Postoperative Pancreatic Fistula in 33 Consecutive Pancreaticoduodenectomies: Experience at a Tertiary Center

Postoperative Pancreatic Fistula in 33 Consecutive Pancreaticoduodenectomies: Experience at a Tertiary Center | 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 Postoperative Pancreatic Fistula in 33 Consecutive Pancreaticoduodenectomies: Experience at a Tertiary Center Dimpy Ajit Shah, Harsh Jayeshkumar Barot, Nitin A Borle, Rajendra Habib This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7386858/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Postoperative pancreatic fistula (POPF) remains a significant complication following pancreaticoduodenectomy (PD). This study evaluates the incidence and risk factors associated with POPF in a cohort of consecutive PDs using the ISGPS 2016 definition. Methods A retrospective review was performed on 33 consecutive patients undergoing upfront PD between 2022 and 2024 at a tertiary center. Clinical and operative data were collected. POPF was defined and graded per ISGPS 2016. Univariate and multivariate analyses assessed associations with clinically relevant POPF (Grade B/C). Results Mean age was 51 years (SD ± 10.56), and 42.4% were female. The most common indication was ampullary carcinoma (39.39%). Open PD was performed in 97% of cases. Mean MPD diameter was 4.93 mm (SD ± 2.17), with average blood loss of 1005.4 mL (SD ± 516.23). Clinically relevant POPF occurred in 18.18% (n = 6), equally distributed between Grades B and C. Biochemical leaks were seen in 24.24% (n = 8). POPF was not significantly associated with age (p = 0.49), BMI (p = 0.82), albumin (p = 0.72), or MPD diameter (p = 0.10). Conclusion The rate of clinically relevant POPF was 18.18%. No significant preoperative or intraoperative predictors were identified. These findings support the multifactorial nature of POPF and the importance of continued refinement in surgical and perioperative strategies. Introduction Pancreaticoduodenectomy (PD), also known as the Whipple procedure, remains the cornerstone surgical treatment for malignant and select benign conditions of the pancreatic head, distal bile duct, ampulla of Vater, and duodenum. Despite significant advances in perioperative care, surgical technique, and patient selection, the procedure is still associated with considerable morbidity, the most feared and common complication being the postoperative pancreatic fistula (POPF). POPF is defined as an abnormal communication between the pancreatic ductal system and another epithelialized surface containing pancreatic secretions. It can result in intra-abdominal collections, hemorrhage, sepsis, and prolonged hospital stays, severely impacting patient recovery and healthcare costs. The reported incidence of POPF varies widely, ranging from 5% to 30% depending on patient risk factors, gland characteristics, and institutional volume and expertise (1–3). In 2016, the International Study Group on Pancreatic Surgery (ISGPS) updated its definition and classification of POPF to distinguish clinically relevant fistulas (Grade B and C) from asymptomatic biochemical leaks (4). This revision aimed to standardize outcome reporting and guide clinical decision-making, enabling better stratification and management of patients. Since then, numerous studies have explored risk factors and predictive models for POPF, identifying gland texture, small main pancreatic duct (MPD) diameter, elevated BMI, and hypoalbuminemia as key contributors (5–8). Among these, the combination of a soft pancreas and a non-dilated duct is consistently highlighted as a high-risk configuration. Several risk scoring systems, such as the Fistula Risk Score (FRS), have attempted to integrate these and other intraoperative variables to predict POPF development with varying success (9,10). Nonetheless, despite these tools and a growing body of literature, the ability to precisely predict and prevent POPF remains limited. Additionally, there remains institutional variability in surgical approach (open vs. minimally invasive), pancreatoenteric anastomotic techniques (duct-to-mucosa vs. invagination), use of intraoperative drains, and perioperative management protocols. These factors contribute to differences in POPF rates and may confound the identification of consistent predictors across patient populations (11–13). The present study was conducted to assess the incidence of POPF using ISGPS 2016 criteria in a contemporary cohort undergoing PD at a tertiary care center. Furthermore, we aimed to explore associations between POPF and various demographic, clinical, and intraoperative variables, thereby evaluating the generalizability of previously reported risk factors in our institutional setting. Materials and Methods Study Design and Setting This was a retrospective observational study conducted at the Department of General Surgery, BYL Nair Charitable hospital and TNMC, tertiary care academic referral center in Mumbai. The study was approved by the Institutional Ethics Committee and conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all patients prior to inclusion in the study. Participants were informed about the nature and purpose of the research, and their voluntary participation was ensured. