Diagnostic yield from symptomatic gastroscopy in the UK: British Society of Gastroenterology analysis using data from the National Endoscopy Database.

OBJECTIVE: This national analysis aimed to calculate the diagnostic yield from gastroscopy for common symptoms, guiding improved resource utilisation. DESIGN: A cross-sectional study was conducted of diagnostic gastroscopies between 1 March 2019 and 29 February 2020 using the UK National Endoscopy Database. Mixed-effect logistic regression models were used, incorporating random (endoscopist) and fixed (symptoms, age and sex) effects on two dependent variables (endoscopic cancer; Barrett's oesophagus (BO) diagnosis). Adjusted positive predictive values (aPPVs) were calculated. RESULTS: 382 370 diagnostic gastroscopies were analysed; 30.4% were performed in patients aged <50 and 57.7% on female patients. The overall unadjusted PPV for cancer was 1.0% (males 1.7%; females 0.6%, p<0.01). Other major pathology was found in 9.1% of procedures, whereas 89.9% reported only normal findings or minor pathology (92.5% in females; 94.6% in patients <50).Highest cancer aPPVs were reached in the over 50s (1.3%), in those with dysphagia (3.0%) or weight loss plus another symptom (1.4%). Cancer aPPVs for all other symptoms were below 1%, and for those under 50, remained below 1% regardless of symptom. Overall, 73.7% of gastroscopies were carried out in patient groups where aPPV cancer was <1%.The overall unadjusted PPV for BO was 4.1% (males 6.1%; females 2.7%, p<0.01). The aPPV for BO for reflux was 5.8% and ranged from 3.2% to 4.0% for other symptoms. CONCLUSIONS: Cancer yield was highest in elderly male patients, and those over 50 with dysphagia. Three-quarters of all gastroscopies were performed on patients whose cancer risk was <1%, suggesting inefficient resource utilisation.

Diagnostic yield from symptomatic lower gastrointestinal endoscopy in the UK: A British Society of Gastroenterology analysis using data from the National Endoscopy Database.

BACKGROUND: The value of lower gastrointestinal endoscopy (LGIE; colonoscopy or sigmoidoscopy) relates to its ability to detect clinically relevant findings, predominantly cancers, preneoplastic polyps or inflammatory bowel disease. There are concerns that many LGIEs are performed on low-risk patients with limited benefit. AIMS: To determine the diagnostic outcomes of LGIE for common symptoms. METHODS: We performed a cross-sectional study of diagnostic LGIE between March 2019 and February 2020 using the UK National Endoscopy Database. We used mixed-effects logistic regression models, incorporating random (endoscopist) and fixed (symptoms, patient age, and sex) effects upon two dependent variables (large polyp [≥10 mm] and cancer diagnosis). Adjusted positive predictive values (aPPVs) were calculated. RESULTS: We analysed 384,510 LGIEs; 33.2% were performed on patients aged under 50 and 53.6% on women. Regarding colonoscopies, the unadjusted PPV for cancer was 1.5% (95% CI: 1.4-1.5); higher for men than women (1.9% vs. 1.1%, p < 0.01). The PPV for large polyps was 3.2% (95% CI: 3.1-3.2). The highest colonoscopy cancer aPPVs were in the over 50s (1.9%) and in those with rectal bleeding (2.5%) or anaemia (2.1%). Cancer aPPVs for other symptoms were <1% despite representing 54.3% of activity. In patients under 50, aPPVs were 0.4% for cancer and 1.6% for large polyps. Results were similar for sigmoidoscopy. CONCLUSIONS: Most colonoscopies were performed on patients with low-risk symptoms, where cancer risk was similar to the general population. Cancer and large polyp yield was highest in elderly patients with rectal bleeding or anaemia, although still fell short of FIT-based screening yields.

Transverse emittance growth of proton sources from laser-irradiated sub-µm-thin planar targets.

Proton bunches with maximum energies between 12 and 22 MeV were emitted from submicrometer-thin plastic foils upon irradiation by laser pulses with peak intensity of 4×10^{20}W/cm^{2}. The images of the protons by a magnetic quadrupole doublet on a screen remained consistently larger by a factor of 10 compared to expectations drawn from the ultralow transverse emittance values reported for thick foil targets. Analytic estimates and particle-in-cell simulations attribute this drastically increased emittance to formerly excluded Coulomb collisions between charged particles. The presence of carbon ions and significant transparency likely play a decisive role. This observation is highly relevant because such thin, partially transparent foils are considered ideal for optimizing maximum proton energies.

