INTRODUCTION:Racial differences in antitumoral immunity have been identified in a variety of cancers and may contribute to survival disparities, but limited data exist exploring the molecular differences in pancreatic adenocarcinoma (PDAC). Using racially diverse PDAC datasets, we explored biologic differences that may drive disparities between African American (AA) and European American (EA) PDAC patients. METHODS:Genomic PDAC mutational data was analyzed for mutational differences based on race. In a separate cohort, surgical PDAC specimens were processed for both tissue microarray and multiplex gene expression analysis using NanoString. RESULTS:Of the 4679 patient samples in the mutational dataset, AA PDAC patients had significantly more TP53 mutations compared to the EA cohort. The tissue microarray included 12 AA and 41 EA surgically resected treatment-naive PDAC samples. NanoString analysis revealed significant differences between AA and EA groups in immunologic gene annotations (P < 0.05). CONCLUSIONS:In the present study, we demonstrated that across racially diverse datasets, there exist molecular and microenvironmental differences between AA and EA patients that may contribute to cancer survival disparities. Defining molecular differences underlying PDAC racial disparities is an essential step in advancing care and improving outcomes for AA patients that suffer worse survival across cancer types.

Abstract Introduction: Obesity, defined as a body mass index (BMI) > 30 kg/m2, increases the risk of benign and malignant pancreatic diseases. One mainstay of treatment for certain pancreatic conditions involves surgical resection with pancreaticoduodenectomy, a technically complex operation with high complication risk. In this analysis, we hypothesized that obesity and morbid obesity would adversely impact perioperative outcomes for the pancreaticoduodenectomy procedure. Methods: Retrospective study design using a large, single institution surgical database (2004-2024; n = 948) that was queried for non-underweight, non-metastatic pancreatic diseases treated with pancreaticoduodenectomy. Patients were categorized as non- obese (BMI < 30), obese (BMI >/= 30), or morbid obesity (BMI >/= 40) based on pre-operative BMI. Odds Ratio (OR) of having a post-operative complication was the primary outcome. Results: In this study, 948 patients were included for analysis. Compared to non- obese (n=675) patients, obesity (n=273) was associated with increased frequency of biliary fistula (2.6% vs. 0.9%, p = 0.036), urinary retention (9.9% and 5.8%, p = 0.013), longer mean operating time (451.5 vs. 425.9 minutes, p = 0.0009), higher intraoperative blood loss (150 mL vs 100 mL, p = 0.007), and smaller pancreatic duct diameter (3.4 vs 4.9 mm, p = 0.0008). On sub-analysis, compared to non-obese patients, morbid obesity (n=75) was associated with increased frequency of wound seroma (5.3% vs.1.6%, p=0.018), higher 90-day mortality (5.3% vs. 1.6%, p=0.016), longer mean operating time (482.6 vs. 429.0 minutes, p<0.0001), higher intraoperative blood loss (150 vs. 120 mL, p=0.032), smaller pancreatic duct diameter (3.3 vs. 3.8 mm, p=0.041), greater intraoperative fluids administration (4306. vs. 3673.9 mL, p = 0.009), and longer hospital length of stay (9.1 vs. 7.1 days, p = 0.014). Although obese and morbidly obese patients experienced longer and more challenging operations, the overall risk of experiencing any postoperative complication was not significantly different compared to non- obese patients on adjusted analysis. Conclusions: Obesity and morbid obesity are associated with longer and more technically challenging pancreatic operations. However, contrary to our hypothesis, this increase in surgical complexity was not associated with a significantly increased risk of postoperative complicationson adjusted analysis. Citation Format: Hannah M Engebretson, Kyle W Blackburn, Centura R Anbarasu, Cary M Hsu, Eric J Silberfein, Samir S Awad, Eugene A Choi, Christy Y Chai, Ramsey E Camp, George M Van Buren, William E Fisher, Derek J Erstad. Impact of obesity on Pancreaticoduodenectomy procedure perioperative outcomes [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B003.

Adrenal lesions (ALs) are often detected in patients with multiple endocrine neoplasia type 1 (MEN1). However, they are not well described in MEN1, making their clinical management unclear. This study examined the prevalence and outcomes of ALs found in MEN1. We performed a retrospective chart review of patients diagnosed with MEN1 from 1990 to 2021. ALs were diagnosed using abdominal or thoracic imaging and classified as being unilateral or bilateral, having single or multiple nodules, and as having diffuse enlargement or not. Measurable nodular lesions were analyzed for their size and growth over time. Patients' clinical and radiographic characteristics were collected. We identified 382 patients with MEN1, 89 (23.3%) of whom had ALs. The mean age at detection was 47 +/- 11.9 years. We documented 101 measurable nodular lesions (mean size, 17.5 mm; range, 3-123 mm). Twenty-seven nodules (26.7%) were smaller than 1 cm. Watchful waiting was indicated in 79 (78.2%) patients, of whom 28 (35.4%) had growing lesions. Functional lesions were diagnosed in 6 (15.8%) of 38 that had functional work-up (diagnoses: pheochromocytoma (n = 2), adrenocorticotropic hormone-dependent hypercortisolism (n = 2), hyperandrogenism (n = 1), hyperaldosteronism (n = 1)); surgery was indicated for 5 (83.3%; n = 12 nodules), 2 of whom had bilateral, diffuse adrenal enlargement. Two patients were diagnosed with adrenocortical carcinoma and two with neoplasms of uncertain malignant potential. Radiographic or clinical progression of ALs is uncommon. Malignancy should be suspected on the basis of a lesion's growth rate and size. A baseline hormonal work-up is recommended, and no further biochemical work-up is suggested when the initial assessment shows nonfunctioning lesions.