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Patient Selection We reviewed the records of 33 consecutive patients who underwent pancreaticoduodenectomy (PD) between 2022 and 2024. All patients underwent surgery with curative intent for periampullary or pancreatic head lesions. Exclusion criteria included: Palliative procedures or bypass surgeries without PD Redo surgeries Incomplete or missing medical records Only patients undergoing upfront surgery (no neoadjuvant therapy) were included to maintain a uniform cohort. Clinical trial number: not applicable. Data Collection Patient data were extracted from electronic medical records, operative notes, and postoperative charts. The following parameters were recorded: Demographic and Clinical Variables: Age Sex Body mass index (BMI) Weight Serum albumin (preoperative, within 2 weeks before surgery) Comorbidities (e.g., diabetes, hypertension) Surgical and Intraoperative Details: Indication for surgery (final histopathological diagnosis) Operative approach (open or laparoscopic) Main pancreatic duct (MPD) diameter (measured intraoperatively or radiologically) Estimated intraoperative blood loss Pancreatic texture (soft or firm, as documented by the surgeon) Postoperative Outcomes: Development of postoperative pancreatic fistula (POPF) POPF classification using ISGPS 2016 guidelines: Biochemical leak: Elevated amylase in drain fluid on or after postoperative day 3 without clinical impact Grade B: POPF requiring a change in clinical management (e.g., antibiotics, prolonged drainage, or percutaneous intervention) Grade C: POPF with severe clinical sequelae including reoperation, organ failure, or death Length of hospital stay Surgical site infections or other complications Surgical Technique A standard Whipple procedure was performed in all cases. The pancreas was transected at the neck, and pancreatojejunostomy was performed using either duct-to-mucosa or invagination technique based on intraoperative assessment. A single-surgeon or multi-consultant team approach was employed. Closed-suction drains were routinely placed near the pancreatic and biliary anastomoses and monitored for output and amylase content from postoperative day 1 onward. POPF Diagnosis and Monitoring Drain fluid was routinely analyzed for amylase on postoperative day (POD) 3, and earlier if clinically indicated. POPF was diagnosed and graded per the ISGPS 2016 classification. Patients with biochemical leaks were managed conservatively. Grade B and C fistulas were treated with antibiotics, nutritional support, radiological drainage, or reoperation based on severity. Statistical Analysis Statistical analyses were performed using statistical software R version R 4.3.2. Continuous variables were expressed as means ± standard deviations (SD) or medians with interquartile ranges (IQR), as appropriate. Categorical variables were reported as frequencies and percentages. Univariate Analysis: To assess associations between variables and clinically relevant POPF (Grade B or C), we used: Chi-square test or Fisher’s exact test for categorical variables Student’s t-test or Mann–Whitney U test for continuous variables Multivariate Analysis: Variables with p < 0.10 in univariate analysis were entered into a binary logistic regression model to identify independent predictors of POPF. A p-value < 0.05 was considered statistically significant. Results Patient Demographics and Clinical Characteristics The study included 33 patients who underwent pancreaticoduodenectomy (PD). The mean age was 51 years (SD ±10.56), with 42.4% (n=14) being female. The mean weight was 58.9 kg (SD ±9.90), and the median body mass index (BMI) was 24.01 (IQR 2.5). Table 1 shows baseline characteristics of patients *Albumin levels were not significantly associated with POPF in univariate analysis (p = 0.72). Surgical Indications and Intraoperative Details Ampullary carcinoma was the most frequent indication for PD (39.39%), followed by duodenal carcinoma (33.33%), distal cholangiocarcinoma (27.27%), and pancreatic adenocarcinoma (6.06%). Table 2 shows distribution of diagnosis across cases of periampullary cancer A standard open approach was used in 32 cases (97.0%), and one patient (3.0%) underwent laparoscopic PD. The mean diameter of the main pancreatic duct (MPD) was 4.93 mm (SD ±2.17), and the mean estimated intraoperative blood loss was 1005.4 mL (SD ±516.23). Table 3 shows the approach used for pancreaticoduodenectomy Incidence and Classification of POPF A total of 8 patients (24.24%) developed a biochemical leak. Clinically relevant postoperative pancreatic fistula (CR-POPF), defined as ISGPS Grade B or C, occurred in 6 patients (18.18%): 3 (9.09%) with Grade B and 3 (9.09%) with Grade C. Table 4: description of POPF incidence showing clinical relevant fistula Risk Factor Analysis Univariate analysis did not show a significant relationship between POPF (CR-POPF) and any of the clinical or intraoperative variables studied, including age (p = 0.49), BMI (p = 0.82), serum albumin (p = 0.72), or MPD diameter (p = 0.10). Multivariate logistic regression similarly revealed no statistically significant predictors of POPF, with all variables having p-values > 0.05. 