Endoscopic Assessment of Local Resectability of Colorectal Malignancies.

Background: The endoscopic assessment of colorectal malignancies primarily aims at deciding on the local resectability. Local resectability is defined by the risk of lymphonodal metastasis. Summary: The gross morphology as well as the surface and vessel patterns provide valuable information prior to endoscopic resection. Various classifications have been standardized to assist endoscopists during endoscopic assessment. Key Message: The macroscopic assessment of colorectal malignancies should include the Paris and laterally spreading tumor (LST) classification as well as chromoendoscopic assessments such as Kudo's pit pattern and the Japanese NBI Expert Team classifications to describe the vessel and surface patterns.

Automatic three-dimensional reconstruction of the oesophagus in achalasia patients undergoing POEM: an innovative approach for evaluating treatment outcomes.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is a standard treatment option for achalasia patients. Treatment response varies due to factors such as achalasia type, degree of dilatation, pressure and distensibility indices. We present an innovative approach for treatment response prediction based on an automatic three-dimensional (3-D) reconstruction of the tubular oesophagus (TE) and the lower oesophageal sphincter (LES) in patients undergoing POEM for achalasia. METHODS: A software was developed, integrating data from high-resolution manometry, timed barium oesophagogram and endoscopic images to automatically generate 3-D reconstructions of the TE and LES. Novel normative indices for TE (volume×pressure) and LES (volume/pressure) were automatically integrated, facilitating pre-POEM and post-POEM comparisons. Treatment response was evaluated by changes in volumetric and pressure indices for the TE and the LES before as well as 3 and 12 months after POEM. In addition, these values were compared with normal value indices of non-achalasia patients. RESULTS: 50 treatment-naive achalasia patients were enrolled prospectively. The mean TE index decreased significantly (p<0.0001) and the mean LES index increased significantly 3 months post-POEM (p<0.0001). In the 12-month follow-up, no further significant change of value indices between 3 and 12 months post-POEM was seen. 3 months post-POEM mean LES index approached the mean LES of the healthy control group (p=0.077). CONCLUSION: 3-D reconstruction provides an interactive, dynamic visualisation of the oesophagus, serving as a comprehensive tool for evaluating treatment response. It may contribute to refining our approach to achalasia treatment and optimising treatment outcomes. TRIAL REGISTRATION NUMBER: 22-0149.

Influence of artificial intelligence on the diagnostic performance of endoscopists in the assessment of Barrett's esophagus: a tandem randomized and video trial.

BACKGROUND: This study evaluated the effect of an artificial intelligence (AI)-based clinical decision support system on the performance and diagnostic confidence of endoscopists in their assessment of Barrett's esophagus (BE). METHODS: 96 standardized endoscopy videos were assessed by 22 endoscopists with varying degrees of BE experience from 12 centers. Assessment was randomized into two video sets: group A (review first without AI and second with AI) and group B (review first with AI and second without AI). Endoscopists were required to evaluate each video for the presence of Barrett's esophagus-related neoplasia (BERN) and then decide on a spot for a targeted biopsy. After the second assessment, they were allowed to change their clinical decision and confidence level. RESULTS: AI had a stand-alone sensitivity, specificity, and accuracy of 92.2%, 68.9%, and 81.3%, respectively. Without AI, BE experts had an overall sensitivity, specificity, and accuracy of 83.3%, 58.1%, and 71.5%, respectively. With AI, BE nonexperts showed a significant improvement in sensitivity and specificity when videos were assessed a second time with AI (sensitivity 69.8% [95%CI 65.2%-74.2%] to 78.0% [95%CI 74.0%-82.0%]; specificity 67.3% [95%CI 62.5%-72.2%] to 72.7% [95%CI 68.2%-77.3%]). In addition, the diagnostic confidence of BE nonexperts improved significantly with AI. CONCLUSION: BE nonexperts benefitted significantly from additional AI. BE experts and nonexperts remained significantly below the stand-alone performance of AI, suggesting that there may be other factors influencing endoscopists' decisions to follow or discard AI advice.

