Whether laparoscopic approach to gastrectomy for gastric cancer (GC) reduces the risk of pneumonia remains unknown. In this study, we compared pneumonia outcomes for patients with GC who underwent either laparoscopic gastrectomy (LG) or open gastrectomy (OG). The ACS NSQIP database was queried to identify patients with GC who underwent LG or OG between Jan 2012 - Dec 2018. Outcomes were compared using regression models. A post-hoc analysis was performed for elderly patients. The study cohort included 2661 patients, 23.4 % undergoing LG. Laparoscopic approach lowered pneumonia risk (OR 0.47, p = .028) and reduced hospital length of stay, (5.3 vs 7.1 days, p < .001). Elderly patients undergoing LG demonstrated similar benefits. Risk factors for pneumonia included advanced age, dyspnea and weight-loss, whereas laparoscopic approach reduced this risk. LG in patients with GC has both statistically and clinically significant advantages over OG with respect to pneumonia. Further studies are needed to validate the relationship between postoperative pneumonia and surgical approach for gastrectomy.
19 August 2024 in Cancer Epidemiology, Biomarkers & Prevention
Background: Various population-based studies have shown Hispanic/Latino ethnicity is a risk factor for worse survival in patients with gastric cancer linked to disparate access to care. We aimed to address whether Hispanic patients treated within safety-net hospital systems continue to experience this survival deficit compared to non-Hispanic patients. Methods: We performed a retrospective cohort study comparing survival between Hispanic and non-Hispanic patients diagnosed with gastric adenocarcinoma between January 1, 2016, and December 31, 2020, within Los Angeles County’s safety-net hospital system. Gastric cancer–specific survival was compared between the two cohorts using the Kaplan–Meier estimate and Cox proportional-hazards regression model. Results: In total, 448 patients who received care from five medical centers were included; 348 (77.7%) patients self-identified as Hispanic and 100 (22.3%) as non-Hispanic. Mean follow-up time was 2.0 years (median 0.91 years, IQR, 0.34–2.5 years). Hispanic patients were found to be diagnosed at a younger age (55.6 vs. 60.7 years, P < 0.01), demonstrate higher state area deprivation index (6.4 vs. 5.0, P < 0.01), and present with metastatic disease (59.8% vs. 45%, P = 0.04). After adjusting social and oncologic variables, Hispanic ethnicity remained an independent risk factor for worse survival [HR 1.56, (95% CI, 1.06–2.28); P = 0.02]. Conclusions: Hispanic patients treated within a large, multicenter safety-net hospital system experience worse survival compared to non-Hispanic patients. This suggests ethnic disparities exist within safety-net hospital systems, independent of known clinicopathologic factors. Impact: Improving outcomes for Hispanic patients with gastric cancer requires future efforts aimed at defining and addressing these unidentified barriers to care. See related In the Spotlight, p. 12
Background: Although IGF2BP3 has been implicated in tumorigenesis and poor outcomes in multiple cancers, its role in soft-tissue sarcoma (STS) remains unknown. Preliminary data have suggested an association with IGF2BP3 expression among patients with well-differentiated/dedifferentiated liposarcoma (WD/DD LPS), a disease where molecular risk stratification is lacking. Methods: We examined the survival associations of IGF2BP3 via univariate and multivariate Cox regression in three unique datasets: (1) the Cancer Genome Atlas (TCGA), (2) an in-house gene microarray, and (3) an in-house tissue microarray (TMA). A fourth dataset, representing an independent in-house TMA, was used for validation. Results: Within the TCGA dataset, IGF2BP3 expression was a poor prognostic factor uniquely in DD LPS (OS 1.6 vs. 5.0 years, p = 0.009). Within the microarray dataset, IGF2BP3 expression in WD/DD LPS was associated with worse survival (OS 7.7 vs. 21.5 years, p = 0.02). IGF2BP3 protein expression also portended worse survival in WD/DD LPS (OS 3.7 vs. 13.8 years, p < 0.001), which was confirmed in our validation cohort (OS 2.7 vs. 14.9 years, p < 0.001). In the multivariate model, IGF2BP3 was an independent risk factor for OS, (HR 2.55, p = 0.034). Conclusion: IGF2BP3 is highly expressed in a subset of WD/DD LPS. Across independent datasets, IGF2BP3 is also a biomarker of disease progression and worse survival.