Endoscopic En Bloc Versus Piecemeal Resection of Large Nonpedunculated Colonic Adenomas : A Randomized Comparative Trial.

BACKGROUND: Endoscopic resection of adenomas prevents colorectal cancer, but the optimal technique for larger lesions is controversial. Piecemeal endoscopic mucosal resection (EMR) has a low adverse event (AE) rate but a variable recurrence rate necessitating early follow-up. Endoscopic submucosal dissection (ESD) can reduce recurrence but may increase AEs. OBJECTIVE: To compare ESD and EMR for large colonic adenomas. DESIGN: Participant-masked, parallel-group, superiority, randomized controlled trial. (ClinicalTrials.gov: NCT03962868). SETTING: Multicenter study involving 6 French referral centers from November 2019 to February 2021. PARTICIPANTS: Patients with large (≥25 mm) benign colonic lesions referred for resection. INTERVENTION: The patients were randomly assigned by computer 1:1 (stratification by lesion location and center) to ESD or EMR. MEASUREMENTS: The primary end point was 6-month local recurrence (neoplastic tissue on endoscopic assessment and scar biopsy). The secondary end points were technical failure, en bloc R0 resection, and cumulative AEs. RESULTS: In total, 360 patients were randomly assigned to ESD (n = 178) or EMR (n = 182). In the primary analysis set (n = 318 lesions in 318 patients), recurrence occurred after 1 of 161 ESDs (0.6%) and 8 of 157 EMRs (5.1%) (relative risk, 0.12 [95% CI, 0.01 to 0.96]). No recurrence occurred in R0-resected cases (90%) after ESD. The AEs occurred more often after ESD than EMR (35.6% vs. 24.5%, respectively; relative risk, 1.4 [CI, 1.0 to 2.0]). LIMITATION: Procedures were performed under general anesthesia during hospitalization in accordance with the French health system. CONCLUSION: Compared with EMR, ESD reduces the 6-month recurrence rate, obviating the need for systematic early follow-up colonoscopy at the cost of more AEs. PRIMARY FUNDING SOURCE: French Ministry of Health.

A Gradient of Intestinal Inflammation in Primary Sclerosing Cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a progressive liver disease associated with inflammatory bowel disease (IBD). The percentage of PSC patients diagnosed with concomitant IBD varies considerably between studies. This raises the question whether all PSC patients would show intestinal inflammation if screened thoroughly, even in the absence of symptoms. METHODS: To address this question, we collected intestinal biopsies of healthy controls (n = 34), PSC (n = 25), PSC-IBD (n = 41), and IBD (n = 51) patients in a cross-sectional study and carried out cytokine expression profiling, 16S sequencing, in-depth histology, and endoscopy scoring. RESULTS: We found that the vast majority of PSC patients even without clinically manifest IBD showed infiltration of immune cells and increased expression of IL17A and IFNG in intestinal biopsies. However, expression of IL10 and FOXP3 were likewise increased, which may explain why these PSC patients have intestinal inflammation only on a molecular level. This subclinical inflammation in PSC patients was focused in the distal colon, whereas PSC-IBD patients showed inflammation either at the distal colon or on the right side of the colon and the terminal ileum. Furthermore, we observed that PSC patients without IBD showed signs of dysbiosis and exhibited a distinct microbial profile compared with healthy controls. CONCLUSIONS: We found a gradient of intestinal inflammation in the vast majority of PSC patients even in the absence of IBD. Thus, further studies evaluating the effect of anti-inflammatory therapies in PSC patients and their impact on the emergence of clinically manifest IBD and colorectal cancer development are needed.

Minimally invasive intrathoracic negative-pressure therapy and flexible thoracoscopy (FlexVATS) for patients with pleural empyema.

