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Importance: Patients with achalasia face a higher risk of developing esophageal cancer (EC), but the surveillance strategies for these patients remain controversial due to the long disease duration and the lack of identified risk factors., Objective: To investigate the prevalence of esophageal Candida infection among patients with achalasia and to assess the association of Candida infection with EC risk within this population., Design, Setting, and Participants: This retrospective cohort study included patients with achalasia diagnosed at or referred for treatment and monitoring to the Erasmus University Medical Center in Rotterdam, the Netherlands, between January 1, 1980, and May 31, 2024. Data analysis was conducted from August 1 to October 31, 2024., Exposure: Esophageal Candida infection., Main Outcomes and Measures: The primary outcomes were the prevalence of esophageal Candida infection and its association with EC development among patients with achalasia. Associations were estimated using time-dependent Cox proportional hazards regression models with esophageal Candida infection as a time-varying covariate, adjusting for age at diagnosis and sex., Results: This study included 234 patients with achalasia (median [IQR] age at diagnosis, 45 [32-63] years; 117 [50%] male), with a median follow-up time of 13 (4-22) years. Esophageal Candida infection was identified in 29 patients (12%), while EC was observed in 24 patients (10%). Esophageal cancer risk analysis was performed for 207 patients with 2 or more consecutive endoscopy follow-up visits (median [IQR] age at diagnosis, 43 [32-60] years; 104 [50%] male). The median (IQR) follow-up time for this subgroup was 16 (9-26) years. Among these patients, esophageal Candida infection was independently associated with an increased risk of EC (adjusted hazard ratio [AHR], 8.24 [95% CI, 2.97-22.89]). Additionally, age at diagnosis (AHR, 1.06 [95% CI, 1.03-1.10]) and male sex (AHR, 3.34 [95% CI, 1.08-10.36]) were independently associated with EC risk., Conclusions and Relevance: This retrospective cohort study found that prior esophageal Candida infection, older age at diagnosis, and male sex were associated with increased risk of EC among patients with achalasia. These findings provide an important rationale for optimizing the monitoring of patients with achalasia.

Introduction: Laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) are the most frequently performed procedures in bariatric surgery. In patients with morbid obesity and gastro-oesophageal reflux disease (GORD), LRYGB is the most accepted procedure. For patients with a contraindication for LRYGB or a strong preference for LSG, the Nissen-Sleeve procedure may be a viable new option. The aim of this study is to compare effectiveness of Nissen-Sleeve with LRYGB., Method and Analysis: This is a single-centre, phase III, parallel-group randomised controlled trial in a high-volume bariatric centre in the Netherlands. A total of 88 patients with morbid obesity and GORD will be randomised to evaluate non-inferiority of Nissen-Sleeve versus LRYGB (non-inferiority margin 15%, power 80%, one-sided α 0.025, 9% drop out). Patients with morbid obesity aged 18 years and older with GORD according to the Montreal definition will be included after obtaining informed consent. Exclusion criteria are achalasia, neoplastic abnormalities diagnosed during endoscopy, super obesity (body mass index ≥50 kg/m 2 ), Crohn's disease and medical history of major abdominal surgery. After randomisation, all patients will undergo an upper gastrointestinal endoscopy. Patients in the Nissen-Sleeve arm will undergo a timed barium oesophagram to exclude oesophageal motility disorders. Patients will complete six questionnaires at baseline and every year until 5 years of follow-up. At day 1 postoperative, patients in the Nissen-Sleeve arm will undergo a swallow X-ray to confirm passage. At 1 year, all patients will undergo another endoscopy. The primary outcome is GORD status. Absence of GORD is defined as <8 points on the GORD questionnaire. Secondary outcome measures are long-term GORD improvement; failure rate of procedure; health-related quality of live; weight loss; proton pump inhibitor use; postoperative complications <30 days and >30 days; length of hospital stay; duration of primary surgery; effect on comorbidities; presence and grade of oesophagitis (grade A-D) and/or presence of Barrett's oesophagus and cost-effectiveness., Ethics and Dissemination: The protocol was approved by the Medical Research Ethics Committees United (MEC-U), Nieuwegein, on 15 September 2021. Written informed consent will be obtained for all participants in the study. The study results will be disseminated through peer-reviewed publications and conference presentations., Trial Registration Number: NL9789; The Netherlands Trial Registry., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In the absence of rapid on-side pathological evaluation, endoscopy staff generally "smears" endoscopic ultrasound guided fine needle aspiration (EUS-FNA) specimens on a glass slide. As this technique is vulnerable to preparation artifacts, we assessed if its quality could be improved through a smear-preparation-training for endoscopy staff., Methods: In this prospective pilot study, 10 endosonographers and 12 endoscopy nurses from seven regional EUS-centers in the Netherlands were invited to participate in a EUS-FNA smear-preparation-training. Subsequently, post training slides derived from solid pancreatic lesions were compared to pre-training "control" slides. Primary outcome was to assess if the training positively affects smear quality and, consequently, diagnostic accuracy of EUS-FNA of solid pancreatic lesions., Results: Participants collected and prepared 71 cases, mostly pancreatic head lesions (48%). Sixty-eight controls were selected from the pretraining period. The presence of artifacts was comparable for smears performed before and after training (76% vs 82%, P = .36). Likewise, smear cellularity (≥50% target cells) before and after training did not differ (44% (30/68) vs 49% (35/71), P = .48). Similar, no difference in diagnostic accuracy for malignancy was detected (P = .10)., Conclusion: In this pilot EUS-FNA smear-preparation-training for endoscopy personnel, smear quality and diagnostic accuracy were not improved after the training. Based on these results, we plan to further study other training programs and possibilities., (© 2020 The Authors. Diagnostic Cytopathology published by Wiley Periodicals LLC.)

