Endocrine surgery and the surgeon-scientist: Bridging the gap between a rich history and a bright future.

INTRODUCTION: We evaluate National Institutes of Health (NIH) data to describe endocrine surgical research performed by surgeons in the United States. METHODS: An internal NIH database was queried for endocrine surgery-related grants awarded to surgeons in 2010, 2015, and 2020. The grants were then compared based on cost, grant type, research type, and endocrine topic. RESULTS: Eighteen grants ($6.4 M) focused on endocrine surgery-related research topics were identified in 2020, 17 ($7.3 M) in 2015, and 11 ($3.8 M) in 2010. In 2020, 14 grants were basic science and 4 were clinical outcomes, and pancreatic endocrine disease and thyroid disease each comprised 6 grants. R01 and R21 grants comprised 10 (55.6%) of the grants in 2020, compared to 10 (58.5%) in 2015 and 8 (72.7%) in 2010, while K08 and K23 grants increased to 4 (22.2%) in 2020 from 2 (11.8%) in 2015 and none in 2010. CONCLUSION: There were more K-awards focused on endocrine surgery-related research in 2020 compared to 2015 and 2010, suggesting the pipeline is growing.

Breast Surgical Oncology Fellowship applicant selection and ranking: A survey of Society of Surgical Oncology programs.

BACKGROUND AND OBJECTIVES: In 2003, the Society of Surgical Oncology (SSO) initiated a breast surgical oncology fellowship, which has now grown to 60 SSO accredited programs as of 2021. Limited knowledge exists on the traits of successful applicants and the factors influencing the rank list. METHODS: A web-based, anonymous survey was sent to all SSO Breast Surgical Oncology Fellowship program directors. The survey consisted of 26 questions. Descriptive statistics were used to analyze survey responses and evaluate impact on applicant interview and rank list. RESULTS: Thirty-four programs (57% response rate) completed the survey. Programs received an average of 70 applications and granted 24 interviews. Most programs reported a minimum ABSITE cut-off score (n = 28, 82%) and a defined publication requirement (n = 22, 65%), including a first-author requirement (n = 18, 53%) to extend an invitation to interview. For postinterview rank, applicant interpersonal skills were highly valued. The interview was the most important aspect for the rank list. CONCLUSIONS: Many programs have ABSITE and publication thresholds before offering an interview. Upon receiving interview invitation, the applicant's interview performance, interpersonal skills, and letters of recommendation were the most important aspect in rank list decision making.

Predictors of post-operative pancreatic fistula formation in pancreatic neuroendocrine tumors: A national surgical quality improvement program analysis.

BACKGROUND: Post-operative pancreatic fistula (POPF) is a serious complication following pancreas surgery. We aimed to establish factors associated with POPF specifically in patients with pancreatic neuroendocrine tumors (PNET). METHODS: The 2014-2018 American College of Surgeons National Surgical Quality Improvement Program database was querried for patients undergoing resection for PNET. The impact of patient, tumor, and operative factors on POPF formation was evaluated. RESULTS: 3532 patient underwent resections for PNET. The POPF rate was significantly higher in patients with PNET (24.8%) versus non-PNET (16.4%) (p < 0.0001). Male sex (OR 1.45, 95% CI 1.11-1.89), enucleation (OR 3.14, 95% CI 1.10-8.98), pancreaticoduodenectomy (OR 1.51, 95% CI 1.13-2.03), small duct size <3 mm (OR 3.24, 95% CI 1.62-6.48), and soft gland texture (OR 1.81, 95% CI 1.18-2.77) were independently associated with POPF in PNET patients on multivariable analysis. CONCLUSIONS: POPF is more common in patients undergoing resection for PNET and is dictated primarily by surgical approach and gland characteristics.

Adjuvant chemotherapy is associated with improved overall survival in select patients with Stage II colon cancer: A National Cancer Database analysis.