To determine whether a new surgical method using a flexible endoscope (FlexVATS) to perform sparing debridement and apply negative-pressure therapy without extensive decortication may be an alternative treatment option for empyema. Surgical treatment of pleural empyema is associated with considerable postoperative complications and mortality rates, and alternative treatment options are being explored to improve patient outcomes. This was a prospective case series. Seventeen consecutive patients treated with FlexVATS between February 2021 and August 2022 were included in the study. Only patients for whom FlexVATS was the first therapeutic intervention for pleural empyema were included. Treatment success, defined as infection resolution, was the primary endpoint of the study. The secondary endpoints were length of hospital stay, 90-day mortality, and empyema cavity volume reduction. Patients who had previously been treated for pleural empyema by either drainage or surgery were excluded. The trial was performed as a single-centre study at a tertiary medical centre in Germany. In total, 17 patients with pleural empyema were included in the study. The median (IQR) duration of vacuum treatment was 15 days (8-35 days). Twelve of the 17 (71%) patients were successfully treated, and a significant reduction in the empyema cavity volume was observed. 41% of the dressing changes were performed outside the operating room. Compared with a historic cohort of conventionally treated patients (decortication via VATS or thoracotomy), the 90-day mortality rates tended to be lower without reaching statistical significance. Three patients (18%) died in hospital during treatment. No negative pressure-therapy-related complications were observed. FlexVATS therapy is a promising alternative therapy for both healthy and debilitated patients with pleural empyema. Larger randomised trials are required to validate this treatment option.

Challenges in the interdisciplinary treatment of leakages after left-sided colorectal surgery: endoscopic negative pressure therapy, open-pore film drainage therapy and beyond.

PURPOSE: The treatment of anastomotic leakage after left colorectal surgery remains challenging. Since its introduction, endoscopic negative pressure therapy (ENPT) has proven to be advantageous, reducing the necessity of surgical revision. The aim of our study is to present our experience with endoscopic treatment of colorectal leakages and to identify potential factors influencing treatment outcome. METHODS: Patients who underwent endoscopic treatment of colorectal leakage were retrospectively analyzed. Primary endpoint was the healing rate and success of endoscopic therapy. RESULTS: We identified 59 patients treated with ENPT between January 2009 and December 2019. The overall closure rate was 83%, whereas only 60% of the patients were successfully treated with ENPT and 23% needed further surgery. The time between diagnosis of leakage and uptake of endoscopic treatment did not influence the closure rate, but patients with chronic fistula (> 4 weeks) showed a significantly higher reoperation rate than those with an acute fistula (94% vs 6%, p = 0.01). CONCLUSION: ENPT is a successful treatment option for colorectal leakages, which appears to be more favorable when started early. Further studies are still needed to better describe its healing potential, but it deserves an integral role in the interdisciplinary treatment of anastomotic leakages.

Variability in adenoma detection rate in control groups of randomized colonoscopy trials: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Adenoma detection rate (ADR) is still the main surrogate outcome parameter of screening colonoscopy, but most studies include mixed indications, and basic ADR is quite variable. We therefore looked at the control groups in randomized ADR trials using advanced imaging or mechanical methods to find out whether indications or other factors influence ADR levels. METHODS: Patients in the control groups of randomized controlled trials (RCTs) on ADR increase using various methods were collected based on a systematic review; this control group had to use high-definition white-light endoscopy performed between 2008 and 2021. Random-effects meta-analysis was used to pool ADR in control groups and its 95% confidence interval (CI) according to clinical (indication and demographic), study setting (tandem/parallel, number of centers, sample size), and technical (type of intervention, withdrawal time) parameters. Interstudy heterogeneity was reported with the I2 statistic. Multivariable mixed-effects meta-regression was performed for potentially relevant variables. RESULTS: From 80 studies, 25,304 patients in the respective control groups were included. ADR in control arms varied between 8.2% and 68.1% with a high degree of heterogeneity (I2 = 95.1%; random-effect pooled value, 37.5%; 95% CI, 34.6‒40.5). There was no difference in ADR levels between primary colonoscopy screening (12 RCTs, 15%) and mixed indications including screening/surveillance and diagnostic colonoscopy; however, fecal immunochemical testing as an indication for colonoscopy was an independent predictor of ADR (odds ratio [OR], 1.6; 95% CI, 1.1-2.4). Other well-known parameters were confirmed by our analysis such as age (OR, 1.038; 95% CI, 1.004-1.074), sex (male sex: OR, 1.02; 95% CI, 1.01-1.03), and withdrawal time (OR, 1.1; 95% CI, 1.0-1.1). The type of intervention (imaging vs mechanical) had no influence, but methodologic factors did: More recent year of publication and smaller sample size were associated with higher ADR. CONCLUSIONS: A high level of variability was found in the level of ADR in the control groups of RCTs. With regards to indications, only fecal immunochemical test-based colonoscopy studies influenced basic ADR, and primary colonoscopy screening appeared to be similar to other indications. Standardization for variables related to clinical, methodologic, and technical parameters is required to achieve generalizability and reproducibility.

