Comparison of Endoscopic Mucosal Resection versus Endoscopic Submucosal Dissection for Barrett's Neoplasia and Esophageal Adenocarcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are both accepted resection strategies for Barrett's esophagus-related neoplasia and esophageal adenocarcinoma (EAC). However, a lack of consensus exists regarding which technique offers superior outcomes. This study aims to systematically review the evidence comparing EMR versus ESD in treating Barrett's neoplasia and EAC. METHODS: We searched three databases (Embase, MEDLINE, Cochrane Central) until October 2023. We included studies comparing the efficacy of EMR and ESD for Barrett's neoplasia and EAC. Primary outcomes include en bloc, R0, and curative resection, complete remission of dysplasia (CRD), and local recurrence. Secondary outcomes encompass adverse events. RESULTS: Our search identified 905 records. Eleven studies were included in the final analyses. Data showed significantly higher en bloc resection rates with ESD [odds ratio(OR)=27.36 (95% confidence intervals(CI):7.12-105.21), p<0.01, 6 studies]. R0 resection rates were significantly higher with ESD [OR=5.73 (95%CI:2.32-14.16), p<0.01, 7 studies]. Curative resection rates tended to be higher with ESD [OR=3.49 (95%CI:0.86-14.14), p=0.080, 4 studies]. There was no significant difference in CRD rates [OR=0.92 (95%CI:0.37-2.26),p=0.86, 3 studies]. Local recurrence rates tended to be lower with ESD [OR=0.35 (95%CI: 0.11-1.04), p=0.058, 10 studies]. As for adverse events, there was no significant difference in bleeding, perforation, and postoperative stricture rates. CONCLUSIONS: This systematic review and meta-analysis demonstrates that ESD achieves higher en bloc, R0 and curative resection rates, with a tendency toward lower recurrence rates. These results suggest that ESD may be a more effective option for managing Barrett's neoplasia and EAC.

Endoscopic features of low-grade dysplastic Barrett's.

Background and study aims Barrett's esophagus (BE) with low-grade dysplasia (LGD) is considered usually endoscopically invisible and the endoscopic features are not well described. This study aimed to: 1) evaluate the frequency of visible BE-LGD; 2) compare rates of BE-LGD detection in the community versus a Barrett's referral unit (BRU); and 3) evaluate the endoscopic features of BE-LGD. Patients and methods This was a retrospective analysis of a prospectively observed cohort of 497 patients referred to a BRU with dysplastic BE between 2008 and 2022. BE-LGD was defined as confirmation of LGD by expert gastrointestinal pathologist(s). Endoscopy reports, images and histology reports were reviewed to evaluate the frequency of endoscopically identifiable BE-LGD and their endoscopic features. Results A total of 135 patients (27.2%) had confirmed BE-LGD, of whom 15 (11.1%) had visible LGD identified in the community. After BRU assessment, visible LGD was detected in 68 patients (50.4%). Three phenotypes were observed: (A) Non-visible LGD; (B) Elevated (Paris 0-IIa) lesions; and (C) Flat (Paris 0-IIb) lesions with abnormal mucosal and/or vascular patterns with clear demarcation from regular flat BE. The majority (64.7%) of visible LGD was flat lesions with abnormal mucosal and vascular patterns. Endoscopic detection of BE-LGD increased over time (38.7% (2009-2012) vs. 54.3% (2018-2022)). Conclusions In this cohort, 50.4% of true BE-LGD was endoscopically visible, with increased recognition endoscopically over time and a higher rate of visible LGD detected at a BRU when compared with the community. BRU assessment of BE-LGD remains crucial; however, improving endoscopy surveillance quality in the community is equally important.

Location and appearance of dysplastic Barrett's esophagus recurrence after endoscopic eradication therapy: no additional yield from random biopsy sampling neosquamous mucosa.

