The road to tailored adjuvant chemotherapy for all four non-pancreatic periampullary cancers: An international multimethod cohort study.

BACKGROUND: Despite differences in tumour behaviour and characteristics between duodenal adenocarcinoma (DAC), the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype of ampullary adenocarcinoma and distal cholangiocarcinoma (dCCA), the effect of adjuvant chemotherapy (ACT) on these cancers, as well as the optimal ACT regimen, has not been comprehensively assessed. This study aims to assess the influence of tailored ACT on DAC, dCCA, AmpIT, and AmpPB. PATIENTS AND METHODS: Patients after pancreatoduodenectomy for non-pancreatic periampullary adenocarcinoma were identified and collected from 36 tertiary centres between 2010 - 2021. Per non-pancreatic periampullary tumour type, the effect of adjuvant chemotherapy and the main relevant regimens of adjuvant chemotherapy were compared. The primary outcome was overall survival (OS). RESULTS: The study included a total of 2866 patients with DAC (n = 330), AmpIT (n = 765), AmpPB (n = 819), and dCCA (n = 952). Among them, 1329 received ACT, and 1537 did not. ACT was associated with significant improvement in OS for AmpPB (P = 0.004) and dCCA (P < 0.001). Moreover, for patients with dCCA, capecitabine mono ACT provided the greatest OS benefit compared to gemcitabine (P = 0.004) and gemcitabine - cisplatin (P = 0.001). For patients with AmpPB, no superior ACT regime was found (P > 0.226). ACT was not associated with improved OS for DAC and AmpIT (P = 0.113 and P = 0.445, respectively). DISCUSSION: Patients with resected AmpPB and dCCA appear to benefit from ACT. While the optimal ACT for AmpPB remains undetermined, it appears that dCCA shows the most favourable response to capecitabine monotherapy. Tailored adjuvant treatments are essential for enhancing prognosis across all four non-pancreatic periampullary adenocarcinomas.

Evaluating the safety and efficacy of a novel polysaccharide hemostatic system during surgery: A multicenter multispecialty prospective randomized controlled trial.

Background: Operative blood loss is associated with postoperative morbidity and mortality in surgery. Hemostatic agents are used as adjuncts for hemostasis during surgery and help to prevent postoperative bleeding. We evaluated the safety and efficacy of an investigational polysaccharide hemostatic (PH) topical product compared to a U.S. Food and Drug Administration (FDA)-approved control in clinical use comprising microporous polysaccharide hemospheres (MPH) to achieve hemostasis of bleeding surfaces during surgery. Study design: This prospective multicenter trial enrolled patients undergoing open elective cardiac, general, or urologic surgery. Patients were stratified by bleeding severity and therapeutic area, then randomized 1:1 to receive PH or MPH. Bleeding assessments occurred intraoperatively using a novel bleeding assessment methodology. Primary endpoint was noninferiority as compared with control via effective hemostasis at 7 min. Patients were monitored and followed daily in the postoperative period until time of discharge and again at 6 weeks. Overall survival was assessed in oncology patients at 24 months. Safety of PH vs. MPH was determined by comparing relative incidence of adverse events. Results: Across 19 centers, 324 (161 PH, 163 MPH) patients were randomized (48 % general surgery, 27 % cardiac surgery, and 25 % urologic surgery). PH was noninferior to MPH and met the primary endpoint of hemostatic success at 7 min at a non-inferiority margin of 10 %. No significant differences were found in adverse event rates. Six deaths were reported within the 6-week follow-up period. No difference in overall survival was observed at 2 years (76 % PH vs. 74 % MPH, P = .66) for patients undergoing cancer operations. Conclusion: Across three therapeutic areas, PH was noninferior to MPH at all hemostasis assessment time points with no safety concerns. PH is an effective alternative to MPH for hemostasis during surgery.ClinicalTrials.gov Identifier: NCT02359994.

Contemporary Outcomes of Transduodenal Sphincteroplasty: the Importance of Surgical Quality.

