Financial Toxicity of Long-Term Survivors Who Underwent Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Pancreatoduodenectomy (PD) for pancreatic cancer has a profound impact on patients' lives. However, the long-term financial implications are poorly understood. OBJECTIVE: Assess the financial burden of long-term survivors who underwent PD. METHODS: Patients who underwent PD between January 2011 and June 2019 were identified. To evaluate the long-term financial burden, patients surviving ≥ 3 years post-resection were prospectively surveyed using the Comprehensive Score for financial Toxicity (COST-FACIT) and a customized institutionally developed questionnaire. A logistic regression model predicting high financial toxicity was used to identify predictive factors. RESULTS: Among 238 eligible patients, 137 (57.6%) responded. Responders had a median age of 66 (59-73) years, with 86.7% identifying as financial prosperous or comfortable. However, 33.3% experienced financial distress due to treatment costs, 27.3% demonstrated high financial toxicity on the COST-FACIT survey, and 37.2% made sacrifices to afford treatment. Only 8.9% stated that the treatment costs influenced their decisions, and the majority (85.9%) did not discuss financial implications with healthcare providers. Multivariable analysis identified younger age as a risk factor for high financial toxicity. CONCLUSION: One in three long-term survivors experienced high financial toxicity, with younger age being a predictor. This emphasizes the need for efforts to provide comprehensive support and guidance to patients to navigate their oncological journey.

Impact of proton pump inhibitors on pathologic response rates following fluoropyrimidine-based neoadjuvant chemotherapy in pancreatic cancer patients.

BACKGROUND: Proton pump inhibitors (PPIs) negatively impact fluoropyrimidine-based chemotherapy efficacy in colorectal cancer. This study assessed PPI impact on major pathologic response (mPR) rates of pancreatic adenocarcinoma (PDAC) patients receiving fluoropyrimidine-based chemotherapy. METHODS: An institutional retrospective review of resected PDAC patients receiving neoadjuvant fluoropyrimidine-based chemotherapy (98% FOLFIRINOX) from 2011 to 2021 was conducted. Outcomes were stratified by use or nonuse of PPIs within 6 months of neoadjuvant chemotherapy initiation. Primary outcome was mPR defined as complete or near complete response. RESULTS: Among 540 patients included, the median age was 64 (IQR: 60-70) years, 297 (55%) were male, and 202 (37%) were PPI users. 170 (31%) patients had mPR with similar rates among PPI users and nonusers (29% vs. 33%, p = 0.38). No difference in mPR was seen between PPI users and nonusers receiving chemoradiation (35% vs. 36%, p = 0.89) or ≥8 cycles of NAC (33% vs. 36%, p = 0.55). Median OS for PPI users was 30.9 versus 31.7 months for nonusers (p = 0.62). On multivariable analysis, PPI therapy was not associated with decreased survival. CONCLUSION: PPI usage did not significantly influence mPR or OS following neoadjuvant fluoropyrimidine-based chemotherapy in resected PDAC patients. Further analysis of all patients, not just those who underwent resection, is required.

Tranexamic Acid in Patients Undergoing Liver Resection: The HeLiX Randomized Clinical Trial.

