Background Endoscopic resection (ER) is an important treatment for high-grade intraepithelial neoplasia and early cancer in Barrett's esophagus. ER-cap requires submucosal lifting and positioning of ...a snare in the cap, making it technically demanding and laborious. Multiband mucosectomy (MBM) uses a modified variceal band ligator and requires no submucosal lifting or positioning of a snare. Objective To compare ER-cap and MBM for piecemeal ER of early Barrett's neoplasia. Design Randomized, controlled trial. Setting Tertiary-care and community-care centers. Patients This study involved 84 patients (64 men; median age 70 years) undergoing piecemeal ER of Barrett's neoplasia. Intervention Piecemeal ER was performed by using ER-cap (n = 42) or MBM (n = 42). Main Outcome Measurements Safety, efficacy, procedure time, costs. Results Procedure time (34 vs 50 minutes; P = .02) and costs (€240 vs €322; P < .01) were significantly less with MBM compared with ER-cap. MBM resulted in smaller resection specimens than ER-cap (18 ×13 mm vs 20 × 15 mm; P < .01). Maximum thicknesses of specimens and resected submucosa were not significantly different. There were no clinically relevant bleeding episodes. Four perforations occurred, 3 with ER-cap, 1 with MBM ( P = not significant). Limitations Potential bias because of different levels of experience among participating endoscopists. Conclusion Piecemeal ER with MBM is faster and cheaper than with ER-cap. Despite the lack of submucosal lifting, MBM appears not to be associated with more perforations. Although MBM results in slightly smaller specimens, the clinical relevance of this may be limited because depth of resections does not differ between both techniques. MBM may thus be preferred for piecemeal ER of early Barrett's neoplasia. (Clinical trial registration number: NTR1435.)
Radiofrequency ablation (RFA)±endoscopic resection (ER) is the preferred treatment for early neoplasia in Barrett's oesophagus (BE). We aimed to report short-term and long-term outcomes for all 1384 ...patients treated in the Netherlands (NL) from 2008 to 2018, with uniform treatment and follow-up (FU) in a centralised setting.
Endoscopic therapy for early BE neoplasia in NL is centralised in nine expert centres with specifically trained endoscopists and pathologists that adhere to a joint protocol. Prospectively collected data are registered in a uniform database. Patients with low/high-grade dysplasia or low-risk cancer, were treated by ER of visible lesions followed by trimonthly RFA sessions of any residual BE until complete eradication of BE (CE-BE). Patients with ER alone were not included.
After ER (62% of cases; 43% low-risk cancers) and median 1 circumferential and 2 focal RFA (p25-p75 0-1; 1-2) per patient, CE-BE was achieved in 94% (1270/1348). Adverse events occurred in 21% (268/1386), most commonly oesophageal stenosis (15%), all were managed endoscopically. A total of 1154 patients with CE-BE were analysed for long-term outcomes. During median 43 months (22-69) and 4 endoscopies (1-5), 38 patients developed dysplastic recurrence (3%, annual recurrence risk 1%), all were detected as endoscopically visible abnormalities. Random biopsies from a normal appearing cardia showed intestinal metaplasia (IM) in 14% and neoplasia in 0%. A finding of IM in the cardia was reproduced during further FU in only 33%, none progressed to neoplasia. Frequent FU visits in the first year of FU were not associated with recurrence risk.
In a setting of centralised care, RFA±ER is effective for eradication of Barrett's related neoplasia and has remarkably low rates of dysplastic recurrence. Our data support more lenient FU intervals, with emphasis on careful endoscopic inspection. Random biopsies from neosquamous epithelium and cardia are of questionable value.
NL7039.
It is unclear whether patients with basal ganglia calcifications (BGC) should undergo infectious disease testing as part of their diagnostic work-up. We investigated the occurrence of possibly ...associated infections in patients with BGC diagnosed with Fahr's disease or syndrome and consecutively performed a systematic review of published infectious diseases associated with BGC.
In a cross-sectional study, we evaluated infections in non-immunocompromised patients aged ≥ 18 years with BGC in the Netherlands, who were diagnosed with Fahr's disease or syndrome after an extensive multidisciplinary diagnostic work-up. Pathogens that were assessed included the following:
sp., cytomegalovirus, human herpesvirus type 6/8, human immunodeficiency virus (HIV),
, rubella virus, and
. Next, a systematic review was performed using MEDLINE and Embase (2002-2023).