BACKGROUND: Sphincter of Oddi dysfunction (SOD) is managed primarily by endoscopic sphincterotomy (ES); however, surgical transduodenal sphincteroplasty (TDS) is a treatment option for select patients. In our high-volume pancreatico-biliary practice, we have observed variable outcomes among TDS patients; therefore, we sought to determine preoperative predictors of durable improvement in quality of life. METHODS: SOD patients treated by TDS between January 2006 and December 2015 were studied. The primary outcome measure was long-term changes in quality of life after sphincteroplasty. The secondary outcome measure examined postoperative outcomes, including postoperative complications, need for repeat procedures, and readmission rates. Perioperative data were abstracted, and the SF-36 quality-of-life (QoL) survey was administered. Standard statistical analysis included non-parametric methods to examine bivariate associations. RESULTS: Eighty-eight patients had an average follow-up duration of 6.7 (± 2.9) years. Thirty (34%) patients were naïve to endoscopic therapy. Patients with prior endoscopy averaged 2.1 procedures (range 1 to 13) prior to surgery. Perioperative morbidity was 27%; one postoperative death was caused by severe acute pancreatitis. Twenty-nine (33%) patients required subsequent biliary-pancreatic procedures. QoL analysis from available patients showed that 66% were improved or much improved. With multivariable analysis including SOD type and prior endoscopic instrumentation, freedom from surgical complication was the only variable that correlated significantly with a good outcome (p < 0.02). CONCLUSION: Surgical transduodenal sphincteroplasty provides durable symptom management for select patients with sphincter of Oddi dysfunction. Minimizing surgical complications optimizes long-term outcomes.

Do Weekend Discharges Impact Readmission Rate in Patients Undergoing Pancreatic Surgery?

BACKGROUND: Weekend readmissions have been previously associated with increased mortality after pancreatic resection, but the effect of weekend discharge is less understood. In this study, we aim to determine the impact of weekend discharges on 30-day readmission rate after pancreatic surgery. METHODS: All patients who underwent pancreatic surgery at a single, high-volume institution between 2013 and 2021 were retrospectively reviewed from a targeted, institutional ACS-NSQIP database. Patients who died prior to discharge were excluded. Multivariable logistic regression was used to assess the relationship between readmission and weekend discharge. RESULTS: Out of 2042 patients who underwent pancreatectomy, 418 patients (20.5%) were discharged on the weekend. Weekend discharge was associated with fewer Whipple surgeries, fewer open surgical approaches, and shorter operative time. Patients discharged on the weekend were also less likely to have had postoperative complications such as delayed gastric emptying (DGE) (6.7% vs 12.6%, p < 0.01) and were more frequently discharged to home (91.1% vs. 85.3%, p < 0.01). Thirty-day readmission rate was almost identical between groups (14.8% vs 14.8%, p = 0.997). On multivariable analysis, 30-day readmission was independently associated with DGE (OR (95% CI): 3.48 (2.31-5.23), p < 0.01), postoperative pancreatic fistula (3.36 (2.34-4.83), p < 0.01), myocardial infarction, and perioperative blood transfusion, but not weekend discharge (1.02 (0.72-1.43), p = 0.93). Readmission rate also did not differ significantly when including Friday discharges in the weekend group (15.2% vs 14.6%, p = 0.72). CONCLUSIONS: With careful clinical decision making, patients may safely be discharged on the weekend after pancreatic surgery without increasing 30-day readmission rate.

Patients with deleterious germline mutations: A heterogeneous population for pancreatic cancer screening?

