Cleary, Sean P.

ABSTRACT 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.

ImportanceTranexamic 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.ObjectiveTo determine whether tranexamic acid reduces red blood cell transfusion within 7 days of liver resection.Design, Setting, and ParticipantsMulticenter 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.InterventionsTranexamic 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 MeasuresThe primary outcome was receipt of red blood cell transfusion within 7 days of surgery.ResultsThe 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 RelevanceAmong patients undergoing liver resection for a cancer-related indication, tranexamic acid did not reduce bleeding or blood transfusion but increased perioperative complications.Trial RegistrationClinicalTrials.gov Identifier: NCT02261415

Biliary tract cancers, including cholangiocarcinoma, gallbladder, and ampulla of Vater cancers, rank second among hepatobiliary cancers, known for their poor prognoses. The United States has witnessed a notable increase in intrahepatic cholangiocarcinoma incidence. This study examines the incidence and survival outcomes of biliary tract cancers in Olmsted County, Minnesota from 1976 to 2018. Using data from the Rochester Epidemiology Project (REP), residents aged 20 and above were analyzed across four eras. Incidence rates were calculated and adjusted for age and sex, and temporal trends were assessed using Poisson regression. Intrahepatic cholangiocarcinoma exhibited a significant escalation in incidence rates over time, while gallbladder cancers showed a decline among women. Median survival times for biliary tract cancers notably improved. These findings confirm the rising incidence of intrahepatic cholangiocarcinoma and suggest improving survival rates. Nevertheless, the overall prognosis for biliary tract cancers remains very poor, emphasizing the continual need for enhanced management strategies and further research.

e16301 Background: Outcomes for patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) remain poor with a mean overall survival (OS) of 11 months. Irreversible electroporation (IRE) is a method of local tumor ablation that causes cell death by disrupting homeostasis in the cell membrane. Previous research suggests IRE can be useful in the multi-disciplinary treatment of Stage 3 PDAC. The present study was designed to assess the effectiveness and safety of IRE for Stage 3 PDAC in a real-world setting after induction chemotherapy. Methods: Patients with Stage 3 PDAC treated with IRE were prospectively enrolled in a multicenter registry study. Enrollment required 3 months of active multi-agent chemotherapy, with no progression before IRE treatment. Endpoints were 30- and 90-day mortality from enrollment and the new onset of an adverse event (AE). Results: 87 patients were enrolled in the registry between May 2019 and May 2023. Mean age was 64.0 ± 8.4 years, 57.5% were female and mean tumor diameter was 2.2 ± 0.7 cm. Mean time from diagnosis to IRE treatment was 8.9 ± 4.9 months. All subjects underwent induction chemotherapy with the most common being FOLFIRINOX alone, gemcitabine with albumin-bound paclitaxel, or a combination of both in 47 (54.0%) patients. Thirty-seven (42.5%) patients had prior radiation therapy. All procedures were performed using an open approach with 50 (57.5%) for in-situ tumor ablation and 37 (42.5%) with the intent of margin accentuation in combination with resection. Major adjunctive procedures were performed for 70 (80.5%) patients. Common adjunctive surgeries were cholecystectomy (33.3%), Whipple procedure (28.7%) and either distal or subtotal pancreatectomy (11.4%). Mean IRE delivery time was 55.7 ± 54.5 minutes with an average of 3.1 probes (range 2 to 6) used per procedure. There was a mean of 1031.1 ± 882.1 pulses delivered per procedure. The 30- and 90-day mortality was 3/87 (3.4%) and 4/82 (4.9%) respectively. There were 21 (24.1%) patients who developed AEs related to IRE treatment during the 90-day post-procedure period (9 patients had AEs that were definitely related to IRE, 5 probably and 7 possibly). Of these related events, only three were Grade 4 or higher (arterial hemorrhage, cardiac arrest, and septic shock). Overall, gastrointestinal related AEs were the most common representing 16 of the 28 (57.1%) of all AEs associated with the IRE procedure. One patient died within 30 days of the procedure due to an intraperitoneal arterial hemorrhage that was deemed to be definitely related to the IRE treatment. Conclusions: The use of IRE for curative intent tumor ablation alone or in combination with resection following induction chemotherapy in patients with locally advanced Stage 3 PDAC has acceptable safety and is associated with acceptable morbidity and mortality rates in appropriately selected patients. Clinical trial information: NCT03899649 .