Evaluation of a single-use gastroscope in patients presenting with suspected upper gastrointestinal hemorrhage: a pilot feasibility study (One-Scope I).

BACKGROUND : Outbreaks of multidrug-resistant bacteria due to contaminated duodenoscopes and infection risks during the COVID-19 pandemic have driven the development of single-use endoscopes. The first single-use gastroscope is now available in Europe. Besides waste disposal and cost issues, the infection risk and performance remain unclear. We aimed to evaluate a single-use gastroscope in patients with signs of upper gastrointestinal bleeding. METHODS : 20 consecutive patients presenting with clinical signs of upper gastrointestinal bleeding between October and November 2022 were included in this case series. The primary aim was technical success, defined as access to the descending duodenum and adequate assessment of the upper gastrointestinal tract for the presence of a bleeding site. RESULTS : The primary aim was achieved in 19/20 patients (95 %). The bleeding site was identified in 18 patients. A therapeutic intervention was performed in six patients (two cap-mounted clips, one standard hemostatic clip, two variceal band ligations, one hemostatic powder, two adrenaline injections); technical and clinical success were achieved in all six patients. Two crossovers to a standard gastroscope occurred. CONCLUSIONS : Use of single-use gastroscopes may be feasible for patients presenting for urgent endoscopic evaluation and treatment of upper gastrointestinal bleeding.

Impact of Small Intestinal Bacterial Overgrowth in Patients with Inflammatory Bowel Disease and Other Gastrointestinal Disorders-A Retrospective Analysis in a Tertiary Single Center and Review of the Literature.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is often found in patients with gut dysbiosis such as irritable bowel syndrome. Recently, the association of SIBO and inflammatory bowel disease (IBD) has been described in some cases. While clinical symptoms might be similar in IBD and SIBO, treatment is quite different for both diseases. Therefore, the differentiation between SIBO or a flare in IBD patients is key to optimizing treatment for these patients. METHODS: We retrospectively investigated our patients with IBD receiving a glucose breath test for SIBO and correlated the results with the clinical symptoms (clinical remission or active disease). RESULTS: 128 patients with the diagnosis "colitis" were analyzed in our cohort. Fifty-three (41.4%) patients had Crohn's disease and 22 (17.2%) patients were suffering from ulcerative colitis. Seventy-four (57.8%) were female and 54 (42.2%) were male patients. A total of 18 (14.1%) patients had a positive testing for SIBO. Eleven (61.1%) cases were associated with CD patients and two (11.1%) with UC. IBD patients in clinical remission had a positive SIBO in six (19.4%) cases, while IBD patients with active disease were positive in nine (15.3%) cases. The proportion of positive SIBO in active IBD patients was higher; however, it did not reach significance. Older age was a risk factor for SIBO in patients with CD (p < 0.003). CONCLUSIONS: In our study, we could show that an increased amount of SIBO was found in IBD patients and was especially more frequent in patients with CD than in those with UC. In UC patients, SIBO rates were not different to patients with other gastrointestinal diseases investigated (e.g., infectious colitis, collagenous colitis, or irritable bowel syndrome). In active IBD, positive SIBO was detected more often numerically compared to quiescent disease; however, due to the low number of patients included, it was not significant. However, older age was a significant risk factor for SIBO in patients with CD. SIBO is of clinical relevance in the vulnerable patient cohort with IBD, and its real prevalence and impact needs to be investigated in further and larger clinical trials.

Efficacy and Safety of Vedolizumab in Patients with Inflammatory Bowel Disease in Association with Vedolizumab Drug Levels.