The cross-sectional study included 54 patients (median age 65 years). We did not observe any possible related infections to the BGC in this population. Prior infection with
occurred in 28%, and in 94%, IgG rubella antibodies were present. The positive tests were considered to be incidental findings by the multidisciplinary team since these infections are only associated with BGC when congenitally contracted and all patients presented with adult-onset symptoms. The systematic search yielded 47 articles, including 24 narrative reviews/textbooks and 23 original studies (11 case series, 6 cross-sectional and 4 cohort studies, and 2 systematic reviews). Most studies reported congenital infections associated with BGC (cytomegalovirus, HIV, rubella virus, Zika virus). Only two studies reported acquired pathogens (chronic active Epstein-Barr virus and
). The quality of evidence was low.
In our cross-sectional study and systematic review, we found no convincing evidence that acquired infections are causing BGC in adults. Therefore, we argue against routine testing for infections in non-immunocompromised adults with BGC in Western countries.
Optical biopsy in Barrett's oesophagus (BE) using endocytoscopy (EC) could optimize endoscopic screening. However, the identification of dysplasia is challenging due to the complex interpretation of ...the highly detailed images. Therefore, we assessed whether using artificial intelligence (AI) as second assessor could help gastroenterologists in interpreting endocytoscopic BE images. First, we prospectively videotaped 52 BE patients with EC. Then we trained and tested the AI pm distinct datasets drawn from 83,277 frames, developed an endocytoscopic BE classification system, and designed online training and testing modules. We invited two successive cohorts for these online modules: 10 endoscopists to validate the classification system and 12 gastroenterologists to evaluate AI as second assessor by providing six of them with the option to request AI assistance. Training the endoscopists in the classification system established an improved sensitivity of 90.0% (+32.67%,
< 0.001) and an accuracy of 77.67% (+13.0%,
= 0.020) compared with the baseline. However, these values deteriorated at follow-up (-16.67%,
< 0.001 and -8.0%,
= 0.009). Contrastingly, AI-assisted gastroenterologists maintained high sensitivity and accuracy at follow-up, subsequently outperforming the unassisted gastroenterologists (+20.0%,
= 0.025 and +12.22%,
= 0.05). Thus, best diagnostic scores for the identification of dysplasia emerged through human-machine collaboration between trained gastroenterologists with AI as the second assessor. Therefore, AI could support clinical implementation of optical biopsies through EC.
Endoscopic eradication therapy with radiofrequency ablation (RFA) is effective in most patients with Barrett's esophagus (BE). However, some patients experience poor healing and/or poor squamous ...regeneration. We evaluated incidence and treatment outcomes of poor healing and poor squamous regeneration.
We included all patients treated with RFA for early BE neoplasia from a nationwide Dutch registry based on a joint treatment protocol. Poor healing (active inflammatory changes or visible ulcerations ≥ 3 months post-RFA), poor squamous regeneration (< 50 % squamous regeneration), and treatment success (complete eradication of BE CE-BE) were evaluated.
1386 patients (median BE C2M5) underwent RFA with baseline low grade dysplasia (27 %), high grade dysplasia (30 %), or early cancer (43 %). In 134 patients with poor healing (10 %), additional time and acid suppression resulted in complete esophageal healing, and 67/134 (50 %) had normal squamous regeneration with 97 % CE-BE. Overall, 74 patients had poor squamous regeneration (5 %). Compared with patients with normal regeneration, patients with poor squamous regeneration had a higher risk for treatment failure (64 % vs. 2 %, relative risk RR 27 95 % confidence interval CI 18-40) and progression to advanced disease (15 % vs. < 1 %, RR 30 95 %CI 12-81). Higher body mass index, longer BE segment, reflux esophagitis, and < 50 % squamous regeneration after baseline endoscopic resection were independently associated with poor squamous regeneration in multivariable logistic regression.
In half of the patients with poor healing, additional time and acid suppression led to normal squamous regeneration and excellent treatment outcomes. In patients with poor squamous regeneration, however, the risk for treatment failure and progression to advanced disease was significantly increased.