Importance: Tranexamic acid reduces bleeding and blood transfusion in many types of surgery, but its effect in patients undergoing liver resection for a cancer-related indication remains unclear. Objective: To determine whether tranexamic acid reduces red blood cell transfusion within 7 days of liver resection. Design, Setting, and Participants: Multicenter randomized clinical trial of tranexamic acid vs placebo conducted from December 1, 2014, to November 8, 2022, at 10 hepatopancreaticobiliary sites in Canada and 1 site in the United States, with 90-day follow-up. Participants, clinicians, and data collectors were blinded to allocation. A volunteer sample of 1384 patients undergoing liver resection for a cancer-related indication met eligibility criteria and consented to randomization. Interventions: Tranexamic acid (1-g bolus followed by 1-g infusion over 8 hours; n = 619) or matching placebo (n = 626) beginning at induction of anesthesia. Main Outcomes and Measures: The primary outcome was receipt of red blood cell transfusion within 7 days of surgery. Results: The primary analysis included 1245 participants (mean age, 63.2 years; 39.8% female; 56.1% with a diagnosis of colorectal liver metastases). Perioperative characteristics were similar between groups. Red blood cell transfusion occurred in 16.3% of participants (n = 101) in the tranexamic acid group and 14.5% (n = 91) in the placebo group (odds ratio, 1.15 [95% CI, 0.84-1.56]; P = .38; absolute difference, 2% [95% CI, -2% to 6%]). Measured intraoperative blood loss (tranexamic acid, 817.3 mL; placebo, 836.7 mL; P = .75) and total estimated blood loss over 7 days (tranexamic acid, 1504.0 mL; placebo, 1551.2 mL; P = .38) were similar between groups. Participants receiving tranexamic acid experienced significantly more complications compared with placebo (odds ratio, 1.28 [95% CI, 1.02-1.60]; P = .03), with no significant difference in venous thromboembolism (odds ratio, 1.68 [95% CI, 0.95-3.07]; P = .08). Conclusions and Relevance: Among patients undergoing liver resection for a cancer-related indication, tranexamic acid did not reduce bleeding or blood transfusion but increased perioperative complications. Trial Registration: ClinicalTrials.gov Identifier: NCT02261415.

Impact of metabolic and bariatric surgery on weight loss and insulin requirements in type 1 and insulin-treated type 2 diabetes.

Metabolic and Bariatric Surgery (MBS) is effective in improving metabolic outcomes and reducing weight in patients with obesity and diabetes, with less explored benefits in type 1 diabetes (T1D). This study aimed to evaluate the impact of MBS on weight loss and insulin requirements in T1D patients compared to insulin-treated type 2 diabetes (T2D) patients over a 5-year period. This retrospective analysis included patients who underwent primary sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) with a confirmed preoperative diagnosis of either T1D or insulin-treated T2D. Primary endpoints focusing on weight loss and secondary outcomes assessing changes in insulin dosage and glycemic control. After 5 years, weight loss was similar across groups, with total weight loss at 14.2% for T1D and 17.6% for insulin-treated T2D in SG, and 22.6% for T1D vs. 26.8% for insulin-treated T2D in RYGB. Additionally, there was a significant reduction in median daily insulin doses from 140.5 units at baseline to 77.5 units at 1 year postoperatively, sustained at 90 units at 5 years. The differential impact of MBS procedure was also highlighted, where RYGB patients showed a more pronounced and enduring decrease in insulin requirements compared to SG.

Failed recovery after pancreatoduodenectomy: A significant problem even without surgical complications.

BACKGROUND: The absence of surgical complications has traditionally been used to define successful recovery after pancreas surgery. However, patient-reported outcome measures as metrics of a challenging recovery may be superior to objective morbidity. This study aims to evaluate the use of patient-reported outcomes in assessing recovery after pancreas surgery. METHODS: Patients scheduled for pancreatoduodenectomy were prospectively enrolled between 2016 to 2018. Patient-reported outcomes were collected using the linear analog self-assessment questionnaire preoperatively and on postoperative days 2, 7, 14, 30, and monthly until 6 months. Patients were also asked if they felt fully recovered at 30 days and 6 months. Thirty-day surgical morbidity was prospectively assessed, and the comprehensive complication index at 30 days was used to categorize morbidity as major or multiple minor complications (comprehensive complication index ≥26.2) vs uncomplicated (comprehensive complication index <26.2). Clinically significant International Study Group Pancreas Surgery Grade B and C pancreatic fistulas and delayed gastric emptying were reported. χ2 and Kruskal-Wallis tests were used to assess associations with recovery by 6 months and quality of life throughout the postoperative period. RESULTS: Of 116 patients who met inclusion criteria and were enrolled, 32 (28%) had major or multiple minor complications (comprehensive complication index ≥26.2). Overall, fewer than 1 in 10 patients (7%) reported feeling fully recovered at 30 days postoperatively, whereas 55% reported feeling fully recovered at 6 months. Of patients suffering major morbidity, 62% did not recover by 6 months, whereas 38% of those in the uncomplicated group reported not being recovered at 6 months (P = .03). Patients who experienced delayed gastric emptying reported low quality-of-life scores at 1 month (P = .04) compared to those with no delayed gastric emptying, but this did not persist at 6 months (P = .80). Postoperative pancreatic fistula was not associated with quality of life at 1 or 6 months (both P > .05). In the uncomplicated patients, age, sex, surgical approach, and cancer status were not associated with failed recovery at 6 months (all P > .05), and healthier patients (American Society of Anesthesiologists 1-2) were less likely to report complete recovery (42% vs 69% American Society of Anesthesiologists 3-4, P = .04). With the exception of higher preoperative pain scores (mean 2.3 [standard deviation 2.4] among patients not fully recovered at 6 months vs 1.6 [2.2] among those fully recovered, P = .04), preoperative patient-reported outcomes were not associated with failed recovery at 6 months (all P > .05). However, lower 30-day quality of life, social activity, pain, and fatigue scores were associated with incomplete recovery at 6 months. CONCLUSION: More than 1 in 3 patients with an uncomplicated course do not feel fully recovered from pancreas surgery at 6 months; the presence of surgical complications did not universally correspond with recovery failure. In patients with complications, delayed gastric emptying appears to drive quality of life more significantly than postoperative pancreatic fistula. In patients with uncomplicated recovery, healthier patients were less likely to report full recovery at 6 months. Thirty-day patient-reported outcomes may be able to identify patients who are at risk of incomplete long-term recovery.

