surgery. 1990;107(5):521\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSu CH, Tsay SH, Wu CC, et al. Factors influencing postoperative morbidity, mortality, and survival after resection for hilar cholangiocarcinoma. Ann Surg. 1996;223(4):384\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSauvanet A, Boher JM, Paye F, et al. Severe Jaundice Increases Early Severe Morbidity and Decreases Long-Term Survival after Pancreaticoduodenectomy for Pancreatic Adenocarcinoma. J Am Coll Surg. 2015;221(2):380\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStupin V, Abramov I, Gahramanov T, et al. Comparative Study of the Results of Operations in Patients with Tumor and Non-Tumor Obstructive Jaundice Who Received and Did Not Receive Antioxidant Therapy for the Correction of Endotoxemia, Glycolysis, and Oxidative Stress. 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Bile and circulating HMGB1 contributes to systemic inflammation in obstructive jaundice. J Surg Res. 2018;228:14\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDe Pastena M, Marchegiani G, Paiella S, et al. Impact of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy: an analysis of 1500 consecutive cases. Dig Endosc. 2018;30(6):777\u0026ndash;84.\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":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Malignant obstruction jaundice, Preoperative bilirubin, Pancreaticoduodenectomy, Distal cholangiocarcinoma, Postoperative complications","lastPublishedDoi":"10.21203/rs.3.rs-7746301/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7746301/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction\u003c/h2\u003e\u003cp\u003eIt is currently unclear what the optimal level of preoperative bilirubin is for pancreaticoduodenectomy(PD) to reduce severe complications. The aim of this study is to identify the optimal bilirubin level of patients with hyperbilirubinemia undergoing PD.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eReceiver operating characteristic (ROC) curve(AUC) based on the highest Youden index was used to determine cut-off value of the optimal preoperative bilirubin that were associated with increases in 90-day mortality. Subgroup comparisons analyses were performed for patients with preoperative bilirubin according to the cut-off value.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003ePreoperative bilirubin\u0026thinsp;\u0026gt;\u0026thinsp;163 \u0026micro;mol/L was associated with an increase in 90-day mortality rate(P\u0026thinsp;=\u0026thinsp;0.001). Significantly more patients with preoperative bilirubin\u0026thinsp;\u0026gt;\u0026thinsp;163 \u0026micro;mol/L had biliary leakage (16.39% vs 3.7%; p\u0026thinsp;=\u0026thinsp;0.026). Although there were more infections, postoperative bleeding and transfusion, delayed gastric emptying, reoperation, ICU use and pancreatic fistula in patients with preoperative bilirubin\u0026thinsp;\u0026gt;\u0026thinsp;163 \u0026micro;mol/L compared to \u0026le;\u0026thinsp;163 \u0026micro;mol/L, there was no statistically significant difference. Disease-free survival did not differ much between the two groups (p\u0026thinsp;=\u0026thinsp;0.418). The 5-year overall survival rate was 23.4% in patients with preoperative bilirubin\u0026thinsp;\u0026le;\u0026thinsp;163 \u0026micro;mol/L and 16.2% in patients with preoperative bilirubin\u0026thinsp;\u0026gt;\u0026thinsp;163 \u0026micro;mol/L, overall survival was significantly better in patients with preoperative bilirubin\u0026thinsp;\u0026le;\u0026thinsp;163 \u0026micro;mol/L (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThe cut-off value of preoperative bilirubin level of 163 \u0026micro;mol/L is recommended, as the study showed that preoperative bilirubin level\u0026thinsp;\u0026le;\u0026thinsp;163 \u0026micro;mol/L significantly reduced the 90-day mortality, complications and got better survival after PD for distal cholangiocarcinoma.\u003c/p\u003e","manuscriptTitle":"The optimal preoperative bilirubin level before pancreaticoduodenectomy for distal cholangiocarcinoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-06 05:20:50","doi":"10.21203/rs.3.rs-7746301/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-11-13T03:47:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"295904515392773428374430870480006897228","date":"2025-11-04T23:07:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"72968801536333427154996970737516680014","date":"2025-11-03T00:04:56+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-24T23:43:51+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-30T17:57:05+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-30T07:53:09+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-30T07:50:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2025-09-30T02:19:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"aaab3758-d0ba-4fdb-b860-8b7c4f3b68e0","owner":[],"postedDate":"November 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-11-06T05:20:51+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-06 05:20:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7746301","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7746301","identity":"rs-7746301","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}