A prospective pilot study of a gluten-free diet for primary sclerosing cholangitis and associated colitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a progressive bile duct disease associated with inflammatory bowel disease (PSC-IBD). AIM: To investigate whether patients with PSC-IBD benefit from a gluten-free and amylase trypsin inhibitor (ATI)-free diet (GFD). METHODS: We performed a prospective clinical pilot study administering an eight-week GFD. The primary outcomes were colonic inflammation assessed by proctosigmoidoscopy, and liver stiffness (surrogate for fibrosis, inflammation and cholestasis) measured by transient elastography before and after GFD. Amongst the secondary (exploratory) outcomes were colonic mucosal and serum cytokine/chemokine changes, the intestinal microbiome and transcriptome dynamics, and shifts in serum markers of hepatic fibrogenesis. RESULTS: Fifteen patients with PSC-IBD completed the study. The study did not meet its primary outcome: the endoscopic score and liver stiffness remained unchanged. However, the expression of pro-inflammatory mucosal cytokines and chemokines such as IL6, IL8, CCL2, and TNFα was significantly down-regulated. Two critical markers of liver fibrosis and matrix remodelling, thrombospondin-2 and -4, decreased significantly. The microbiota composition changed slightly, including a decrease in the pathogen Romboutsia ilealis. The intestinal transcriptome indicated a gut barrier improvement. Pruritus, fatigue, overall well-being, faecal calprotectin levels, and serum alkaline phosphatase did not change significantly. CONCLUSIONS: This study did not demonstrate a clinical improvement with short-term GFD in patients with PSC-IBD. However, a gluten/ATI-free diet may improve biomarkers of intestinal inflammation and barrier function in these patients with associated changes in the enteric microbiota. Further investigation of the therapeutic potential of the GFD in PSC-IBD is warranted.

MELD-Lactate Predicts Poor Outcome in Variceal Bleeding in Cirrhosis.

BACKGROUND: Predictors of poor outcome associated with variceal bleeding remain suboptimal. In patients with cirrhosis, serum lactate combined with Model for End-Stage Liver Disease (MELD-LA) improved prediction across heterogeneous populations. However, prognostic properties have not yet been assessed in the context of variceal bleeding. AIMS: We aimed to evaluate the predictive performance of MELD-LA compared to MELD, lactate, and nadir hemoglobin in cirrhosis patients with variceal bleeding. METHODS: In this multicenter study, we identified 472 patients with variceal bleeding from a German primary cohort (University Hospitals Hamburg/Frankfurt/Cologne), and two independent external validation cohorts [Veterans Affairs (VA), Baylor University]. Discrimination for 30-day mortality was analyzed and scores were compared. MELD-LA was evaluated separately in validation cohorts to ensure consistency of findings. RESULTS: In contrast to nadir hemoglobin, MELD and peak-lactate at time of bleeding were significantly higher in 30-day non-survivors in the primary cohort (p = 0.708; p < 0.001). MELD-LA had excellent discrimination for 30-day mortality (AUROC 0.82, 95% CI 0.76-0.88), better than MELD and peak-lactate (AUROC 0.78, 95% CI 0.71-0.84; AUROC 0.73, 95% CI 0.66-0.81). MELD-LA predicted 30-day mortality independently of age, sex, severity of liver disease and vasopressor support (HR 1.29 per 1-point-increase of MELD-LA; 95% CI 1.19-1.41; p < 0.001). Similarly, MELD-LA demonstrated excellent discrimination for 30-day mortality in the VA (AUROC = 0.86, 95% CI 0.79-0.93) and Baylor cohort (AUROC = 0.85, 95% CI 0.74-0.95). CONCLUSIONS: MELD-LA significantly improves discrimination of short-term mortality associated with variceal bleeding, compared to MELD, peak-lactate and nadir hemoglobin. Thus, MELD-LA might represent a useful and objective marker for risk assessment and therapeutic intervention in patients with variceal bleeding.

GWAS meta-analysis of 16 790 patients with Barrett's oesophagus and oesophageal adenocarcinoma identifies 16 novel genetic risk loci and provides insights into disease aetiology beyond the single marker level.