Implications of pregnancy on MCN of the pancreas: A multicentric case-control study.

BACKGROUND: Mucinous cystic neoplasms (MCN) of the pancreas express estrogen and progesterone receptors. Several case reports describe MCN increasing in size during gestation. The aim of this study is to assess if pregnancy is a risk factor for malignant degeneration of MCN. METHODS: All female patients who underwent pancreatic resection of a MCN between 2011 and 2021 were included. MCN resected or diagnosed within 12 months of gestation were defined perigestational. MCN with high grade dysplasia or an invasive component were classified in the high grade (HG) group. The primary outcome was defined as the correlation between exposure to gestation and peri-gestational MCN to development of HG-MCN. RESULTS: The study includes 176 patients, 25 (14 %) forming the HG group, and 151 (86 %) forming the low grade (LG) group. LG and HG groups had a similar distribution of systemic contraceptives use (26 % vs. 16 %, p = 0.262), and perigestational MCN (7 % vs 16 %, p = 0.108). At univariate analysis cyst size ≥10 cm (OR 5.3, p < 0.001) was associated to HG degeneration. Peri gestational MCN positively correlated with cyst size (R = 0.18, p = 0.020). In the subgroup of 14 perigestational MCN patients 29 % had HG-MCN and 71 % experienced cyst growth during gestation with an average growth of 55.1 ± 18 mm. CONCLUSIONS: Perigestational MCN are associated to increased cyst diameter, and in the subset of patients affected by MCN during gestation a high rate of growth was observed. Patients with a MCN and pregnancy desire should undergo multidisciplinary counselling.

Neuroendocrine Tumors of Unknown Primary in the Setting of Cytoreductive Hepatectomy.

BACKGROUND: Surgical cytoreduction for neuroendocrine tumor liver metastasis (NETLM) consistently shows positive long-term outcomes. Despite reservations in guidelines for surgery when the primary tumor is unidentified (UP-NET), this study compared the surgical and oncologic long-term outcomes between patients with these rare cases undergoing cytoreductive surgery and patients who had liver resection for known primaries. METHODS: The study identified 32 unknown primary liver metastases (UP-NETLM) in 522 retrospectively evaluated patients who underwent resection of well-differentiated NETLM between January 2000 and December 2020. Tumor and patient characteristics were compared with those in 490 cases of liver metastasis from small intestinal (SI-NETLM) or pancreatic (pNETLM) primaries. Survival analysis was performed to highlight long-term outcome differences. Surgical outcomes were compared between liver resections alone and simultaneous primary resections to assess surgical risk distinctions. RESULTS: The UP-NET patients had fewer NETLMs (p = 0.004), which on the average were larger than SI-NETLMs or pNETLMs (p = 0.002). Expression of Ki-67 was balanced among the groups. Major hepatectomy was performed more often in the UP-NETLM group (p = 0.017). The 10-year survival rate of 53% for UP-NETLM was comparable with that for SI-NETML (58%; p = 0.463) and pNETLMs (47%; p = 0.497). The median hepatic progression-free survival was 26 months for the UP-NETLM patients and 25 months for the SI-NETLM patients compared to 12 months for the pNETLM patients (p < 0.001). Perioperative mortality was lower than 2%, and severe postoperative morbidity occurred in 21%, similarly distributed among all the groups. CONCLUSION: The surgical risk and long-term outcomes for the UP-NETLM patients were comparable with those for other NETLM cases, affirming the validity of equally aggressive surgical cytoreduction as a therapeutic option in carefully selected cases.

