Polymicrobial Bacteriobilia Is Associated with 90-Day Mortality After PancreaticoduodenectomyABSTRACT
Introduction: Bacteriobilia is common in patients undergoing pancreaticoduodenectomy (PD), particularly after preoperative biliary drainage. Its impact on perioperative outcomes and extended early mortality remains controversial. This study evaluated the association between intraoperative bile cultures and early postoperative outcomes following PD for periampullary tumors.
Methods: This retrospective cohort study included 176 patients who underwent PD with intraoperative bile culture between 2013 and 2024 at a tertiary center. Patients were stratified according to bacteriobilia status. Perioperative variables, postoperative complications (Clavien-Dindo classification), and mortality at 30, 60, and 90 days were analyzed. Multivariable logistic regression identified independent predictors of bacteriobilia and early mortality.
Results: Bacteriobilia was detected in 146 patients (83%), with 70% presenting polymicrobial cultures. Preoperative ERCP (OR 23.48; 95% CI 6.47-85.22; p<0.001) and biliary stent placement (OR 8.78; 95% CI 1.98-38.86; p=0.004) independently predicted bacteriobilia. Overall mortality was 12.5% at 30 days, 16.0% at 60 days, and 16.5% at 90 days. Bacteriobilia per se was not associated with increased major morbidity or mortality. However, polymicrobial bile cultures were independently associated with higher mortality at 60 (OR 2.32; 95% CI 1.35-3.88; p=0.004) and 90 days (OR 20.07; 95% CI 1.32-304.81; p=0.031), after adjustment for vascular resection, bleeding, transfusion, and severe complications.
Conclusions: Although bacteriobilia is highly prevalent after preoperative biliary drainage, it does not independently worsen perioperative outcomes. Polymicrobial bile cultures were associated with increased 60- and 90-day mortality and may identify a subgroup of patients with greater biological and perioperative complexity, highlighting the importance of microbiological stratification and extended mortality assessment after PD.
Keywords:
Pancreaticoduodenectomy; Bacteriobilia; Biliary Tract Infections; Cholangiopancreatography, Endoscopic Retrograde; Postoperative Complications
RESUMO
Introdução: A bacteriobilia é comum em pacientes submetidos à duodenopancreatectomia (DP), especialmente após drenagem biliar pré-operatória. Seu impacto sobre os desfechos perioperatórios e a mortalidade precoce estendida permanece controverso. Este estudo avaliou a associação entre culturas de bile obtidas no intraoperatório e os desfechos pós-operatórios precoces após DP por tumores periampulares.
Métodos: Este estudo de coorte retrospectivo incluiu 176 pacientes submetidos à DP com coleta de cultura de bile no intraoperatório entre 2013 e 2024, em um centro terciário. Os pacientes foram estratificados de acordo com a presença de bacteriobilia. Foram analisadas variáveis perioperatórias, complicações pós-operatórias (classificação de Clavien-Dindo) e mortalidade em 30, 60 e 90 dias. Modelos de regressão logística multivariada foram utilizados para identificar preditores independentes de bacteriobilia e de mortalidade precoce.
Resultados: Bacteriobilia foi identificada em 146 pacientes (83%), dos quais 70% apresentaram culturas polimicrobianas. A colangiopancreatografia retrógrada endoscópica (CPRE) pré-operatória (OR 23,48; IC95% 6,47-85,22; p<0,001) e a colocação de prótese biliar (OR 8,78; IC95% 1,98-38,86; p=0,004) foram preditores independentes de bacteriobilia. A mortalidade global foi de 12,5% em 30 dias, 16,0% em 60 dias e 16,5% em 90 dias. A bacteriobilia, isoladamente, não esteve associada ao aumento da morbidade maior ou da mortalidade. Entretanto, culturas de bile polimicrobianas foram independentemente associadas à maior mortalidade em 60 dias (OR 2,32; IC95% 1,35-3,88; p=0,004) e em 90 dias (OR 20,07; IC95% 1,32-304,81; p=0,031), após ajuste para ressecção vascular, sangramento, transfusão e complicações graves.
Conclusões: Embora a bacteriobilia seja altamente prevalente após drenagem biliar pré-operatória, ela não piora de forma independente os desfechos perioperatórios. Em contrapartida, culturas de bile polimicrobianas estiveram associadas ao aumento da mortalidade em 60 e 90 dias, podendo identificar um subgrupo de pacientes com maior complexidade biológica e perioperatória, ressaltando a importância da estratificação microbiológica e da avaliação da mortalidade estendida após a duodenopancreatectomia.
Palavras-chave:
Duodenopancreatectomia; Bacteriobilia; Infecções das Vias Biliares; Colangiopancreatografia Retrógrada Endoscópica; Complicações Pós-Operatórias
INTRODUCTION
Periampullary neoplasms comprise a heterogeneous group of tumors arising near the ampulla of Vater, including pancreatic ductal adenocarcinoma, distal cholangiocarcinoma, duodenal adenocarcinoma, and ampullary carcinoma1-5. Despite their anatomical proximity, these tumors exhibit distinct biological behaviors and prognoses that directly influence surgical outcomes and perioperative risk2,3.