BACKGROUND: Vedolizumab (VDZ) is a well-established and important therapeutic option in the treatment of patients with inflammatory bowel disease (IBD). However, the significance of therapeutic drug monitoring (TDM) with VDZ remains a contradictory field in daily clinical practice. Our study aims to clarify the predictive impact of VDZ drug levels in long-term clinical outcomes in a real-world cohort. METHODS: Patients with moderate to severe ulcerative colitis (UC) and Crohn's disease (CD) from a tertiary IBD referral center at the University Hospital Augsburg, Germany, were enrolled in this single-center retrospective data analysis. Clinical and endoscopic data were collected at month 6, month 12, and at the last time of follow-up, and outcomes were correlated with VDZ levels at week 6. RESULTS: This study included 95 patients, 68.4% (n = 65) with UC, 24.2% (n = 23) with CD, and 7.4% (n = 7) with indeterminate colitis (CI). Patients with a mean VDZ treatment time of 17.83 months ± 14.56 showed clinical response in 29.5% (n = 28) and clinical remission in 45.3% (n = 43) at the end of the study. Endoscopic response occurred in 20.0% (n = 19) and endoscopic remission in 29.5% (n = 28) at the end of the study. The sustained beneficial effect of VDZ was also reflected in a significant change in biomarker levels. VDZ trough level at week 6 was determined in 48.4% (n = 46) with a mean of 41.79 µg/mL ± 24.58. A significant association between VDZ level at week 6 and both short and long-term outcomes could not be demonstrated. However, numerically higher VDZ levels were seen in patients with endoscopic and clinical improvement at month 6 and at the time of last follow-up. CONCLUSIONS: This study demonstrated efficacy and safety for VDZ in a real-world cohort. Although, for some parameters, a clear trend for higher VDZ levels at week 6 was seen, the efficacy of VDZ was not significantly correlated to VDZ level at week 6, which questions the predictive value of VDZ levels in the real world.

An artificial intelligence algorithm is highly accurate for detecting endoscopic features of eosinophilic esophagitis.

The endoscopic features associated with eosinophilic esophagitis (EoE) may be missed during routine endoscopy. We aimed to develop and evaluate an Artificial Intelligence (AI) algorithm for detecting and quantifying the endoscopic features of EoE in white light images, supplemented by the EoE Endoscopic Reference Score (EREFS). An AI algorithm (AI-EoE) was constructed and trained to differentiate between EoE and normal esophagus using endoscopic white light images extracted from the database of the University Hospital Augsburg. In addition to binary classification, a second algorithm was trained with specific auxiliary branches for each EREFS feature (AI-EoE-EREFS). The AI algorithms were evaluated on an external data set from the University of North Carolina, Chapel Hill (UNC), and compared with the performance of human endoscopists with varying levels of experience. The overall sensitivity, specificity, and accuracy of AI-EoE were 0.93 for all measures, while the AUC was 0.986. With additional auxiliary branches for the EREFS categories, the AI algorithm (AI-EoE-EREFS) performance improved to 0.96, 0.94, 0.95, and 0.992 for sensitivity, specificity, accuracy, and AUC, respectively. AI-EoE and AI-EoE-EREFS performed significantly better than endoscopy beginners and senior fellows on the same set of images. An AI algorithm can be trained to detect and quantify endoscopic features of EoE with excellent performance scores. The addition of the EREFS criteria improved the performance of the AI algorithm, which performed significantly better than endoscopists with a lower or medium experience level.

Antibody Response to SARS-CoV-2 Vaccination in Patients with Inflammatory Bowel Disease: Results of a Single-Center Cohort Study in a Tertiary Hospital in Germany.

