Influence of endoscopic submucosal dissection on esophageal motility.

AIM: To assess esophageal motility after esophageal endoscopic submucosal dissection (ESD). METHODS: Twelve patients (6 men and 6 women) aged 53-64 years (mean age, 58 years) who underwent regular examination 3-12 mo after esophageal ESD for neoplasms of the esophageal body were included in this study. The ESD procedure was performed under deep sedation using a combination of propofol and fentanyl, and involved a submucosal injection to lift the lesion and use of a dual-knife and an insulated-tip knife to create a circumferential incision around the lesion extending into the submucosa. Esophageal motility was examined using a high-resolution manometry system. Dysphagia was graded using a five-point scale according to the Mellow and Pinkas scoring system. Patient symptoms and the results of esophageal manometry were then analyzed. RESULTS: Of the 12 patients enrolled, 1 patient had grade 2 dysphagia, 1 patient had grade 1 dysphagia, and 3 patients complained of sporadic dysphagia. Ineffective esophageal motility was observed in 5 of 6 patients with above semi-circumference of resection extension. Of these 5 patients, 1 patient complained of grade 2 dysphagia (with esophageal stricture), one patient complained of grade 1 dysphagia, and 3 patients complained of sporadic dysphagia. Normal esophageal body manometry was observed in all 6 patients with below semi-circumference of resection extension. The 6 patients with normal esophageal motility did not complain of dysphagia. CONCLUSION: Extensive esophageal ESD may cause esophageal dysmotility in some patients, and might also have an influence on dysphagia although without esophageal stricture.

Characteristics of achalasia subtypes in untreated Chinese patients: a high-resolution manometry study.

OBJECTIVE: To evaluate and compare the clinical characteristics, manometric results and treatment outcomes of different subtypes of achalasia in untreated Chinese patients using high-resolution esophageal manometry. METHODS: A total of 75 achalasia patients and 34 healthy controls were enrolled in the study, and three achalasia subtypes were determined based on the Chicago classification. Clinical characteristics, manometric and treatment outcomes were compared. RESULTS: In all, 25 patients were classified as type I, 46 as type II and 4 as type III. The mean overall length of lower esophageal sphincter (LES) in type III was significantly longer than those in the controls and type I patients (P < 0.05), and abdominal LES length was significantly longer in type III than those in controls, type I and type II patients. All subtypes of achalasia had higher resting and residual LES pressures than those found in healthy controls (P < 0.05). Resting upper esophageal sphincter (UES) pressure in type III patients was significantly lower than those in healthy controls and type I patients, whereas types I and II patients had higher residual UES pressures compared with healthy controls (P < 0.05). Type II patients had a better response to the treatment than type I and III patients. CONCLUSIONS: Type II is more common in untreated Chinese achalasia patients, and type II patients had better treatment outcomes than other types of patients. Large-sample multicenter trials are necessary in the future.

Structural and functional characterizations reveal the importance of a zinc binding domain in Bloom's syndrome helicase.

Bloom's syndrome (BS) is an autosomal recessive human disorder characterized by genomic instability and a predisposition to a wide variety of cancers. The gene mutated in BS, BLM, encodes a protein containing three domains: an N-terminal domain whose function remains elusive, a helicase domain characterized by seven 'signature' motifs conserved in a wide range of helicases and a C-terminal extension that can be further divided into two sub-domains: RecQ-Ct and HRDC. The RecQ-Ct domain appears essential because two point-mutations altering highly conserved cysteine residues within this domain have been found in BS patients. We report herein that BLM contains a zinc ion. Modelling studies suggest that four conserved cysteine residues within the RecQ-Ct domain coordinate this zinc ion and subsequent mutagenesis studies further confirm this prediction. Biochemical and biophysical studies show that the ATPase, helicase and DNA binding activities of the mutants are severely modified. Structural analysis of both wild-type and mutant proteins reveal that alteration of cysteine residues does not significantly change the overall conformation. The observed defects in ATPase and helicase activities were inferred to result from a compromise of DNA binding. Our results implicate an important role of this zinc binding domain in both DNA binding and protein conformation. They could be pivotal for understanding the molecular basis of BS disease.