Abstract Introduction: Laparoscopy with peritoneal lavage enhances staging accuracy in patients with pancreatic ductal adenocarcinoma (PDAC). Occult intra-abdominal metastases are identified by staging laparoscopy in approximately 20% of patients with radiologically localized PDAC. Peritoneal fluid cytology has limited sensitivity in detecting occult intra-abdominal metastasis. Methylated DNA markers (MDMs) can accurately detect PDAC from tumor tissue, blood, and pancreatic secretions. This study aims to assess the feasibility of assaying MDMs in peritoneal lavage fluid obtained at the time of staging laparoscopy for patients with PDAC. Methods: Peritoneal lavage fluid (25-60 mL) obtained from patients with PDAC at the time of staging laparoscopy was centrifuged for 10 minutes at 1200 × g. The pellet was resuspended and aliquoted into 200µL tubes and frozen at -80°C. DNA extracted from one aliquot was assayed for mutant KRAS (G12A and G13D) and then bisulfite converted to measure 13 MDMs (GRIN2D, CD1D, ZNF781, FER1L4, RYR2, CLEC11A, AK055957, LRRC4, MAX.CHR5.4295, HOXA1, PRKCB, SHISA9, NTRK3) and a normalizing reference gene (B3GALT6) using quantitative methylation specific PCR. The association of KRAS and the average signal from the 13 MDMs (MDMscore) with intra-abdominal metastasis (Y/N) was assessed with the area under the receiver operator characteristic curve (AUC). Results: Among 48 PDAC patients, staging laparoscopy revealed intra-abdominal metastasis in 15 (31%). Of the 15 intra-abdominal metastases, 6 were found to have biopsy-confirmed intra-abdominal metastasis and positive peritoneal cytology, 4 were positive on peritoneal cytology alone, and 5 had biopsy-confirmed intra-abdominal metastasis alone. The sensitivity of the MDMscore for intra-abdominal metastasis was 87% (CI: 60-98%) at 90% (CI: 76-98%) specificity whereas the sensitivity for KRAS was 40% (CI: 16-68%) at 85% (CI: 68-95) specificity. The AUC for the MDMscore was 0.98 (CI: 0.94-1.00) compared to 0.62 (CI: 0.48-0.77) for that of KRAS (p<0.0001). Conclusion: MDMs assayed from peritoneal lavage fluid collected during staging laparoscopy is a novel tool for accurate molecular staging of PDAC. These early results warrant further study in a larger cohort to assess impact on peritoneal staging and its clinical utility in the neoadjuvant treatment paradigm of PDAC. Citation Format: Kalika Maheshwari, Calise K. Berger, William R. Taylor, Douglas W. Mahoney, Kelli N. Burger, Adriana M. Delgado, Karen A. Doering, Heather M. Streich, Patrick H. Foote, Sean P. Cleary, Travis E. Grotz, Micheal L. Kendrick, Rory L. Smoot, Patrick P. Starlinger, Cornelius A. Thiels, Mark J. Truty, Susanne G. Warner, John B. Kisiel, Shounak Majumder. Methylated DNA markers for detection of peritoneal metastasis in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3784.

Background and Aims: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP). Approach and Results: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP, rs9842969, (0.51, [0.40–0.65]); 5p15.33, TERT, rs2242652, (0.70, (0.62–0.79]); 19q13.11, TM6SF2, rs58542926, (1.49, [1.29–1.72]); 19p13.11 MAU2, rs58489806, (1.53, (1.33–1.75]); and 22q13.31, PNPLA3, rs738409, (1.66, [1.51–1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74–0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC. Conclusions: Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.