30-day mortality was 9,09%(3/33). Rest of the patients are alive and under surveillance. Discussion Postoperative pancreatic fistula (POPF) remains a persistent challenge in pancreatic surgery, contributing to prolonged hospitalization, increased costs, and higher morbidity. In our series of 33 consecutive pancreaticoduodenectomies (PDs), the incidence of clinically relevant POPF (CR-POPF; Grade B and C) was 18.18%, with an additional 24.24% of patients developing biochemical leaks. These findings align closely with those reported in major series using the ISGPS 2016 definition, which estimate CR-POPF rates ranging from 10% to 25% depending on patient population and institutional volume (1,2). Several studies have attempted to identify predisposing factors for POPF, including soft pancreatic texture, small duct diameter, high BMI, intraoperative blood loss, and low preoperative albumin levels (3–6). However, similar to the findings of Sahakyan et al., our analysis did not identify any significant association between these variables and POPF development (7). This lack of predictive clarity reinforces the concept that POPF results from a complex interplay of patient, disease, and technical factors (8,9). The mean main pancreatic duct (MPD) diameter in our cohort was 4.93 mm, which falls near the commonly cited 3–5 mm threshold associated with increased leak risk (10). While a trend toward significance was noted (p = 0.10), the association was not statistically robust. Prior work by Roberts et al. and Callery et al. incorporated duct size into risk scoring systems such as the Fistula Risk Score (FRS), highlighting the relevance of this parameter (11,12). Yet, our findings underscore that MPD diameter alone may not be a reliable predictor, particularly in heterogeneous real-world populations. Additionally, our study found no correlation between POPF and other potential risk factors such as BMI or serum albumin. This contrasts with results from several prospective cohorts where low albumin was a consistent predictor of poor outcomes (13,14). The relatively small sample size in our study likely contributed to this discrepancy and limited the power to detect modest associations. The distribution of POPF grades in our cohort was evenly split between Grade B and C, with three patients in each category. Grade C fistulas carry significantly higher morbidity and may require reoperation, total parenteral nutrition, or interventional radiology support (15). While our dataset does not allow for robust analysis of outcomes based on POPF grade, the equal distribution highlights the potential severity of this complication and the importance of vigilant monitoring and early intervention. Interestingly, our observed biochemical leak rate (24.24%) was higher than some reported series, which may reflect institutional differences in drain management and surveillance protocols (16). ISGPS 2016 guidelines define biochemical leaks as clinically insignificant; however, they still necessitate careful follow-up to ensure they do not progress to CR-POPF (3,17). Finally, while most surgeries in our cohort were performed via open approach (97%), one laparoscopic case was included. The role of minimally invasive pancreatic surgery in reducing POPF remains controversial. Some meta-analyses have reported comparable or even reduced rates of POPF with laparoscopic PD in high-volume centers (18,19), though this has not been universally reproduced. Our single laparoscopic case precludes meaningful conclusions but highlights a potential area for further exploration. Limitations: This study is limited by its retrospective design, small sample size, and single-center scope. Additionally, we did not account for certain operative variables such as gland texture or anastomotic technique details, both of which are known POPF modifiers (20). Despite these limitations, our data add to the growing literature suggesting the multifactorial and sometimes unpredictable nature of POPF. Declarations Ethics approval and consent to participate This study was approved by the Institutional Ethics Committee (ECARP: Ethics Committee for Academic Projects) of TNMC and BYL Nair Ch. Hospital (Approval No: ECARP/2022/154). Written informed consent was obtained from all participants prior to inclusion in the study. Consent for publication Not applicable, as no identifying information of participants is included in this manuscript. Availability of data and materials The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors’ contributions Dr. Dimpy Ajit Shah : Conceptualization, methodology, data collection Dr. Harsh Jayeshkumar Barot: Data curation, validation, analysis, manuscript writing, statistical analysis Dr. Rajendra Habib: results interpretation, manuscript editing. Dr. Nitin Ashok Borle : Supervision, project administration, final approval of manuscript. All authors have read and approved the final manuscript. Acknowledgements The authors would like to thank the surgical team, nursing staff, and data management unit of [Institution Name] for their invaluable support in conducting this study. References Bassi C, Marchegiani G, Dervenis C, et al. The 2016 update of the ISGPS definition and grading of postoperative pancreatic fistula. Surgery. 