Evaluation of Nationwide Trends in Nodal Sampling Guideline Adherence for Gastric Cancer: 2005-2017.

INTRODUCTION: Surgical resection is the primary curative treatment for localized gastric cancer. A multitude of research supports surgical nodal sampling guidelines. Though there are known disparities in adherence to nodal sampling, it is unclear how hospital program-level disparities have changed over time. The purpose of this study is to evaluate trends in program-level disparities in adherence to gastric cancer nodal sampling guidelines. METHODS: Patients who underwent resection of gastric cancer from 2005 to 2017 were identified in the National Cancer Database. Patients treated at academic programs were compared to those treated at nonacademic programs, and rates and trends of adherence to nodal sampling guidelines (defined as ≥15 lymph nodes) were determined. Adjusted multivariable analysis was used to determine likelihood of nodal sampling adherence while controlling for sociodemographic, clinical, hospital, and travel distance characteristics. RESULTS: A total of 55,421 patients were included with 27,201 (49.1%) of patients meeting adherence criteria for lymph node sampling. Academic programs treated 44.4% of the total cohort. Overall, lymph node sampling criteria were met in 59.2% of patients treated at high-volume academic programs and 37.0% of patients treated at low-volume nonacademic programs (incidence rate ratios 0.67, 95% confidence interval 0.63-0.72 versus high-volume academic programs). Adherence rates improved from 2005 to 2017 for both low-volume nonacademic programs (27.8% in 2005 to 50.1% in 2017) and high-volume academic programs (46.0% in 2005 to 69.8% in 2017, P < 0.001). CONCLUSIONS: Though adherence rates have improved from 2005 to 2017, high-volume academic programs were more likely to adhere to lymph node sampling guidelines for gastric cancer.

Association between travel distance and overall survival among patients with adrenocortical carcinoma.

BACKGROUND AND OBJECTIVES: Regionalization of care is associated with improved perioperative outcomes after adrenalectomy. However, the relationship between travel distance and treatment of adrenocortical carcinoma (ACC) is unknown. We investigated the association between travel distance, treatment, and overall survival (OS) among patients with ACC. METHODS: Patients diagnosed with ACC between 2004 and 2017 were identified with the National Cancer Database. Long distance was defined as the highest quintile of travel (≥42.2 miles). The likelihood of surgical management and adjuvant chemotherapy (AC) were determined. The association between travel distance, treatment, and OS was evaluated. RESULTS: Of 3492 patients with ACC included, 2337 (66.9%) received surgery. Rural residents were more likely to travel long distances for surgery than metropolitan residents (65.8% vs. 15.5%, p < 0.001), and surgery was associated with improved OS (HR 0.43, 95% CI 0.34-0.54). Overall, 807 (23.1%) patients received AC with rates decreasing approximately 1% per 4-mile travel distance increase. Also, long distance travel was associated with worse OS among surgically treated patients (HR 1.21, 95% CI 1.05-1.40). CONCLUSIONS: Surgery was associated with improved overall survival for patients with ACC. However, increased travel distance was associated with lower likelihood to receive adjuvant chemotherapy and decreased overall survival.

Protein Tyrosine Phosphatase SHP-1 Modulates T Cell Responses by Controlling Cbl-b Degradation.

Previously, we demonstrated that CD28 and CTLA-4 signaling control Casitas-B-lineage lymphoma (Cbl)-b protein expression, which is critical for T cell activation and tolerance induction. However, the molecular mechanism(s) of this regulation remains to be elucidated. In this study, we found that Cbl-b fails to undergo tyrosine phosphorylation upon CD3 stimulation because SHP-1 is recruited to and dephosphorylates Cbl-b, whereas CD28 costimulation abrogates this interaction. In support of this finding, T cells lacking SHP-1 display heightened tyrosine phosphorylation and ubiquitination of Cbl-b upon TCR stimulation, which correlates with decreased levels of Cbl-b protein. The aberrant Th2 phenotype observed in T cell-specific Shp1(-/-) mice is reminiscent of heightened Th2 response in Cblb(-/-) mice. Indeed, overexpressing Cbl-b in T cell-specific Shp1(-/-) T cells not only inhibits heightened Th2 differentiation in vitro, but also Th2 responses and allergic airway inflammation in vivo. Therefore, SHP-1 regulates Cbl-b-mediated T cell responses by controlling its tyrosine phosphorylation and ubiquitination.

Utilization of Neoadjuvant Therapy for Localized Gastric Gastrointestinal Stromal Tumors and the Association with Survival.

BACKGROUND: For gastric GISTs, neoadjuvant imatinib is most often reserved for tumors near the gastroesophageal junction, multi-visceral involvement, or limited metastatic disease. Whether localized gastric GISTs benefit from neoadjuvant therapy (NAT) remains unknown. We sought to examine factors associated with NAT utilization for localized gastric GISTs and evaluate implications on survival. METHODS: The National Cancer Database identified patients with localized gastric GISTs treated with NAT (2010-2020), excluding tumors extending beyond the gastric wall, located in the cardia, or with metastatic disease. Multivariable logistic regression assessed characteristics of NAT use. After 1:1 propensity score matching, Kaplan-Meier methods and multivariable Cox regression assessed overall survival (OS). RESULTS: Of 7,203 patients, 762 (10.6%) received NAT followed by resection. On multivariable analysis, increasing tumor size was associated with NAT use (<2.0cm vs 2.0-5.0cm OR:2.03, 95%CI 1.19-3.47, p=0.010; vs >5cm OR:16.87, 95%CI 10.02-28.40, p<0.001). After propensity score matching, 1,506 patients remained. Median OS for NAT was 46.0 months vs 43.0 months for resection (p=0.059) which was independently predictive of improved survival (HR:0.89; 95%CI 0.80-0.99, p=0.041). Subgroup analysis by tumor size showed no survival differences for tumors <2.0cm or 2.0-5.0cm. Median OS was higher for tumors >5.0cm treated with NAT (NAT:45.4 months [IQR 29.5-65.9]. vs upfront resection:42.3 months [26.9-62.8]) and associated with improved survival on multivariable analysis (HR:0.88; 95%CI 0.78-0.99, p=0.040). CONCLUSION: Although patients who received NAT had improved survival, this was primarily due to tumors >5.0cm. Expanding NAT selection criteria to include localized gastric GISTs >5.0cm may improve outcomes and warrants investigation through clinical trials.

Selective surgical excision of high-risk lesions.

Intraductal papilloma, flat epithelial atypia, radial scar, atypical lobular hyperplasia, and lobular carcinoma in situ have historically been referred to as high-risk lesions and managed with routine surgical excision after diagnosis on core needle biopsy. The misnomer high-risk stems from high rates of upgrade to malignancy reported in historic literature. However, recent studies have found much lower upgrade rates, <2%, than previously thought. These findings are explained by advances in imaging technology, larger-bore biopsy needles, and emphasis on radiology-pathology concordance. Concordant lesions have a low upgrade risk and can be managed with radiographic and clinical surveillance instead of surgical excision. Surgical de-escalation is feasible for many of these lesions with careful multidisciplinary review and a detailed risk-benefit discussion with patients.