BACKGROUND AND OBJECTIVES: Modest data exist on the benefits of screening and surveillance for pancreatic cancer (PC) in high-risk individuals. Intraductal papillary mucinous neoplasms (IPMN) are known precursors to PC. We hypothesized that patients with high-risk deleterious germline mutations have a higher prevalence of IPMN. METHODS: All patients undergoing prospective screening at a single institution from 2013 to 2019 were reviewed. RESULTS: Of 1166 patients screened, 358 (31%) possessed germline mutations and/or family history of PC (mutations n = 201/358, 56%, family history n = 226/358, 63%) (median follow-up 2.7 years). IPMN was found in 127 patients (35.5%). The prevalence of IPMN in mutation carriers (18%) was higher than in the general population (p < 0.01). Germline mutation was an independent predictor of IPMN (odds ratio [OR] = 3.2; p < 0.01), while family history was not (p = 0.22). IPMN prevalence was distributed unevenly between mutation types (67%-Peutz-Jeghers; 43%-HNPCC, 24%-BRCA2; 17%-ATM; 9%-BRCA1; 0%-CDKN2A and PALB2). CONCLUSION: In this series, 18% of mutation carriers harbored IPMN, higher than the general population. Germline mutation, but not a family history of PC, was independently associated with IPMN. This prevalence varied across mutation subtypes, suggesting not all mutation carriers develop precancerous lesions. Genetic testing for patients with a positive family history may improve screening modalities for this high-risk population.

Closed Incision Negative Pressure Therapy to Reduce Surgical Site Infection in High-Risk Gastrointestinal Surgery: A Randomized Controlled Trial.

BACKGROUND: Despite institutional perioperative bundles and national infection prevention guidelines, surgical site infection (SSI) after a major abdominal operation remains a significant source of morbidity. Negative pressure therapy (NPT) has revolutionized care for open wounds but the role of closed incision NPT (ciNPT) remains unclear. STUDY DESIGN: We conducted a multi-institutional randomized controlled trial evaluating SSI after major elective colorectal or hepatopancreatobiliary surgery (Clinical Trial Registration: NCT01905397). Patients were randomized to receive conventional wound care vs ciNPT (Prevena Incision Management System, 3M Health Care, San Antonio, TX). The primary endpoint was postoperative incisional SSI. SSI incidence was evaluated at inpatient days 4 or 5 and again at postoperative day 30. With 144 patients studied, the estimated power was 85% for detecting a difference in SSIs between 17% and 5% (conventional vs ciNPT; 1-sided α = 0.1). Secondary endpoints included SSI type, length of stay, 30-day readmission, and mortality. T-tests were used to compare continuous variables between treatments; similarly, chi-square tests were used to compare categorical variables. A p value of <0.05 was considered significant, except in the primary comparison of incisional and organ SSIs. RESULTS: During the 2013 to 2021 time period, 164 patients were randomized, and of those, 138 were evaluable (ciNPT n = 63; conventional n = 75). Incisional SSIs occurred in 9 (14%) patients in the ciNPT group and 13 (17%) patients in the conventional group (p = 0.31). Organ or space SSIs occurred in 7 (11%) patients in the ciNPT group and 10 (13%) in the conventional therapy group (p = 0.35). CONCLUSIONS: In this multi-institutional, randomized controlled trial of patients undergoing colorectal or hepatopancreatobiliary surgery, incidence of incisional SSIs between ciNPT and conventional wound therapy was not statistically significant. Future trials should focus on patient populations undergoing specific procedures types that have the highest risk for SSI.

Neoadjuvant therapy at local versus outside institutions does not adversely impact surgical timing or long-term outcomes in patients with pancreatic adenocarcinoma.

BACKGROUND: Although high-volume centers are known to have better surgical outcomes, patients with pancreatic adenocarcinoma often receive chemotherapy at treatment centers closer to home. This study aimed to determine whether treatment site of neoadjuvant therapy relative to surgery location impacts surgical timing and long-term outcomes. METHODS: All patients with pancreatic adenocarcinoma who underwent oncologic resection at a single, high-volume institution between January 2016 and February 2020 and had neoadjuvant chemotherapy before surgery were queried from a prospectively maintained database. Patients were sorted based on location of neoadjuvant chemotherapy. RESULTS: A total of 179 patients were included in the study. Seventy-four (41.3%) patients received neoadjuvant chemotherapy at the same institution as their surgery (group A), 20 (11.2%) received chemotherapy outside of their surgical institution but within the same hospital/healthcare system (group B), and 85 (47.5%) received chemotherapy at an outside location (group C). The time from completion of neoadjuvant therapy to surgery was not significantly different between groups (A vs B vs C median [interquartile range]: 34.5 [14] vs 41.5 [24] vs 36 [22] days, P = .08). Thirty-day readmission rate was lower in group A (n (%): 1 (1.4%) vs 2 (10.0%) vs 11 (12.9%), P = .02). However, the 90-day mortality and overall survival did not differ significantly between groups. CONCLUSION: Patients may receive neoadjuvant therapy at local centers without impacting surgical scheduling. Although these patients may experience higher postoperative readmission rates, perioperative mortality and long-term survival are not adversely affected by location of chemotherapy. Multidisciplinary care can be effectively practiced in different locations without affecting overall outcomes in patients with pancreatic adenocarcinoma.