Background and Aims: Endoscopic resection is often feasible for submucosal invasive colorectal cancers (T1 CRCs) and usually judged as complete. If histology casts doubt on the radicality of resection margins, adjuvant surgical resection is advised, although residual intramural cancer is found in only 5% to 15% of patients. We assessed the sensitivity of biopsy specimens from the resection area for residual intramural cancer as a potential tool to estimate the preoperative risk of residual intramural cancer in patients without risk factors for lymph node metastasis (LNM)., Methods: In this multicenter prospective cohort study, patients with complete endoscopic resection of T1 CRC, scheduled for adjuvant resection due to pathologically unclear resection margins, but absent risk factors for LNM, were asked to consent to second-look endoscopy with biopsies. The results were compared with the pathology results of the surgical resection specimen (criterion standard)., Results: One hundred three patients were included. In total, 85% of resected lesions were unexpectedly malignant, and 45% were removed using a piecemeal resection technique. Sixty-four adjuvant surgical resections and 39 local full-thickness resections were performed. Residual intramural cancer was found in 7 patients (6.8%). Two of these patients had cancer in second-look biopsy specimens, resulting in a sensitivity of 28% (95% confidence interval, <58%). The preoperative risk of residual intramural cancer in the case of negative biopsy specimens was not significantly reduced (P = .61)., Conclusions: The sensitivity of second-look endoscopy with biopsies for residual intramural cancer after endoscopic resection of CRC is low. Therefore, it should not be used in the decision whether or not to perform adjuvant resection. (Clinical trial registration number: NCT02328664.)., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and study aims  The traditional "smear technique" for processing and assessing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is sensitive to artifacts. Processing and evaluation of specimens collected in a liquid medium, liquid-based cytology (LBC) may be a solution. We compared the diagnostic value of EUS-FNA smears to LBC in pancreatic solid lesions in the absence of rapid on-site evaluation (ROSE). Patients and methods  Consecutive patients who required EUS-FNA of a solid pancreatic lesion were included in seven hospitals in the Netherlands and followed for at least 12 months. Specimens from the first pass were split into two smears and a vial for LBC (using ThinPrep and/or Cell block). Smear and LBC were compared in terms of diagnostic accuracy for malignancy, sample quality, and diagnostic agreement between three cytopathologists. Results  Diagnostic accuracy for malignancy was higher for LBC (82 % (58/71)) than for smear (66 % (47/71), P  = 0.04), but did not differ when smears were compared to ThinPrep (71 % (30/42), P  = 0.56) or Cell block (62 % (39/63), P  = 0.61) individually. Artifacts were less often present in ThinPrep (57 % (24/42), P  = 0.02) or Cell block samples (40 % (25/63), P  < 0.001) than smears (76 % (54/71)). Agreement on malignancy was equally good for smears and LBC (ĸ = 0.71 versus ĸ = 0.70, P  = 0.98), but lower for ThinPrep (ĸ = 0.26, P  = 0.01) than smears. Conclusion  After a single pass, LBC provides higher diagnostic accuracy than the conventional smear technique for EUS-FNA of solid pancreatic lesions in the absence of ROSE. Therefore, LBC, may be an alternative to the conventional smear technique, especially in centers lacking ROSE., Competing Interests: Competing interests None