2017;161(3):584–591. Kawai M, Tani M, Hirono S, et al. Risk factors for clinically relevant POPF after PD: a large single-center study. World J Surg. 2009;33(12):2670–2678. Callery MP, Pratt WB, Kent TS, et al. A prospectively validated clinical risk score accurately predicts POPF after PD. J Am Coll Surg. 2013;216(1):1–14. Roberts KJ, Sutcliffe RP, Marudanayagam R, et al. Scoring system to predict pancreatic fistula after pancreaticoduodenectomy. Ann Surg. 2012;256(6):1059–1067. Sahakyan MA, et al. Predictors of clinically relevant POPF: analysis of 110 patients. HPB. 2021;23(5):665–672. De Pastena M, Marchegiani G, Paiella S, et al. Impact of BMI on surgical outcomes after pancreatic resection. Br J Surg. 2019;106(12):1552–1560. Van Buren G, Bloomston M, Hughes SJ, et al. A prospective multicenter trial of PD with high-risk features. Ann Surg. 2014;259(4):702–708. Pedrazzoli S. Pancreatic fistula: review of risk factors and prevention strategies. World J Gastroenterol. 2015;21(4):929–943. Andrianello S, Marchegiani G, Malleo G, et al. Intraoperative factors influencing POPF in PD: an observational study. Surgery. 2017;162(1):43–52. Hackert T, Werner J, Weitz J, et al. Unrecognized risk factors for POPF. Ann Surg Oncol. 2011;18(6):1620–1628. Adham M, et al. Standardized classification of surgical complications after pancreatic resection. HPB. 2011;13(8):584–589. Andren-Sandberg A, Ansorge C. State-of-the-art management of POPF. Scand J Surg. 2012;101(3):165–172. Rungsakulkij N, et al. The impact of serum albumin on pancreatic anastomotic failure. BMC Gastroenterol. 2020;20(1):1–7. Bellin MD, et al. Preoperative nutrition in high-risk pancreas surgery. Nutr Clin Pract. 2015;30(4):507–513. Pratt WB, et al. Clinical outcomes of Grade C pancreatic fistula. J Gastrointest Surg. 2007;11(12):1640–1646. McMillan MT, et al. Drain management after pancreatic resection: a meta-analysis. J Gastrointest Surg. 2015;19(11):1919–1927. Jang JY, et al. What is the significance of a biochemical leak after PD? Surgery. 2018;163(3):554–560. Poves I, et al. Laparoscopic vs. open PD in a high-volume center: a randomized trial. Ann Surg. 2018;268(5):731–738. Zureikat AH, et al. Minimally invasive PD in 500 consecutive patients. Ann Surg. 2019;270(4):612–621. Ansorge C, et al. Pancreatic anastomosis technique and POPF: a systematic review. HPB. 2012;14(8):500–507. Tables Tables 1 to 4 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files whipples.csv Table1234.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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Despite significant advances in perioperative care, surgical technique, and patient selection, the procedure is still associated with considerable morbidity, the most feared and common complication being the postoperative pancreatic fistula (POPF).\u003c/p\u003e\u003cp\u003ePOPF is defined as an abnormal communication between the pancreatic ductal system and another epithelialized surface containing pancreatic secretions. It can result in intra-abdominal collections, hemorrhage, sepsis, and prolonged hospital stays, severely impacting patient recovery and healthcare costs. The reported incidence of POPF varies widely, ranging from 5% to 30% depending on patient risk factors, gland characteristics, and institutional volume and expertise (1\u0026ndash;3).\u003c/p\u003e\u003cp\u003eIn 2016, the International Study Group on Pancreatic Surgery (ISGPS) updated its definition and classification of POPF to distinguish clinically relevant fistulas (Grade B and C) from asymptomatic biochemical leaks (4). This revision aimed to standardize outcome reporting and guide clinical decision-making, enabling better stratification and management of patients. Since then, numerous studies have explored risk factors and predictive models for POPF, identifying gland texture, small main pancreatic duct (MPD) diameter, elevated BMI, and hypoalbuminemia as key contributors (5\u0026ndash;8).\u003c/p\u003e\u003cp\u003eAmong these, the combination of a soft pancreas and a non-dilated duct is consistently highlighted as a high-risk configuration. Several risk scoring systems, such as the Fistula Risk Score (FRS), have attempted to integrate these and other intraoperative variables to predict POPF development with varying success (9,10). Nonetheless, despite these tools and a growing body of literature, the ability to precisely predict and prevent POPF remains limited.