Outcomes of Visceral Arterial Interposition Graft Reconstruction for Locally Advanced Pancreatic Cancer.

OBJECTIVE: The aim of this study is to determine perioperative outcomes and the patency of interposition conduits for visceral arterial reconstruction in this setting. SUMMARY BACKGROUND DATA: Visceral arterial encasement in locally advanced pancreatic cancer was historically a contraindication for surgery. With modern effective neoadjuvant strategies, our recent experience has made advanced vascular resection and reconstruction feasible in selected patients. METHODS: A retrospective review was performed of patients undergoing pancreatic tumor resection with en bloc arterial resection and interposition revascularization between 6/2002-10/2022. Endpoints included graft patency, vascular-related complications, reinterventions, morbidity, and mortality. RESULTS: Visceral arterial reconstruction with interposition grafting was performed in 111 patients undergoing en bloc arterial resections for pancreatic cancer. Graft types included autologous arterial conduits (n=66, 58 superficial femoral artery (SFA) and 8 splenic artery), cryopreserved arterial allografts (n=24), autologous saphenous veins (n=12), synthetic conduits (n=8), and composite autologous artery and synthetic (n=1). Perioperative 90-day mortality decreased significantly over time to 5% in the last six years. Vascular complications related to arterial reconstruction occurred in 11% (n=12) and included pseudoaneurysm (n=6), graft thrombus (n=2), stenosis requiring reintervention (n=2), hepatic failure (n=1), and hepatic and intestinal ischemia (n=1). Nine (8%) patients underwent vascular-related reinterventions. After median follow-up of 17-months, primary patency was 81% for the entire cohort and was highest in the SFA group (95%). The donor limb/harvest site complication rate was 8% with 100% primary patency. CONCLUSION: Visceral arterial resection with interposition reconstruction for locally advanced pancreatic cancer can be performed with acceptable vascular morbidity and durable patency. Autologous SFA was the most suitable conduit for reconstructions in our experience, with highest primary patency.

Comprehensive outcomes after Roux-en-Y gastric bypass with a near-complete 15-year follow-up.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass has a well-established safety and efficacy profile in the short and mid-term. Long-term outcomes remain limited in the literature, especially for follow-up periods of >10 years. The purpose of the study is to evaluate the long-term durability and safety of laparoscopic Roux-en-Y gastric bypass over a near-complete 15-year follow-up. METHODS: This is a single-center retrospective cohort study of patients who underwent primary laparoscopic Roux-en-Y gastric bypass between 2008 and 2009 with ≥14-year follow-up. Data collected and analyzed were weight loss, obesity-related medical condition resolution and recurrence, weight recurrence, complication rate, and mortality rate. RESULTS: A total of 264 patients were included. Patients were predominantly female (81.8%), and the mean age and preoperative body mass index were 48.5 ± 12.2 years and 44.9 ± 7.3 kg/m2, respectively. The maximum mean percentage total weight loss achieved at 1 year was 31.5% ± 5.7% and was consistently >20% throughout follow-up. Sustained resolution of obesity-related medical conditions was achieved with a remission rate of 60.8% for type 2 diabetes mellitus, 46.7% for denoted dyslipidemia, and 40% for hypertension. Obesity-related medical condition recurrence was observed with a recurrence rate of 24.1% for type 2 diabetes mellitus, 17.9% for hypertension, and 14.8% for denoted dyslipidemia. Significant factors associated with weight loss were maximum percentage total weight loss and preoperative type 2 diabetes mellitus. Over 15 years, the weight recurrence rate was 51.1%, with predictors of higher preoperative body mass index and preoperative type 2 diabetes mellitus. CONCLUSION: Laparoscopic Roux-en-Y gastric bypass provides sustainable weight loss over a 15-year period, with consistent long-term weight-loss outcomes and resolution of obesity-related medical conditions sustained for ≥10 years after surgery.