Biliary obstruction is a common manifestation of periampullary tumors and frequently results in obstructive jaundice. Prolonged cholestasis is associated with metabolic, immunological, and hemodynamic disturbances that increase surgical risk and postoperative morbidity6-9. In addition, biliary stasis facilitates bacterial colonization of the biliary tree, increasing the risk of cholangitis and bacteriobilia10-13.
Pancreaticoduodenectomy (PD) remains the standard treatment for most resectable periampullary neoplasms. Although mortality has substantially decreased in high-volume centers, postoperative morbidity remains considerable, particularly among patients with advanced age, comorbidities, malnutrition, and prolonged jaundice1,6-9. Consequently, perioperative infectious factors have gained increasing attention as potential determinants of postoperative outcomes.
Under normal conditions, the biliary tract is considered sterile14,15. However, biliary obstruction, endoscopic manipulation, and biliary drainage procedures-particularly endoscopic retrograde cholangiopancreatography (ERCP) with stent placement-promote bacterial colonization of bile16-19. Several studies have associated bacteriobilia with surgical site infections, intra-abdominal sepsis, pancreatic fistula, bile leakage, and postoperative hemorrhage after PD18-20.
Nevertheless, the clinical impact of bacteriobilia remains controversial. While some studies have reported increased postoperative morbidity, others have not demonstrated a consistent association with early mortality12-15. More recent evidence suggests that microbiological characteristics, particularly polymicrobial and multidrug-resistant bile cultures, may be more relevant than bacteriobilia itself in determining postoperative outcomes and extended mortality16,17. In parallel, 90-day mortality has emerged as a more comprehensive quality indicator than traditional 30-day mortality in pancreatic surgery, as it captures complications occurring beyond the immediate postoperative period5.
Few studies have specifically evaluated the relationship between microbiological complexity (polymicrobial versus monomicrobial bacteriobilia) and extended postoperative mortality after PD. Therefore, the present study aimed to evaluate intraoperative bile culture findings and microbiological profiles in patients undergoing pancreaticoduodenectomy for periampullary neoplasms, correlating these findings with perioperative variables, postoperative outcomes, and mortality at 30, 60, and 90 days.
METHODS
Study Design
This was a retrospective longitudinal cohort study that included patients who underwent pancreaticoduodenectomy at a tertiary-level university hospital between 2013 and 2024. Potential participants were identified through the electronic surgical database and medical records using the keywords “pancreaticoduodenectomy,” “pancreatectomy,” and “duodenectomy”. After initial screening, patients who underwent intraoperative bile collection for microbiological analysis were identified. Both electronic and physical medical records of all eligible patients were reviewed.
Patients were divided into two main groups according to the presence or absence of bacteriobilia, and perioperative and postoperative outcomes were compared between groups. The study protocol was approved by the Research Ethics Committee of the Faculdade de Ciências Médicas - UNICAMP (approval number 6.416.522; CAAE: 73914923.7.0000.5404).
Study Population
Adult patients (≥18 years) of both sexes who underwent pancreaticoduodenectomy, with or without pylorus preservation, for periampullary lesions between 2013 and 2024 who had intraoperative bile collection for microbiological analysis were included.
Exclusion criteria were vulnerable individuals (minors or patients with severe intellectual disabilities), patients who underwent other surgical procedures, those without intraoperative bile culture, and cases with incomplete medical records. Periampullary tumors were defined as neoplasms originating in anatomical sites adjacent to the ampulla of Vater, including the pancreatic head, distal common bile duct, and duodenal papilla.
A total of 338 patients were initially identified, of whom 176 met the inclusion criteria and were included in the final analysis. The main reasons for exclusion were misclassification of surgical procedures under the pancreaticoduodenectomy code and absence of intraoperative bile culture (n = 84). A flowchart depicting patient selection is shown in Figure 1.
Surgical Technique
Pancreaticoduodenectomy was performed via a bilateral subcostal incision following standard oncologic principles. Classic Whipple or pylorus-preserving procedures were undertaken according to tumor characteristics, with vascular resection performed when indicated. Reconstruction was completed using single- or double-loop techniques per institutional protocol.
Study Variables
Demographic, anthropometric, clinical, surgical, laboratory, microbiological, histopathological, and outcome-related variables were analyzed.
Demographic variables included age, sex, and self-reported ethnicity. Anthropometric variables included weight and body mass index (BMI). Clinical and surgical variables comprised comorbidities, tumor-related symptoms, medication use, preoperative biliary drainage and stent placement, preoperative imaging findings, preoperative clinical status assessed by the American Society of Anesthesiologists (ASA) score and ECOG performance status, surgical technique and reconstruction type, perioperative variables (operative time, estimated blood loss, intensive care unit stay, use of vasoactive drugs, mechanical ventilation, length of hospital stay), postoperative complications classified according to the Clavien-Dindo system21, and mortality at 30, 60, and 90 days.