BACKGROUND AND OBJECTIVES: Guidelines for Stage II colon cancer recommend adjuvant chemotherapy (AC) only for tumors with high-risk features, but long-term outcomes data are mixed. We aimed to determine if AC was associated with a survival benefit in this population. METHODS: Patients were identified from the National Cancer Database and included if they met the following criteria: diagnosis of Stage II colon cancer, surgery, survival data, and complete data on six high-risk features. The cohort of 57 335 patients was stratified by receipt of AC. Subgroup analysis was performed on patients under the age of 65 years with no comorbidities. Overall survival (OS) was the primary endpoint. RESULTS: An increasing number of high-risk features was associated with significantly decreased median OS. AC was associated with significantly increased OS for patients with 0, 1, 2, and ≥3 high-risk features. On subgroup analysis, receipt of AC was associated with a reduced risk of death (hazard ratio: 0.66; confidence interval: 0.59-0.74). For patients in the subgroup who had a T4 tumor, AC was associated with increased OS (92.7 vs. 83.6 months). CONCLUSIONS: AC should be considered for all younger, healthy patients with Stage II colon cancer and may be associated with a survival benefit for patients with T4 disease.

Patient demographics, clinicopathologic features, and outcomes in wild-type gastrointestinal stromal tumor: a national cohort analysis.

Wild-type KIT and PDGFRA gastrointestinal stromal tumors (GIST) are rare tumors with limited treatment options. We sought to determine the clinicopathologic features of wild-type GIST and identify factors that influence overall survival (OS) using a large national database. Retrospective evaluation of patients with wild-type GIST in the National Cancer Database (NCDB) was performed. Demographic, clinicopathologic, and treatment data were analyzed. Features associated with OS were investigated using Kaplan-Meier analysis and Cox proportional hazards model. 244 patients with median diagnosis age of 59 years (95% CI 57-63) were identified. The stomach was the most common primary site (57%) followed by the small intestine (35%). Surgical resection was performed on 85% of patients and 53% of patients received systemic therapy. Factors associated with decreased OS on multivariable analysis included small intestine primary (HR 2.72, 95% CI 1.13-6.69, P = 0.026) and > 5 mitoses per 50 HPF (HR 4.77, 95% CI 1.86-13.2, P = 0.001). Wild-type GISTs may be identified in older patients, with most arising in the stomach and small bowel. Surgery remains the principal treatment modality. Small intestine primary site and high mitotic count were associated with abbreviated OS.

Location of Gastrointestinal Stromal Tumor (GIST) in the Stomach Predicts Tumor Mutation Profile and Drug Sensitivity.

PURPOSE: Gastrointestinal stromal tumors (GIST) commonly arise in different regions of the stomach and are driven by various mutations (most often in KIT, PDGFRA, and SDHx). We hypothesized that the anatomic location of gastric GIST is associated with unique genomic profiles and distinct driver mutations. EXPERIMENTAL DESIGN: We compared KIT versus non-KIT status with tumor location within the National Cancer Database (NCDB) for 2,418 patients with primary gastric GIST. Additionally, we compiled an international cohort (TransAtlantic GIST Collaborative, TAGC) of 236 patients and reviewed sequencing results, cross-sectional imaging, and operative reports. Subgroup analyses were performed for tumors located proximally versus distally. Risk factors for KIT versus non-KIT tumors were identified using multivariate regression analysis. A random forest machine learning model was then developed to determine feature importance. RESULTS: Within the NCDB cohort, non-KIT mutants dominated distal tumor locations (P < 0.03). Proximal GIST were almost exclusively KIT mutant (96%) in the TAGC cohort, whereas 100% of PDGFRA and SDH-mutant GIST occurred in the distal stomach. On multivariate regression analysis, tumor location was associated with KIT versus non-KIT mutations. Using random forest machine learning analysis, stomach location was the most important feature for predicting mutation status. CONCLUSIONS: We provide the first evidence that the mutational landscape of gastric GIST is related to tumor location. Proximal gastric GIST are overwhelmingly KIT mutant, irrespective of morphology or age, whereas distal tumors display non-KIT genomic diversity. Anatomic location of gastric GIST may therefore provide immediate guidance for clinical treatment decisions and selective confirmatory genomic testing when resources are limited.