\u003c/p\u003e\u003cp\u003eAdditionally, there remains institutional variability in surgical approach (open vs. minimally invasive), pancreatoenteric anastomotic techniques (duct-to-mucosa vs. invagination), use of intraoperative drains, and perioperative management protocols. These factors contribute to differences in POPF rates and may confound the identification of consistent predictors across patient populations (11\u0026ndash;13).\u003c/p\u003e\u003cp\u003eThe present study was conducted to assess the incidence of POPF using ISGPS 2016 criteria in a contemporary cohort undergoing PD at a tertiary care center. Furthermore, we aimed to explore associations between POPF and various demographic, clinical, and intraoperative variables, thereby evaluating the generalizability of previously reported risk factors in our institutional setting.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eStudy Design and Setting\u003c/p\u003e\n\u003cp\u003eThis was a retrospective observational study conducted at the Department of General Surgery, BYL Nair Charitable hospital and TNMC, tertiary care academic referral center in Mumbai. The study was approved by the Institutional Ethics Committee and conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all patients prior to inclusion in the study. Participants were informed about the nature and purpose of the research, and their voluntary participation was ensured.\u003c/p\u003e\n\u003cp\u003eFunding\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003ePatient Selection\u003c/p\u003e\n\u003cp\u003eWe reviewed the records of 33 consecutive patients who underwent pancreaticoduodenectomy (PD) between 2022 and 2024. All patients underwent surgery with curative intent for periampullary or pancreatic head lesions. Exclusion criteria included:\u003c/p\u003e\n\u003cp\u003ePalliative procedures or bypass surgeries without PD\u003c/p\u003e\n\u003cp\u003eRedo surgeries\u003c/p\u003e\n\u003cp\u003eIncomplete or missing medical records\u003c/p\u003e\n\u003cp\u003eOnly patients undergoing upfront surgery (no neoadjuvant therapy) were included to maintain a uniform cohort.\u003c/p\u003e\n\u003cp\u003eClinical trial number: not applicable.\u003c/p\u003e\n\u003cp\u003eData Collection\u003c/p\u003e\n\u003cp\u003ePatient data were extracted from electronic medical records, operative notes, and postoperative charts. The following parameters were recorded:\u003c/p\u003e\n\u003cp\u003eDemographic and Clinical Variables:\u003c/p\u003e\n\u003cp\u003eAge\u003c/p\u003e\n\u003cp\u003eSex\u003c/p\u003e\n\u003cp\u003eBody mass index (BMI)\u003c/p\u003e\n\u003cp\u003eWeight\u003c/p\u003e\n\u003cp\u003eSerum albumin (preoperative, within 2 weeks before surgery)\u003c/p\u003e\n\u003cp\u003eComorbidities (e.g., diabetes, hypertension)\u003c/p\u003e\n\u003cp\u003eSurgical and Intraoperative Details:\u003c/p\u003e\n\u003cp\u003eIndication for surgery (final histopathological diagnosis)\u003c/p\u003e\n\u003cp\u003eOperative approach (open or laparoscopic)\u003c/p\u003e\n\u003cp\u003eMain pancreatic duct (MPD) diameter (measured intraoperatively or radiologically)\u003c/p\u003e\n\u003cp\u003eEstimated intraoperative blood loss\u003c/p\u003e\n\u003cp\u003ePancreatic texture (soft or firm, as documented by the surgeon)\u003c/p\u003e\n\u003cp\u003ePostoperative Outcomes:\u003c/p\u003e\n\u003cp\u003eDevelopment of postoperative pancreatic fistula (POPF)\u003c/p\u003e\n\u003cp\u003ePOPF classification using ISGPS 2016 guidelines:\u003c/p\u003e\n\u003cp\u003eBiochemical leak: Elevated amylase in drain fluid on or after postoperative day 3 without clinical impact\u003c/p\u003e\n\u003cp\u003eGrade B: POPF requiring a change in clinical management (e.g., antibiotics, prolonged drainage, or percutaneous intervention)\u003c/p\u003e\n\u003cp\u003eGrade C: POPF with severe clinical sequelae including reoperation, organ failure, or death\u003c/p\u003e\n\u003cp\u003eLength of hospital stay\u003c/p\u003e\n\u003cp\u003eSurgical site infections or other complications\u003c/p\u003e\n\u003cp\u003eSurgical Technique\u003c/p\u003e\n\u003cp\u003eA standard Whipple procedure was performed in all cases. The pancreas was transected at the neck, and pancreatojejunostomy was performed using either duct-to-mucosa or invagination technique based on intraoperative assessment. A single-surgeon or multi-consultant team approach was employed. Closed-suction drains were routinely placed near the pancreatic and biliary anastomoses and monitored for output and amylase content from postoperative day 1 onward.\u003c/p\u003e\n\u003cp\u003ePOPF Diagnosis and Monitoring\u003c/p\u003e\n\u003cp\u003eDrain fluid was routinely analyzed for amylase on postoperative day (POD) 3, and earlier if clinically indicated. POPF was diagnosed and graded per the ISGPS 2016 classification. Patients with biochemical leaks were managed conservatively. Grade B and C fistulas were treated with antibiotics, nutritional support, radiological drainage, or reoperation based on severity.