Background Safety-net hospitals (SNHs) provide a substantial segment of the U.S. population with complex health needs, yet the breadth of oncologic services available at SNHs remains unclear.Methods A survey on cancer-care delivery was distributed to oncology providers at stand-alone California SNHs. The survey queried feasibility, access, and wait times for screening exams, diagnostic tests, procedures, and specialist services for comprehensive cancer care.Results Of 15 SNHs queried, nine (60%) responded. Access to full-time surgical specialists varied considerably: 33% lacked breast surgeons and urologists, 44% lacked surgical oncologists/hepatobiliary and colorectal surgeons, 56% lacked thoracic surgeons, 67% lacked endocrine surgeons, and 89% lacked orthopedic oncologists. Most hospitals (78%) employ general surgeons to perform cancer operations. Specific procedures are performed with the following frequency: right hemicolectomy/LAR/APR 89%, gastrectomy 78%, pulmonary lobectomy 78%, pancreaticoduodenectomy 67%, melanoma surgery 67%, major hepatectomy 56%. Robotic surgery is available at two-thirds of SNHs. One hospital offered CRS/HIPEC, and no respondent site provided regional intraoperative chemotherapy techniques.Conclusions Like the United States as a whole, much cancer surgery in respondent California SNHs is performed by general surgeons. Significant gaps in subspecialty and advanced therapies persist, potentially requiring patients to travel long distances to tertiary centers and limiting access to comprehensive cancer care.

BACKGROUND:Colorectal liver metastases (CRLMs) remain a leading cause of death in patients with colorectal cancer and require increasingly sophisticated multidisciplinary management. Recent advances in systemic therapy, molecular profiling, hepatic surgery, liver-directed therapies, and liver transplantation have expanded treatment options while increasing the complexity of clinical decision-making. Herein we summarize the proceedings and expert recommendations from the 2026 Society for Surgery of the Alimentary Tract-Society of Surgical Oncology Joint Expert Symposium at Digestive Disease Week. METHODS:An expert multidisciplinary panel comprising hepatopancreatobiliary surgical oncologists, hepatologists, transplant surgeons, and translational surgeon-scientists reviewed contemporary evidence and emerging data across the spectrum of CRLM management. Recommendations were synthesized through expert review and panel discussion. RESULTS:The symposium highlighted evolving concepts in CRLM biology, including mechanisms of immune evasion within the hepatic tumor microenvironment and novel immunotherapeutic strategies. Current evidence supporting biologically tailored perioperative systemic therapy based on tumor sidedness and RAS/BRAF status was reviewed, along with optimized regimens and timing to reduce liver injury, and the emerging role of circulating tumor DNA in guiding adjuvant treatment. Contemporary surgical strategies emphasized parenchymal preservation, minimally invasive techniques, ablation, and maximizing salvageability after recurrence. Expanding indications for liver-directed therapies, arterial infusion, and liver transplantation in carefully selected patients with unresectable liver-limited disease were also discussed, incorporating data from recent randomized clinical trials. CONCLUSION:Contemporary management of CRLM increasingly relies on individualized treatment strategies guided by tumor biology, preservation of hepatic reserve, and coordinated multidisciplinary decision-making. Integrating the latest evidence with expert discussion provides practical recommendations for optimizing long-term oncologic outcomes while identifying key areas for future clinical investigation.