Value of Surgical Cytoreduction in Patients with Small Intestinal Neuroendocrine Tumors Metastatic to the Liver and Peritoneum.

BACKGROUND: Cytoreductive hepatectomy can improve survival and symptoms of hormonal excess in patients with small intestinal neuroendocrine tumor (siNET) liver metastases, but whether to proceed when peritoneal metastases are encountered at the time of planned cytoreductive hepatectomy is controversial. METHODS: This was a retrospective review of patients who underwent surgical management of metastatic siNETs at Mayo Clinic between 2000 and 2020. Patients who underwent cytoreductive operation for isolated liver metastases or both liver and peritoneal metastases were compared. RESULTS: Of 261 patients who underwent cytoreductive operation for siNETs, 211 had isolated liver metastases and 50 had liver and peritoneal metastases. Complete cytoreduction was achieved in 78% of patients with isolated liver metastases and 56% of those with liver and peritoneal metastases (p = 0.002). After complete cytoreduction, median overall survival (OS) was 11.5 years for isolated liver metastases and 11.2 years for liver and peritoneal metastases (p = 0.10), and relief of carcinoid syndrome was ≥ 97% in both groups. After incomplete cytoreduction with debulking of > 90% of hepatic disease and/or closing Lyon score of 1-2, median OS was 6.4 years for isolated liver metastases and 7.1 years for liver and peritoneal metastases (p = 0.12). CONCLUSIONS: Patients with siNETs metastatic to both the liver and peritoneum have favorable outcomes after aggressive surgical cytoreduction, with the best outcomes observed after complete cytoreduction. Therefore, the presence of peritoneal metastases should not by itself preclude surgical cytoreduction in this population.

Single anastomosis duodenal switch versus Roux-en-Y gastric bypass in patients with BMI ≥ 50 kg/m2: a multi-centered comparative analysis.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) has consistently demonstrated excellent weight loss and comorbidity resolution. However, outcomes vary based on patient's BMI. Single anastomosis duodeno-ileostomy with sleeve (SADI-S) is a novel procedure with promising short-term results. The long-term outcomes of SADI-S in patients with BMI ≥ 50 kg/m2 are not well described. We aim to compare the safety and efficacy of SADI-S with RYGB in this patient population. METHODS: We performed a multicenter retrospective study of patients with a BMI ≥ 50 kg/m2 who underwent RYGB or SADI-S between 2008 and 2023. Patient demographics, peri- and post-operative characteristics were collected. Complication rates were reported at 6, 12, 24, and 60 months postoperatively. A multivariate linear regression was used to evaluate and compare weight loss outcomes between both procedures. RESULTS: A total of 968 patients (343 RYGB and 625 SADI-S; 68.3% female, age 42.9 ± 12.1 years; BMI 57.3 ± 6.7 kg/m2) with a mean follow-up of 3.6 ± 3.6 years were included. Patients who underwent RYGB were older, more likely to be female, and have a higher rate of sleep apnea (p < 0.001), hypertension (p = 0.015), dyslipidemia (p < 0.001), and type 2 diabetes (p = 0.016) at baseline. The rate of bariatric surgery-specific complications was lower after SADI-S compared to RYGB. We reported no bariatric surgery related deaths after 1 year following both procedures. SADI-S demonstrated statistically higher and sustained weight loss at each time interval compared to RYGB (p < 0.001) even after controlling for multiple confounders. Lastly, the rate of surgical non-responders was lower in the SADI-S cohort. CONCLUSIONS: In our cohort, SADI-S was associated with higher and sustained weight-loss results compared to RYGB. Comorbidity resolution was also higher after SADI-S. Both procedures demonstrate a similar safety profile. Further studies are required to validate the long-term safety of SADI-S compared to other bariatric procedures.