BACKGROUND: COVID-19 is a viral disease caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), first described in 2019, with a significant impact on everyday life since then. In December 2020, the first vaccine against COVID-19 from BioNTech/Pfizer was approved for the first time. However, little is known about the immune response to vaccination in patients with inflammatory bowel disease (IBD) and immunomodulators or biologics. The aim of our study was to investigate antibody response to SARS-CoV-2 vaccination in patients with IBD receiving immunomodulators or biologics compared to healthy controls. METHODS: This was a single-center study with a retrospective observational design. Seventy-two patients with ulcerative colitis or Crohn's disease were included. Matching data from 72 healthy employees of our hospital were used as the control group. Data were matched by propensity score to patients with IBD. Blood samples were taken from both groups for antibody response, and both groups received an accompanying questionnaire. RESULTS: Sixty-five (90.3%) patients of the IBD group reported taking immunomodulatory therapy. The mean antibody level for all IBD patients was 1,257.1 U/mL (standard deviation [SD] 1,109.626) in males and 1,500.1 U/mL (SD 1142.760) in female IBD patients after full vaccination. Compared to the healthy group, reduced antibody response could be detected (IBD group 1,383.76 U/mL SD 1,125.617; control group 1,885.65 U/mL SD 727.572, p < 0.05). In this group, blood samples were taken with an average of 61.9 days after the first vaccination. There was no vaccination failure in the IBD group after 2 vaccinations. After the first vaccination, side effects, including muscle pain, pain at the injection site, and fatigue, were reported more often in IBD patients than in the control group (total symptoms IBD group 58.3%, control group 34.5%, p < 0.007). The opposite occurred after the second vaccination when side effects were higher in the control group (total symptoms IBD group 55.4%, control group 76%, p = 0.077). There was a trend to a reduced immune response in elderly patients. Disease duration and concomitant immunomodulatory therapy (TNF-alpha blockers, interleukin inhibitors, integrin inhibitors, methotrexate, or azathioprine) had no impact on the immune response. However, longer time to last medication given and time passed to vaccination in patients with IBD seems to have a positive impact on antibody levels. CONCLUSION: Overall, we could show a high antibody response to vaccination with COVID-19 in all patients with IBD after 2 vaccinations. Vaccination was well tolerated, and no other adverse events were detected. Concomitant immunomodulatory therapy (TNF-alpha blockers, interleukin inhibitors, integrin inhibitors, methotrexate, or azathioprine) had no impact on seroconversion. Further evaluation of antibody titers over time is mandatory to detect early the need for re-vaccination in these patients.

[Effects of SARS-CoV-2 Infection on Symptoms and Therapy of Inflammatory Bowel Disease]. / Auswirkungen einer SARS-CoV-2-Infektion auf Symptomatik und Therapie chronisch-entzündlicher Darmerkrankungen.

INTRODUCTION: The influence of a SARS-CoV-2 infection on inflammatory bowel disease (IBD) has not yet been well characterized and it is unclear whether this requires an adaptation of the immunosuppressive therapy. METHODS: A national register was established for the retrospective documentation of clinical parameters and changes in immunosuppressive therapy in SARS-CoV-2 infected IBD patients. RESULTS: In total, only 3 of 185 IBD patients (1.6 %) were tested for SARS-CoV-2 infection because of abdominal symptoms. In the course of COVID-19 disease, 43.5 % developed diarrhea, abdominal pain or hematochezia (risk of hospitalization with vs. without abdominal symptoms: 20.0 % vs. 10.6 %, p < 0.01). With active IBD at the time of SARS-CoV-2 detection, there was an increased risk of hospitalization (remission 11.2 %, active IBD 23.3 % p < 0.05). IBD-specific therapy remained unchanged in 115 patients (71.4 %); the most common change was an interruption of systemic therapy (16.2 %). DISCUSSION: New abdominal symptoms often appeared in SARS-CoV-2 infected IBD patients. However, these only rarely led to SARS-CoV-2 testing. A high IBD activity at the time of SARS-CoV-2 detection was associated with an increased risk of hospitalization.

Underwater vs Conventional Endoscopic Mucosal Resection of Large Sessile or Flat Colorectal Polyps: A Prospective Randomized Controlled Trial.