Importance:Subsets of pancreatic cystic lesions (PCLs) are the only radiographically evident precursors to pancreatic cancer. Guidelines prioritize cyst size and high-risk features to determine the need for resection. However, the true prevalence of PCLs and risk factors for their development in the general population remain unknown, as available data are often biased by imaging performed in symptomatic patients. Objective:To determine prevalence of PCLs in an asymptomatic North American cohort using size-based risk categorization and identify associated demographic factors and exposures. Design, Setting, Participants:This cross-sectional study included asymptomatic individuals who underwent rapid whole-body magnetic resonance imaging using a commercially available 1.5T device for general preventive screening between January 1, 2020, and May 31, 2023. Scans were interpreted by certified radiologists using standardized synoptic reporting templates. Diagnostic free-text reports were analyzed, and positive reports underwent independent additional review. Data were analyzed from February 4, 2024, to March 6, 2025. Exposures:Participant demographic information and lifestyle exposures. Main Outcomes and Measures:Prevalence of PCLs based on size-based risk categorization. Results:Among 21 651 individuals undergoing screening MRI (11 050 [51.0%] male; median age, 51 [IQR, 42-61] years), 1509 (7.0%) had an incidental PCL (776 [51.4%] female), and age- and sex-standardized prevalence was 6.3%. The median age was higher in individuals with PCLs (61 [IQR, 51-69] vs 50 [IQR, 41-60] years). Prevalence increased with age, from 86 of 4223 (2.0%) 39 years or younger to 229 of 5720 (4.0%) aged 40 to 49 years, 390 of 5586 (7.0%) aged 50 to 59 years, 467 of 4049 (11.5%) aged 60 to 65 years, 268 of 1741 (15.4%) aged 70 to 79 years, and 69 of 332 (20.8%) 80 years or older (P < .001). Most cysts (1449 [96.0%]) were less than 2 cm, 1200 (79.5%) were less than 1 cm, and 17 (1.1%) were 3 cm or larger (0.08% of all scans). Independent factors associated with PCLs included being 65 years or older (odds ratio [OR], 3.03; 95% CI, 2.67-3.45), female sex (OR, 1.13; 95% CI, 1.002-1.27), personal history of pancreatitis (OR, 2.65; 95% CI, 1.66-4.08) or pancreatic ductal adenocarcinoma (PDAC) (OR, 20.98; 95% CI 3.70-161.45), family history of PDAC (OR, 1.40; 95% CI, 1.04-1.86), alcohol consumption (OR, 1.15; 95% CI, 1.01-1.31), and Latin American (OR, 1.79; 95% CI, 1.43-2.23) or Middle Eastern (OR, 1.40; 95% CI, 1.03-1.86) ethnicity. Asian ethnicity (OR, 0.79; 95% CI, 0.66-0.95) was associated with lower PCL prevalence. Conclusions and Relevance:In this cross-sectional study of 21 651 individuals, incidental PCLs were common (6.3%) and found in as many as 20.8% of older individuals undergoing whole-body MRI screening, with 1492 PCLs (98.9%) of all PCLs being less than 3 cm.