Hepatocellular carcinoma (HCC) is an aggressive form of liver cancer that arises in a background of chronic hepatic injury. Metabolic syndrome-associated fatty liver disease (MAFLD) and its severe form, nonalcoholic steatohepatitis (NASH), are increasingly common mechanisms for new HCC cases. NASH-HCC patients are frequently obese and medically complex, posing challenges for clinical management. In this review, we discuss NASH-specific challenges and the associated implications, including benefits of minimally invasive operative approaches in obese patients; the value of y90 as a locoregional therapy; and the roles of weight loss and immunotherapy in disease management. The relevant literature was identified through queries of PubMed, Google Scholar, and clinicaltrials.gov. Provider understanding of clinical nuances specific to NASH-HCC can improve treatment strategy and patient outcomes.

Objective: Previous studies have demonstrated synergistic antitumor effects of angiotensin system inhibition (ASI) combined with cisplatin therapy in pancreatic cancer. This study examines whether or not synergistic antitumor effects occur with combination ASI and cisplatin treatment in lung cancer, and whether or not ASI-induced changes in epithelial-mesenchymal transition play a role in the mechanism of this antitumor phenomenon. Methods: A set of lung cancer cell lines representing a spectrum of epithelial to mesenchymal phenotypes were identified and characterized. Response of epithelial-mesenchymal transition markers to losartan was characterized. Cell culture models of lung cancer were next treated with losartan, cisplatin, or combination of both. Markers of epithelial-mesenchymal transition or surrogates of other signaling pathways (AKT, Stat3, and programmed death-ligand), and cell viability were quantified. Findings were confirmed in both allogenic and syngeneic in vivo murine flank tumor models. Results: Losartan treatment significantly increased E-cadherin and reduced vimentin in human lung cancer cell lines. Combination treatment with losartan and cisplatin enhanced epithelial markers, reduced mesenchymal markers, inhibited promesenchymal signaling mediators, and reduced cell viability. Findings were confirmed in vivo in a murine flank tumor model with transition from mesenchymal to epithelial phenotype and reduced tumor size following combination losartan and cisplatin treatment. Conclusions: Combination losartan and cisplatin treatment attenuates the epithelial-mesenchymal transition pathway and enhances the cytotoxic effect of chemotherapy with in vitro and in vivo models of non-small cell lung cancer. This study suggests an important role for ASI therapy in the treatment of lung cancer.

Appendiceal neoplasms have a propensity for peritoneal dissemination. The standard of care for select individuals is CRS/HIPEC. In the current 8th AJCC Staging system, a finding of only intraperitoneal acellular mucin (M1a) is classified as Stage IVa. There is concern that the current AJCC system may over-stage patients. This was a single-institution retrospective review of 164 cases of mucinous appendiceal neoplasm. Patients undergoing CRS/HIPEC with M1a disease were compared to patients with peritoneal deposits containing tumor cells (well-differentiated adenocarcinoma; low-grade mucinous carcinoma peritonei—M1b,G1). Overall and recurrence-free survival were assessed. Median age was 51 years, 70

IntroductionPancreatic adenocarcinoma (PDAC) is an aggressive tumor with limited response to both chemotherapy and immunotherapy. Pre-treatment tumor features within the tumor immune microenvironment (TiME) may influence treatment response. We hypothesized that the pre-treatment TiME composition differs between metastatic and primary lesions and would be associated with response to modified FOLFIRINOX (mFFX) or gemcitabine-based (Gem-based) therapy.MethodsUsing RNAseq data from a cohort of treatment-naïve, advanced PDAC patients in the COMPASS trial, differential gene expression analysis of key immunomodulatory genes in were analyzed based on multiple parameters including tumor site, response to mFFX, and response to Gem-based treatment. The relative proportions of immune cell infiltration were defined using CIBERSORTx and Dirichlet regression.Results145 samples were included in the analysis; 83 received mFFX, 62 received Gem-based therapy. Metastatic liver samples had both increased macrophage (1.2 times more, p < 0.05) and increased eosinophil infiltration (1.4 times more, p < 0.05) compared to primary lesion samples. Further analysis of the specific macrophage phenotypes revealed an increased M2 macrophage fraction in the liver samples. The pre-treatment CD8 T-cell, dendritic cell, and neutrophil infiltration of metastatic samples were associated with therapy response to mFFX (p < 0.05), while mast cell infiltration was associated with response to Gem-based therapy (p < 0.05). Multiple immunoinhibitory genes such as ADORA2A, CSF1R, KDR/VEGFR2, LAG3, PDCD1LG2, and TGFB1 and immunostimulatory genes including C10orf54, CXCL12, and TNFSF14/LIGHT were significantly associated with worse survival in patients who received mFFX (p = 0.01). There were no immunomodulatory genes associated with survival in the Gem-based cohort. DiscussionOur evidence implies that essential differences in the PDAC TiME exist between primary and metastatic tumors and an inflamed pretreatment TiME is associated with mFFX response. Defining components of the PDAC TiME that influence therapy response will provide opportunities for targeted therapeutic strategies that may need to be accounted for in designing personalized therapy to improve outcomes.