Obesity Worsens Local and Systemic Complications of Necrotizing Pancreatitis and Prolongs Disease Course.

BACKGROUND: Obesity is epidemic in the USA. Limited data exist examining obesity's influence on necrotizing pancreatitis (NP) disease course. METHODS: Retrospective review of prospectively maintained database of 571 adult necrotizing pancreatitis patients treated between 2007 and 2018. Patients were grouped according to body mass index (BMI) at disease onset. Patient characteristics, necrotizing pancreatitis course, and outcomes were compared between non-obese (BMI < 30) and obese (BMI > 30) patients. RESULTS: Among 536 patients with BMI data available, 304 (57%) were obese (BMI > 30), and 232 (43%) were non-obese (BMI < 30). NP etiology in the obese group was more commonly biliary (55% versus 46%, p = 0.04) or secondary to hypertriglyceridemia (10% versus 2%, p < 0.001) and less commonly alcohol (17% versus 26%, p = 0.01). Obese patients had a higher incidence of baseline comorbid disease. The CT severity index was similar between groups though obese patients had a higher rate of > 50% pancreatic gland necrosis (27% versus 19%, p = 0.02). The rates of infected necrosis and organ failure were higher among obese patients. Percutaneous drainage was more common in obese patients. Time to first necrosis intervention was earlier with increasing BMI. NP disease duration was longer in obese patients. The overall mortality rate of non-obese and obese patients did not differ. However, mortality rate increased with increasing BMI. CONCLUSION: Necrotizing pancreatitis in obese patients is characterized by a prolonged disease course, a higher risk of organ failure, infected necrosis, and the need for early necrosis-related intervention. Mortality increases with increasing BMI.

Portal Vein Thrombosis After Venous Reconstruction During Pancreatectomy: Timing and Risks.

BACKGROUND: Numerous studies have shown that portal vein resection during pancreatectomy can help achieve complete tumor clearance and long term-survival. While the safety of vascular resection during pancreatectomy is well documented, the risk of superior mesenteric vein/portal vein (SMV/PV) thrombosis after reconstruction remains unclear. This study aimed to describe the incidence and risk factors of SMV/PV thrombosis after vein reconstruction during pancreatectomy. METHODS: All patients who underwent portal vein resection (PVR) during pancreatectomy (2007-2019) were identified from a single institution prospective clinical database. Demographic and clinical data, operative and pathological findings, and postoperative outcomes were analyzed. RESULTS: Pancreatectomy with PVR was performed in 220 patients (mean age 65.1 years, male/female ratio 0.96). Thrombosis occurred in 36 (16.4%) patients after a median of 15.5 days [IQR 38.5, 1-786 days]. SMV/PV patency rates were 92.7% and 88.7% at 1 and 3 months, respectively. The rate of SMV/PV thrombosis varied according to SMV/PV reconstruction technique: 12.8% after venorrhaphy, 13.2% end-to-end anastomosis, 22.6% autologous vein, and 83.3% synthetic graft interposition (p < 0.0001). SMV/PV thrombosis was associated with increased 90-day mortality (16.7% vs 4.9%, p = 0.02) and overall 30-day complication rate (69.4% vs 42.9%, p = 0.006). Pancreatectomy type, neoadjuvant chemoradiation, pathologic tumor venous invasion, resection margin status, and manner of perioperative anticoagulation did not influence the incidence of PV thrombosis. SMV/PV thrombosis was associated with a nearly 5-times increased risk of postoperative sepsis after pancreatectomy. CONCLUSION: Portal vein thrombosis developed in 16% of patients who underwent pancreatectomy with PVR at a median of 15 days. PVR with synthetic interposition graft carries the highest risk for thrombosis.