QuestionWhat is the diagnostic accuracy of carbohydrate antigen 19.9 (CA19.9) with current cutoff of >= 37 U/mL or greater for detecting high-grade dysplasia (HGD) and invasive carcinoma (IC) in patients diagnosed with intraductal papillary mucinous neoplasm?FindingsIn this systematic review and meta-analysis including 24 studies and 5281 patients reporting CA19.9 use for resected intraductal papillary mucinous neoplasm using pathology as the reference standard, pooled estimates of diagnostic accuracy for HGD or IC demonstrated low sensitivity, high specificity.MeaningThese findings suggest CA19.9 with the current cutoff should not be used as a screening test to rule out HGD and IC nor as standalone marker. This systematic review and meta-analysis evaluates the diagnostic accuracy of serum carbohydrate antigen 19.9 (CA19.9) level to identify patients with intraductal papillary mucinous neoplasm at high risk of high-grade dysplasia and invasive carcinoma. ImportanceCurrent guidelines recommend routine assessment of serum carbohydrate antigen 19.9 (CA19.9) at diagnosis and during follow-up of patients with intraductal papillary mucinous neoplasm (IPMN) to detect high-grade dysplasia (HGD) and invasive carcinoma (IC). Guidelines consider an elevated serum CA19.9 level (>= 37 U/mL) a worrisome feature and a relative indication for surgery.ObjectiveTo evaluate the diagnostic accuracy of CA19.9 for identifying patients with IPMN at high risk of HGD and IC.Data SourcesPubMed, Embase (Ovid), and Web of Science databases (inception to March 1, 2025).Study SelectionStudies reporting on diagnostic accuracy of CA19.9 (cut-off 37 U/mL) in patients with resected IPMN.Data Extraction and SynthesisData extraction was completed by 3 reviewers (March to December 2025). Risk of bias was assessed using the QUADAS-2 tool and evidence certainty with Grading of Recommendations Assessment, Development and Evaluation. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies reporting guidelines and the Cochrane Diagnostic Test Accuracy protocol were applied for overall conduct. A random-effects meta-analysis was conducted in December 2025 to obtain a pooled estimate of diagnostic accuracy. Main pancreatic duct involvement and rate of HGD or IC were assessed using meta-regression. Summary receiver operating characteristics curves were generated. The area under the curve (AUC) was calculated as overall test performance.Main Outcomes and MeasuresDiagnostic accuracy of serum CA19.9 (>= 37 U/mL), reported as pooled sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratios (NLR), diagnostic odds ratio (DOR), and AUC and their 95% CIs. Pathology was considered as reference standard.ResultsOverall, 24 studies assessing 5281 patients with IPMN were included. Mean age was 64.7 (95% CI, 62.24-67.10) years, and 2919 patients (55%) were male. Serum CA19.9 data were available for 4653 patients (88.1%), with 966 patients (20.8%) showing elevated levels. Pooled estimates of diagnostic accuracy for HGD or IC (present in 1939 patients [41.7%]) demonstrated sensitivity of 0.35 (95% CI, 0.29-0.43), specificity of 0.90 (95% CI, 0.87-0.92), PLR of 3.37 (95% CI, 2.56-4.44), NLR of 0.72 (95% CI, 0.65-0.80), DOR of 4.67 (95% CI, 3.26-6.70), and AUC of 0.78 (95% CI, 0.74-0.82).Conclusions And RelevanceIn this systematic review and meta-analysis, CA19.9 with the current cutoff (37 U/mL) demonstrated poor performance in excluding HGD or IC and only modest value for ruling in IC. These findings suggest CA19.9 should not be used as a standalone or screening test, while its limited rule-in value may aid decision-making in patients with moderate pretest probability. Future studies should investigate whether different cutoffs and dynamic trends could improve diagnostic accuracy.

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are a common entity with a prevalence in the general population that increases with age. Depending on the involvement of the main pancreatic duct , they can be divided into main-duct (MD), mixed-duct, and branch-duct (BD) variants. Most BD-IPMNs are low-risk and surveilled, while MD-IPMNs are generally resected. When necessary, a standard pancreatic resection with lymphadenectomy is recommended. The use of molecular profiling , intraoperative pancreatoscopy, and surveillance end points are discussed.

Background Colorectal liver metastases (CRLM) remain the leading cause of death in patients with colorectal cancer and require increasingly sophisticated multidisciplinary management. Recent advances in systemic therapy, molecular profiling, hepatic surgery, liver-directed therapies, and liver transplantation have expanded treatment options while increasing the complexity of clinical decision making. This review summarizes the proceedings and expert recommendations from the 2026 Society for Surgery of the Alimentary Tract (SSAT)–Society of Surgical Oncology (SSO) Joint Expert Symposium at Digestive Disease Week. Methods An expert multidisciplinary panel of surgical oncologists, hepatologists, medical oncologists, transplant surgeons, and translational scientists reviewed contemporary evidence and emerging data across the spectrum of CRLM management. Recommendations were synthesized through expert consensus and panel discussion. Results The symposium highlighted evolving concepts in CRLM biology, including mechanisms of immune evasion within the hepatic tumor microenvironment and novel immunotherapeutic strategies. Current evidence supporting biologically tailored perioperative systemic therapy based on tumor sidedness and RAS/BRAF status was reviewed, along with the emerging role of circulating tumor DNA in guiding adjuvant treatment. Contemporary surgical strategies emphasized parenchymal preservation, minimally invasive techniques, thermal ablation, and maximizing salvageability after recurrence. Expanding indications for liver-directed therapies and liver transplantation in carefully selected patients with unresectable liver-limited disease were also discussed, incorporating recent randomized clinical trial data. Conclusions Contemporary management of CRLM increasingly relies on individualized treatment strategies guided by tumor biology, preservation of hepatic reserve, and coordinated multidisciplinary decision making. Integrating the latest evidence with expert consensus provides practical recommendations to optimize long-term oncologic outcomes while identifying key areas for future clinical investigation.