BACKGROUND AND AIMS: Surveillance after complete remission of intestinal metaplasia (CRIM) is essential. Current recommendations are to sample visible lesions first, followed by random 4-quadrant biopsy sampling of the original Barrett's esophagus (BE) length. To inform post-CRIM surveillance protocols, we aimed to identify the anatomic location, appearance, and histology of BE recurrences. METHODS: We performed an analysis of 216 patients who achieved CRIM after endoscopic eradication therapy for dysplastic BE at a Barrett's Referral Unit between 2008 and 2021. The anatomic location, recurrence histology, and endoscopic appearance of dysplastic recurrences were evaluated. RESULTS: After a median of 5.5 years (interquartile range, 2.9-7.2) of follow-up after CRIM, 57 patients (26.4%) developed nondysplastic BE (NDBE) recurrence and 18 patients (8.3%) developed dysplastic recurrence. From 8158 routine surveillance biopsy samplings of normal-appearing tubular esophageal neosquamous epithelium, the yield for recurrent NDBE or dysplasia was 0%. One hundred percent of dysplastic tubular esophageal recurrences were visible and in BE islands, whereas 77.8% of gastroesophageal junction dysplastic recurrences were nonvisible. Four distinct endoscopic features suspicious for recurrent advanced dysplasia or neoplasia were identified: buried or subsquamous BE, irregular mucosal pattern, loss of vascular pattern, and nodularity or depression. CONCLUSIONS: The yield of routine surveillance biopsy sampling of normal-appearing tubular esophageal neosquamous epithelium was zero. BE islands with indistinct mucosal or loss of vascular pattern, nodularity or depression, and/or signs of buried BE should raise clinician suspicion for advanced dysplasia or neoplasia recurrence. We suggest a new surveillance biopsy sampling protocol with a focus on meticulous inspection, followed by targeted biopsy sampling of visible lesions and random 4-quadrant biopsy sampling of the gastroesophageal junction.

Gastrointestinal Involvement of Eosinophilic Granulomatosis with Polyangiitis with Histological Evidence of Treatment Response.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis of small to medium vessels. Gastrointestinal involvement is uncommon and is associated with higher mortality. Treatment is based on empiric evidence. In this article, we report a case of EGPA-related pancolitis and stricturing small bowel disease managed with a combination of mepolizumab and surgical resection.

Deferasirox-induced liver injury and Fanconi syndrome in a beta-thalassemia major male.

A 33-year-old male presenting with subacute abdominal pain was found to have hyperbilirubinaemia, hypokalaemia and hyponatraemia. This was in the setting of transitioning between deferasirox iron chelator formulations, from dispersible tablets to film-coated tablets for ongoing treatment of chronic iron overload secondary to transfusion requirement for beta-thalassemia major. A liver biopsy demonstrated acute cholestasis with patchy confluent hepatocellular necrosis and mild to moderate microvesicular steatosis. Based on the histological, biochemical and clinical findings, the diagnosis of hepatotoxicity and Fanconi-like syndrome was made. The patient improved clinically and biochemically with cessation of the deferasirox film-coated tablets and supportive management. To our knowledge, this is the first case report of hepatotoxicity and Fanconi-like syndrome occurring due to deferasirox film-coated tablets with previous tolerance of dispersible deferasirox tablets. It is important to raise clinical awareness of this potentially severe complication.

Could Adherence to Quality of Care Indicators for Hospitalized Patients With Cirrhosis-Related Ascites Improve Clinical Outcomes?

OBJECTIVES: The diagnosis of cirrhotic ascites is associated with significant morbidity, mortality, and reduced health-related quality of life. Adherence by health professionals to quality indicators (QIs) of care for ascites is low. We evaluated the effect of adherence to ascites QIs on clinical outcomes for patients hospitalized with new onset cirrhotic ascites. METHODS: The medical records of 302 patients admitted with new onset cirrhotic ascites were interrogated for demographic and clinical data and adherence to eight Delphi panel-derived QIs for ascites management. Associations between adherence to each QI and 30-day emergent readmission and 90-day mortality were analyzed. RESULTS: The majority of patients were males (68.9%) over 50 years of age (mean 57±12.83 years) with alcohol-related cirrhosis (59%). Twenty-nine percent were readmitted within 30 days. Patients who received an abdominal paracentesis within 30 days of ascites diagnosis (QI 1, relative risk (RR) 0.41, P=0.004) or during index hospitalization (QI 2, RR 0.57, P=0.006) were significantly less likely to experience a 30-day emergent readmission. Baseline serum bilirubin >2.5 mg/dl was associated with increased 30-day cirrhosis-related readmission (RR 1.51, P=0.03). A total of 18.5% of patients died within 90 days of index admission; median interval to death was 139 days (37-562 days). Pneumonia was the most frequent cause of death. Independent predictors of 90-day mortality included older age (odds ratio (OR) 1.03, P=0.03), increased Model for End-stage Liver Disease (MELD)-Na score (OR 1.06, P=0.05), primary SBP prophylaxis (QI 7, OR 2.30, P=0.04), and readmission within 30 days (OR 30.26, P<0.001). Discharge prescription of diuretics (QI 8, OR 0.28, P=0.01) was associated with reduced 90-day mortality. CONCLUSIONS: Early paracentesis in patients with new onset cirrhotic ascites lowers 30-day readmission rates, and early initiation of diuretic therapy lowers 90-day mortality.