Laboratory variables included pre- and postoperative biochemical results. Microbiological variables included the presence or absence of bacteriobilia. Histopathological variables included tumor site, tumor size, and presence of vascular invasion (arterial, venous, or both). Postoperative follow-up variables included overall survival and disease-free survival.
Primary and Secondary Outcomes
The primary outcome was 90-day postoperative mortality. Secondary outcomes included 30-day mortality, 60-day mortality, major postoperative complications, Clavien-Dindo grade III or higher complications, and factors associated with bacteriobilia.
Preoperative Biliary Drainage
Preoperative biliary drainage was routinely performed in patients admitted with total bilirubin levels ≥15 mg/dL. Drainage was preferentially achieved via endoscopic retrograde cholangiopancreatography (ERCP). Plastic or metallic biliary stents were preferentially used in patients with pancreatic head or distal bile duct tumors. In contrast, patients with ampullary tumors frequently underwent endoscopic sphincterotomy alone without stent placement whenever adequate biliary drainage could be achieved.
Bile Collection
Intraoperative bile cultures were routinely obtained immediately after transection of the common hepatic duct. Bile was directly collected by the operating surgeon into a sterile container and promptly transported to the microbiology laboratory for culture and antimicrobial susceptibility testing. Samples were inoculated onto standard microbiological media, including blood agar and MacConkey agar, and incubated under routine laboratory conditions. Bacterial identification and antimicrobial susceptibility testing were performed using conventional microbiological methods and automated systems routinely employed by the institution. A culture was considered positive when bacterial growth was detected in any culture medium. Culture processing and interpretation followed standardized institutional microbiological protocols throughout the study period.
Antimicrobial Prophylaxis
Perioperative antibiotic prophylaxis was routinely performed with ampicillin-sulbactam. In patients with documented allergy, ciprofloxacin or clindamycin were used according to institutional protocols. Antimicrobial therapy was subsequently adjusted whenever bile culture and susceptibility testing indicated the need for alternative coverage.
Statistical Analysis
Descriptive analysis was performed using frequency tables for categorical variables and measures of central tendency and dispersion (mean, standard deviation, median, minimum, and maximum) for continuous variables. Group comparisons were conducted using the Mann-Whitney or Kruskal-Wallis tests (with Dunn’s post hoc test when applicable) for continuous variables and the chi-square or Fisher’s exact test for categorical variables.
Generalized estimating equations (GEE) with maximum likelihood estimation were used to evaluate the longitudinal evolution of selected outcomes. A significance level of 5% was adopted. Statistical analyses were performed using SAS System for Windows version 9.4 (SAS Institute Inc., Cary, NC, USA) and R version 4.2.2 (The R Foundation for Statistical Computing).
After univariate analysis, multivariate logistic regression models were constructed to identify variables independently associated with outcomes, including variables with p < 0.25 in univariate analysis. Conventional logistic regression was used for all primary multivariable models. Due to the limited number of events and instability of coefficient estimates observed in the 90-day mortality model, ridge-penalized logistic regression and bootstrap resampling were additionally performed as sensitivity analyses. The direction and magnitude of the association between polymicrobial bacteriobilia and 90-day mortality remained consistent across these analyses. Variables with no variability or infinite odds ratios were excluded from final models due to unreliable estimation.
RESULTS
Patient characteristics
A total of 176 patients who underwent pancreaticoduodenectomy for periampullary tumors were included. The cohort had a mean age of 61.2 ± 9.9 years, with 98 women (55.7%) and 78 men (44.3%). Most patients were jaundiced at presentation (90%), and preoperative biliary drainage was performed in 138 cases (79.3%), predominantly by endoscopic retrograde cholangiopancreatography (ERCP). Biliary stents were placed in 107 patients (61%), most commonly plastic stents, whereas metallic stents were reserved for selected cases. Among patients undergoing ERCP, the mean number of procedures was 1.19 ± 0.51 per patient, and the median interval between drainage and pancreaticoduodenectomy was 42 days (IQR 30-64 days). In patients with ampullary tumors, adequate biliary decompression was often achieved by endoscopic sphincterotomy alone, explaining the discrepancy between the number of patients undergoing biliary drainage and those receiving stents.
Vascular resection was required in 50 procedures (28.4%), and the mean operative time was 307 ± 52.7 minutes, with an estimated blood loss of 1,016 ± 742 mL.
The complete description of these data is presented in the Supplementary Material (Table S1).
Prevalence and determinants of bacteriobilia
Intraoperative bile cultures were positive in 146 patients (83%), while 30 patients (17%) had negative cultures. Among positive cultures, 70% were polymicrobial. The most frequently isolated organisms were Escherichia coli, Klebsiella spp., Enterococcus spp., and Enterobacter spp (Supplementary Material - Table S2).