Importance:Current guidelines recommend routine assessment of serum carbohydrate antigen 19.9 (CA19.9) at diagnosis and during follow-up of patients with intraductal papillary mucinous neoplasm (IPMN) to detect high-grade dysplasia (HGD) and invasive carcinoma (IC). Guidelines consider an elevated serum CA19.9 level (≥37 U/mL) a worrisome feature and a relative indication for surgery. Objective:To evaluate the diagnostic accuracy of CA19.9 for identifying patients with IPMN at high risk of HGD and IC. Data Sources:PubMed, Embase (Ovid), and Web of Science databases (inception to March 1, 2025). Study Selection:Studies reporting on diagnostic accuracy of CA19.9 (cut-off 37 U/mL) in patients with resected IPMN. Data Extraction and Synthesis:Data extraction was completed by 3 reviewers (March to December 2025). Risk of bias was assessed using the QUADAS-2 tool and evidence certainty with Grading of Recommendations Assessment, Development and Evaluation. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies reporting guidelines and the Cochrane Diagnostic Test Accuracy protocol were applied for overall conduct. A random-effects meta-analysis was conducted in December 2025 to obtain a pooled estimate of diagnostic accuracy. Main pancreatic duct involvement and rate of HGD or IC were assessed using meta-regression. Summary receiver operating characteristics curves were generated. The area under the curve (AUC) was calculated as overall test performance. Main Outcomes and Measures:Diagnostic accuracy of serum CA19.9 (≥37 U/mL), reported as pooled sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratios (NLR), diagnostic odds ratio (DOR), and AUC and their 95% CIs. Pathology was considered as reference standard. Results:Overall, 24 studies assessing 5281 patients with IPMN were included. Mean age was 64.7 (95% CI, 62.24-67.10) years, and 2919 patients (55%) were male. Serum CA19.9 data were available for 4653 patients (88.1%), with 966 patients (20.8%) showing elevated levels. Pooled estimates of diagnostic accuracy for HGD or IC (present in 1939 patients [41.7%]) demonstrated sensitivity of 0.35 (95% CI, 0.29-0.43), specificity of 0.90 (95% CI, 0.87-0.92), PLR of 3.37 (95% CI, 2.56-4.44), NLR of 0.72 (95% CI, 0.65-0.80), DOR of 4.67 (95% CI, 3.26-6.70), and AUC of 0.78 (95% CI, 0.74-0.82). Conclusions And Relevance:In this systematic review and meta-analysis, CA19.9 with the current cutoff (37 U/mL) demonstrated poor performance in excluding HGD or IC and only modest value for ruling in IC. These findings suggest CA19.9 should not be used as a standalone or screening test, while its limited rule-in value may aid decision-making in patients with moderate pretest probability. Future studies should investigate whether different cutoffs and dynamic trends could improve diagnostic accuracy.

Abstract Background Early detection of melanoma recurrence and progression remains a clinical challenge, which relies on physical examination and imaging. Circulating tumor DNA offers a noninvasive, dynamic biomarker that may identify molecular recurrence before clinical progression. We aimed to evaluate the prognostic and predictive value of longitudinal, tumor-informed ctDNA testing across multiple melanoma care settings. Methods We retrospectively analyzed 56 consecutive melanoma patients who underwent serial ctDNA testing using a tumor-informed assay (Signatera™) at a single institution. Fifty-six patients with evaluable ctDNA results were stratified into three cohorts based on the treatment context at the time of ctDNA testing: (A) no active treatment (n = 20), (B) adjuvant therapy (n = 14), and (C) active treatment for known disease (n = 22). We evaluated disease-free survival (DFS), overall survival (OS), and longitudinal ctDNA dynamics in relation to clinical outcomes. Results Median clinical follow-up was 48.0 (IQR 24.7–94.1) months. In Cohorts A and B (HR 12.3, 95% CI 1.1–1138.6), detectable ctDNA at any timepoint was significantly associated with inferior DFS. Conversely, 90% of patients in Cohorts A and B combined with undetectable ctDNA remained recurrence-free. In Cohort C, rising or persistently positive ctDNA was seen in 81.8% of patients who progressed. Longitudinal ctDNA trends were more informative than isolated timepoints, with increases preceding radiologic progression by a median of 11.4 (IQR 5.0–13.1) months. Conclusions and relevance Tumor-informed ctDNA testing offers clinically meaningful insight across melanoma care settings. Rising or positive ctDNA frequently anticipates disease progression, supporting its use for MRD surveillance and treatment response monitoring in dermatology and oncology practice.