\u003c/p\u003e\n\u003cp\u003eStatistical Analysis\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed using statistical software R version R 4.3.2. Continuous variables were expressed as means \u0026plusmn; standard deviations (SD) or medians with interquartile ranges (IQR), as appropriate. Categorical variables were reported as frequencies and percentages.\u003c/p\u003e\n\u003cp\u003eUnivariate Analysis:\u003c/p\u003e\n\u003cp\u003eTo assess associations between variables and clinically relevant POPF (Grade B or C), we used:\u003c/p\u003e\n\u003cp\u003eChi-square test or Fisher\u0026rsquo;s exact test for categorical variables\u003c/p\u003e\n\u003cp\u003eStudent\u0026rsquo;s t-test or Mann\u0026ndash;Whitney U test for continuous variables\u003c/p\u003e\n\u003cp\u003eMultivariate Analysis:\u003c/p\u003e\n\u003cp\u003eVariables with p \u0026lt; 0.10 in univariate analysis were entered into a binary logistic regression model to identify independent predictors of POPF. A p-value \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003ePatient Demographics and Clinical Characteristics\u003c/p\u003e\n\u003cp\u003eThe study included 33 patients who underwent pancreaticoduodenectomy (PD). The mean age was 51 years (SD \u0026plusmn;10.56), with 42.4% (n=14) being female. The mean weight was 58.9 kg (SD \u0026plusmn;9.90), and the median body mass index (BMI) was 24.01 (IQR 2.5).\u003c/p\u003e\n\u003cp\u003eTable 1 shows baseline characteristics of patients\u003c/p\u003e\n\u003cp\u003e*Albumin levels were not significantly associated with POPF in univariate analysis (p = 0.72).\u003c/p\u003e\n\u003cp\u003eSurgical Indications and Intraoperative Details\u003c/p\u003e\n\u003cp\u003eAmpullary carcinoma was the most frequent indication for PD (39.39%), followed by duodenal carcinoma (33.33%), distal cholangiocarcinoma (27.27%), and pancreatic adenocarcinoma (6.06%).\u003c/p\u003e\n\u003cp\u003eTable 2 shows distribution of diagnosis across cases of periampullary cancer\u003c/p\u003e\n\u003cp\u003eA standard open approach was used in 32 cases (97.0%), and one patient (3.0%) underwent laparoscopic PD. The mean diameter of the main pancreatic duct (MPD) was 4.93 mm (SD \u0026plusmn;2.17), and the mean estimated intraoperative blood loss was 1005.4 mL (SD \u0026plusmn;516.23).\u003c/p\u003e\n\u003cp\u003eTable 3 shows the approach used for pancreaticoduodenectomy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIncidence and Classification of POPF\u003c/p\u003e\n\u003cp\u003eA total of 8 patients (24.24%) developed a biochemical leak. Clinically relevant postoperative pancreatic fistula (CR-POPF), defined as ISGPS Grade B or C, occurred in 6 patients (18.18%): 3 (9.09%) with Grade B and 3 (9.09%) with Grade C.\u003c/p\u003e\n\u003cp\u003eTable 4: description of POPF incidence showing clinical relevant fistula\u003c/p\u003e\n\u003cp\u003eRisk Factor Analysis\u003c/p\u003e\n\u003cp\u003eUnivariate analysis did not show a significant relationship between POPF (CR-POPF) and any of the clinical or intraoperative variables studied, including age (p = 0.49), BMI (p = 0.82), serum albumin (p = 0.72), or MPD diameter (p = 0.10). Multivariate logistic regression similarly revealed no statistically significant predictors of POPF, with all variables having p-values \u0026gt; 0.05.\u003c/p\u003e\n\u003cp\u003e30-day mortality was 9,09%(3/33). Rest of the patients are alive and under surveillance.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePostoperative pancreatic fistula (POPF) remains a persistent challenge in pancreatic surgery, contributing to prolonged hospitalization, increased costs, and higher morbidity. In our series of 33 consecutive pancreaticoduodenectomies (PDs), the incidence of clinically relevant POPF (CR-POPF; Grade B and C) was 18.18%, with an additional 24.24% of patients developing biochemical leaks. These findings align closely with those reported in major series using the ISGPS 2016 definition, which estimate CR-POPF rates ranging from 10% to 25% depending on patient population and institutional volume (1,2).\u003c/p\u003e\n\n\u003cp\u003eSeveral studies have attempted to identify predisposing factors for POPF, including soft pancreatic texture, small duct diameter, high BMI, intraoperative blood loss, and low preoperative albumin levels (3\u0026ndash;6). However, similar to the findings of Sahakyan et al., our analysis did not identify any significant association between these variables and POPF development (7). This lack of predictive clarity reinforces the concept that POPF results from a complex interplay of patient, disease, and technical factors (8,9).\u003c/p\u003e\n\n\u003cp\u003eThe mean main pancreatic duct (MPD) diameter in our cohort was 4.93 mm, which falls near the commonly cited 3\u0026ndash;5 mm threshold associated with increased leak risk (10). While a trend toward significance was noted (p = 0.10), the association was not statistically robust. Prior work by Roberts et al. and Callery et al. incorporated duct size into risk scoring systems such as the Fistula Risk Score (FRS), highlighting the relevance of this parameter (11,12). Yet, our findings underscore that MPD diameter alone may not be a reliable predictor, particularly in heterogeneous real-world populations.