Previous studies have reported cases of primary melanoma of the breast parenchyma (PMBP), but the pathogenesis of this disease remains poorly understood. We review the presentation and outcomes of reported cases and provide detailed pathological analysis of four additional cases. Furthermore, we discuss potential theories regarding the pathogenesis of this clinical presentation. We identified 29 published studies (n = 95 patients) and report four new cases (n = 99). Ninety-one (92 %) patients were female, with a median age of 50 years. Previous skin melanomas were reported by 56 % of patients, with the trunk being the most common location (32.7 %) followed by the upper extremities (20 %). The most common tumor location reported (n = 73) was the right (49 %) upper outer quadrant (56 %). The median time from skin melanoma diagnosis to the presence of a breast mass was 65 months (1–192). Nodal status at presentation was reported in n = 67 (68 %) patients. Of these, positive nodal metastases were seen in 40.3 %, while distant metastatic disease at presentation was reported in 30 % of patients. Surgery was performed in 66 %, being partial mastectomy (PM) the most common procedure in 82 %. Adjuvant therapy was described in 38 patients. The reported (n = 12) median survival was 11.5 (1–70) months. Melanomas identified in the breast parenchyma are likely the result of nodal or hematogenous spread from previously known or unknown melanomas, and should not be considered as PMBP. Management should be multidisciplinary, including surgical excision aimed at obtaining negative margins with lymphadenectomy of clinically positive nodes and neoadjuvant/adjuvant immunotherapy.
Background: Gastric cancer disproportionately impacts populations in resource‐limited settings. Within a safety‐net network, we assessed the utility of computed tomography (CT) as a single staging modality.Methods: We utilized a clinical database of gastric cancer patients treated within the Los Angeles County safety‐net hospital system from 2016 to 2023 in conjunction with retrospective imaging review by certified radiologists. We assessed agreement between clinical and pathological staging for patients who underwent curative gastrectomy using the Kappa coefficient.Results: Of 107 patients with available CT imaging, 43.9% (n = 47) were staged with CT as a single modality. Most tumors displayed infiltrating (75%) or diffuse (28%) morphology, 41% displayed adequate gastric distention and regional lymphadenopathy was common (68%). Twenty‐nine patients underwent curative gastrectomy. Overall agreement was minimal (κ = 0.29, 95% CI [0.071−0.51], p = 0.022), weak for T3/T4 tumors (κ = 0.50, 95% CI [0.17−0.82], p < 0.01), and weak for Hispanic/Latino patients (κ = 0.47, 95% CI [0.19−0.76], p < 0.01).Conclusions: There was minimal agreement between clinical and pathologic staging when assessing clinical stage by CT imaging alone, suggesting that CT is not adequate as a single modality staging tool. While every effort should be made to obtain multimodal staging, larger studies are warranted to improve CT imaging protocols for staging in resource‐limited settings.
Background: mTORC1 activity is dependent on the presence of micronutrients, including Asparagine (Asn), to promote anabolic cell signaling in many cancers. We hypothesized that targeting Asn metabolism would inhibit tumor growth by reducing mTORC1 activity in well-differentiated (WD)/dedifferentiated (DD) liposarcoma (LPS). Methods: Human tumor metabolomic analysis was utilized to compare abundance of Asn in WD vs. DD LPS. Gene set enrichment analysis (GSEA) compared relative expression among metabolic pathways upregulated in DD vs. WD LPS. Proliferation assays were performed for LPS cell lines and organoid models by using the combination treatment of electron transport chain (ETC) inhibitors with Asn-free media. 13C-Glucose-labeling metabolomics evaluated the effects of combination treatment on nucleotide synthesis. Murine xenograft models were used to assess the effects of ETC inhibition combined with PEGylated L-Asparaginase (PEG-Asnase) on tumor growth and mTORC1 signaling. Results: Asn was enriched in DD LPS compared to WD LPS. GSEA indicated that mTORC1 signaling was upregulated in DD LPS. Within available LPS cell lines and organoid models, the combination of ETC inhibition with Asn-free media resulted in reduced cell proliferation. Combination treatment inhibited nucleotide synthesis and promoted cell cycle arrest. In vivo, the combination of ETC inhibition with PEG-Asnase restricted tumor growth. Conclusions: Asn enrichment and mTORC1 upregulation are important factors contributing to WD/DD LPS tumor progression. Effective targeting strategies require limiting access to extracellular Asn and inhibition of de novo synthesis mechanisms. The combination of PEG-Asnase with ETC inhibition is an effective therapy to restrict tumor growth in WD/DD LPS.