The microenvironment and immune infiltrate population of colorectal tumors can serve as a stronger predictor of patient survival than microsatellite-status or traditional T- or N-staging. This study aimed to leverage transcriptomic techniques to identify specific immune cell populations and their ratios associated with cancer recurrence in colorectal cancer patients. The goal was to identify patients who could benefit from early adjuvant interventions, identify those at higher risk of recurrence for surveillance, and identify potential combinatorial immunotherapy strategies tailored to this disease. We found that a lower ratio of cytotoxic lymphocyte: monocytic lineage cells, and not microsatellite-status, was associated with cancer recurrence. Additional differential gene expression analysis of the monocytic lineage demonstrated that genes specifically associated with tumor associated macrophages and a protumoral phenotype were overexpressed in the tumor microenvironment in patients that went on to have recurrent disease. Gene Ontology analysis revealed that pathways associated with pro-tumoral extracellular matrix remodeling were suppressed in tumors exhibiting a high cytotoxic lymphocyte: monocytic lineage ratio, suggesting a diminished propensity for tumor progression. The development of these prognostic markers not only associates with colorectal cancer recurrence, aiding in risk stratification and guiding adjuvant therapy decisions for resected early-stage patients, but also suggests that effective colon cancer treatments will likely require a combination of cytotoxic T-cell-directed immunomodulation and targeted inhibition of tumor-associated macrophages.

Liver metastases (LM) in melanoma are linked to poor prognosis, reduced immunotherapy efficacy, and survival, likely due to a suppressive liver immune microenvironment. We hypothesized that LM induces distinct, detectable immune changes in blood and tumor biopsies, supported by our prior preclinical findings. We set to immunophenotype tissues from stage IV melanoma patients to identify systemic and local immune changes, uncover immune tolerance mechanisms, and define biomarkers distinguishing LM-associated suppression. These insights aim to inform strategies to overcome liver-specific immune tolerance, enhance immunotherapy predictability and efficacy, and improve clinical outcomes for LM+ melanoma patients. Peripheral blood and tumor samples were longitudinally collected from advanced melanoma patients pre, during, and post treatment clinic visits and/or surgeries. Clinical data, including imaging, treatment, and bloodwork, were obtained. Stage IV patients were stratified into two cohorts: LM+ and LM-. Fresh tumor and blood tissues were immunophenotyped by 12-24 color flow cytometry. In tumor specimens, ICOS expression on CD8+ subsets were significantly reduced in LM+ patients. Three distinct CD8+ T cell subsets were identified correlating with LM status. In peripheral blood, LM+ patients exhibited significantly lower frequencies of HLA-DR+CD8+ and HLA-DR+CD11c+CD11b-CD8+ subsets compared to LM- patients, while the CD11c+CD11b-CD8+ subset was significantly higher. Similarly, in tumor tissue, LM+ patients showed an increased frequency of CD11c+CD11b-CD8+ subset and a decreased frequency of HLA-DR+CD8+ subset. These observations underscore potential functional differences in immunity between LM+ and LM- patients. These subsets warrant further studies on the immune dynamics of melanoma LM. Our parallel immunophenotyping of melanoma clinical samples is a foundational step towards developing predictive/prognostic biomarkers to distinguish between LM+ and LM- patients and their outcomes. We identified distinct T-cell subsets with differential representation between cohorts, with reduced expression of ICOS in CD8+ subsets and enrichment of CD11c+CD11b-CD8+ subset in LM+ patients. The functional roles of these subsets require further investigation. Given the immune-regulatory nature of the liver tumor microenvironment and clinical manifestations in LM+ patients, we hypothesize that the CD11c+CD11b-CD8+ subset exhibits a regulatory phenotype, contributing to immune suppression and tumor progression. We aim to characterize this subset at phenotypic, transcriptional, and functional levels, elucidating its role in LM-mediated immune modulation. These findings will inform the development of novel biomarkers and therapeutic strategies for melanoma patients with metastatic disease. Shao Tao, Zang Han, Asha Bunyan, Adil Daud, Ajay Maker, James Lee. Distinct CD8+T cell subsets in advanced melanoma patients with liver metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7125.