Development and Characterization of Human Primary Cholangiocarcinoma Cell Lines.

Cholangiocarcinoma (CCA) is the second most common primary liver tumor and is associated with late diagnosis, limited treatment options, and a 5-year survival rate of around 30%. CCA cell lines were first established in 1971, and since then, only 70 to 80 CCA cell lines have been established. These cell lines have been essential in basic and translational research to understand and identify novel mechanistic pathways, biomarkers, and disease-specific genes. Each CCA cell line has unique characteristics, reflecting a specific genotype, sex-related properties, and patient-related signatures, making them scientifically and commercially valuable. CCA cell lines are crucial in the use of novel technologies, such as three-dimensional organoid models, which help to model the tumor microenvironment and cell-to-cell crosstalk between tumor-neighboring cells. This review highlights crucial information on CCA cell lines, including: i) type of CCA (eg, intra- or extrahepatic), ii) isolation source (eg, primary tumor or xenograft), iii) chemical digestion method (eg, trypsin or collagenase), iv) cell-sorting method (colony isolation or removal of fibroblasts), v) maintenance-medium choice (eg, RPMI or Dulbecco's modified Eagle's medium), vi) cell morphology (eg, spindle or polygonal shape), and vii) doubling time of cells.

Contemporary Intervention in Necrotizing Pancreatitis: Improved Understanding Changing Practice.

BACKGROUND: Treatment of necrotizing pancreatitis (NP) has shifted in favor of a minimally invasive step-up approach rather than early open pancreatic debridement. We hypothesized that this paradigm shift would be reflected in the intervention, morbidity, and mortality profile of NP patients. STUDY DESIGN: Single-institution retrospective review of 767 NP patients treated between 2005 and 2019. Two eras of NP intervention were identified relative to the introduction of a minimally invasive approach to NP. Patients treated between 2005 and 2010 were classified as the "early" group and compared with patients treated between 2011 and 2019, classified as the "late" group. RESULTS: In total, 299 NP patients comprised the early group and 468 patients comprised the late group. No differences were seen in patient demographics, comorbidity profile, or NP etiology between groups. Necrosis volume, necrosis location, CT severity index (CTSI), and rates of infected necrosis were similar between groups. No difference was seen in mortality. Mechanical intervention for NP was more common in the early than the late group (86% vs. 73%, p < 0.001). Time to first intervention was similar between groups (79 ± 7d vs. 75 ± 6d). The early group had higher rates of open pancreatic debridement (72% vs. 55%, p < 0.001). Endoscopic intervention was less common in the early than the late group (7% vs. 16%, p < 0.001). NP disease duration was longer in the early than the late group (223 ± 12d vs. 179 ± 7d, p = 0.001). CONCLUSION: Contemporary management of necrotizing pancreatitis is marked by less frequent operative debridement and shorter disease duration.

Investigating the incidence, impact, and severity of pulmonary complications after hepatectomy: A single institution experience.