BACKGROUND Pancreatobiliary (PB) disorders, especially cancer, negatively impact patients' health-related quality of life (HRQoL). However, the influence of baseline, pre-intervention HRQoL on peri-operative and oncologic outcomes has not been well-defined. We hypothesized that low baseline HRQoL is associated with worse peri-operative and long-term survival outcomes for PB surgical patients. STUDY DESIGN Pre-treatment FACT-Hep survey results and clinical data from PB patients (2008-2016) from a single center's prospective database were analyzed. Survey responses were aggregated into composite scores and divided into quintiles. Patients in the highest quintile of HRQoL were compared to patients in the bottom four quintiles combined. Overall (OS) and disease-free (DFS) were analyzed using the Kaplan-Meier method. Logistic and cox regressions were used to determine associations between quintiles of HRQoL scores and 30-day complications and long-term survival, respectively. RESULTS Of 162 patients evaluated, 99 had malignancy, and 63 had benign disease. Median follow-up was 31 months. Baseline HRQoL scores were similar for benign and malignant disease (p=0.42) and were not associated with the development of any (p=0.08) or major complications (p=0.64). Patients with highest quintile HRQoL scores had longer 3-year OS (84.6 vs 61.7%, p = 0.03) compared to patients in the lowest four quintiles of HRQoL. Among cancer patients only, those with highest quintile scores had longer 3-year OS (81.6 vs 47.4%, p = 0.02). On multivariable analysis, highest quintile HRQoL scores were associated with longer OS and DFS for patients with malignancy. CONCLUSIONS Pre-treatment HRQoL was associated with both OS and DFS among PB patients and might have prognostic utility. Future studies are necessary to determine whether patients with poorer HRQoL may benefit from targeted psycho-social interventions.

BACKGROUNDMinimally invasive, robotic techniques for hepatobiliary procedures offer the potential for accelerated recovery and reduced opioid usage. Robotic pancreaticoduodenectomy is a technically challenging procedure with a complex reconstruction. In this regard, standardization of the pancreaticojejunostomy technique is critical for safe adoption of robotic technology in pancreatic surgery.STUDY DESIGNWe demonstrate the primary steps and associated principles to perform a robotic pancreaticojejunostomy using a modified Blumgart/Nagakawa technique.RESULTSKey steps to this procedure include: 1) exposure and positioning of the pancreatic remnant and jejunal limb; 2) transpancreatic suture placement using augmented sutures with bulldog clamps for organization; 3) duct-to-mucosa anastomosis with well-defined order of suture placement and knot-tying for optimal exposure, tissue handling, and technical ease; 4) completion of the anterior row of transpancreatic sutures using Lapra-TY clips for gentle, but firm tissue apposition; and 5) placement of omental flap and surgical drains in proximity to the reconstruction.CONCLUSIONWe described our technique for performing a robotic pancreaticojejunostomy, which compensates for the technical limitations of the robotic approach. These adjustments in combination with the magnified surgical vision and augmented skill associated with the robotic platform allow for safe and reliable performance of the pancreaticojejunostomy technique.

Background In most CKDs, lysyl oxidase oxidation of collagen forms allysine side chains, which then form stable crosslinks. We hypothesized that MRI with the allysine-targeted probe Gd-oxyamine (OA) could be used to measure this process and noninvasively detect renal fibrosis. Methods Two mouse models were used: hereditary nephritis in Col4a3-deficient mice (Alport model) and a glomerulonephritis model, nephrotoxic nephritis (NTN). MRI measured the difference in kidney relaxation rate, ΔR1, after intravenous Gd-OA administration. Renal tissue was collected for biochemical and histological analysis. Results ΔR1 was increased in the renal cortex of NTN mice and in both the cortex and the medulla of Alport mice. Ex vivo tissue analyses showed increased collagen and Gd-OA levels in fibrotic renal tissues and a high correlation between tissue collagen and ΔR1. Conclusions Magnetic resonance imaging using Gd-OA is potentially a valuable tool for detecting and staging renal fibrogenesis.