Bacteriobilia was strongly associated with preoperative ERCP (89.6% vs. 30%, p < 0.001) and biliary stent placement (71.9% vs. 6.7%, p < 0.001) (Table 1). In multivariable logistic regression, ERCP (OR = 23.48; 95% CI 6.47-85.22; p < 0.001) and biliary stenting (OR = 8.78; 95% CI 1.98-38.86; p = 0.004) were the only independent predictors of bacteriobilia (Table 2).
Bacteriobilia and perioperative outcomes
The presence of bacteriobilia per se was not associated with increased operative time, blood loss, need for transfusion, reoperation, length of hospital or ICU stay, or overall postoperative morbidity. Rates of major complications (Clavien-Dindo ≥ III) were similar between patients with and without bacteriobilia (34.9% vs. 53.3%, p = 0.06) (Supplementary Table S3). Likewise, bacteriobilia alone was not associated with increased mortality at 30, 60, or 90 days.
Table 3 presents the complete comparison between individuals with or without bacteriobilia regarding perioperative outcomes.
Polymicrobial bile cultures and early mortality
In contrast, polymicrobial bile cultures were significantly associated with worse early outcomes. Patients with polymicrobial bacteriobilia had higher mortality at 30 days (p = 0.0195), 60 days (p = 0.0083), and 90 days (p = 0.0062) (Supplementary Table S4).
After adjustment for major perioperative confounders, including vascular resection, postoperative bleeding, transfusion, and severe complications (Clavien-Dindo ≥ III), polymicrobial bile cultures remained independently associated with mortality at both 60 days (OR = 2.32; 95% CI 1.35-3.88; p = 0.004) and 90 days (OR = 20.07; 95% CI 1.32-304.81; p = 0.031) (Table 4 and Figure 2).
Models adjusted for vascular resection, postoperative bleeding, transfusion, ERCP, and major complications (Clavien-Dindo ≥ III). CI: confidence interval; ERCP: endoscopic retrograde cholangiopancreatography.
Early mortality
Overall mortality rates were 12.5% at 30 days, 16.0% at 60 days, and 16.5% at 90 days. The leading cause of death was septic shock secondary to abdominal complications, including pancreatic, biliary, or enteric fistulas. Other causes included hepatic failure related to vascular thrombosis and hemodynamic complications associated with systemic inflammatory response syndrome.
DISCUSSION
Key findings
In this single-center cohort of patients undergoing pancreaticoduodenectomy for periampullary tumors, bacteriobilia was highly prevalent and strongly associated with preoperative biliary drainage. However, bacteriobilia per se was not associated with worse perioperative outcomes or increased early mortality. In contrast, polymicrobial bile cultures were independently associated with higher mortality at 60 and 90 days, even after adjustment for major surgical and postoperative confounders.
These findings suggest that the clinical impact of biliary contamination is heterogeneous and that microbiological characteristics, rather than the mere presence of bacteriobilia, may identify a subgroup of patients at increased risk of adverse postoperative outcomes, consistent with previous reports evaluating extended mortality after pancreatic surgery22-25.
Bacteriobilia and perioperative outcomes
The overall rate of bacteriobilia observed in this study (83%) is higher than that reported in several international series, likely reflecting the high prevalence of obstructive jaundice and preoperative biliary drainage among patients referred to tertiary centers in settings where access to specialized care may be delayed26-30. Despite this high prevalence, bacteriobilia alone was not associated with increased rates of major postoperative complications, surgical site infection, or early mortality.
Previous studies have reported conflicting results regarding the impact of bacteriobilia on postoperative outcomes, often analyzing bile contamination as a binary variable31-33. Our findings suggest that this approach may not fully capture the complexity of biliary microbial colonization and may partially explain the heterogeneity observed across studies.
Polymicrobial bile cultures and early mortality
A key finding of the present study is the observed independent association between polymicrobial bile cultures and mortality at 60 and 90 days, although the latter estimate should be interpreted cautiously given the limited number of events. While early (30-day) mortality appeared to be predominantly related to intraoperative factors, such as vascular resection and major bleeding, later mortality seemed to reflect the cumulative impact of postoperative complications and physiological stress.
These findings are consistent with previous studies demonstrating that polymicrobial or multidrug-resistant bacteriobilia is associated with increased postoperative morbidity and prolonged recovery following pancreatic surgery34-41. Although the underlying mechanisms were not directly evaluated in the present study, polymicrobial colonization may reflect prolonged biliary obstruction, repeated endoscopic manipulation, or other factors associated with greater perioperative complexity.
Importantly, polymicrobial bacteriobilia remained independently associated with mortality after adjustment for surgical complexity and severe postoperative complications, suggesting that it may represent a marker of increased biological and perioperative vulnerability rather than a direct causal determinant of adverse outcomes.
