Faculty Bibliography

BACKGROUND:Frailty is a physiologic state that affects perioperative outcomes. Studies evaluating the impact of frailty on long-term oncologic outcomes are limited. This study evaluated perioperative and long-term oncologic outcomes for elderly patients undergoing colorectal surgery. METHODS:Patients older than 65 years at the time of colorectal resection between July 2011 and September 2020 at Roswell Park Comprehensive Cancer Center were identified. Variables from the National Surgical Quality Improvement Program (NSQIP), the tumor registry, and electronic medical records (EMRs) were used to identify frail patients using the revised Risk Analysis Index (RAI-A) score. A score of 38 or higher defined a patient as "frail." Perioperative outcomes were evaluated using logistic regression and chi-square, and oncologic outcomes were evaluated using Kaplan-Meier analysis. RESULTS:The study analyzed 411 patients. The mean age at surgery was 75.1 years. The median RAI-A score was 37, and 29.9 % of the patients were frail. The frail patients had significantly higher rates of overall complications (30.1 % vs 14.6 %; p < 0.001). They also had significantly higher rates of postoperative hospitalization longer than 30 days, postoperative delirium, and discharge to rehabilitation. No mortality differences were observed. The 318 patients with colorectal adenocarcinoma undergoing curative-intent resection were evaluated for oncologic outcomes. No differences with frailty in terms of overall survival, disease-specific survival, or progression-free survival were observed except for frail patients with stage 0 or 1 adenocarcinoma, who had worse overall survival than non-frail patients but equivalent other outcomes. CONCLUSIONS:For elderly patients undergoing colorectal surgery, frailty is associated with higher postoperative complications, discharge to rehabitation, and prolonged hospitalization rates. Frailty does not affect long-term oncologic outcomes, so frail elderly patients gain the same oncologic benefit with surgery as non-frail patients.

BACKGROUND:In addition to treating hyperlipidemia and atherosclerosis, statins have demonstrated anti-inflammatory and antitumor activity in various cancers. We evaluate this effect in esophageal cancer patients undergoing esophagectomy. METHODS:Esophageal cancer patients undergoing esophagectomy at Roswell Park Comprehensive Cancer Center between March 2007 and December 2015 were included. Association between presurgery statin use and relevant variables with overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) was analyzed using Cox hazards. Survival analyses were independently performed for body mass index (BMI)-based subgroups. RESULTS:There was no significant association between statin use and outcomes overall. However, in subgroup analysis, there was significant association between statin use and outcomes in patients with BMI ≥ 30. Multivariable analysis in obese patients demonstrated the association of statins with improved OS (hazard ratio [HR]: 0.46, p = 0.025), DSS (HR: 0.39, p = 0.015), and RFS (HR: 0.38, p = 0.022). The only other variable significantly associated with all three outcome measures was stage. CONCLUSIONS:Statin use is associated with improved OS, DSS, and RFS of obese patients in resected esophageal cancer. BMI could be investigated as a biomarker for adjunctive statin use in future studies.

Despite low mutational burden, immune checkpoint inhibitors have demonstrated promising results in a significant minority of hepatocellular carcinoma (HCC) patients with advanced disease. We hypothesized that HCC patients with higher levels of CD8+ T cell infiltration reflect an immune-inflamed cohort which has improved oncologic outcomes. 355 HCC patients with clinical and transcriptome data in the Cancer Genome Atlas (TCGA) and 151 HCC patients from cohort GSE7624 were analyzed. xCell computational algorithm was used to analyze immune cell infiltration in these patients. Each cohort was divided into high and low expression by the highest 2 terciles value. Gene Set Enrichment Analysis was performed to identify enriched gene sets. High CD8 score associated with improved overall survival in both cohorts (both P < 0.05). High score correlates with early BCLC stage (P = 0.035) but not AJCC stage. High CD8 also correlated with increased IFN-γ response (p = 0.038), lymphocyte infiltration (P < 0.001), and leukocyte fraction (P < 0.001). It was associated with increased polyclonality of T cell (P < 0.001) and B cell response (P = 0.017). High CD8 score correlated with increased cytolytic activity score (P < 0.001) and expression of multiple immune checkpoints including PD-1, PD-L1, CTLA-4 and Lag3 (all P < 0.001). There was no correlation to tumor mutational burden and neoantigens. GSEA demonstrated upregulation of several gene sets involved in inflammatory response and IFN-γ response. In conclusion, HCC patients with high CD8 score demonstrated favorable oncologic outcomes, which may be due to immune-mediated tumor cell attack. Furthermore, CD8 score may be a potentially useful biomarker to select patients for immune checkpoint inhibition.

[This corrects the article DOI: 10.1371/journal.pone.0176139.].

A 56-year-old man presented to the emergency department with painless jaundice and weight loss. Abdominal ultrasound detected dilation of the common bile duct and the intrahepatic bile ducts. Follow-up with endoscopic retrograde cholangiography exposed a stricture of the common hepatic duct, with cholangioscopy identifying an infiltrating tumor. Biopsy revealed a granular cell tumor, which was confirmed by positive S-100 immunohistochemical staining. Surgical excision confirmed granular cell tumor of the bile duct with morphological features suggestive of malignancy.

BACKGROUND:Despite improvements in cancer management, most pancreatic cancers are still diagnosed at an advanced stage. We have recently identified promoter DNA methylation of the genes ADAMTS1 and BNC1 as potential blood biomarkers of pancreas cancer. In this study, we validate this biomarker panel in peripheral cell-free tumor DNA of patients with pancreatic cancer. RESULTS:Sensitivity and specificity for each gene are as follows: ADAMTS1 87.2% and 95.8% (AUC = 0.91; 95% CI 0.71-0.86) and BNC1 64.1% and 93.7% (AUC = 0.79; 95% CI 0.63-0.78). When using methylation of either gene as a combination panel, sensitivity increases to 97.3% and specificity to 91.6% (AUC = 0.95; 95% CI 0.77-0.90). Adding pre-operative CA 19-9 values to the combined two-gene methylation panel did not improve sensitivity. Methylation of ADAMTS1 was found to be positive in 87.5% (7/8) of stage I, 77.8% (7/9) of stage IIA, and 90% (18/20) of stage IIB disease. Similarly, BNC1 was positive in 62.5% (5/8) of stage I patients, 55.6% (5/9) of stage IIA, and 65% (13/20) of patients with stage IIB disease. The two-gene panel (ADAMTS1 and/or BNC1) was positive in 100% (8/8) of stage I, 88.9% (8/9) of stage IIA, and 100% (20/20) of stage IIB disease. The sensitivity and specificity of the two-gene panel for localized pancreatic cancer (stages I and II), where the cancer is eligible for surgical resection with curative potential, was 94.8% and 91.6% respectively. Additionally, the two-gene panel exhibited an AUC of 0.95 (95% CI 0.90-0.98) compared to 57.1% for CA 19-9 alone. CONCLUSION:The methylation status of ADAMTS1 and BNC1 in cfDNA shows promise for detecting pancreatic cancer during the early stages when curative resection of the tumor is still possible. This minimally invasive blood-based biomarker panel could be used as a promising tool for diagnosis and screening in a select subset of high-risk populations.