Background: Covered esophageal self-expandable metal stents (SEMSs) are currently used for palliation of malignant dysphagia. The optimal extent of the covering to prevent recurrent obstruction is unknown. Therefore, we aimed to compare fully covered (FC) versus partially covered (PC) SEMSs in patients with incurable malignant esophageal stenosis., Methods: In this multicenter randomized controlled trial, 98 incurable patients with dysphagia caused by a malignant stricture of the esophagus or cardia were randomized 1:1 to an FC-SEMS or PC-SEMS. The primary outcome was recurrent obstruction after endoscopic SEMS placement. Secondary outcomes were technical and clinical success, adverse events, and health-related quality of life (HRQoL). Patients were followed until 6 months after SEMS placement or to SEMS removal, second SEMS insertion, or death, whichever came first., Results: Recurrent obstruction after SEMS placement was similar for both types of stents: 19 % for FC-SEMSs and 22 % for PC-SEMSs ( P  = 0.65). The times to recurrent obstruction did not differ. The frequency of adverse events was similar between the two groups, with major adverse events occurring in 38 % and 47 % of patients for FC-SEMSs and PC-SEMSs, respectively ( P  = 0.34). No significant differences were seen in technical success, improvement of dysphagia, and HRQoL. Proximal esophageal stenosis and female sex were independently associated with recurrent obstruction and/or major adverse events., Conclusions: Esophageal FC-SEMSs did not reveal a lower recurrent obstruction rate compared with PC-SEMSs in the palliative management of malignant dysphagia., Competing Interests: Manon C. W. Spaander has received funding for reserach from Scientific. Marco J. Bruno is a consultant and lecturer for Boston Scientific and Cook Medical., (© Georg Thieme Verlag KG Stuttgart · New York.)

Acquired angioedema is a rare disorder caused by an acquired deficiency of C1 inhibitor. It is characterized by nonpitting, nonpruritic subcutaneous or submucosal edema of the skin, or of the respiratory or gastrointestinal tract. When localized in the gastrointestinal tract, it can cause severe abdominal pain, mimicking an acute surgical abdomen, or chronic recurrent pain of moderate intensity. We report a case of a 48-year-old man presenting with recurrent episodes of hypotension and abdominal pain. Computed tomography of the abdomen showed edema of the small bowel. The first determinations of C1 inhibitor level and activity, measured in a symptom-free period, were normal. Repetition of the laboratory tests in the acute phase, however, showed a low C1 inhibitor level. Further diagnostic work-up indicated an acquired C1 inhibitor deficiency caused by a monoclonal gammopathy. He was treated with tranexamic acid as prophylaxis for his frequent attacks and to date, he has remained symptom free. Acquired C1 inhibitor deficiency is a rare cause of angioedema and is, among others, related to autoantibodies and abnormal B-cell proliferation, for example monoclonal gammopathy. The diagnosis of acquired C1 inhibitor deficiency is made on the basis of the medical history and on the level and activity of plasma C4, C1q, and C1 inhibitor. In case of high suspicion and a normal C1 inhibitor activity, it is recommended to repeat this test during an angioedema attack. Early diagnosis is important for the treatment of severe, potentially life-threatening attacks and to start prophylactic treatment in patients with frequent or severe angioedema attacks.