BACKGROUND & AIMS: Conventional endoscopic mucosal resection (CEMR) with submucosal injection is the current standard for the resection of large, nonmalignant colorectal polyps. We investigated whether underwater endoscopic mucosal resection (UEMR) is superior to CEMR for large (20-40mm) sessile or flat colorectal polyps. METHODS: In this prospective randomized controlled study, patients with sessile or flat colorectal polyps between 20 and 40 mm in size were randomly assigned to UEMR or CEMR. The primary outcome was the recurrence rate after 6 months. Secondary outcomes included en bloc and R0 resection rates, number of resected pieces, procedure time, and adverse events. RESULTS: En bloc resection rates were 33.3% in the UEMR group and 18.4% in the CEMR group (P = .045); R0 resection rates were 32.1% and 15.8% for UEMR vs CEMR, respectively (P = .025). UEMR was performed with significantly fewer pieces compared to CEMR (2 pieces: 45.5% UEMR vs 17.7% CEMR; P = .001). The overall recurrence rate did not differ between both groups (P = .253); however, subgroup analysis showed a significant difference in favor of UEMR for lesions of >30 mm to ≤40 mm in size (P = .031). The resection time was significantly shorter in the UEMR group (8 vs 14 minutes; P < .001). Adverse events did not differ between both groups (P = .611). CONCLUSIONS: UEMR is superior to CEMR regarding en bloc resection, R0 resection, and procedure time for large colorectal lesions and shows significantly lower recurrence rates for lesions >30 mm to ≤40 mm in size. UEMR should be considered for the endoscopic resection of large colorectal polyps.

Higher rate of en bloc resection with underwater than conventional endoscopic mucosal resection: A meta-analysis.

OBJECTIVES: Previous meta-analysis including nonrandomized studies showed marginal benefit of underwater endoscopic mucosal resection(U-EMR) compared to conventional EMR(C-EMR) in terms of polypectomy outcomes. We evaluated U-EMR compared to C-EMR in the treatment of colorectal polyps with respect to effectiveness and safety by analyzing only randomized controlled trials(RCTs). MATERIAL AND METHODS: PubMed and Cochrane Library databases were searched for RCTs published until 11/2020, evaluating U-EMR vs. C-EMR regarding en bloc resection, post-endoscopic resection adenoma recurrence, complete resection, adverse events rates and difference in resection time. Abstracts from Digestive Disease Week, United European Gastroenterology Week and ESGE Days meetings were also searched. Effect size on outcomes is presented as risk ratio(RR; 95% confidence interval[CI]) or mean difference(MD; 95%CI). The I2 test was used for quantifying heterogeneity, while Grading of Recommendations Assessment, Development and Evaluation(GRADE) was used to assess strength of evidence. RESULTS: Six RCTs analyzing outcomes from 1157 colorectal polypectomies(U-EMR589;C-EMR,568) were included. U-EMR associated with significant higher rate of en bloc resection compared to C-EMR [RR(95%CI):1.26(1.01-1.58); Chi² for heterogeneity=30.43, P<0.0001; I²=84%, GRADE: Very low]. This effect was more prominent regarding resection of polyps sized ≥20 mm compared to polyps <20 mm [RR(95%CI):1.64(1.22-2.20) vs. 1.10(0.98-1.23)]. Post-resection recurrence [RR(95%CI):0.52(0.28-0.94);GRADE:Low] was lower significantly in U-EMR group. In contrast, no significant difference was detected between U-EMR and C-EMR regarding complete resection [RR(95%CI): 1.06(0.91-1.24) GRADE:Very low] and adverse events occurrence[RR(95%CI):1.00 (0.72-1.39); GRADE:Low]. CONCLUSION: Meta-analysis of RCTs supports that U-EMR resection achieves higher rate of en bloc resection compared to conventional EMR. This effect is driven when resecting large(≥20 mm) polyps.

Next-generation sequencing reveals the mutational landscape of clinically diagnosed Usher syndrome: copy number variations, phenocopies, a predominant target for translational read-through, and PEX26 mutated in Heimler syndrome.

