Microbiomic profiles of bile in patients with benign and malignant pancreaticobiliary disease.

BACKGROUND: The prognostic and pathophysiologic significance of the biliary microbiota in pancreaticobiliary malignancies is little understood. Our goal was to find malignancy-related microbiomic fingerprints in bile samples taken from patients with benign and malignant pancreaticobiliary diseases. METHODS: Bile specimens were collected from consenting patients during routine endoscopic retrograde cholangiopancreatography. We used PowerViral RNA/DNA Isolation kit to extract DNA from bile specimens. The Illumina 16S Metagenomic Sequencing Library Preparation guide was used to amplify the bacterial 16S rRNA gene and create libraries. QIIME (Quantitative Insights Into Microbial Ecology), Bioconductor phyloseq, microbiomeSeq, and mixMC packages were used for post-sequencing analysis. RESULTS: Of 46 enrolled patients, 32 patients had pancreatic cancers, 6 had cholangiocarcinoma and 1 had gallbladder cancer. Rest of the patients had benign diseases including gallstones, and acute and chronic pancreatitis. We used multivariate approach in mixMC to classify Operational Taxonomic Units (OTUs). Doing this, we found a predominance of genera Dickeya (p = 0.00008), [Eubacterium] hallii group (p = 0.0004), Bacteroides (p = 0.0006), Faecalibacterium (p = 0.006), Escherichia-Shigella (p = 0.008), and Ruminococcus 1 (p = 0.008) in bile samples from pancreaticobiliary cancers as compared to benign diseases. Additionally, bile samples from patients with pancreatic cancer exhibited a predominance of genus Rothia (p = 0.008) as compared to those with cholangiocarcinoma, whereas bile samples from patients with cholangiocarcinoma exhibited a predominance of genera Akkermansia (p = 0.031) and Achromobacter (p = 0.031) as compared to those with pancreatic cancers. CONCLUSIONS: Both benign and malignant pancreaticobiliary diseases have distinct microbiomic fingerprints. The relative abundance of OTUs in bile samples varies between patients with benign and malignant pancreaticobiliary diseases, as well as between cholangiocarcinoma and pancreatic cancer. Our data suggest that either these OTUs play a role in carcinogenesis or that benign disease-specific microenvironmental changes differ from cancer-specific microenvironmental changes, resulting to a clear separation of OTU clusters. We need more research to confirm and expand on our findings.

Impact of P16 Positivity on Clinical Outcomes in Nasopharyngeal Carcinoma: A Single Institution Study.

Introduction Nasopharyngeal carcinoma (NPC) is a rare malignancy with unique geographical distribution. It is prevalent in East and Southeast Asia and rare in non-endemic countries like the USA. P16 is a tumor suppressor gene and there are limited studies with inconsistent results describing the association of its positivity in immunohistochemistry and clinical outcomes. In this retrospective study, we compared progression-free survival (PFS) and overall survival (OS) based on p16 positivity in 60 patients with NPC. Materials and methods Patients aged above 18 years and followed between July 2015 and December 2020 were included in the study. P16 positivity was based on the immunohistochemistry of the biopsy sample. We compared PFS and OS among all p16-positive and negative patients, and then among patients with advanced disease (stage III or IV), and between p16-positive, negative, and unknown status patients. Results There were 15 p16-positive, and 28 p16-negative, with a median age of 54.3 years and 55.7 years respectively. Most patients in both groups were male, Caucasian, and had advanced disease (stage III or stage IV). Both median PFS (p=0.838) and OS (p=0.776) were 84 months in the p16-negative group but were not reached during the study period in the p16-positive group. Among advanced-stage patients, the PFS (p=0.873), and OS (p=0.773) of both groups were not statistically significant. P16 status was unknown for 17 patients, and PFS (p=0.785) and OS (p=0.901), when compared among patients with p16-positive, negative, and unknown status, were also statistically non-significant. Discussion and conclusion Our analysis suggests that p16 status does not predict clinical outcomes in NPC patients. Our sample size was limited but is larger than most studies describing this association. With different studies in the literature reporting disparate findings, we recommend larger prospective studies to better illustrate the impact of p16 positivity on clinical outcomes in NPC.

Risk of thromboembolism in patients with ALK- and EGFR-mutant lung cancer: A cohort study.