BACKGROUND:Robotic surgery has been developed as an additional minimally invasive approach to pancreatectomy. We assessed case selection and perioperative outcomes in patients undergoing robotic pancreatectomy for pancreatic adenocarcinoma over time. METHODS:The National Cancer Database (2010-2019) was queried to identify all pancreatic adenocarcinoma patients that underwent robotic pancreatoduodenectomy (RPD) or distal pancreatectomy (RDP). Two periods were established: Early cohort (2010-2014) and Modern cohort (2015-2019). RESULTS:Of 2245 patients who underwent RPD or RDP, 78.4 % of RPD and 77.6 % of RDP were in the Modern cohort. Robotic approach increased from 2010 to 2019 (RPD: 1.1 %-7.5 %, RDP: 2.2 %-19.4 %; both p < 0.001). Compared to Early, Modern RPD patients were more likely to have non-private insurance (68.5 % vs. 58.7 %), and both RPD (47.0 % vs. 23.4 %) and RDP (47.3 % vs. 32.1 %) patients were more frequently treated in non-academic hospitals (all p < 0.01). Shorter LOS was noted in the Modern RPD (6 vs. 8 days) and RDP cohorts (5 vs. 6 days, both p < 0.001), without differences in readmission/mortality. In RPD and RDP, no differences in overall survival were observed between the eras. CONCLUSIONS:Robotic pancreatectomy for pancreatic adenocarcinoma has increased over time with greater inclusion of patients and hospital types while outcomes have remained similar.

Immunity to solid tumors is associated with the hallmarks of cancer-associated inflammation and the ability of immune mechanisms to limit tumor progression. Application of expanded tumor-infiltrating lymphocyte adoptive T cell therapy (TIL ACT) in clinical trials is now practiced at many sites around the world. Prior to immune checkpoint blockade (ICB), an approximate 50% objective response rate was consistently observed across multiple institutions for patients with melanoma. This now-approved strategy approaches 35% in recent studies from the USA and 49% with more highly selected patients in Europe. Here, we focus on early TIL studies in non-melanoma epithelial neoplasms. Increased understanding of cancer immunology has allowed changes in the TIL expansion process to include: (1) initial generation of TIL from fragments, (2) use of specialized large-scale culture vessels, (3) use of the rapid expansion protocol to enable 'young' TIL prosecution, and (4) treatment regimens employing non-myeloablative (NMA) chemotherapy followed by brief interleukin-2 administration. NMA leads to homeostatic proliferation of the transferred T cells, engraftment, profound neutropenia and lymphopenia, and improved clinical outcome. A key success of TIL ACT relies on the quality, specificity, and number of pre-existing TIL. This, in turn, is highly influenced by the suppressive tumor microenvironment. Thus, any means to alter 'cold tumor (non-T cell inflamed)' to 'hot tumor (T cell inflamed)' is theoretically desirable to improve both the quality and quantity of TIL obtained before harvest. Combinations of other immunotherapies such as application of ICB, co-stimulatory molecule agonist antibodies, autophagy inhibition, and dendritic cell support strategies could provide additional- improvements in TIL therapy and enable harnessing of the adaptive immune response to enhance the clinical outcome of TIL-ACT patients.