Early versus 90-day mortality as a quality metric
The distinction between 30-day and 90-day mortality is particularly relevant in pancreatic surgery. In our cohort, mortality beyond 30 days appeared to reflect the cumulative impact of postoperative complications and physiological stress rather than isolated intraoperative events. These findings support previous reports demonstrating that 90-day mortality provides a more comprehensive assessment of surgical quality after pancreaticoduodenectomy than traditional 30-day metrics42,43.
Preoperative biliary drainage and clinical implications
Preoperative biliary drainage was strongly associated with bacteriobilia and polymicrobial colonization, corroborating previous reports34-41. However, in the present study, the absence of biliary drainage was also associated with increased mortality at 60 and 90 days, suggesting that severe untreated cholestasis may carry its own risks in selected patients.
These findings highlight the importance of individualized decision-making regarding preoperative biliary drainage, particularly in populations with delayed diagnosis, advanced jaundice, and limited physiological reserve, as frequently observed in developing healthcare systems26,27. While several studies advocate immediate surgery in selected patients30-32, our results suggest that, in high-risk settings, preoperative drainage may mitigate some of the adverse effects associated with prolonged cholestasis.
Clinical interpretation and antibiotic considerations
The association between polymicrobial bacteriobilia and adverse outcomes highlights the potential value of microbiological assessment in perioperative management. Previous studies have reported increased morbidity and infectious complications among patients with polymicrobial or multidrug-resistant bile cultures28,29,38,39.
Although our study was not designed to evaluate antimicrobial strategies, these findings support the continued investigation of individualized perioperative approaches in high-risk patients and reinforce the potential role of intraoperative bile cultures in postoperative clinical decision-making.
Limitations
This study has limitations inherent to its retrospective design, including potential selection bias and limited ability to infer causality. The single-center nature of the cohort may restrict generalizability, particularly to institutions with different referral patterns or drainage policies. In addition, bile cultures were qualitative, and bacterial load, microbial ecology, and biofilm-related characteristics were not evaluated. Although this study covered an extended period, institutional protocols regarding bile collection, perioperative antibiotic prophylaxis, and postoperative management remained largely unchanged, minimizing the potential impact of temporal practice variations on the observed results. Another limitation is the instability of the effect estimate for the association between polymicrobial bacteriobilia and 90-day mortality, reflected by the wide confidence interval. This likely resulted from the limited number of mortality events available for multivariable analysis. Although ridge-penalized regression and bootstrap resampling were performed as sensitivity analyses and yielded consistent results, residual statistical uncertainty remains. Therefore, this finding should be interpreted cautiously and considered hypothesis-generating.
Despite these limitations, the observed association between polymicrobial bacteriobilia and extended postoperative mortality remained consistent across sensitivity analyses and may warrant further investigation in larger prospective cohorts..
CONCLUSIONS
Bacteriobilia is highly prevalent among patients undergoing pancreaticoduodenectomy, particularly following preoperative biliary drainage, but does not independently worsen perioperative outcomes. In contrast, polymicrobial bile cultures were associated with increased 60- and 90-day mortality and may identify a subgroup of patients with greater biological and perioperative complexity rather than a direct causal determinant of adverse outcomes. These findings should be interpreted as hypothesis-generating and warrant validation in larger prospective studies.
SUPPLEMENTARY MATERIAL
SUPPLEMENTARY MATERIAL
REFERENCES
-
1 Abu Hilal M, Uijterwijk BA, Lemmers DHL, Janssen BV, Besselink MG, Bianchi D, et al. The Brescia International Multidisciplinary Consensus Guidelines on the Optimal Pathology Assessment and Multidisciplinary Pathways of Non-Pancreatic Neoplasms in and Around the Ampulla of Vater (PERIPAN). United European Gastroenterol J. 2025;13(7):1048-1068. doi: 10.1002/ueg2.70074.
» https://doi.org/10.1002/ueg2.70074 -
2 Uijterwijk BA, Lemmers DH, Ghidini M, Wilmink H, Zaniboni A, Salvia R, et al. ISGACA Consortium. The Five Periampullary Cancers, not Just Different Siblings but Different Families: An International Multicenter Cohort Study. Ann Surg Oncol. 2024;31(9):6157-6169. doi: 10.1245/s10434-024-15555-8.
» https://doi.org/10.1245/s10434-024-15555-8 -
3 Chiorean EG, Chiaro MD, Tempero MA, Malafa MP, Benson AB, Cardin DB, et al. Ampullary Adenocarcinoma, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2023;21(7):753-782. doi: 10.6004/jnccn.2023.0034.
» https://doi.org/10.6004/jnccn.2023.0034 - 4 Skórzewska M, Kurzawa P, Ciszewski T, Pelc Z, Polkowski WP. Controversies in the diagnosis and treatment of periampullary tumours. Surg Oncol. 2022;44:101853.