Outcomes of Neoadjuvant Chemotherapy for Invasive Intraductal Papillary Mucinous Neoplasm Compared with de Novo Pancreatic Adenocarcinoma.

BACKGROUND: The management of invasive intraductal papillary mucinous cystic neoplasm (I-IPMN) does not differ from de novo pancreatic ductal adenocarcinoma (PDAC); however, I-IPMNs are debated to have better prognosis. Despite being managed similarly to PDAC, no data are available on the response of I-IPMN to neoadjuvant chemotherapy. METHODS: All patients undergoing pancreatic resection for a pancreatic adenocarcinoma from 2011 to 2022 were included. The PDAC and I-IPMN cohorts were compared to evaluate response to neoadjuvant therapy (NAT) and overall survival (OS). RESULTS: This study included 1052 PDAC patients and 105 I-IPMN patients. NAT was performed in 25% of I-IPMN patients and 65% of PDAC patients. I-IPMN showed a similar pattern of pathological response to NAT compared with PDAC (p = 0.231). Furthermore, positron emission tomography (PET) response (71% vs. 61%; p = 0.447), CA19.9 normalization (85% vs. 76%, p = 0.290), and radiological response (32% vs. 37%, p = 0.628) were comparable between I-IPMN and PDAC. A significantly higher OS and disease-free survival (DFS) of I-IPMN was denoted by Kaplan-Meier analysis, with a p-value of < 0.001 in both plots. In a multivariate analysis, I-IPMN histology was independently associated with lower risk of recurrence and death. CONCLUSIONS: I-IPMN patients have a longer OS and DFS after surgical treatment when compared with PDAC patients. The more favorable oncologic outcome of I-IPMNs does not seem to be related to early detection, as I-IPMN histological subclass is independently associated with a lower risk of disease recurrence. Moreover, neoadjuvant effect on I-IPMN was non-inferior to PDAC in terms of pathological, CA19.9, PET, and radiological response and thus can be considered in selected patients.

Laparoscopic Median Arcuate Ligament Release: Surgical Technique and Clinical Outcomes.

BACKGROUND: Median arcuate ligament syndrome (MALS) is characterized by a constellation of symptoms related to the compression of the celiac artery trunk. Laparoscopic release of the ligament has demonstrated its effectiveness in alleviating these symptoms while showing lower postoperative complication rates, reduced hospital stays, and improved clinical outcomes. This study describes a single institution's experience with this procedure and reports on the preoperative assessment, surgical technique, and clinical outcomes of patients with MALS. METHODS: We performed a retrospective chart review of all patients who underwent a primary laparoscopic MAL release (MALR) at a single high-volume academic institution from June 2021 to July 2023. Patient demographics, preoperative assessment, postoperative complications, and resolution of preoperative symptoms data were collected. RESULTS: A total of 30 patients underwent laparoscopic MALR, with 76.7% being female and a mean age of 33.4±16.3 years. The most common presenting symptom was postprandial epigastric pain (100%), followed by abdominal pain and nausea (83.3%), among others. The preoperative evaluation for all patients included a duplex mesenteric doppler and CT angiogram during inspiration and expiration and 3D reconstruction. Successful laparoscopic decompression of the celiac artery was achieved in 96.6% of cases, with only one conversion to an open procedure. There was only one reported early (<30 d postoperatively) complication with no subsequent late complications or mortality. None of the patients required reintervention or reoperation. Only 1 patient required postoperative celiac plexus/splanchnic block injection to alleviate pain. CONCLUSIONS: MALS can be effectively and safely managed using a laparoscopic approach when performed by an experienced minimally invasive surgeon. Further studies with longer follow-ups are needed to confirm the long-term effectiveness of this technique.

Long-Term Outcomes of Bariatric Surgery in Patients on Chronic Anticoagulation.