Preoperative serum chromogranin-a is predictive of survival in locoregional jejuno-ileal small bowel neuroendocrine tumors.

BACKGROUND: Small bowel neuroendocrine tumors (SB-NET) frequently metastasize to regional lymphatic or distant sites. Although most prognostication of SB-NET focuses on lymph node involvement, findings from studies of neuroendocrine tumors from other primary sites have suggested that preoperative serum chromogranin-A (CgA) levels may provide a more accurate metric. METHODS: Using the National Cancer Database (2004-2016), we analyzed patients with locoregional SB-NET who underwent curative resection including an adequate lymphadenectomy (n = 1,274). A statistically optimized cut-point was used to dichotomize CgA cohort based on preoperative serum CgA levels. RESULTS: We determined that a CgA ≥139 ng/mL identified patients with significantly shorter estimated mean overall survival (6.6 years vs 7.6 years, log-rank P = .00001). These patients were also older (63 vs 57 years, P < .001) and had higher rates of poorly differentiated tumors (2.1% vs 0.7%, P = .04) or primary tumors >1 cm (88.2% vs 79.2%, P = .001). Clinical features associated with shorter overall survival included preoperative CgA ≥139 ng/mL (HR = 2.19, 95% CI 1.22-3.92; P = .009), age at diagnosis (HR = 1.06, 95% CI 1.03-1.09; P < .001), Charlson-Deyo score ≥2 (HR = 3.93, 95% CI 1.71-9.01; P = .001), and poorly differentiated tumors (HR = 11.22, 95% CI 4.16-30.24; P < .001). Neither lymph node metastasis nor T-stage were independently associated with shorter overall survival in patients with locoregional SB-NET. CONCLUSION: Elevated preoperative serum CgA is an adverse prognostic marker associated with shorter overall survival in patients with locoregional SB-NET.

Thyroid Nodule Molecular Testing: Is It Ready for Prime Time?

Cytologically indeterminate thyroid nodules remain a diagnostic and clinical challenge, and molecular testing has been advocated and advanced as a diagnostic modality to help guide treatment. While studies have expounded on the improved diagnostic certainty with these tests, data demonstrating meaningful clinical impact and supporting their routine use is still limited at best. In this review, we discuss the limitations regarding diagnostic accuracy, impact on surgical decision-making and outcomes, and cost-effectiveness of molecular testing. By highlighting the limitations of these tests, we aim to promote more thoughtful utilization of these tools in the management of thyroid nodules going forward.

Pancreatic neuroendocrine tumor presenting in indolent systemic mastocytosis: A case report.

INTRODUCTION: Systemic mastocystosis, a disorder of clonal mast cell expansion presents with symptoms of flushing, pruritus, musculoskeletal pain, gastrointestinal cramping and vascular instability. Patients with neuroendocrine tumors may present with similar symptoms due to the release of vasoactive mediators in both diseases. We report the co-occurrence of systemic mastocytosis and a neuroendocrine pancreatic tumor for which the patient received disease-specific treatment. CASE PRESENTATION: A 58-year-old woman with a history of indolent systemic mastocytosis and a serum tryptase of 51 ng/mL was diagnosed with a solid pancreatic lesion on ultrasound when assessing for organomegaly. Lesional biopsy was consistent with a pancreatic neuroendocrine tumor which was successfully resected. DISCUSSION: Presenting symptoms such as skin rashes, flushing, fatigue and diarrhea, are similar for systemic mastocytosis and neuroendocrine tumors. The co-occurrence of both diseases has not been previously reported. Activating mutations in KIT, which are a hallmark of systemic mastocytosis, may drive neoplastic proliferation in neuroendocrine tumors. Furthermore, mast cells infiltrating pancreatic tissue may have a trophic effect on the development of pancreatic neuroendocrine tumors. CONCLUSION: While challenging to diagnose both diseases presenting with similar symptoms, recognition of these distinct diseases is necessary to ensure timely treatment.