-
5 Are C, Dhir M, Ravipati L. History of pancreaticoduodenectomy: early misconceptions, initial milestones and the pioneers. HPB (Oxford). 2011;13(6):377-84. doi: 10.1111/j.1477-2574.2011.00305.x.
» https://doi.org/10.1111/j.1477-2574.2011.00305.x - 6 Crile G Jr. The advantages of bypass operations over radical pancreatoduodenectomy in the treatment of pancreatic carcinoma. Surg Gynecol Obstet. 1970;130(6):1049-53.
-
7 Cameron JL, Riall TS, Coleman J, Belcher KA. One thousand consecutive pancreaticoduodenectomies. Ann Surg. 2006;244(1):10-5. doi: 10.1097/01.sla.0000217673.04165.ea.
» https://doi.org/10.1097/01.sla.0000217673.04165.ea -
8 Pavlidis ET, Pavlidis TE. Pathophysiological consequences of obstructive jaundice and perioperative management. Hepatobiliary Pancreat Dis Int. 2018;17(1):17-21. doi: 10.1016/j.hbpd.2018.01.008.
» https://doi.org/10.1016/j.hbpd.2018.01.008 -
9 Van Laethem JL, De Broux S, Eisendrath P, Cremer M, Le Moine O, Devière J. Clinical impact of biliary drainage and jaundice resolution in patients with obstructive metastases at the hilum. Am J Gastroenterol. 2003;98(6):1271-7. doi: 10.1111/j.1572-0241.2003.07504.x.
» https://doi.org/10.1111/j.1572-0241.2003.07504.x -
10 Nehme F, Lee JH. Preoperative biliary drainage for pancreatic cancer. Dig Endosc. 2022;34(3):428-438. doi: 10.1111/den.14081.
» https://doi.org/10.1111/den.14081 -
11 Tamm EP, Silverman PM, Charnsangavej C, Evans DB. Diagnosis, staging, and surveillance of pancreatic cancer. AJR Am J Roentgenol. 2003;180(5):1311-23. doi: 10.2214/ajr.180.5.1801311.
» https://doi.org/10.2214/ajr.180.5.1801311 -
12 Sutton TL, O'Grady J, Martindale R, Mayo SC, Gilbert EW, Sheppard BC. Intraoperative Bile Culture in Pancreaticoduodenectomy: Teaching Old Dogma New Tricks. J Gastrointest Surg. 2022;26(1):30-38. doi: 10.1007/s11605-021-05182-z.
» https://doi.org/10.1007/s11605-021-05182-z -
13 Gavazzi F, Ridolfi C, Capretti G, Angiolini MR, Morelli P, Casari E, et al. Role of preoperative biliary stents, bile contamination and antibiotic prophylaxis in surgical site infections after pancreaticoduodenectomy. BMC Gastroenterol. 2016;16:43. doi: 10.1186/s12876-016-0460-1.
» https://doi.org/10.1186/s12876-016-0460-1 -
14 Sandini M, Honselmann KC, Cereda M, Angrisani M, Gavazzi F, Wellner U, et al. The Relative Role of Bile Bacterial Isolation on Outcome in Stent-Bearing Patients Undergoing Pancreatoduodenectomy. J Gastrointest Surg. 2020;24(10):2269-2276. doi: 10.1007/s11605-019-04388-6.
» https://doi.org/10.1007/s11605-019-04388-6 -
15 Maatman TK, Weber DJ, Qureshi B, Ceppa EP, Nakeeb A, Schmidt CM, et al. Does the Microbiology of Bactibilia Drive Postoperative Complications After Pancreatoduodenectomy? J Gastrointest Surg. 2020;24(11):2544-2550. doi: 10.1007/s11605-019-04432-5.
» https://doi.org/10.1007/s11605-019-04432-5 -
16 Wang Q, Gurusamy KS, Lin H, Xie X, Wang C. Preoperative biliary drainage for obstructive jaundice. Cochrane Database Syst Rev. 2008;(3):CD005444. doi: 10.1002/14651858.CD005444.pub2.
» https://doi.org/10.1002/14651858.CD005444.pub2 -
17 Sewnath ME, Birjmohun RS, Rauws EAl, Huibregtse K, Obertop H, Gouma DJ. The effect of preoperative bilary drainage on postoperative complications after pancreaticoduodenectomy. J Am Coil Surg. 2001;192:726-34. doi: 10.1016/s1072-7515(01)00819-5.
» https://doi.org/10.1016/s1072-7515(01)00819-5 -
18 van der Gaag NA, Rauws EA, van Eijck CH, Bruno MJ, van der Harst E, Kubben FJ, et al. Preoperative biliary drainage for cancer of the head of the pancreas. N Engl J Med. 2010;362(2):129-37. doi: 10.1056/NEJMoa0903230.
» https://doi.org/10.1056/NEJMoa0903230 -
19 Forster K, Klein F, Simon N, Chhatwal P, Ziesing S, Heidrich B, Solbach P. Cultivation-based characterization of biliary microbiota in bile samples collected during routine endoscopic retrograde cholangiography: 10 years of experience at a tertiary center. Eur J Gastroenterol Hepatol. 2023;35(10):1159-1167. doi: 10.1097/MEG.0000000000002633.
