"The Prognostic Role of Aspartate Transaminase to Platelet Ratio Index (APRI) on Outcomes Following Non-emergent Minor Hepatectomy".

INTRODUCTION: Fibrosis and cirrhosis are associated with worse outcomes after hepatectomy. Aspartate transaminase to platelet ratio index (APRI) is associated with fibrosis and cirrhosis in hepatitis C patients. However, APRI has not been studied to predict outcomes after hepatectomy in patients without viral hepatitis. METHODS: We reviewed the ACS-NSQIP dataset to identify patients who underwent a minor hepatectomy between 2014 and 2021. We excluded patients with viral hepatitis or ascites as well as patients who underwent emergent operations or biliary reconstruction. APRI was calculated using the following equation: (AST/40)/(platelet count) × 100. APRI ≥0.7 was used to identify significant fibrosis. Univariable analysis was performed to identify factors associated with APRI ≥0.7, transfusion, serious morbidity, overall morbidity, and 30-day mortality. Multivariable logistic regression was performed to identify adjusted predictors of these outcomes. RESULTS: Of the 18,069 patients who met inclusion criteria, 1630 (9.0%) patients had an APRI ≥0.7. A perioperative blood transfusion was administered to 2139 (11.8%). Overall morbidity, serious morbidity, and mortality were experienced by 3162 (17.5%), 2475 (13.7%), and 131 (.7%) patients, respectively. APRI ≥0.7 was an independent predictor of transfusion (adjusted OR: 1.48 [1.26-1.74], P < .001), overall morbidity (1.17 [1.02-1.33], P = .022), and mortality (1.97 [1.22-3.06], P = .004). Transfusion was an independent predictor of overall morbidity (3.31 [2.99-3.65], P < .001), serious morbidity (3.70 [3.33-4.11], P < .001), and mortality (5.73 [4.01-8.14], P < .001). CONCLUSIONS: APRI ≥0.7 is associated with perioperative transfusion, overall morbidity, and 30-day mortality. APRI may serve as a noninvasive tool to risk stratify patients prior to elective minor hepatectomy.

Early-stage gastric and gastroesophageal junction cancer: Is there a survival benefit to neoadjuvant therapy?

BACKGROUND: Several randomized controlled trials have evaluated the efficacy of neoadjuvant chemotherapy in the management of resectable gastric cancer. Most patients in these studies had node-positive disease or more advanced T stage. The benefit of neoadjuvant therapy in patients with early-stage gastric cancer remains unclear. METHODS: We queried the National Cancer Data Base to identify patients presenting with clinical stage IB gastric adenocarcinoma between 2006 and 2015. Multivariable logistic regression was used to identify factors associated with receipt of neoadjuvant therapy. Patients undergoing neoadjuvant therapy were 1:1 propensity matched for age, year of diagnosis, Charlson index, insurance, tumor location, tumor grade, surgical approach, lymph nodes examined, and receipt of adjuvant therapy. Log rank testing was used to evaluate differences in overall survival between matched cohorts. RESULTS: A total of 1,258 patients met the inclusion criteria; 402 (32%) received neoadjuvant therapy. On multivariable logistic regression, increasing age (odds ratio 0.52, 95% confidence interval 0.34-0.80) was associated with reduced adjusted odds of undergoing neoadjuvant therapy, whereas proximal tumor location (odds ratio 3.67, 95% confidence interval 2.71-4.99) and poorly differentiated histology (odds ratio 1.78, 95% confidence interval 1.00-3.16) were associated with an increased adjusted odds of undergoing neoadjuvant therapy. A total of 271 patients undergoing neoadjuvant therapy were successfully matched to 271 patients undergoing upfront resection. There was no statistically significant difference in 5-year overall survival (58.8% vs 50.3%, P = .512) between matched cohorts. CONCLUSION: Neoadjuvant therapy does not appear to be associated with an overall survival benefit in patients with stage IB stage gastric cancer.

Small-sized gastrointestinal stromal tumors: Is there an association between expectant management and overall survival?

BACKGROUND: Small-sized gastrointestinal stromal tumors (GISTs) have limited malignant potential. Few studies evaluate the safety and efficacy of expectant management (EM) for patients presenting with small GIST. METHODS: We queried the National Cancer Database to identify patients ≤65 years presenting with GISTs smaller than 3 cm in size between 2004 and 2015. Patients undergoing EM were 1:3 propensity score matched for relevant covariates to patients undergoing resection. Kaplan-Meier (KM) analysis of matched cohorts was used to evaluate the association between EM and overall survival (OS). RESULTS: 1330 patients met inclusion criteria; 966 (72.6%) had gastric GISTs. 1196 (89.9%) underwent resection; 134 (10.1%) EM. 117 patients undergoing EM were propensity-matched to 356 patients undergoing resection. There was no difference in 5-year OS between patients undergoing EM and those undergoing resection (95.7% vs 92.6%, p = 0.4882). CONCLUSIONS: Survival for small GISTs is similar with expectant management or resection.

Positive microscopic surgical margins: Is there an association with survival in resected small gastrointestinal stromal tumors?