INTRODUCTION: Thromboembolism (TE) is common in patients with non-small cell lung cancer (NSCLC) and is associated with worse outcomes. Recent advances in the understanding of NSCLC have led to the identification of molecular subtypes such as anaplastic lymphocyte kinase (ALK) and epidermal growth factor receptor (EGFR) mutations. The association of these subtypes with risk of TE has not been fully explored. METHODS: We conducted a retrospective cohort study of consecutive NSCLC patients seen at the Cleveland Clinic from July 2002 through July 2017 for whom molecular classification and follow-up were available. TE events included deep vein thrombosis (DVT), pulmonary embolism (PE), visceral vein thrombosis (VVT), and arterial events. TE-free survival and overall survival rates for each of the molecular subtypes (wild-type, ALK-mutant, and EGFR-mutant) were estimated by the Kaplan-Meier method. Cox proportional hazard regression analysis was used to identify factors associated with the endpoints TE and overall survival. TE was analyzed as a conditional, time-dependent covariate to assess its impact with respect to overall survival. RESULTS: The study population consisted of 461 patients. Approximately half were females (n = 263, 57%) and 58% (n = 270) were older than 65 years. TE occurred in 98 of 461 patients (21.3%) during a median follow-up of 33.1 months. The highest cumulative rates of TE were observed in patients with ALK-mutant NSCLC (N = 20/46, 43.5%) followed by patients with EGFR-mutant cancers (N = 35/165, 21.2%) and wild-type cancers (N = 43/250, 17.2%) P < .05. Cumulative incidence of TE at 6 months of follow-up was 15.7% (95% confidence interval [CI]: 5.0%-26.4%) for ALK-mutant cancers, 8.8% (95% CI: 4.4%-13.2%) for EGFR-mutant cancers, and 9.2% (95% CI: 5.4%-12.9%) for wild-type cancers. Patients who experienced TE had worse overall survival (all patients: hazard ratio = 2.8 95% CI 2.1-3.6, P < .001). CONCLUSIONS: Patients with ALK-mutant advanced lung adenocarcinoma have the highest rate of TE. TE is associated with worse survival across molecular subtypes. These findings should be taken into consideration in decision-making regarding thromboprophylaxis.

Clinical outcomes of isolated distal deep vein thrombosis versus proximal venous thromboembolism in cancer patients: The Cleveland Clinic experience.

BACKGROUND: Previous studies suggest isolated distal deep vein thrombosis (IDDVT) has a self-limited clinical course. However, these studies excluded cancer patients, who remain a high-risk population. In addition, studies to evaluate the long-term clinical outcomes of IDDVT in cancer patients have been limited. Here, we report outcomes from our experience in treating cancer-associated IDDVT versus proximal venous thromboembolism (VTE). METHODS: We prospectively evaluated a cohort of patients referred to our cancer-associated thrombosis clinic from August 2014 through May 2018. We compared clinical characteristics, anticoagulation prescription, VTE recurrence, overall survival, major bleeding, and subsequent hospital admission between cancer patients with IDDVT and proximal VTE. A propensity score matching method was used to reduce bias from confounding variables. RESULTS: Of 1100 patients referred to the clinic, 124 IDDVT and 178 proximal VTE events were analyzed. After propensity score matching, 96 patients were included in each cohort. There was no difference in the rate of recurrent VTE between cancer patients with proximal VTE vs IDDVT, with or without matching (matched: hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.31-1.92; P = .58). There was no difference in overall survival between cancer patients with proximal VTE vs. IDDVT with or without matching (matched: HR, 1.18; 95% CI, 0.77-1.82; P = .45). Furthermore, subsequent hospital admissions and major bleeding events were similar between patients with proximal VTE events versus IDDVT. CONCLUSIONS: Cancer patients with IDDVT have similar outcomes as their proximal counterparts, including rate of recurrence and overall survival. These findings suggest treatment of cancer-associated IDDVT should mirror treatment of proximal events.

Posttransplant maintenance therapy for acute leukemias.

PURPOSE OF REVIEW: Allogeneic hematopoietic stem cell transplantation cures a significant proportion of patients with hematological malignancies. Unfortunately, leukemia recurrence is the main cause of transplant failure. Risk factors for relapse include presence of minimal residual disease and a variety of well-recognized leukemia prognostic factors. Posttransplant therapy could decrease the risk of leukemia relapse and is under investigation. In this review, we summarize the current research in maintenance therapy for the prevention of acute leukemia recurrence after allogeneic transplant. RECENT FINDINGS: Epigenetic modifiers, tyrosine kinase inhibitors, and antibody-drug conjugates are among potential maintenance therapies given their side-effect profile and many are currently under investigation. In the posttransplant setting, the phase I/II data are maturing and have been encouraging enough to lead to the initiation of multicenter phase III randomized clinical trials. SUMMARY: Currently, there is no standard of care for posttransplant maintenance for acute leukemias. Further investigation into the efficacy and safety of posttransplant maintenance is warranted given phase I/II clinical trials results. Beyond chemo-immunotherapy, the use of targeted cellular therapy, such as chimeric antigen receptor T cells, is a potential therapy as well.