OBJECTIVE: Oesophageal cancer (EC) is the sixth leading cause of cancer-related deaths. Oesophageal adenocarcinoma (EA), with Barrett's oesophagus (BE) as a precursor lesion, is the most prevalent EC subtype in the Western world. This study aims to contribute to better understand the genetic causes of BE/EA by leveraging genome wide association studies (GWAS), genetic correlation analyses and polygenic risk modelling. DESIGN: We combined data from previous GWAS with new cohorts, increasing the sample size to 16 790 BE/EA cases and 32 476 controls. We also carried out a transcriptome wide association study (TWAS) using expression data from disease-relevant tissues to identify BE/EA candidate genes. To investigate the relationship with reported BE/EA risk factors, a linkage disequilibrium score regression (LDSR) analysis was performed. BE/EA risk models were developed combining clinical/lifestyle risk factors with polygenic risk scores (PRS) derived from the GWAS meta-analysis. RESULTS: The GWAS meta-analysis identified 27 BE and/or EA risk loci, 11 of which were novel. The TWAS identified promising BE/EA candidate genes at seven GWAS loci and at five additional risk loci. The LDSR analysis led to the identification of novel genetic correlations and pointed to differences in BE and EA aetiology. Gastro-oesophageal reflux disease appeared to contribute stronger to the metaplastic BE transformation than to EA development. Finally, combining PRS with BE/EA risk factors improved the performance of the risk models. CONCLUSION: Our findings provide further insights into BE/EA aetiology and its relationship to risk factors. The results lay the foundation for future follow-up studies to identify underlying disease mechanisms and improving risk prediction.

Bile Duct Colonization With Enterococcus sp. Associates With Disease Progression in Primary Sclerosing Cholangitis.

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is characterized by chronic inflammation of the biliary mucosa. Bile ducts in PSC are often colonized with bacteria. Although accumulating evidence demonstrates the importance of microbiota for mucosal immunity, little is known about the impact of bile duct colonization with bacteria on the clinical course of PSC. METHODS: Bile samples were sent to culture during endoscopic retrograde cholangio-pancreatography before the administration of peri-interventional antibiotics. Procedures during overt bacterial cholangitis or with prior antibiotic treatment were excluded. The primary endpoint was defined as a composite clinical endpoint of decompensated cirrhosis and/or liver transplantation or death. RESULTS: A cohort of 189 patients with 591 bile fluid cultures was included. In multivariable Cox regression analysis, the presence of Enterococci (present in 28% of the patients), but not of other bacterial species, conferred risk of disease progression with a hazard ratio of 3.61 (95% confidence interval, 1.6-8.11; P = .002) to reach the composite clinical endpoint. Fungobilia, present in 19.6% of patients, was confirmed to associate with disease progression with a hazard ratio of 3.25 (95% confidence interval, 1.87-5.66; P < .001) to reach the composite clinical endpoint. CONCLUSIONS: The novel association of biliary colonization by Enterococci with disease progression underlines the importance of microbiota-mucosal interplay for the pathogenesis of PSC. These results should stimulate further mechanistic studies on the role of microbiota in PSC and highlight potential new therapeutic targets for a disease without effective treatment options.

Second-generation distal attachment cuff for adenoma detection in screening colonoscopy: a randomized multicenter study.

BACKGROUND AND AIMS: Randomized studies have demonstrated that a distal attachment cap with rubber side arms, the Endocuff Vision (ECV; Olympus America, Center Valley, Pa, USA), increased colonoscopic adenoma detection rate (ADR) in various mixed patient collectives. This is the first study to evaluate its use in a primary colonoscopic screening program. METHODS: Patients over age 55 years undergoing screening colonoscopy in 9 German private offices in Berlin and Hamburg were randomized to either the study group using ECV or the control group using high-definition colonoscopies (standard of care). The main outcome parameter was ADR, whereas secondary outcomes were detection rates of all adenomas per colonoscopy (APCs), of adenoma subgroups, and of hyperplastic polyps. RESULTS: Of 1416 patients (mean age, 61.1 years; 51.8% women), with a median of 41 examinations per examiner (n = 23; interquartile range, 12-81), 700 were examined with ECV and 716 without. Adjusting for the effects of the colonoscopies, ADR was 39.5% (95% confidence interval [CI], 32.6%-46.3%) in the ECV group versus 32.2% (95% CI, 25.9%-38.6%) in the control group, which resulted in an increase of 7.2% (95% CI, 2.3%-12.2%; P = .004). The increase in ADR was mainly because of small polyps, with adjusted ADRs for adenomas <10 mm of 33.3% (95% CI, 26.5%-40.2%) for study patients versus 24.0% (95% CI, 18.2%-29.8%) for control patients (P < .001). APC was also significantly increased (.57 ECV vs .51 control subjects, P = .045). CONCLUSIONS: A distal attachment cap with side arms significantly increased the ADR in patients undergoing primary colonoscopic screening. Because of the correlation of ADR and interval cancer, its use should be encouraged, especially in this setting. (Clinical trial registration number: NCT03442738.).