BACKGROUND: Postoperative pulmonary complications are a common cause of postoperative morbidity in patients undergoing hepatectomy. This study aimed to identify risk factors, define severity, and evaluate the impact of postoperative pulmonary complications on postoperative morbidity after hepatectomy. METHOD: We used a prospective database in identifying all hepatectomies from 2013 to 2018. The database was then augmented using extensive review of medical records. The Strasburg system was used in categorizing resections per complexity: major hepatic resection and minor hepatic resection, whereas the Clavien-Dindo system was used in defining postoperative pulmonary complications per severity. Potential confounders were controlled for on multiple regression models. RESULTS: A total of 702 cases were identified: major hepatic resection 413 (60%) and minor hepatic resection 289 (40%). Patients demonstrated comparable characteristics, but the postoperative pulmonary complications group was more likely to have chronic obstructive pulmonary disease (10% vs 5%; P = .02). Severe postoperative pulmonary complications among major hepatectomy was observed in 38 patients (13%). Predictors for severe postoperative pulmonary complications requiring intervention included postoperative liver failure (odds ratio = 2.8; P = .002) and biliary fistula (odds ratio = 3.5; P = .001). In addition, the occurrence of severe postoperative pulmonary complications markedly hindered recovery, increasing length of stay by 4.4-fold and readmission rates by 3-fold (P < .001). On multivariable analysis, postoperative pulmonary complications significantly increase postoperative length of stay (8 vs 5 days; P < .001) and readmission (odds ratio = 3.2; P = .001). Mortality was similar (1% vs 4%; P = .066). CONCLUSION: Postoperative pulmonary complications are a major cause of delayed recovery and worse outcomes after hepatectomy. Further, postoperative liver failure and biliary fistula can predict the occurrence of severe postoperative pulmonary complications among major hepatic resection and the associated need for readmission with these complications.

AHPBA guidelines for managing VTE prophylaxis and anticoagulation for pancreatic surgery.

BACKGROUND: Major abdominal surgery and malignancy lead to a hypercoagulable state, with a risk of venous thromboembolism (VTE) of approximately 3% after pancreatic surgery. No guidelines exist to assist surgeons in managing VTE prophylaxis or anticoagulation in patients undergoing elective pancreatic surgery for malignancy or premalignant lesions. A systematic review specific to VTE prophylaxis and anticoagulation after resectional pancreatic surgery is herein provided. METHODS: Six topic areas are reviewed: pre- and perioperative VTE prophylaxis, early postoperative VTE prophylaxis, extended outpatient VTE prophylaxis, management of chronic anticoagulation, anti-coagulation after vascular reconstruction, and treatment of VTE. A Medline and PubMED search was completed with systematic medical literature review for each topic. Level of evidence was graded and strength of recommendation ranked according to the GRADE (Grades of Recommendation Assessment, Development and Evaluation) system for practice guidelines. RESULTS: Levels of evidence and strength of recommendations are presented. DISCUSSION: While strong data exist to guide management of chronic anticoagulation and treatment of VTE, data for anticoagulation after reconstruction is inconclusive and support for perioperative chemoprophylaxis with pancreatic surgery is similarly limited. The risk of post-pancreatectomy hemorrhage often exceeds that of thrombosis. The role of universal chemoprophylaxis must therefore be examined critically, particularly in the preoperative setting.

Biliary Stricture After Necrotizing Pancreatitis: An Underappreciated Challenge.

OBJECTIVE: Biliary stricture in necrotizing pancreatitis (NP) has not been systematically categorized; therefore, we sought to define the incidence and natural history of biliary stricture caused by NP. SUMMARY OF BACKGROUND DATA: Benign biliary stricture occurs secondary to bile duct injury, anastomotic narrowing, or chronic inflammation and fibrosis. The profound locoregional inflammatory response of NP creates challenging biliary strictures. METHODS: NP patients treated between 2005 and 2019 were reviewed. Biliary stricture was identified on cholangiography as narrowing of the extrahepatic biliary tree to <75% of the diameter of the unaffected duct. Biliary stricture risk factors and outcomes were evaluated. RESULTS: Among 743 NP patients, 64 died, 13 were lost to follow-up; therefore, a total of 666 patients were included in the final cohort. Biliary stricture developed in 108 (16%) patients. Mean follow up was 3.5 ±â€Š3.3 years. Median time from NP onset to biliary stricture diagnosis was 4.2 months (interquartile range, 1.8 to 10.9). Presentation was commonly clinical or biochemical jaundice, n = 30 (28%) each. Risk factors for stricture development were splanchnic vein thrombosis and pancreatic head parenchymal necrosis. Median time to stricture resolution was 6.0 months after onset (2.8 to 9.8). A mean of 3.3 ±â€Š2.3 procedures were performed. Surgical intervention was required in 22 (20%) patients. Endoscopic treatment failed in 17% (17/99) of patients and was not associated with stricture length. Operative treatment of biliary stricture was more likely in patients with infected necrosis or NP disease duration ≥6 months. CONCLUSION: Biliary stricture occurs frequently after NP and is associated with splanchnic vein thrombosis and pancreatic head necrosis. Surgical correction was performed in 20%.