» https://doi.org/10.1097/MEG.0000000000002633 -
20 van der Gaag NA, de Castro SM, Rauws EA, Bruno MJ, van Eijck CH, Kuipers EJ, et al. Preoperative biliary drainage for periampullary tumors causing obstructive jaundice; DRainage vs. (direct) OPeration (DROP-trial). BMC Surg. 2007;7:3. doi: 10.1186/1471-2482-7-3.
» https://doi.org/10.1186/1471-2482-7-3 -
21 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):205-213. doi: 10.1097/01.sla.0000133083.54934.ae.
» https://doi.org/10.1097/01.sla.0000133083.54934.ae -
22 Kagedan DJ, Mosko JD, Dixon ME, Karanicolas PJ, Wei AC, Goyert N, et al. Changes in preoperative endoscopic and percutaneous bile drainage in patients with periampullary cancer undergoing pancreaticoduodenectomy in Ontario: effect on clinical practice of a randomized trial. Curr Oncol. 2018;25(5):e430-e435. doi: 10.3747/co.25.4007.
» https://doi.org/10.3747/co.25.4007 -
23 Yamamoto Y, Sugiura T, Esaki M, Takahashi Y, Arita J, Hashimoto M, et al. Impact of biliary drainage method before pancreaticoduodenectomy on short- and long-term outcomes in patients with periampullary carcinoma and obstructive jaundice: A multicenter retrospective analysis. Surgery. 2024;176(3):616-625. doi: 10.1016/j.surg.2024.05.011.
» https://doi.org/10.1016/j.surg.2024.05.011 -
24 Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, Rice LB, et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis. 2009;48(1):1-12. doi: 10.1086/595011.
» https://doi.org/10.1086/595011 -
25 Ishiwatari H, Sato J, Sakamoto H, Doi T, Ono H. Current status of preoperative endoscopic biliary drainage for distal and hilar biliary obstruction. Dig Endosc. 2024;36(9):969-980. doi: 10.1111/den.14786.
» https://doi.org/10.1111/den.14786 -
26 Dupont B, Dejardin O, Kam W, Launay L, Mosquet L, Gloro R, et al. Impact of timing of access to endoscopic drainage and social determinants of health on the prognosis of patients with periampullary cancer diagnosed through jaundice: a multicenter retrospective study. Ther Adv Gastroenterol. 2026;19:17562848261426095. doi: 10.1177/17562848261426095.
» https://doi.org/10.1177/17562848261426095 -
27 Pandey M, Dilip TR, Chopade A, Shrikhande SV, Bhandare M. Financial burden due to distance traveled to access treatment from specialized cancer hospitals in public sector in India: a case study of patients treated for gastric and pancreatic cancer. J Cancer Policy. 2025;45:100632. doi: 10.1016/j.jcpo.2025.100632.
» https://doi.org/10.1016/j.jcpo.2025.100632 -
28 Rustgi SD, Amin SP, Kim MK, Nagula S, Kumta NA, DiMaio CJ, Boffetta P, Lucas AL. Age, socioeconomic features, and clinical factors predict receipt of endoscopic retrograde cholangiopancreatography in pancreatic cancer. World J Gastrointest Endosc. 2019;11(2):133-144. doi: 10.4253/wjge.v11.i2.133.
» https://doi.org/10.4253/wjge.v11.i2.133 -
29 Soares PFDC, Gestic MA, Utrini MP, Callejas-Neto F, Chaim EA, Cazzo E. Epidemiological profile, referral routes and diagnostic accuracy of cases of acute cholangitis among individuals with obstructive jaundice admitted to a tertiary-level university hospital: a cross-sectional study. Sao Paulo Med J. 2019;137(6):491-497. doi: 10.1590/1516-3180.2019.0109170919.
» https://doi.org/10.1590/1516-3180.2019.0109170919 -
30 Gilliam AD, Lobo DN, Rowlands BJ, Beckingham IJ. The 'two-week' target for the diagnosis of pancreatic carcinoma: an achievable aim? Eur J Surg Oncol. 2003;29(7):575-9. doi: 10.1016/s0748-7983(03)00112-4.
» https://doi.org/10.1016/s0748-7983(03)00112-4 -
31 Liang X, Shi LG, Hao J, Liu AA, Chen DL, Hu XG, Shao CH. Risk factors and managements of hemorrhage associated with pancreatic fistula after pancreaticoduodenectomy. Hepatobiliary Pancreat Dis Int. 2017;16(5):537-544. doi: 10.1016/S1499-3872(17)60061-4.
» https://doi.org/10.1016/S1499-3872(17)60061-4 -
32 Li Z, Zhang Z, Hu W, Zeng Y, Liu X, Mai G, et al. Pancreaticoduodenectomy with preoperative obstructive jaundice: drainage or not. Pancreas. 2009;38(4):379-86. doi: 10.1097/MPA.0b013e31819f638b.