Feasibility and Efficacy of Adjuvant Chemotherapy With Gemcitabine After Liver Transplantation for Perihilar Cholangiocarcinoma - A Multi-Center, Randomized, Controlled Trial (pro-duct001).

Background: Liver transplantation (LT) is considered a therapeutic option for unresectable perihilar cholangiocarcinoma (PHC) within defined criteria. It remains uncertain whether patients can safely receive adjuvant chemotherapy after LT. Methods: We performed a prospective, multi-center, randomized, non-blinded two-arm trial (pro-duct001). Patients after LT for unresectable PHC within defined criteria were randomized to adjuvant gemcitabine (LT-Gem group) and LT alone (LT alone group). The primary objective was to investigate if adjuvant chemotherapy is feasible in ≥ 85% of patients after LT. The primary endpoint was the percentage of patients completing the 24 weeks course of adjuvant chemotherapy. Secondary endpoints included overall survival (OS) and disease-free (DFS), and complication rates. Results: Twelve patients underwent LT for PHC, of which six (50%) were eligible for randomization (LT-Gem: three patients, LT alone: three patients). Two out of three patients discontinued adjuvant chemotherapy after LT due to intolerance. The study was prematurely terminated due to slow enrollment. One patient with PHC had underlying primary sclerosing cholangitis (PSC). Tumor-free margins could be achieved in all patients. In both the LT-Gem and the LT alone group, the cumulative 1-, 3-, and 5-year OS and DFS rates were 100%, 100%, 67%, and 100%, 67% and 67%, respectively. Conclusions: This prospective, multi-center study was prematurely terminated due to slow enrollment and a statement on the defined endpoints cannot be made. Nevertheless, long-term survival data are consistent with available retrospective data and confirm defined criteria for LT. Since more evidence of LT per se in unresectable PHC is urgently needed, a prospective, non-randomized follow-up study (pro-duct002) has since been launched.

Combined endoscopic-percutaneous treatment of upper gastrointestinal enterocutaneous fistula using vacuum therapy and resorbable plug insertion (Vac-Plug).

After gastrointestinal resections, leakages can occur, persist despite conventional therapy and result in enterocutaneous fistulae. We developed a combination method using flexible endoscopic techniques to seal the enteric orifice with an absorbable plug in addition to a percutaneously and fistuloscopically guided open-pore film drainage (Vac-Plug method). We retrospectively searched our endoscopy database to identify patients treated with the outlined technique. The clinical and pathological data were assessed, the method analyzed and characterized and the technical and clinical success determined. We identified 14 patients that were treated with the Vac-Plug method (4 females, 10 males with a mean age of 56 years, range 50-74). The patients were treated over a time period of 23 days (range 4-119) in between one to thirteen interventions (mean n = 5). One patient had to be excluded due to short follow-up after successful closure. Seventy-seven percent (10/13) were successfully treated with a median follow-up of 453 days (range 35-1246) thereafter. No treatment related complications occurred during the therapy. The data of the analysis showed that the Vac-Plug therapy is safe and successful in a relevant proportion of the patients. It is easy to learn and to apply and is well tolerated. In our opinion, it is a promising addition to the armamentarium of interventional methods of these difficult to treat patients. Of course, its usefulness must be further validated in larger prospective studies.

A video based benchmark data set (ENDOTEST) to evaluate computer-aided polyp detection systems.