BACKGROUND: Few studies evaluate the relationships between surgical approach, histologic margin, and overall survival in gastrointestinal stromal tumor. We test the hypothesis that margin positive resection is associated with compromised overall survival. METHODS: We queried the National Cancer Data Base to identify patients undergoing resections for gastrointestinal stromal tumors ≤3 cm in size between 2010 and 2015. Multivariable logistic regression was used to identify factors associated with positive microscopic margins on final pathology. Cox proportional hazard methods were used to evaluate factors associated with overall survival. RESULTS: 2064 patients met inclusion criteria; 135 (6.5%) had a microscopically positive surgical margin. On multivariable regression, minimally invasive approach was not associated with risk of a positive margin (OR 1.06 95% CI [0.71, 1.59]). On Cox analysis, positive margin status was not associated with OS (R1: 1.03, CI [0.46-2.31], reference R0). CONCLUSIONS: Positive microscopic surgical margins are not associated with compromised overall survival in patients undergoing resection of small gastrointestinal stromal tumors. Minimally invasive surgical approaches do not compromise oncologic outcomes in these cases.

Adjuvant systemic therapy for small bowel gastrointestinal stromal tumor (GIST): Is there a survival benefit after R0 resection?

BACKGROUND: The utility of adjuvant systemic therapy in small bowel gastrointestinal stromal tumor remains unclear. METHODS: We queried the National Cancer Data Base for individuals having enterectomy to negative margins for small bowel gastrointestinal stromal tumor between 2010 and 2015. Subjects were categorized by tumor size (2.1-5 cm, 5.1-10 cm, >10 cm) and histologic grade (≤5 mitoses/50 high-power field and >5 mitoses/50 high-power field). Cox proportional hazard analysis was performed to evaluate the association between adjuvant therapy and overall survival. RESULTS: One thousand five hundred fifty-nine patients met the inclusion criteria. On univariate comparison to resection alone, adjuvant therapy was associated with improved overall survival for individuals with high-grade tumors of intermediate and large size (85% vs 48%, P = .010; 75% vs 47%, P = .003) but not for those with high-grade tumors of small size or low-grade tumors of any size. On multivariable analysis adjusted for age, comorbid disease state, and tumor size, adjuvant therapy was independently associated with reduced risk of mortality for high-grade (hazard ratio 0.37, 95% confidence interval: 0.21-0.64) but not low-grade tumors. CONCLUSION: Adjuvant therapy after R0 resection for small bowel gastrointestinal stromal tumor should be administered after careful consideration of the size and grade of a patient's tumor.

Adjuvant systemic therapy for intermediate and large gastric gastrointestinal stromal tumors (GISTs): Is there a survival benefit following margin negative surgical resection?

BACKGROUND: The value of adjuvant systemic therapy after margin-negative resection for gastric gastrointestinal stromal tumors (GISTs) remains unclear. METHODS: The National Cancer Data Base was queried to identify patients undergoing margin negative resections for gastric GISTs >2 cm between 2010 and 2015. Patients were stratified by tumor size (small: 2.1-5 cm, intermediate: 5.1-10 cm, large: >10 cm), histologic grade (low: ≤5 mitoses/50 HPF and high: >5 mitoses/50 HPF), and use of adjuvant therapy. Multivariable cox proportional hazard methods were used to compare overall survival (OS). RESULTS: 3520 patients met inclusion criteria. Adjuvant therapy was associated with a statistical improvement in OS (86% vs. 76%, p = 0.014) for those with large tumors but had no measurable effect in patients with small or intermediate sized tumors. On multivariable analysis, this association was independent of grade. CONCLUSIONS: Adjuvant therapy is associated with improved OS for patients with gastric GISTs >10 cm but provides no statistically significant benefit in OS for those with GISTs 2-10 cm.

Clinically resectable acinar cell carcinoma of the pancreas: Is there a benefit to adjuvant systemic therapy?

BACKGROUND: Prior studies of adjuvant systemic therapy in pancreatic acinar cell carcinoma have been underpowered. METHODS: We queried the National Cancer Data Base to identify patients presenting with resectable (clinical stage I and II) acinar cell carcinoma between 2004 and 2015. Multivariable Cox Regression was used to evaluate the association between overall survival and systemic therapy. RESULTS: 298 patients met inclusion criteria: 38 received no treatment; 60 received systemic therapy alone; 84 received surgical resection alone; 116 underwent resection followed by adjuvant systemic therapy. On univariate analysis, resection was associated with a survival benefit compared to no treatment and systemic therapy alone (3-year overall survival: 57% vs. 26%, p < 0.001). On Cox analysis, use of adjuvant therapy was associated with a survival benefit compared to resection alone (HR 0.54, 95% CI: 0.33-0.89). CONCLUSIONS: Adjuvant therapy is associated with a significant survival benefit in patients with resectable acinar cell carcinoma.

Discovery of Ibomycin, a Complex Macrolactone that Exerts Antifungal Activity by Impeding Endocytic Trafficking and Membrane Function.

Natural products are invaluable historic sources of drugs for infectious diseases; however, the discovery of novel antimicrobial chemical scaffolds has waned in recent years. Concurrently, there is a pressing need for improved therapeutics to treat fungal infections. We employed a co-culture screen to identify ibomycin, a large polyketide macrolactone that has preferential killing activity against Cryptococcus neoformans. Using chemical and genome methods, we determined the structure of ibomycin and identified the biosynthetic cluster responsible for its synthesis. Chemogenomic profiling coupled with cell biological assays link ibomycin bioactivity to membrane function. The preferential activity of ibomycin toward C. neoformans is due to the ability of the compound to selectively permeate its cell wall. These results delineate a novel antifungal agent that is produced by one of the largest documented biosynthetic clusters to date and underscore the fact that there remains significant untapped chemical diversity of natural products with application in antimicrobial research.