To enable early detection of pancreatic cancer from precancerous lesions, we analyze proteins and glycoproteins from 64 intraductal papillary mucinous neoplasms (IPMNs), 55 cyst fluid samples, 104 pancreatic ductal adenocarcinomas (PDACs), and various types of normal samples using mass spectrometry. High-grade IPMNs show enrichment of glycosylation level and tumor progression pathways compared to low-grade lesions. High-grade IPMN associated proteins, such as PLOD3, IRS2, LGALS9, and Trop-2, are identified and validated using immunolabeling and laser microdissection. Some high-grade associated proteins are also detected in pancreatic cyst fluids, which allows us to link proteins and glycoproteins expressed in neoplastic cells to clinically accessible biospecimens. Altered glycosylation level of extracellular matrix (ECM) proteins is observed in IPMNs compared to normal ducts. Additionally, we identify a subset of IPMNs with PDAC-like features, including elevated expression of ECM proteins. These findings offer insight into progression-associated proteins and emphasize the diagnostic and therapeutic potential of these proteins in pancreatic tumors.

BACKGROUND:Postoperative morbidity and mortality rates from pancreaticoduodenectomy (PD) have significantly decreased, allowing for greater consideration of patients with severe comorbidities. This study aimed to evaluate the effect of previous coronary artery intervention on morbidity and mortality among patients who underwent PD. METHODS:Patients who underwent PD were identified from the American College of Surgeon National Surgical Quality Improvement Program database. Patients with previous coronary artery intervention received either balloon dilatation or stent placement. The main outcome measures included in-hospital mortality and postoperative myocardial infarction (MI). RESULTS:Of 10,848 patients who underwent PD, 698 (6.4%) received previous coronary artery intervention. Compared with patients without coronary artery intervention, those with previous coronary artery intervention were older (65 vs 70 years, respectively; P <.001), were less likely to be female (50.2% vs 26.4%, respectively; P <.001), and had higher median body mass index (26 vs 27 kg/m2, respectively; P =.003). Compared with patients not in the angioplasty/stent cohort, those in the angioplasty/stent cohort were more likely to have diabetes mellitus (22.0% vs 39.3%, respectively), functional impairment (2.4% vs 4.9%, respectively), chronic obstructive pulmonary disease (4.1% vs 8.2%, respectively), hypertension (51.2% vs 86.2%, respectively), and bleeding disorders (2.2% vs 8.0%, respectively) (all P <.001). Compared with patients not in the angioplasty/stent cohort, those in the stent/angioplasty group were more likely to have postoperative complications (41.0% vs 51.4%, respectively; P <.001). Previous stent/angioplasty procedure (odds ratio [OR], 2.61 [95% CI, 1.42-4.57]; P =.001) was associated with developing postoperative MI but was not an independent predictor of in-hospital mortality (OR, 1.19 [95% CI, 0.81-1.70]; P =.369). CONCLUSION:Previous stent placement/angioplasty was not associated with increased in-hospital mortality in patients who underwent PD, despite being correlated with an increased risk of MI and severe complications. Previous coronary artery angioplasty and/or stenting is not an absolute contraindication for PD, but patients should be medically optimized preoperatively to mitigate the risk of major adverse cardiac events.

Colorectal cancer and liver metastases are a leading cause of cancer-related mortality. Overexpression of the immunostimulatory cytokine TNFSF14/LIGHT associates with improved survival and correlates with increased tumor-infiltrating lymphocytes in patients and a clinically relevant model of colorectal liver metastases. We demonstrate that LIGHT monotherapy activates T cells, but also induces T cell exhaustion and the recruitment of immunosuppressive elements. As colorectal liver metastases exhibit high levels of CTLA-4 expression, we combined LIGHT overexpression with anti-CTLA-4, leading to complete tumor control. The combination functions by homing tumor-infiltrating lymphocytes, inducing tumor antigen-specific T cells, and reversing T cell exhaustion. Whereas both LIGHT overexpression and anti-CTLA-4 increase tumor-promoting macrophages, the combination eliminates this population. The ability of LIGHT overexpression combined with CTLA-4 inhibition to reverse T cell exhaustion and myeloid cell suppression is supported by analysis of complementary patient cohorts and has strong clinical relevance, especially given that liver metastases contribute to immunotherapy resistance across various cancer types.