The Fistula Risk Score Catalog: Toward Precision Medicine for Pancreatic Fistula After Pancreatoduodenectomy.

OBJECTIVE: This study aims to present a full spectrum of individual patient presentations of pancreatic fistula risk, and to define the utility of mitigation strategies amongst some of the most prevalent, and vulnerable scenarios surgeons encounter. BACKGROUND: The FRS has been utilized to identify technical strategies associated with reduced CR-POPF incidence across various risk strata. However, risk-stratification using the FRS has never been investigated with greater granularity. By deriving all possible combinations of FRS elements, individualized risk assessment could be utilized for precision medicine purposes. METHODS: FRS profiles and outcomes of 5533 PDs were accrued from 17 international institutions (2003-2019). The FRS was used to derive 80 unique combinations of patient "scenarios." Risk-matched analyses were conducted using a Bonferroni adjustment to identify scenarios with increased vulnerability for CR-POPF occurrence. Subsequently, these scenarios were analyzed using multivariable regression to explore optimal mitigation approaches. RESULTS: The overall CR-POPF rate was 13.6%. All 80 possible scenarios were encountered, with the most frequent being scenario #1 (8.1%) - the only negligible-risk scenario (CR-POPF rate = 0.7%). The moderate-risk zone had the most scenarios (50), patients (N = 3246), CR-POPFs (65.2%), and greatest non-zero discrepancy in CR-POPF rates between scenarios (18-fold). In the risk-matched analysis, 2 scenarios (#59 and 60) displayed increased vulnerability for CR-POPF relative to the moderate-risk zone (both P < 0.001). Multivariable analysis revealed factors associated with CR-POPF in these scenarios: pancreaticogastrostomy reconstruction [odds ratio (OR) 4.67], omission of drain placement (OR 5.51), and prophylactic octreotide (OR 3.09). When comparing the utilization of best practice strategies to patients who did not have these conjointly utilized, there was a significant decrease in CR-POPF (10.7% vs 35.5%, P < 0.001; OR 0.20, 95% confidence interval 0.12-0.33). CONCLUSION: Through this data, a comprehensive fistula risk catalog has been created and the most clinically-impactful scenarios have been discerned. Focusing on individual scenarios provides a practical way to approach precision medicine, allowing for more directed and efficient management of CR-POPF.

Colon Involvement in Necrotizing Pancreatitis: Incidence, Risk Factors, and Outcomes.

OBJECTIVE: To investigate the incidence, risk factors, and outcomes of colon involvement in patients with necrotizing pancreatitis. SUMMARY/BACKGROUND DATA: Necrotizing pancreatitis is characterized by a profound inflammatory response with local and systemic implications. Mesocolic involvement can compromise colonic blood supply leading to ischemic complications; however, few data exist regarding this problem. We hypothesized that the development of colon involvement in necrotizing pancreatitis (NP) negatively affects morbidity and mortality. METHODS: Six hundred forty-seven NP patients treated between 2005 and 2017 were retrospectively reviewed to identify patients with colon complications, including ischemia, perforation, fistula, stricture/obstruction, and fulminant Clostridium difficile colitis. Clinical characteristics were analyzed to identify risk factors and effect of colon involvement on morbidity and mortality. RESULTS: Colon involvement was seen in 11% (69/647) of NP patients. Ischemia was the most common pathology (n = 29) followed by perforation (n = 18), fistula (n = 12), inflammatory stricture (n = 7), and fulminant C difficile colitis (n = 3). Statistically significant risk factors for developing colon pathology include tobacco use (odds ratio (OR), 2.0; 95% confidence interval (CI), 1.2-3.4, P = 0.009), coronary artery disease (OR, 1.9; 95% CI, 1.1-3.7; P = 0.04), and respiratory failure (OR, 4.7; 95% CI, 1.1-26.3; P = 0.049). When compared with patients without colon involvement, NP patients with colon involvement had significantly increased overall morbidity (86% vs 96%, P = 0.03) and mortality (8% vs 19%, P = 0.002). CONCLUSION: Colon involvement in necrotizing pancreatitis is common; clinical deterioration should prompt its evaluation. Risk factors include tobacco use, coronary artery disease, and respiratory failure. Colon involvement in necrotizing pancreatitis is associated with substantial morbidity and mortality.

