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Tobacco and alcohol use are established risk factors for esophageal squamous cell carcinoma (ESCC). We sought to determine whether these factors act synergistically to increase the risk of ESCC. We performed a systematic literature search in multiple electronic databases regardless of language. Eligible studies were population-based case-control or cohort studies of ESCC that assessed the effects of tobacco and/or alcohol. Departures from multiplicative effects were quantified by the synergy factor (SF); SF >1 indicates positive synergy. Meta-analyses were performed to estimate summary-adjusted odds ratios (ORs) and the summary crude SF using random-effect models. Heterogeneity was defined by Cochrane's Q P<0.10 and the inconsistency index. Systematic review identified 7,629 unique citations, of which 5 were eligible. Either tobacco or alcohol use was associated with a 20-30% increased risk for ESCC compared with nonuse, but the use of both was associated with an approximately threefold risk for ESCC; the summary-adjusted OR for combined alcohol and tobacco use was 3.28 (95% confidence interval (CI)=2.11, 508; Cochrane's Q P value=0.05; I(2)=55.3%). The summary SF for ever-use of both tobacco and alcohol was 1.85 (95% CI=1.45, 2.38; Cochrane's Q P value=0.49; I(2)=0.0%). There is a positive synergistic effect of alcohol and tobacco use for ESCC. The observed combined effect of the two factors is almost double if there were no synergy. Efforts for controlling the burden of ESCC should focus on individuals who use both alcohol and tobacco.

INTRODUCTION:Telehealth is an emerging technology that enables remote video visits between providers and their patients. The role of a telehealth visit prior to high-risk endoscopy has not been evaluated. The purpose of this study was to pilot a patient survey to assess experiences and preferences for different visit types including telehealth (TH), face-to-face (F2F), and direct access (DA) (i.e., without meeting with a GI physician) prior to undergoing advanced endoscopic procedures.METHODS:We developed a survey instrument to assess patient knowledge and preference regarding visit types prior to advanced endoscopic procedures. The survey was refined through input from an expert survey working group. The questionnaire was then administered immediately prior to informed consent to patients undergoing advanced endoscopy procedures at a tertiary referral academic VA medical center. Exclusion criteria included inability to consent and prior exposure to advanced endoscopic procedures. Data were collected on demographics, computer and health literacy, knowledge of procedural risks, benefits, and alternatives, comfort with the proceduralist, visit satisfaction, and overall preference of pre-procedural visit modality. Differences between groups were analyzed using a Chi-Square test.RESULTS:A total of 40 patients completed the pilot questionnaire (Table 1). 20 patients were in the DA group, 11 in the F2F group, and 9 in the TH group. Most respondents in the TH and F2F visit groups (78% and 82%, respectively) were satisfied with their visit types and would choose the same visit modality in the future (Table 2, Figure 1). In contrast, significantly fewer (30%, P = 0.003) in the DA group were satisfied with their visit type. Patients with transportation difficulties were more likely to choose a TH visit (P = 0.018).CONCLUSION:In this pilot survey, a telehealth visit prior to advanced endoscopic procedures appears to be an acceptable alternative to a F2F visit in terms of patient satisfaction. Most respondents preferred a pre-procedural clinic visit with GI (via either telehealth or F2F) over DA, underscoring the importance of a measured discussion about risks and alternatives for high-risk endoscopic procedures. In the future, telehealth could be considered the visit modality of choice for patients referred for advanced endoscopic procedures who live a significant distance from the procedure site. These results will be confirmed with a larger sample in a future study.

IntroductionEndoscopic therapy (ET) and esophagectomy result in similar survival for Barrett’s esophagus (BE) with high-grade dysplasia (HGD) or T1a esophageal adenocarcinoma (EAC), but the long-term quality of life (QOL) has not been compared.AimsWe aimed to compare long-term QOL between patients who had undergone ET versus esophagectomy.MethodsPatients were included if they underwent ET or esophagectomy at the University of Michigan since 2000 for the treatment of HGD or T1a EAC. Two validated survey QOL questionnaires were mailed to the patients. We compared QOL between and within groups (ET = 91, esophagectomy = 62), adjusting for covariates.ResultsThe median time since initial intervention was 6.8 years. Compared to esophagectomy, ET patients tended to be older, had a lower prevalence of EAC, and had a shorter duration since therapy. ET patients had worse adjusted physical and role functioning than esophagectomy patients. However, the adjusted odds ratio (OR) of having symptoms was significantly less with ET for diarrhea (0.287; 95% confidence interval [CI] = 0.114, 0.724), trouble eating (0.207; 0.0766, 0.562), choking (0.325; 0.119, 0.888), coughing (0.291; 0.114, 0.746), and speech difficulty (0.306; 0.0959, 0.978). Amongst the ET patients, we found that the number of therapy sessions and need for dilation were associated with worse outcomes.DiscussionMultiple measures of symptom status were better with ET compared to esophagectomy following treatment of BE with HGD or T1a EAC. We observed worse long-term physical and role functioning in ET patients which could reflect unmeasured baseline functional status rather than a causal effect of ET.

BackgroundCovered self-expandable metal stents (SEMS) are utilized for the management of benign and malignant esophageal conditions; however, covered SEMS are prone to migration. Endoscopic suture fixation may mitigate the migration risk of covered esophageal SEMS. Hence, we conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of endoscopic suture fixation for covered esophageal SEMS.MethodsFollowing PRISMA guidelines, we performed a systematic review from 2011 to 2016 to identify studies (case control/case series) reporting the technical success and migration rate of covered esophageal SEMS following endoscopic suture fixation. We searched multiple electronic databases and conference proceedings. We calculated pooled rates (and 95% confidence intervals [CI]) of technical success and stent migration using a random effects model.ResultsWe identified 14 studies (212 patients) describing covered esophageal SEMS placement with endoscopic suture fixation. When reported, SEMS indications included leak/fistula (n = 75), stricture (n = 65), perforation (n = 10), and achalasia (n = 4). The pooled technical success rate was 96.7% (95% CI 92.3–98.6), without heterogeneity (I2 = 0%). We identified 29 SEMS migrations at rate of 15.9% (95% CI 11.4–21.6), without heterogeneity (I2 = 0%). Publication bias was observed, and using the trim-and-fill method, a more conservative estimate for stent migration was 17.0%. Suture-related adverse events were estimated to occur in 3.7% (95% CI 1.6–8.2) of cases.ConclusionsEndoscopic suture fixation of covered esophageal SEMS appears to reduce stent migration when compared to published rates of non-anchored SEMS. However, SEMS migration still occurs in approximately 1 out of 6 cases despite excellent immediate technical success and low risk of suture-related adverse events.

Pancreatic ductal adenocarcinoma (PDA) is characterized by an immune-suppressive tumor microenvironment that renders it largely refractory to immunotherapy. We implemented a multimodal analysis approach to elucidate the immune landscape in PDA. Using a combination of CyTOF, single-cell RNA sequencing, and multiplex immunohistochemistry on patient tumors, matched blood, and non-malignant samples, we uncovered a complex network of immune-suppressive cellular interactions. These experiments revealed heterogeneous expression of immune checkpoint receptors in individual patient's T cells and increased markers of CD8 T cell dysfunction in advanced disease stage. Tumor-infiltrating CD8 T cells had an increased proportion of cells expressing an exhausted expression profile that included upregulation of the immune checkpoint , a finding that we validated at the protein level. Our findings point to a profound alteration of the immune landscape of tumors, and to patient-specific immune changes that should be taken into account as combination immunotherapy becomes available for pancreatic cancer.