BACKGROUND: Approximately 3% of patients undergoing metabolic and bariatric surgery (MBS) are receiving chronic anticoagulation therapy (CAT) prior to operation. The management of these patients is complex, as it involves balancing the potential risk of thrombosis against that of bleeding. Our primary objective is to assess the long-term bleeding risk in patients undergoing MBS. We also aim to observe the trends in anticoagulant dosing after MBS. METHODS: A single-center retrospective review of patients who underwent either primary Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) with preoperative CAT between 2008 and 2022 was performed. Data on baseline demographics, indication for anticoagulation, type of CAT, and dosing were collected. Events of bleeding and the CAT at event were subsequently evaluated. RESULTS: A total of 132 patients (82 RYGB and 50 SG) initially on CAT were identified, with atrial fibrillation being the most common indication. Incidence of long-term bleeding was significantly higher in the RYGB group (18.3%) compared to the SG group (4%) (p = 0.017) over a total of 5.2 ± 3.8 years. Bleeding marginal ulcer (MU) was the most common cause of bleeding in the RYGB group (13.4%). 84.2% of all bleeding events occurred in patients on chronic Warfarin therapy. CONCLUSION: Long-term CAT is associated with an increased risk of bleeding in RYGB patients, particularly MU bleeds. Patients on CAT seeking MBS should be counseled regarding this risk and potential implications. Direct-acting oral anticoagulants offer promise as an alternative to Warfarin in these patients; further research is necessary to better understand their safety.

An APRI+ALBI Based Multivariable Model as Preoperative Predictor for Posthepatectomy Liver Failure.

OBJECTIVE AND BACKGROUND: Clinically significant posthepatectomy liver failure (PHLF B+C) remains the main cause of mortality after major hepatic resection. This study aimed to establish an APRI+ALBI, aspartate aminotransferase to platelet ratio (APRI) combined with albumin-bilirubin grade (ALBI), based multivariable model (MVM) to predict PHLF and compare its performance to indocyanine green clearance (ICG-R15 or ICG-PDR) and albumin-ICG evaluation (ALICE). METHODS: 12,056 patients from the National Surgical Quality Improvement Program (NSQIP) database were used to generate a MVM to predict PHLF B+C. The model was determined using stepwise backwards elimination. Performance of the model was tested using receiver operating characteristic curve analysis and validated in an international cohort of 2,525 patients. In 620 patients, the APRI+ALBI MVM, trained in the NSQIP cohort, was compared with MVM's based on other liver function tests (ICG clearance, ALICE) by comparing the areas under the curve (AUC). RESULTS: A MVM including APRI+ALBI, age, sex, tumor type and extent of resection was found to predict PHLF B+C with an AUC of 0.77, with comparable performance in the validation cohort (AUC 0.74). In direct comparison with other MVM's based on more expensive and time-consuming liver function tests (ICG clearance, ALICE), the APRI+ALBI MVM demonstrated equal predictive potential for PHLF B+C. A smartphone application for calculation of the APRI+ALBI MVM was designed. CONCLUSION: Risk assessment via the APRI+ALBI MVM for PHLF B+C increases preoperative predictive accuracy and represents an universally available and cost-effective risk assessment prior to hepatectomy, facilitated by a freely available smartphone app.

Marginal Ulcer and Dumping Syndrome in Patients after Duodenal Switch: A Multi-Centered Study.

BACKGROUND: The current design of biliopancreatic diversion with duodenal switch (BPD/DS) and single anastomosis duodenal-ileal bypass with sleeve (SADI-S) emphasizes the importance of the pylorus' preservation to reduce the incidence of marginal ulcer (MU) and dumping. However, no institutional studies have yet reported data on their prevalence. We aimed to assess the incidence of MU and dumping after duodenal switch (DS) and identify the associative factors. METHODS: A multi-center review of patients who underwent BPD/DS or SADI-S between 2008 and 2022. Baseline demographics, symptoms, and management of both complications were collected. Fisher's exact test was used for categorical variables and the independent t-test for continuous variables. RESULTS: A total of 919 patients were included (74.6% female; age 42.5 years; BMI 54.6 kg/m2) with mean follow-up of 31.5 months. Eight patients (0.9%) developed MU and seven (0.8%) had dumping. Patients who developed MU were more likely to be using non-steroidal anti-inflammatory drugs (NSAID) (p = 0.006) and have a longer operation time (p = 0.047). Primary versus revisional surgery, and BDP/DS versus SADI-S were not associated with MU or dumping. CONCLUSIONS: The incidences of MU and dumping after DS were low. NSAID use and a longer operation time were associated with an increased risk of MU, whereas dumping was attributed to poor dietary habits.