Achalasia is a motility disorder of the oesophagus of unknown origin in which loss of relaxation of the lower oesophageal sphincter (LOS) and aperistalsis in the distal oesophagus leads to functional oesophageal obstruction. The treatment is symptomatic, aimed at lowering of the LOS pressure, and may be accompanied by various side effects, including gastro-oesophageal reflux, a risk factor for oesophagitis and its complications. Stasis and fermentation can also lead to inflammation of the oesophageal mucosa, giving rise to hyperplasia of the epithelium, multifocal dysplasia and in some patients eventually squamous cell carcinoma. Unfortunately, the sensitivity and specificity of endoscopical inspection to assess inflammation or dysplasia of the oesophageal lining is low, such that biopsy sampling is necessary for accurate assessment. Although it is generally accepted that achalasia is a pre-malignant disorder, the reported increased risk of patients with achalasia developing a squamous cell carcinoma varies from 0 to 140 times that of the normal population. In addition, achalasia may predispose to Barrett's metaplasia and oesophageal adenocarcinoma, which have been described in case reports after myotomy. Surveillance endoscopy with tissue sampling to detect pre-neoplastic lesions has been recommended, even though this can be very difficult due to mucosal adherence of food as well as hyperplastic changes of the mucosa. In the event of moderate to severe inflammation and/or persisting stasis of food despite adequate LOS pressure-lowering therapy, the surveillance interval should be shortened and performed after a 3-day liquid diet. The exact technique and time intervals still need to be established, however.

Purpose: To evaluate a new noninvasive diagnostic strategy for ruling out deep vein thrombosis consisting of either a combination of low clinical probability and normal ultrasonography or a combination of moderate-to-high clinical probability, normal ultrasonography, and a normal D-dimer test., Subjects and Methods: We studied 811 patients with clinically suspected deep vein thrombosis using a diagnostic management strategy that combined clinical probability, ultrasonography, and measurement of D-dimers. The primary endpoint was venous thromboembolism occurring during a 3-month follow-up., Results: Of the 280 patients (35%) with a low clinical probability, 30 (11%) had an abnormal initial ultrasonography and were treated. Of the other 250 untreated patients with low clinical probability and a normal ultrasonography, 5 (2%; 95% confidence interval [CI]: 1% to 5%) developed a nonfatal venous thromboembolism during follow-up. Of the 531 patients (65%) with a moderate-to-high clinical probability, 300 (56%) had an abnormal ultrasonography. Of the remaining 231 patients with a normal ultrasonography, 148 had a normal D-dimer test; none of these patients developed deep vein thrombosis during follow-up (0%; 95% CI: 0% to 3%). Of the 83 patients with an abnormal D-dimer test, 77 underwent repeat ultrasonography about 1 week later; none of the 64 patients with a second normal ultrasound developed symptomatic deep vein thrombosis during follow-up (0%; 95% CI: 0% to 6%)., Conclusions: This management strategy, which combines clinical probability, ultrasonography, and D-dimer measurements, is practical and safe in ruling out deep vein thrombosis in patients with clinically suspected thrombosis and reduces the need for repeat ultrasonography.

A 34-year-old woman presented two weeks after a visit to Burma with fever peaking up to 39 degrees C, chills, non-productive cough, headache, muscle pain, shortness of breath and a painful swelling on the left lower leg. She was treated immediately with intravenous amoxycillin-clavulanic acid. The Gram negative causative agent of melioidosis, Burkholderia (previously Pseudomonas) pseudomallei, was cultured from samples taken beforehand. The patient then received ceftazidime. She recovered. In view of the risk of relapse she was treated with amoxycillin-clavulanic acid for a further six months. Melioidosis is endemic in Southeast Asia and Northern Australia. It is rarely seen outside these areas. The clinical spectrum of the disease is wide and varies from fulminating sepsis to a subclinical disease and may affect any organ system, usually the lungs. The mortality of the septicaemic form after adequate treatment is 40%. Surviving patients have a high relapse rate (4-20%). Melioidosis can become chronic with formation of abscesses or can remain subclinical for many years, probably because the microorganism can survive within phagocytic cells with a risk of reactivation at moments of immunosuppression. The optimal treatment consists of ceftazidime intravenously for at least two weeks followed by an eradication phase consisting of oral antibiotics for at least 3 months.