\u003c/p\u003e\n\n\u003cp\u003eAdditionally, our study found no correlation between POPF and other potential risk factors such as BMI or serum albumin. This contrasts with results from several prospective cohorts where low albumin was a consistent predictor of poor outcomes (13,14). The relatively small sample size in our study likely contributed to this discrepancy and limited the power to detect modest associations.\u003c/p\u003e\n\n\u003cp\u003eThe distribution of POPF grades in our cohort was evenly split between Grade B and C, with three patients in each category. Grade C fistulas carry significantly higher morbidity and may require reoperation, total parenteral nutrition, or interventional radiology support (15). While our dataset does not allow for robust analysis of outcomes based on POPF grade, the equal distribution highlights the potential severity of this complication and the importance of vigilant monitoring and early intervention.\u003c/p\u003e\n\n\u003cp\u003eInterestingly, our observed biochemical leak rate (24.24%) was higher than some reported series, which may reflect institutional differences in drain management and surveillance protocols (16). ISGPS 2016 guidelines define biochemical leaks as clinically insignificant; however, they still necessitate careful follow-up to ensure they do not progress to CR-POPF (3,17).\u003c/p\u003e\n\n\u003cp\u003eFinally, while most surgeries in our cohort were performed via open approach (97%), one laparoscopic case was included. The role of minimally invasive pancreatic surgery in reducing POPF remains controversial. Some meta-analyses have reported comparable or even reduced rates of POPF with laparoscopic PD in high-volume centers (18,19), though this has not been universally reproduced. Our single laparoscopic case precludes meaningful conclusions but highlights a potential area for further exploration.\u003c/p\u003e\n\n\u003cp\u003eLimitations: This study is limited by its retrospective design, small sample size, and single-center scope. Additionally, we did not account for certain operative variables such as gland texture or anastomotic technique details, both of which are known POPF modifiers (20). Despite these limitations, our data add to the growing literature suggesting the multifactorial and sometimes unpredictable nature of POPF.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;This study was approved by the Institutional Ethics Committee (ECARP: Ethics Committee for Academic Projects) of TNMC and BYL Nair Ch. Hospital (Approval No: ECARP/2022/154). Written informed consent was obtained from all participants prior to inclusion in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Not applicable, as no identifying information of participants is included in this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eDr. Dimpy Ajit Shah\u003c/strong\u003e: Conceptualization, methodology, data collection\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eDr. Harsh Jayeshkumar Barot:\u0026nbsp;\u003c/strong\u003eData curation, validation, analysis, manuscript writing, statistical analysis\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eDr. Rajendra Habib:\u0026nbsp;\u003c/strong\u003e results interpretation, manuscript editing.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eDr. Nitin Ashok Borle\u0026nbsp;\u003c/strong\u003e: Supervision, project administration, final approval of manuscript.\u003cbr\u003e\u0026nbsp;All authors have read and approved the final manuscript.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The authors would like to thank the surgical team, nursing staff, and data management unit of [Institution Name] for their invaluable support in conducting this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eBassi C, Marchegiani G, Dervenis C, et al. The 2016 update of the ISGPS definition and grading of postoperative pancreatic fistula. Surgery. 2017;161(3):584\u0026ndash;591.\u003c/li\u003e\n \u003cli\u003eKawai M, Tani M, Hirono S, et al. Risk factors for clinically relevant POPF after PD: a large single-center study. World J Surg. 2009;33(12):2670\u0026ndash;2678.\u003c/li\u003e\n \u003cli\u003eCallery MP, Pratt WB, Kent TS, et al. A prospectively validated clinical risk score accurately predicts POPF after PD. J Am Coll Surg. 2013;216(1):1\u0026ndash;14.\u003c/li\u003e\n \u003cli\u003eRoberts KJ, Sutcliffe RP, Marudanayagam R, et al. Scoring system to predict pancreatic fistula after pancreaticoduodenectomy. Ann Surg. 2012;256(6):1059\u0026ndash;1067.\u003c/li\u003e\n \u003cli\u003eSahakyan MA, et al. Predictors of clinically relevant POPF: analysis of 110 patients. HPB. 2021;23(5):665\u0026ndash;672.