Early postoperative serum hyperamylasemia: Harbinger of morbidity hiding in plain sight?

BACKGROUND: The clinical significance of postoperative serum pancreatic enzyme elevation after pancreatoduodenectomy is understudied. We hypothesized that elevation in serum enzymes predicts morbidity and mortality after pancreatoduodenectomy. METHODS: Retrospective review of 677 patients who underwent pancreatoduodenectomy at a single institution from 2013 to 2019. Patients were categorized based on serum enzyme concentrations. Patient characteristics, drain amylase, and outcomes among groups were compared. RESULTS: In total, 415 of 677 patients had postoperative serum amylase concentrations measured. Of these, 243 (59%) were normal, 96 (23%) were classified as postoperative serum hyperamylasemia, and 76 (18%) were classified as postoperative acute pancreatitis. Major morbidity was lower among patients with normal enzyme concentration (10%) and higher in patients with postoperative serum hyperamylasemia (23%) and postoperative acute pancreatitis (18%) (P = .008). Patients with normal enzymes were less likely to develop postoperative pancreatic fistula (5%) compared with patients with postoperative serum hyperamylasemia (26%) and postoperative acute pancreatitis (21%) (P < .001) and less likely to develop delayed gastric emptying (9% vs 23% and 20%, respectively); P = .002. No difference in mortality was seen among groups. CONCLUSION: Elevated serum pancreatic enzyme concentration occurs frequently after pancreatoduodenectomy and is associated with increased postoperative morbidity. Serum enzyme concentration should be considered in management after pancreatoduodenectomy.

A risk-adjusted analysis of drain use in pancreaticoduodenectomy: Some is good, but more may not be better.

BACKGROUND: Intraperitoneal drain placement decreases morbidity and mortality in patients who develop a clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). It is unknown whether multiple drains mitigate CR-POPF better than a single drain. We hypothesized that multiple drains decrease the complication burden more than a single drain in cases at greater risk for CR-POPF. METHODS: The Fistula Risk Score (FRS), mitigation strategies (including number of drains placed), and clinical outcomes were obtained from a multi-institutional database of PDs performed from 2003 to 2020. Outcomes were compared between cases utilizing 0, 1, or 2 intraperitoneal drains. Multivariable regression analysis was used to evaluate the optimal drainage approach. RESULTS: A total of 4,292 PDs used 0 (7.3%), 1 (45.2%), or 2 (47.5%) drains with an observed CR-POPF rate of 9.6%, which was higher in intermediate/high FRS zone cases compared with negligible/low FRS zone cases (13% vs 2.4%, P < .001). The number of drains placed also correlated with FRS zone (median of 2 in intermediate/high vs 1 in negligible/low risk cases). In intermediate/high risk cases, the use of 2 drains instead of 1 was not associated with a reduced rate of CR-POPF, average complication burden attributed to a CR-POPF, reoperations, or mortality. Obviation of drains was associated with significant increases in complication burden and mortality - regardless of the FRS zone. CONCLUSION: In intermediate/high risk zone cases, placement of a single drain or multiple drains appears to mitigate the complication burden while use of no drains is associated with inferior outcomes.