Chromosome-wide mapping of DNA methylation patterns in normal and malignant prostate cells reveals pervasive methylation of gene-associated and conserved intergenic sequences.

BACKGROUND: DNA methylation has been linked to genome regulation and dysregulation in health and disease respectively, and methods for characterizing genomic DNA methylation patterns are rapidly emerging. We have developed/refined methods for enrichment of methylated genomic fragments using the methyl-binding domain of the human MBD2 protein (MBD2-MBD) followed by analysis with high-density tiling microarrays. This MBD-chip approach was used to characterize DNA methylation patterns across all non-repetitive sequences of human chromosomes 21 and 22 at high-resolution in normal and malignant prostate cells. RESULTS: Examining this data using computational methods that were designed specifically for DNA methylation tiling array data revealed widespread methylation of both gene promoter and non-promoter regions in cancer and normal cells. In addition to identifying several novel cancer hypermethylated 5' gene upstream regions that mediated epigenetic gene silencing, we also found several hypermethylated 3' gene downstream, intragenic and intergenic regions. The hypermethylated intragenic regions were highly enriched for overlap with intron-exon boundaries, suggesting a possible role in regulation of alternative transcriptional start sites, exon usage and/or splicing. The hypermethylated intergenic regions showed significant enrichment for conservation across vertebrate species. A sampling of these newly identified promoter (ADAMTS1 and SCARF2 genes) and non-promoter (downstream or within DSCR9, C21orf57 and HLCS genes) hypermethylated regions were effective in distinguishing malignant from normal prostate tissues and/or cell lines. CONCLUSIONS: Comparison of chromosome-wide DNA methylation patterns in normal and malignant prostate cells revealed significant methylation of gene-proximal and conserved intergenic sequences. Such analyses can be easily extended for genome-wide methylation analysis in health and disease.

Intensity modulated neutron radiotherapy for the treatment of adenocarcinoma of the prostate.

PURPOSE: This study investigates the enhanced conformality of neutron dose distributions obtainable through the application of intensity modulated neutron radiotherapy (IMNRT) to the treatment of prostate adenocarcinoma. METHODS AND MATERIALS: An in-house algorithm was used to optimize individual segments for IMNRT generated using an organ-at-risk (OAR) avoidance approach. A number of beam orientation schemes were investigated in an attempt to approach an optimum solution. The IMNRT plans were created retrospectively for 5 patients previously treated for prostate adenocarcinoma using fast neutron therapy (FNT), and a comparison of these plans is presented. Dose distributions and dose-volume histograms (DVHs) were analyzed and plans were evaluated based on percentage volumes of rectum and bladder receiving 95%, 80%, and 50% (V(95), V(80), V(50)) of the prescription dose, and on V(60) for both the femoral heads and GM(muscle) group. RESULTS: Plans were normalized such that the IMNRT DVHs for prostate and seminal vesicles were nearly identical to those for conventional FNT plans. Use of IMNRT provided reductions in rectum V(95) and V(80) of 10% (2-27%) and 13% (5-28%), respectively, and reductions in bladder V(95) and V(80) of 12% (3-26%) and 4% (7-10%), respectively. The average decrease in V(60) for the femoral heads was 4.5% (1-18%), with no significant change in V(60) for the GM(muscle) group. CONCLUSIONS: This study provides the first analysis of the application of intensity modulation to neutron radiotherapy. The IMNRT technique provides a substantial reduction in normal tissue dose in the treatment of prostate cancer. This reduction should result in a significant clinical advantage for this and other treatment sites.