Abstract Background Bi-allelic germline mutations of one of the DNA mismatch repair genes, so far predominantly found in PMS2 , cause constitutional MMR-deficiency syndrome. This rare disorder is ...characterised by paediatric intestinal cancer and other malignancies. We report the clinical, immunohistochemical and genetic characterisation of four families with bi-allelic germline PMS2 mutations. We present an overview of the published gastrointestinal manifestations of CMMR-D syndrome and propose recommendations for gastro-intestinal screening. Methods and Results The first proband developed a cerebral angiosarcoma at age 2 and two colorectal adenomas at age 7. Genetic testing identified a complete PMS2 gene deletion and a frameshift c.736_741delinsTGTGTGTGAAG (p.Pro246CysfsX3) mutation. In the second family, both the proband and her brother had multiple intestinal adenomas, initially wrongly diagnosed as familial adenomatous polyposis. A splice site c.2174+1G>A, and a missense c.137G>T (p.Ser46Ile) mutation in PMS2 were identified. The third patient was diagnosed with multiple colorectal adenomas at age 11; he developed a high-grade dysplastic colorectal adenocarcinoma at age 21. Two intragenic PMS2 deletions were found. The fourth proband developed a cerebral anaplastic ganglioma at age 9 and a high-grade colerectal dysplastic adenoma at age 10 and carries a homozygous c.2174+1G>A mutation. Tumours of all patients showed microsatellite instability and/or loss of PMS2 expression. Conclusions Our findings show the association between bi-allelic germline PMS2 mutations and severe childhood-onset gastrointestinal manifestations, and support the notion that patients with early-onset gastrointestinal adenomas and cancer should be investigated for CMMR-D syndrome. We recommend yearly follow-up with colonoscopy from age 6 and simultaneous video-capsule small bowel enteroscopy from age 8.
For palliation of extrahepatic bile duct obstruction, self-expandable metal stents (SEMS) are superior to plastic stents in terms of stent patency and occurrence of stent dysfunction. We assessed ...health-related quality of life (HRQoL) after stent placement to investigate whether this also results in a difference in HRQoL between patients treated with a plastic stent or SEMS.
This randomized multicenter trial included 219 patients who were randomized to receive plastic stent (n=73) or SEMS uncovered (n=75) and covered (n=71); n=146 placement. HRQoL was assessed with two general questionnaires (EQ-5D-3L and QLQ-C30) and one disease-specific questionnaire (PAN-26). Scores were analyzed using linear mixed model regression and included all patients with baseline and at least one follow-up measurement.
HRQoL data were available in 140 of 219 patients (64%); 71 patients (32%) declined participation and in eight patients (4%) only baseline questionnaires were available. On the QLQ-C30, the interaction between follow-up time and type of stent was significantly different on two of five functional scales physical functioning (P=0.004) and emotional functioning (P=0.01) in favor of patients with a SEMS. In addition, patients with SEMS reported significantly less frequent symptoms of fatigue (P=0.01), loss of appetite (P=0.02), and nausea and vomiting (0.04) over time. The EQ-VAS score decreased with time in both treatment groups, indicating a statistically significant decrease in HRQoL over time.
In patients with inoperable malignant extrahepatic bile duct obstruction, SEMS placement results in better scores for general and disease-specific HRQoL over time compared with plastic stent placement.
Abstract Background Barrett's oesophagus can progress towards oesophageal adenocarcinoma through a metaplasia–dysplasia–carcinoma sequence, but the underlying mechanisms are poorly understood. The ...transcription factor GATA6 is known to be involved in columnar differentiation and proliferation, and GATA6 gene amplification was recently linked with poor survival in oesophageal adenocarcinoma. Aim To study the expression of GATA6 during Barrett's oesophagus development and malignant transformation. To determine the prognostic value of GATA6 in oesophageal adenocarcinoma. Methods Two retrospective cohorts were derived from the pathological archive of the University Medical Center Groningen. The first cohort contained 130 tissue samples of normal squamous epithelium, metaplasia, dysplasia and oesophageal adenocarcinoma. The second cohort consisted of a tissue microarray containing tissue from 92 oesophageal adenocarcinoma patients. Immunohistochemistry was used to examine GATA6 protein expression and to correlate GATA6 expression in oesophageal adenocarcinoma with overall and disease-free survival. Results The percentage of GATA6-positive cells was low in squamous epithelium (10%) but increased progressively in Barrett's oesophagus (30%, P < 0.001) and high-grade dysplasia (82%, P = 0.005). GATA6 expression was not associated with overall or disease-free survival in oesophageal adenocarcinoma patients ( P = 0.599 and P = 0.700 respectively). Conclusion GATA6 expression is progressively increased during Barrett's oesophagus development and its malignant transformation. However, no prognostic value of GATA6 expression could be found in oesophageal adenocarcinoma.
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