\u003c/li\u003e\n \u003cli\u003eDe Pastena M, Marchegiani G, Paiella S, et al. Impact of BMI on surgical outcomes after pancreatic resection. Br J Surg. 2019;106(12):1552\u0026ndash;1560.\u003c/li\u003e\n \u003cli\u003eVan Buren G, Bloomston M, Hughes SJ, et al. A prospective multicenter trial of PD with high-risk features. Ann Surg. 2014;259(4):702\u0026ndash;708.\u003c/li\u003e\n \u003cli\u003ePedrazzoli S. Pancreatic fistula: review of risk factors and prevention strategies. World J Gastroenterol. 2015;21(4):929\u0026ndash;943.\u003c/li\u003e\n \u003cli\u003eAndrianello S, Marchegiani G, Malleo G, et al. Intraoperative factors influencing POPF in PD: an observational study. Surgery. 2017;162(1):43\u0026ndash;52.\u003c/li\u003e\n \u003cli\u003eHackert T, Werner J, Weitz J, et al. Unrecognized risk factors for POPF. Ann Surg Oncol. 2011;18(6):1620\u0026ndash;1628.\u003c/li\u003e\n \u003cli\u003eAdham M, et al. Standardized classification of surgical complications after pancreatic resection. HPB. 2011;13(8):584\u0026ndash;589.\u003c/li\u003e\n \u003cli\u003eAndren-Sandberg A, Ansorge C. State-of-the-art management of POPF. Scand J Surg. 2012;101(3):165\u0026ndash;172.\u003c/li\u003e\n \u003cli\u003eRungsakulkij N, et al. The impact of serum albumin on pancreatic anastomotic failure. BMC Gastroenterol. 2020;20(1):1\u0026ndash;7.\u003c/li\u003e\n \u003cli\u003eBellin MD, et al. Preoperative nutrition in high-risk pancreas surgery. Nutr Clin Pract. 2015;30(4):507\u0026ndash;513.\u003c/li\u003e\n \u003cli\u003ePratt WB, et al. Clinical outcomes of Grade C pancreatic fistula. J Gastrointest Surg. 2007;11(12):1640\u0026ndash;1646.\u003c/li\u003e\n \u003cli\u003eMcMillan MT, et al. Drain management after pancreatic resection: a meta-analysis. J Gastrointest Surg. 2015;19(11):1919\u0026ndash;1927.\u003c/li\u003e\n \u003cli\u003eJang JY, et al. What is the significance of a biochemical leak after PD? Surgery. 2018;163(3):554\u0026ndash;560.\u003c/li\u003e\n \u003cli\u003ePoves I, et al. Laparoscopic vs. open PD in a high-volume center: a randomized trial. Ann Surg. 2018;268(5):731\u0026ndash;738.\u003c/li\u003e\n \u003cli\u003eZureikat AH, et al. Minimally invasive PD in 500 consecutive patients. Ann Surg. 2019;270(4):612\u0026ndash;621.\u003c/li\u003e\n \u003cli\u003eAnsorge C, et al. Pancreatic anastomosis technique and POPF: a systematic review. HPB. 2012;14(8):500\u0026ndash;507.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 4 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7386858/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7386858/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) remains a significant complication following pancreaticoduodenectomy (PD). This study evaluates the incidence and risk factors associated with POPF in a cohort of consecutive PDs using the ISGPS 2016 definition.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003e A retrospective review was performed on 33 consecutive patients undergoing upfront PD between 2022 and 2024 at a tertiary center. Clinical and operative data were collected. POPF was defined and graded per ISGPS 2016. Univariate and multivariate analyses assessed associations with clinically relevant POPF (Grade B/C).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eMean age was 51 years (SD\u0026thinsp;\u0026plusmn;\u0026thinsp;10.56), and 42.4% were female. The most common indication was ampullary carcinoma (39.39%). Open PD was performed in 97% of cases. Mean MPD diameter was 4.93 mm (SD\u0026thinsp;\u0026plusmn;\u0026thinsp;2.17), with average blood loss of 1005.4 mL (SD\u0026thinsp;\u0026plusmn;\u0026thinsp;516.23). Clinically relevant POPF occurred in 18.18% (n\u0026thinsp;=\u0026thinsp;6), equally distributed between Grades B and C. Biochemical leaks were seen in 24.24% (n\u0026thinsp;=\u0026thinsp;8). POPF was not significantly associated with age (p\u0026thinsp;=\u0026thinsp;0.49), BMI (p\u0026thinsp;=\u0026thinsp;0.82), albumin (p\u0026thinsp;=\u0026thinsp;0.72), or MPD diameter (p\u0026thinsp;=\u0026thinsp;0.10).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThe rate of clinically relevant POPF was 18.18%. No significant preoperative or intraoperative predictors were identified. These findings support the multifactorial nature of POPF and the importance of continued refinement in surgical and perioperative strategies.\u003c/p\u003e","manuscriptTitle":"Postoperative Pancreatic Fistula in 33 Consecutive Pancreaticoduodenectomies: Experience at a Tertiary Center","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-13 13:53:14","doi":"10.21203/rs.3.rs-7386858/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3145a47d-8db9-4867-85f8-24d9bed6c91a","owner":[],"postedDate":"October 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-28T18:15:37+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-13 13:53:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7386858","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7386858","identity":"rs-7386858","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}