BACKGROUND AND AIMS: Computer-aided polyp detection (CADe) may become a standard for polyp detection during colonoscopy. Several systems are already commercially available. We report on a video-based benchmark technique for the first preclinical assessment of such systems before comparative randomized trials are to be undertaken. Additionally, we compare a commercially available CADe system with our newly developed one. METHODS: ENDOTEST consisted in the combination of two datasets. The validation dataset contained 48 video-snippets with 22,856 manually annotated images of which 53.2% contained polyps. The performance dataset contained 10 full-length screening colonoscopies with 230,898 manually annotated images of which 15.8% contained a polyp. Assessment parameters were accuracy for polyp detection and time delay to first polyp detection after polyp appearance (FDT). Two CADe systems were assessed: a commercial CADe system (GI-Genius, Medtronic), and a self-developed new system (ENDOMIND). The latter being a convolutional neuronal network trained on 194,983 manually labeled images extracted from colonoscopy videos recorded in mainly six different gastroenterologic practices. RESULTS: On the ENDOTEST, both CADe systems detected all polyps in at least one image. The per-frame sensitivity and specificity in full colonoscopies was 48.1% and 93.7%, respectively for GI-Genius; and 54% and 92.7%, respectively for ENDOMIND. Median FDT of ENDOMIND with 217 ms (Inter-Quartile Range(IQR)8-1533) was significantly faster than GI-Genius with 1050 ms (IQR 358-2767, p = 0.003). CONCLUSIONS: Our benchmark ENDOTEST may be helpful for preclinical testing of new CADe devices. There seems to be a correlation between a shorter FDT with a higher sensitivity and a lower specificity for polyp detection.

eQTL Set-Based Association Analysis Identifies Novel Susceptibility Loci for Barrett Esophagus and Esophageal Adenocarcinoma.

BACKGROUND: Over 20 susceptibility single-nucleotide polymorphisms (SNP) have been identified for esophageal adenocarcinoma (EAC) and its precursor, Barrett esophagus (BE), explaining a small portion of heritability. METHODS: Using genetic data from 4,323 BE and 4,116 EAC patients aggregated by international consortia including the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON), we conducted a comprehensive transcriptome-wide association study (TWAS) for BE/EAC, leveraging Genotype Tissue Expression (GTEx) gene-expression data from six tissue types of plausible relevance to EAC etiology: mucosa and muscularis from the esophagus, gastroesophageal (GE) junction, stomach, whole blood, and visceral adipose. Two analytical approaches were taken: standard TWAS using the predicted gene expression from local expression quantitative trait loci (eQTL), and set-based SKAT association using selected eQTLs that predict the gene expression. RESULTS: Although the standard approach did not identify significant signals, the eQTL set-based approach identified eight novel associations, three of which were validated in independent external data (eQTL SNP sets for EXOC3, ZNF641, and HSP90AA1). CONCLUSIONS: This study identified novel genetic susceptibility loci for EAC and BE using an eQTL set-based genetic association approach. IMPACT: This study expanded the pool of genetic susceptibility loci for EAC and BE, suggesting the potential of the eQTL set-based genetic association approach as an alternative method for TWAS analysis.

Management of Esophageal Cancer-Associated Respiratory-Digestive Tract Fistulas.

Respiratory-digestive tract fistulas are fatal complications that occur in esophageal cancer treatment. Interdisciplinary treatment strategies are still evolving, especially in anatomical treatment stratification. Thus, this study aims to evaluate general therapeutic strategies for this rare condition. Medical records were reviewed for esophageal cancer-associated respiratory-digestive tract fistula patients treated between January 2008 and September 2021. Fistulas were classified according to being surgery- and tumor-associated. Treatment strategies, clinical success, and survival were analyzed. A total of 51 patients were identified: 28 had tumor-associated fistulas and 23 surgery-associated fistulas. Risk factors for fistula development such as radiation (OR = 0.290, p = 0.64) or stent implantation (OR = 1.917, p = 0.84) did not correlate with lack of symptom control for RDF patients. In contrast, advanced lymph node metastasis as another risk factor was associated with persistent symptoms after treatment for RDF patients (OR = 0.611, p = 0.01). Clinical success significantly correlated with bilateral fistula repair in surgery-associated fistulas (p = 0.01), while tumor-associated fistulas benefited the most from non-surgical (p = 0.04) or combined surgical and non-surgical intervention (p = 0.04) and a bilateral fistula repair (p = 0.02) in terms of overall survival. The therapeutic strategy should aim for bilateral fistula closure. A multidisciplinary, stepwise approach might have the best chance for restoration or symptom control with optimized overall survival in selected patients.