AbstractBackground and ObjectivesThere is limited research on management of metastatic anal canal squamous cell carcinoma (SCC) to the liver. This study aimed to describe outcomes for patients undergoing liver resection of anal SCC metastases.MethodsA multicenter, retrospective cohort study was conducted by three tertiary‐referral centers. Patients undergoing liver surgery between 2008 and 2022 were included. Cox regression analysis was performed to evaluate predictors of recurrence and survival and Kaplan–Meier analysis was performed for 1‐, 3‐, and 5‐year survival.ResultsTwenty‐one patients underwent liver resection and/or ablation. None were HIV positive and 24% had known HPV infection. 20/21(95%) patients had undergone Nigro protocol for management of the primary tumor with 12/21 (57%) patients experiencing complete response. 4/21 (19%) patients had synchronous liver metastases at time of diagnosis. Median tumor size was 5.0 cm and median tumor number was one. At analysis, 52% remained alive. Median overall survival was 32.2 months. 5‐year overall survival was 50%. Median recurrence‐free survival was 7.7 months and 5‐year recurrence‐free survival was 30%. Need for salvage abdominoperineal resection was negatively associated with recurrence‐free survival. The most common site of recurrence was the liver.ConclusionsLiver resection for metastatic anal SCC can be beneficial for appropriately selected patients.

Despite advances in medical technology, intraoperative adverse events (IAE) continue to occur in hospital’s complex systems. Current approaches to understanding and mitigating IAEs rely on retrospective data analyses to recognize the series of events leading to an IAE. This paper discusses current challenges and highlights the potential of the Operating Room Blackbox (ORBB) system use to enhance patient safety.

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 aspartate aminotransferase to platelet ratio combined with an albumin-bilirubin grade (APRI+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: A total of 12,056 patients from the National Surgical Quality Improvement Program database were used to generate a MVM to predict PHLF B+C. The model was determined using stepwise backwards elimination. The performance of the model was tested using receiver operating characteristic curve analysis and validated in an international cohort of 2525 patients. In 620 patients, the APRI+ALBI MVM, trained in the National Surgical Quality Improvement Program cohort, was compared with the 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 the calculation of the APRI+ALBI MVM was designed. Conclusion: Risk assessment through the APRI+ALBI MVM for PHLF B+C increases preoperative predictive accuracy and represents a universally available and cost-effective risk assessment before hepatectomy, facilitated by a freely available smartphone app.

AbstractBackground and ObjectivesWe assessed the accuracy of preoperative gallium‐68 DOTA‐Tyr3‐octreotate (DOTATATE) positron emission tomography (PET) imaging in estimating multifocality and nodal metastases of small bowel neuroendocrine tumors (sbNETs).MethodsA multicenter analysis was performed on patients with sbNETs who underwent preoperative DOTATATE PET imaging and surgical resection, with manual palpation of the entire length of the small bowel, between January 2016 and August 2022. Preoperative imaging reports and blinded secondary imaging reviews were compared to the final postoperative pathology reports. Descriptive statistics were applied.ResultsOne‐hundred and four patients met inclusion criteria. Pathology showed 53 (51%) patients had multifocal sbNETs and 96 (92%) had nodal metastases. The original preoperative DOTATATE PET imaging identified multifocal sbNET in 28 (27%) patients and lymph node (LN) metastases in 80 (77%) patients. Based on original radiology reports, sensitivity for multifocal sbNET identification was 45%, specificity was 92%, positive predictive value (PPV) was 86%, and negative predictive value (NPV) was 62%. For the identification of LN metastases, sensitivity was 82%, specificity was 88%, PPV was 99%, and NPV was 29%.ConclusionsAlthough DOTATATE PET imaging is specific and relatively accurate, sensitivity and NPV are insufficient to guide surgical planning. Preoperative use should not replace open palpation to identify additional synchronous lesions or to omit regional lymphadenectomy.