Kevin M. Sullivan

Background: Patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) have a poor prognosis. Surgical resection provides the highest chance of improved survival. This study investigates the role of total pancreatectomy (TP) in the surgical management of PDAC based on clinicopathologic characteristics and the effect these factors have on patients' outcomes. Methods: Data from the National Cancer Database for patients undergoing TP or pancreaticoduodenectomy (PD) was analyzed. Statistical tests included Chi‐square test, logistic regression, least squared means, and Cox proportional hazard model to determine frequency and percentage, odds ratios, and hazard ratio, respectively. Results: Of patients receiving PDAC resection, more TP patients were uninsured. Tumors in the pancreatic body or an overlapping locations increase the odds of receiving TP. Most statistically significant differences in clinicopathologic characteristics between the groups were not clinically meaningful. Despite a slight increase in short‐term mortality for stage 2 patients receiving a TP, there was no clinically meaningful difference in overall survival. Conclusion: TP conferred a minimally worsened short‐term survival for stage 2 PDAC, but oncologic outcomes and OS were similar for TP and PD. Therefore, surgical approach should be guided by individual patient characteristics and comorbidities, as long‐term oncologic outcomes between the two procedures are comparable.

Background: Gastric cancer (GC) remains a significant health burden in the U.S, particularly among ethnic minorities. We identified patient-level risk factors contributing to advanced-stage (AS) diagnosis and poor survival to guide strategies to address GC-related health disparities. Methods: We conducted a retrospective cohort analysis of 18,396 histologically confirmed GC cases (4102 early-stage (ES) and 14,294 AS) diagnosed between 2000 and 2019, using data from the California Cancer Registry linked to the California Office of Statewide Health Planning and Development. Eligible cases were adults age ≥ 18 with complete diagnostic and follow-up data. Multivariable logistic and Cox regression models were used to identify predictors of AS-GC and five-year disease-specific (DSS) and overall-survival (OS) outcomes. Analyses were further stratified by Asian and Hispanic subgroups. Results: Korean heritage was the strongest predictor of ES-GC [OR 0.58 (95% CI, 0.47–0.71), p < 0.001] and was independently associated with the lowest GC-specific mortality risk [HR 0.73 (95% CI: 0.67–0.80), p < 0.0001]. The youngest age group (18–44 years) had the highest AS-GC rate (91.4%). Asian ethnicity, receipt of care at NCI-designated cancer centers, and prior upper endoscopy were associated with improved OS and DSS. In contrast, comorbidities such as GERD, diabetes, liver disease, smoking and alcohol abuse, and older age ≥ 75, U.S.-birth, and rural residence were linked to worse outcomes. Conclusions: Distinct demographic, clinical, and healthcare access factors contribute to disparities in GC outcomes. These findings support the development of culturally tailored early-detection programs, and risk-based screening for GC care, particularly in vulnerable populations.

Peritoneal metastasis is a significant source of morbidity and mortality for patients with cancer from gastrointestinal origin such as gastric, colorectal, and appendiceal cancers, and treatment options are limited. Cross‐sectional imaging is limited in sensitivity and specificity, and treating peritoneal metastases is limited by the bioavailability of systemic cytotoxic chemotherapy and metastatic burden. Within this review, we specifically explore the pathophysiology underlying peritoneal metastasis while emphasising the contributions of the tumour microenvironment and immune system.