Oncologic Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Highly Selected Patients with Metastatic Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Peritoneal metastases (PM) from pancreatic ductal adenocarcinoma (PDAC) are currently treated with palliative systemic chemotherapy alone, with unsatisfactory results. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may provide an oncologic benefit for highly selected patients. PATIENTS AND METHODS: Patients with PDAC and isolated PM who completed ≥ 6 months of systemic chemotherapy with objective response between 2017 and 2022 were retrospectively reviewed. All patients met the inclusion/exclusion criteria as per our previously published PDAC CRS/HIPEC protocol. Patients who underwent CRS/HIPEC were compared with matched patients who underwent systemic therapy alone. Overall survival (OS) from diagnosis of PM and progression-free survival (PFS) from CRS/HIPEC was evaluated. RESULTS: In total, 61 patients met the inclusion criteria: 38 underwent systemic therapy alone and 23 CRS/HIPEC. There were no differences in baseline prognostic factors, including age, sex, tumor size, tumor location, anatomic resectability, or serum cancer antigen (CA) 19-9 (p > 0.05). Median OS from PM diagnosis in patients who underwent systemic therapy alone was 19 months with 1, 2, and 3 year OS of 81%, 31%, and 8%, respectively. In contrast, median OS from PM diagnosis in patients who underwent CRS/HIPEC was 41 months with improved 1, 2, and 3 year OS of 91%, 66%, and 59%, respectively (p = 0.002). In the 21 patients who achieved complete cytoreduction (CC-0), no adjuvant therapy was administered and the median PFS was 17 months. CONCLUSIONS: CRS/HIPEC in highly selected patients with PDAC and PM results in promising oncologic outcomes that are unlikely to be achieved with systemic chemotherapy alone. Further investigation is warranted and ongoing (NCT04858009).

Hypoxia-Inducible Factor 1α Stabilization Restores Epigenetic Control of Nitric Oxide Synthase 1 Expression and Reverses Gastroparesis in Female Diabetic Mice.

BACKGROUND & AIMS: Although depletion of neuronal nitric oxide synthase (NOS1)-expressing neurons contributes to gastroparesis, stimulating nitrergic signaling is not an effective therapy. We investigated whether hypoxia-inducible factor 1α (HIF1A), which is activated by high O2 consumption in central neurons, is a Nos1 transcription factor in enteric neurons and whether stabilizing HIF1A reverses gastroparesis. METHODS: Mice with streptozotocin-induced diabetes, human and mouse tissues, NOS1+ mouse neuroblastoma cells, and isolated nitrergic neurons were studied. Gastric emptying of solids and volumes were determined by breath test and single-photon emission computed tomography, respectively. Gene expression was analyzed by RNA-sequencing, microarrays, immunoblotting, and immunofluorescence. Epigenetic assays included chromatin immunoprecipitation sequencing (13 targets), chromosome conformation capture sequencing, and reporter assays. Mechanistic studies used Cre-mediated recombination, RNA interference, and clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-mediated epigenome editing. RESULTS: HIF1A signaling from physiological intracellular hypoxia was active in mouse and human NOS1+ myenteric neurons but reduced in diabetes. Deleting Hif1a in Nos1-expressing neurons reduced NOS1 protein by 50% to 92% and delayed gastric emptying of solids in female but not male mice. Stabilizing HIF1A with roxadustat (FG-4592), which is approved for human use, restored NOS1 and reversed gastroparesis in female diabetic mice. In nitrergic neurons, HIF1A up-regulated Nos1 transcription by binding and activating proximal and distal cis-regulatory elements, including newly discovered super-enhancers, facilitating RNA polymerase loading and pause-release, and by recruiting cohesin to loop anchors to alter chromosome topology. CONCLUSIONS: Pharmacologic HIF1A stabilization is a novel, translatable approach to restoring nitrergic signaling and treating diabetic gastroparesis. The newly recognized effects of HIF1A on chromosome topology may provide insights into physioxia- and ischemia-related organ function.