» https://doi.org/10.1097/MPA.0b013e31819f638b -
33 Iskandar ME, Wayne MG, Steele JG, Cooperman AM. A Tale of 2 Techniques: Preoperative Biliary Drainage and Routine Surgical Drainage with Pancreaticoduodenectomy. Surg Clin North Am. 2018;98(1):49-55. doi: 10.1016/j.suc.2017.09.004.
» https://doi.org/10.1016/j.suc.2017.09.004 -
34 Gong S, Song S, Cheng Q, Huang Y, Tian H, Jing W, et al. Efficacy and safety of preoperative biliary drainage in patients undergoing pancreaticoduodenectomy: an updated systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol. 2021;15(12):1411-1426. doi: 10.1080/17474124.2021.2013805.
» https://doi.org/10.1080/17474124.2021.2013805 -
35 Kone LB, Torres C, Banulescu M, Maker VK, Maker AV. Perioperative Broad-spectrum Antibiotics are Associated With Decreased Surgical Site Infections Compared to 1st-3rd Generation Cephalosporins After Open Pancreaticoduodenectomy in Patients With Jaundice or a Biliary Stent. Ann Surg. 2022;275(6):1175-1183. doi: 10.1097/SLA.0000000000004216.
» https://doi.org/10.1097/SLA.0000000000004216 -
36 Yang Y, Sheng J, Cai Z, Zhu L, Lu C, Mao L, et al. Antibiotic prophylaxis with piperacillin-tazobactam reduces organ/space surgical site infection after pancreaticoduodenectomy: a retrospective and propensity score-matched analysis. BMC Cancer. 2024 Feb;24(1):251. doi: 10.1186/s12885-024-11955-x.
» https://doi.org/10.1186/s12885-024-11955-x -
37 Naffouje SA, Allenson K, Hodul P, Malafa M, Pimiento JM, Anaya DA, et al. Prophylactic Perioperative Antibiotics in Open Pancreaticoduodenectomy: When Less Is More and When It Is Not. A National Surgical Quality Improvement Program Propensity-Matched Analysis. J Surg Res. 2022;279:722-732. doi: 10.1016/j.jss.2022.06.028.
» https://doi.org/10.1016/j.jss.2022.06.028 -
38 Stecca T, Nistri C, Pauletti B, Greco A, Di Giacomo A, Caratozzolo E, et al. Bacteriobilia resistance to antibiotic prophylaxis increases morbidity after pancreaticoduodenectomy: a monocentric retrospective study of 128 patients. Updates Surg. 2020;72(4):1073-1080. doi: 10.1007/s13304-020-00772-z.
» https://doi.org/10.1007/s13304-020-00772-z -
39 Gibiino G, Cucchetti A, Mocchegiani F, Bocchino A, Gaudenzi F, Binda C, et al. Alarming correlation between multidrug-resistant bacteriobilia and morbidity after pancreatic surgery. Dig Liver Dis. 2023;55(11):1502-1508. doi: 10.1016/j.dld.2023.05.012.
» https://doi.org/10.1016/j.dld.2023.05.012 -
40 Yoon SJ, Huh K, Lee O, Jung JH, Han IW, Heo JS, et al. Effect of Intraoperatively Detected Bacteriobilia on Surgical Outcomes After Pancreatoduodenectomy: Analysis of a Prospective Database in a Single Institute. J Gastrointest Surg. 2022;26(10):2158-2166. doi: 10.1007/s11605-022-05405-x.
» https://doi.org/10.1007/s11605-022-05405-x -
41 Blacker S, Lahiri RP, Phillips M, Pinn G, Pencavel TD, Kumar R,et al. Which patients benefit from preoperative biliary drainage in resectable pancreatic cancer? Expert Rev Gastroenterol Hepatol. 2021;15(8):855-863. doi: 10.1080/17474124.2021.1915127.
» https://doi.org/10.1080/17474124.2021.1915127 -
42 Mise Y, Vauthey JN, Zimmitti G, Parker NH, Conrad C, Aloia TA, et al. Ninety-day Postoperative Mortality Is a Legitimate Measure of Hepatopancreatobiliary Surgical Quality. Ann Surg. 2015;262(6):1071-8. doi: 10.1097/SLA.0000000000001048.
» https://doi.org/10.1097/SLA.0000000000001048 -
43 Swanson RS, Pezzi CM, Mallin K, Loomis AM, Winchester DP. The 90-day mortality after pancreatectomy for cancer is double the 30-day mortality: more than 20,000 resections from the national cancer data base. Ann Surg Oncol. 2014;21(13):4059-67. doi: 10.1245/s10434-014-4036-4.
» https://doi.org/10.1245/s10434-014-4036-4
Datasets related to this article will be available upon equest to the corresponding author.