A spectrum of immune states resulting from tumor resident macrophages and T-lymphocytes in the solid tumor microenvironment correlates with patient outcomes. We hypothesized that in gastric cancer (GC), macrophages in a polarized immunosuppressive transcriptional state would be prognostic of poor survival. We derived transcriptomic signatures for M2 (M2_TS, MRC1; MS4A4A; CD36; CCL13; CCL18; CCL23; SLC38A6; FGL2; FN1; MAF) and M1 (M1_TS, CCR7; IL2RA; CXCL11; CCL19; CXCL10; PLA1A; PTX3) macrophages, and cytolytic T-lymphocytes (CTL_TS, GZMA; GZMB; GZMH; GZMM; PRF1). Primary GC in a TCGA stomach cancer dataset was evaluated for signature expressions, and a log-rank test determined overall survival (OS) and the disease-free interval (DFI). In 341 TCGA GC entries, high M2_TS expression was associated with histological types and later stages. Low M2_TS expression was associated with significantly better 5-year OS and DFI. We validated M2_TS in prospectively collected peritoneal fluid of a GC patient cohort (n = 28). Single-cell RNA sequencing was used for signature expression in CD68⁺CD163⁺ cells and the log-rank test compared OS. GC patients with high M2_TS in CD68⁺CD163⁺ cells in their peritoneal fluid had significantly worse OS than those with low expression. Multivariate analyses confirmed M2_TS was significantly and independently associated with survival. As an independent predictor of poor survival, M2_TS may be prognostic in primary tumors and peritoneal fluid of GC patients.

Mahuron KM, et al. J Gastric Cancer. 2024 May;24:e20. https://doi.org/10.5230/jgc.2024.24.e20

Although it can promote effector T-cell function, the summative effect of interleukin-10 (IL-10) in the tumor microenvironment (TME) appears to be suppressive; therefore, blocking this critical regulatory cytokine has therapeutic potential to enhance antitumor immune function. As macrophages efficiently localize to the TME, we hypothesized that they could be used as a delivery vehicle for drugs designed to block this pathway. To test our hypothesis, we created and evaluated genetically engineered macrophages (GEMs) that produce an IL-10-blocking antibody (αIL-10). Healthy donor human peripheral blood mononuclear cells were differentiated and transduced with a novel lentivirus (LV) encoding BT-063, a humanized αIL-10 antibody. The efficacy of αIL-10 GEMs was assessed in human gastrointestinal tumor slice culture models developed from resected specimens of pancreatic ductal adenocarcinoma primary tumors and colorectal cancer liver metastases. LV transduction led to sustained production of BT-063 by αIL-10 GEMs for at least 21 days. Transduction did not alter GEM phenotype as evaluated by flow cytometry, but αIL-10 GEMs produced measurable quantities of BT-063 in the TME that was associated with an ~5-fold higher rate of tumor cell apoptosis than control.

PURPOSE: Nearly half of all Medicare beneficiaries are enrolled in privatized Medicare insurance plans (Medicare Advantage [MA]). Little comparative information is available about access, outcomes, and cost of inpatient cancer surgery between MA and Traditional Medicare (TM) beneficiaries. We set out to assess and compare access, postoperative outcomes, and estimated cost of inpatient cancer surgery among MA and TM beneficiaries.METHODS: Retrospective cohort analysis of MA or TM beneficiaries undergoing elective inpatient cancer surgery (for cancers located in lung, esophagus, stomach, pancreas, liver, colon, or rectum) was performed using the Office of Statewide Health Planning Inpatient Database linked to California Cancer Registry from 2000 to 2020. For each cancer site, risk-standardized access to high-volume hospitals, postoperative 30-day mortality, complications, failure to rescue, and surgery-specific estimated costs were compared between MA and TM beneficiaries.RESULTS: This analysis of 76,655 Medicare beneficiaries (median age 74 years, 51% female, 39% MA) included 31,913 colectomies, 10,358 proctectomies, 4,604 hepatectomies, 2,895 pancreatectomies, 3,639 gastrectomies, 1,555 esophagectomies, and 21,691 lung resections. Except for colon surgery, MA beneficiaries were less likely to receive care at a high-volume hospital. Mortality was significantly higher among MA beneficiaries ( v TM) for gastrectomy (adjusted risk difference [ARD], 1.5%; 95% CI, 0.01 to 2.9; P = .036), pancreatectomy (ARD, 2.0%; CI, 0.80 to 3.3; P = .002), and hepatectomy (ARD, 1.4%; 95% CI, 0.1 to 2.9; P = .04). By contrast, compared with TM, MA beneficiaries incurred lower estimated hospital costs.CONCLUSION: Enrollment in MA plan is associated with lower estimated hospital costs. However, compared with TM, MA beneficiaries had lower access to high-volume hospitals and increased 30-day mortality for stomach, pancreas, or liver surgery.