BACKGROUND: Combined retinal degeneration and sensorineural hearing impairment is mostly due to autosomal recessive Usher syndrome (USH1: congenital deafness, early retinitis pigmentosa (RP); USH2: progressive hearing impairment, RP). METHODS: Sanger sequencing and NGS of 112 genes (Usher syndrome, nonsyndromic deafness, overlapping conditions), MLPA, and array-CGH were conducted in 138 patients clinically diagnosed with Usher syndrome. RESULTS: A molecular diagnosis was achieved in 97% of both USH1 and USH2 patients, with biallelic mutations in 97% (USH1) and 90% (USH2), respectively. Quantitative readout reliably detected CNVs (confirmed by MLPA or array-CGH), qualifying targeted NGS as one tool for detecting point mutations and CNVs. CNVs accounted for 10% of identified USH2A alleles, often in trans to seemingly monoallelic point mutations. We demonstrate PTC124-induced read-through of the common p.Trp3955* nonsense mutation (13% of detected USH2A alleles), a potential therapy target. Usher gene mutations were found in most patients with atypical Usher syndrome, but the diagnosis was adjusted in case of double homozygosity for mutations in OTOA and NR2E3, genes implicated in isolated deafness and RP. Two patients with additional enamel dysplasia had biallelic PEX26 mutations, for the first time linking this gene to Heimler syndrome. CONCLUSION: Targeted NGS not restricted to Usher genes proved beneficial in uncovering conditions mimicking Usher syndrome.

Limited ocular motility in a child with 3q23 microdeletion ("blepharophimosis syndrome plus").

Blepharophimosis syndrome is a recognizable ocular phenotype (blepharophimosis, telecanthus, ptosis, and epicanthus inversus) caused by heterozygous (dominant) intragenic mutation in FOXL2 (chromosome 3q23), which can also cause premature ovarian failure. A deletion that involves not only FOXL2 but also adjacent genes can result in additional clinical features ("blepharophimosis syndrome plus"). Studies of such patients are useful because observed additional clinical features suggest potential functions of genes adjacent to FOXL2. The authors describe a boy with blepharophimosis syndrome plus from a de novo heterozygous 3q22.3-q24 11.2 Mb microdeletion. Among his additional clinical features was bilateral limitation of abduction and supraduction, which suggests that the deleted area includes a gene responsible for ocular motility.

A complex microdeletion 17q12 phenotype in a patient with recurrent de novo membranous nephropathy.

BACKGROUND: Microdeletions on chromosome 17q12 cause of diverse spectrum of disorders and have only recently been identified as a rare cause of Mayer-Rokitansky-Kuester-Hauser-Syndrome (MRKH), which is characterized by uterus aplasia ± partial/complete vaginal aplasia in females with a regular karyotype. For the first time we report about a patient with a 17q12 microdeletion who is affected by MRKH in combination with a vascular and soft tissue disorder. Repeatedly she suffered from kidney transplant failure caused by consuming membranous nephropathy. CASE PRESENTATION: A 38-year-old female patient had been diagnosed with right kidney aplasia, left kidney dysplasia and significantly impaired renal function during infancy. Aged 16 she had to start hemodialysis. Three years later she received her first kidney transplant. Only then she was diagnosed with MRKH. The kidney transplant was lost due to consuming nephrotic syndrome caused by de novo membranous nephropathy, as was a second kidney transplant years later. In addition, a hyperelasticity syndrome affects the patient with congenital joint laxity, kyphoscoliosis, bilateral hip dysplasia, persistent hypermobility of both elbows, knees and hips. Her clinical picture resembles a combination of traits of a hypermobile and a vascular form of Ehlers-Danlos-Syndrome, but no mutations in the COL3A1 gene was underlying. Instead, array-based comparative genomic hybridisation (CGH) detected a heterozygous 1.43 Mb deletion on chromosome 17q12 encompassing the two renal developmental genes HNF1ß and LHX1. CONCLUSIONS: Deletions of HNF1ß have recently drawn significant attention in pediatric nephrology as an important cause of prenatally hyperechogenic kidneys, renal aplasia and renal hypodysplasia. In contrast, membranous nephropathy represents an often-unaccounted cause of nephrotic syndrome in the adult population. A causative connection between theses two conditions has never been postulated, but is suggestive enough in this case to hypothesize it.