A Combination of MUC5AC and CA19-9 Improves the Diagnosis of Pancreatic Cancer: A Multicenter Study.

OBJECTIVES: Pancreatic cancer (PC) is a lethal malignancy that lacks specific diagnostic markers. The present study explores the diagnostic potential of the most differentially overexpressed secretory mucin MUC5AC alone and in combination with CA19-9 using multi-center training and validation sets. METHODS: The expression of MUC5AC in benign pancreatic pathologies, PC precursor lesions, primary PC tissues and metastatic lesions was evaluated by immunohistochemistry. Circulating MUC5AC levels were measured using sandwich ELISA assay developed in-house, and CA19-9 was measured using radioimmunoassay. A combined training set (n=346) was used to evaluate the diagnostic (n=241) and predictive (n=105, total samples 201 from pre- and post-surgical and chemotherapy set) significance of MUC5AC. Results were further validated with a pre-defined cut-off value using independent sets from the Mayo Clinic (n=94) and the University of Pittsburgh Medical Center (n=321). RESULTS: Tissue expression analyses indicated the de novo expression of MUC5AC in pancreatic intraepithelial precursor lesions 1A (PanIN1A); the expression was maintained through all stages of progression to invasive adenocarcinoma. The median circulating MUC5AC levels in patients with resectable early-stage PC (EPC) (stage 1/2; 67.2 ng/ml, IQR: 23.9-382.1) and unresectable late-stage PC (LPC) (stage 3/4; 389.7 ng/ml, IQR: 87.7-948.6) were significantly higher compared with (P-value ≤0.0001) benign controls (BC) (7.2 ng/ml, IQR: 0.4-26.5) and (P-value ≤0.0001) chronic pancreatitis (CP) controls (8.4 ng/ml, IQR: 1.5-19.2). In the diagnostic training set (n=241), MUC5AC efficiently differentiated EPC from healthy controls (HC) (83%/80% sensitive (SN)/specific (SP)), BC (67%/87% SN/SP), and CP (83%/77% SN/SP). Independent validation sets from the Mayo Clinic and UPMC confirmed the diagnostic potential of MUC5AC to differentiate EPC from BC (68%/73%; 65%/83%) and CP (68%/79%; 65%/72%). Furthermore, MUC5AC and CA19-9 combination significantly improved (p-value < 0.001) the diagnostic accuracy for differentiating resectable cases from controls. CONCLUSIONS: MUC5AC is a valuable diagnostic biomarker, either alone or in combination with CA19-9, to differentiate PC from CP and benign controls.

Predictors of academic career placement and scholarly impact in fellowship-trained rhinologists.

BACKGROUND: As rhinology fellowship positions outpace the availability of academic rhinology jobs, it is increasingly important to identify characteristics that are associated with academic placement after fellowship completion. In this study, we evaluated the association of academic characteristics during training with current job placement and posttraining scholarly impact. METHODS: Previous rhinology fellows were identified using publicly available data. Bibliometric indices, training institutions, graduate degrees, and job placement data were used in bivariate and multivariable regression analyses to assess for association with predictors and academic trajectory. RESULTS: Data from 265 rhinologists, all graduating between 1991 and 2020, were included. Most surgeons (n = 185, 70%) held an academic position and 80 (30%) surgeons worked in a nonacademic setting; 93.2% had a Doctor of Medicine (MD) degree and 80.3% were male. Multivariable logistic regression indicated that a designation of MD, compared with Doctor of Osteopathic Medicine (DO; odds ratio [OR], 5.93; 95% confidence interval [CI], 1.97-21.9), number of publications during fellowship (OR, 1.19; 95% CI, 1.02-1.41), and h-index during training (OR, 1.25; 95% CI, 1.07-1.49]) were independently predictive of academic job placement. Meanwhile, number of primary authorships during fellowship (ß = 1.47; 95% CI, 1.07-1.88]), h-index during training (ß = 0.48; 95% CI, 0.25-0.71), and PhD (ß = 4.16; 95% CI, 1.57-6.76) were associated with posttraining h-index. Medical school ranking; graduate degrees, including Master of Science (MS), Master of Business Administration (MBA), and Master of Public Health (MPH); and research metrics before residency were not associated with either academic placement or posttraining h-index. CONCLUSION: The predictors of academic job placement in rhinology are unclear, but h-index during training, and research productivity during fellowship may serve as indicators of an academic career.

Bilateral Lymphatic Spread of Metastatic Basal Cell Carcinoma.

Herein, we report a case of a patient with an abnormal skin lesion that remained unchecked by medical professionals for approximately 20 years. Upon physical examination in the emergency department for a fractured hip, an infiltrative mass was incidentally discovered. The neoplasm was noted to have progressed from an eraser-sized mass to a 3.5-cm invasive lesion. Initial surgical intervention was believed to have been successful in removal, as margins were clear with the exception of 1 indeterminate segment. However, subsequent 1-year follow-up revealed recurrence of the disease with bilateral axillary node and deep muscle involvement. This prompted a more extensive surgical approach complemented with radiation therapy. The patient had remained disease-free for a year.

Clinical presentation and outcome of nonfunctional pancreatic neuroendocrine tumors in a modern cohort.

BACKGROUND: The natural history of nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) is largely unstudied due to its rarity. The primary goal of this study was to characterize clinical features and outcomes of incidental NF-PNETs. METHODS: An institutional review board-approved retrospective study of patients with NF-PNET evaluated by the Surgical Oncology of University of Nebraska Medical Center was performed. Patients were evaluated with dedicated pancreatic and liver imaging using multiphasic computed tomographic scan and dedicated magnetic resonance imaging protocols. RESULTS: Forty-six patients (male, 47.8%) were evaluated, and 35 ultimately resected. Of these, 16 tumors were discovered incidentally. The median age was 62 and 59 years in incidental and symptomatically discovered, respectively. Incidental median size was 2.4 cm vs 6 cm in the symptomatic group, with a P value of .037. The presence of lymphatic and liver metastases was 10% and 25% incidental and 45% and 67% for those with symptoms (lymphatic involvement, P = .05; liver metastases P = .07). Median overall survival was 45 and 76 months (P = .03). CONCLUSIONS: Incidentally discovered NF-PNETs represent a malignancy with more questions than answers. Our series indicates that these cancers are more indolent than previously believed.