A novel fully covered metal stent for unresectable malignant distal biliary obstruction: results of a multicenter prospective study.

Background/Aims: Endoscopic self-expandable metal stent (SEMS) placement is currently the standard technique for treating unresectable malignant distal biliary obstructions (MDBO). Therefore, covered SEMS with longer stent patency and fewer migrations are required. This study aimed to assess the clinical performance of a novel, fully covered SEMS for unresectable MDBO. Methods: This was a multicenter single-arm prospective study. The primary outcome was a non-obstruction rate at 6 months. The secondary outcomes were overall survival (OS), recurrent biliary obstruction (RBO), time to RBO (TRBO), technical and clinical success, and adverse events. Results: A total of 73 patients were enrolled in this study. The non-obstruction rate at 6 months was 61%. The median OS and TRBO were 233 and 216 days, respectively. The technical and clinical success rates were 100% and 97%, respectively. Furthermore, the rate of occurrence of RBO and adverse events was 49% and 21%, respectively. The length of bile duct stenosis (<2.2 cm) was the only significant risk factor for stent migration. Conclusions: The non-obstruction rate of a novel fully covered SEMS for MDBO is comparable to that reported earlier but shorter than expected. Short bile duct stenosis is a significant risk factor for stent migration.

Clinical importance of cold polypectomy during the insertion phase in the left side of the colon and rectum: a multicenter randomized controlled trial (PRESECT study).

BACKGROUND AND AIMS: Colorectal polyps are often detected during the insertion phase of colonoscopy but are commonly removed during the withdrawal phase. We aimed to investigate the clinical advantages of instant removal of colorectal polyps during the insertion phase to determine the appropriate strategy for polyps detected on insertion. METHODS: This prospective, multicenter, randomized trial targeted patients with at least 1 left-sided polyp <10 mm in size detected unintentionally on endoscope insertion from April 2018 to March 2019. Patients were allocated to the following 2 groups: study group, consisting of patients who had polyp removal instantly on insertion, and control group, comprising patients who had the endoscope inserted to the cecum first and polyps removed subsequently on withdrawal. Carbon dioxide gas insufflation and cold polypectomy were applied to minimize the influences of polypectomy on endoscope insertion. Twenty advanced endoscopists from 7 community-based institutions participated in this trial. RESULTS: Of 1451 patients enrolled, 220 patients were eligible for full assessment. Mean total procedure time was significantly shorter in the study group (18.9 vs 22.3 minutes, P < .001). Mean pure cecal intubation time and number of polyps per patient were similar between the 2 groups. In the control group, among 107 polyps found during insertion, 48 (45.8%) required reinspection and 7 (6.5%) were completely missed, with an average reinspection time of approximately 3 minutes. CONCLUSIONS: Polypectomy during the insertion phase in the colon and rectum significantly shortens the total procedure time and eliminates all missed polyps without experiencing any disadvantages.

Factors associated with residual gastroesophageal reflux disease symptoms in patients receiving proton pump inhibitor maintenance therapy.

AIM: To elucidate the factors associated with residual gastroesophageal reflux disease (GERD) symptoms in patients receiving proton pump inhibitor (PPI) maintenance therapy in clinical practice. METHODS: The study included 39 GERD patients receiving maintenance PPI therapy. Residual symptoms were assessed using the Frequency Scale for Symptoms of GERD (FSSG) questionnaire and the Gastrointestinal Symptom Rating Scale (GSRS). The relationships between the FSSG score and patient background factors, including the CYP2C19 genotype, were analyzed. RESULTS: The FSSG scores ranged from 1 to 28 points (median score: 7.5 points), and 19 patients (48.7%) had a score of 8 points or more. The patients' GSRS scores were significantly correlated with their FSSG scores (correlation coefficient = 0.47, P < 0.005). In erosive esophagitis patients, the FSSG scores of the CYP2C19 rapid metabolizers (RMs) were significantly higher than the scores of the poor metabolizers and intermediate metabolizers (total scores: 16.7 ± 8.6 vs 7.8 ± 5.4, P < 0.05; acid reflux-related symptom scores: 12 ± 1.9 vs 2.5 ± 0.8, P < 0.005). In contrast, the FSSG scores of the CYP2C19 RMs in the non-erosive reflux disease patients were significantly lower than those of the other patients (total scores: 5.5 ± 1.0 vs 11.8 ± 6.3, P < 0.05; dysmotility symptom-related scores: 1.0 ± 0.4 vs 6.0 ± 0.8, P < 0.01). CONCLUSION: Approximately half of the GERD patients receiving maintenance PPI therapy had residual symptoms associated with a lower quality of life, and the CYP2C19 genotype appeared to be associated with these residual symptoms.

Ectopic adrenocorticotropic hormone syndrome caused by neuroendocrine carcinoma of the colon.

A 48-year-old woman with a history of autoimmune hemolytic anemia and taking long-term corticosteroid therapy presented with a 3-month history of general fatigue, abdominal distension, and pigmentation. A computed tomography scan of the abdomen showed a tumor in the sigmoid colon and multiple metastatic nodules in the liver. A colonoscopy revealed an obstructing mass with the presence of an irregular ulcer in the sigmoid colon. Following biopsy and histopathological analysis, the patient was diagnosed with neuroendocrine carcinoma (NEC) of the colon. She received her first cycle of chemotherapy, with carboplatin and etoposide. During hospitalization, her pigmentation and hypertension worsened and hypokalemia was observed, all of which suggsted Cushing's syndrome. Her plasma adrenocorticotropic hormone (ACTH) and cortisol levels were high, and an ectopic ACTH-producing tumor was suspected. After a second chemotherapy cycle, she developed neutropenic fever and subsequently died. At autopsy, two histological types were found in the tumor: small cell carcinoma and large cell NEC. Immunohistochemical analysis revealed ACTH in the large cell NEC. This is the first reported case of an ectopic ACTH syndrome caused by NEC of the colon.

Surveillance after colorectal polypectomy; comparison between Japan and U.S.

BACKGROUND: Recently, early detection and early treatment of the colorectal cancer have been enabled by the improvement of endoscopic diagnosis and introduction of new techniques. In Japan, although Japan Polyp Study is running, there is no standard strategy concerning the post-polypectomy colonoscopic surveillance yet. Post-polypectomy colonoscopic surveillance is so far entrusted to each institute or each gastroenterologist at present. MATERIAL AND METHOD: To analyze the present states of the surveillance after polypectomy in Japan, we performed questionary survey and compared them with the results in U.S. and U.S. Multisociety Task Force on colorectal Cancer. A simple random sample of 132 doctors who engaged in a digestive organ disease in plural institutes was obtained. RESULT: Many doctors recommend surveillance every around 1 year regardless of the kind of the polyp. Doctors in Japan tend to recommend postpolypectomy colonoscopic surveillance more frequently than that recommended U.S. Multisociety Task Force on colorectal Cancer. Furthermore in all types of polyps except for 12 mm tubular adenoma with high grade dysplasia, the majority of doctors in Japan recommend post-polypectomy colonoscopic surveillance more frequently than American doctors. Significant difference was found in surveillance of hyperplastic polyp among doctors with 1 to 5 years experience and those with more than 6 years. CONCLUSION: It has been shown that surveillance intervals varies substantially in each doctor. The agreement of the surveillance program in Japan is necessary to standardize the strategy for the post-polypectomy surveillance of the colon.

Predictors of malignant intraductal papillary mucinous neoplasm of the pancreas.

GOALS: The predictors of malignant intraductal papillary mucinous neoplasm (IPMN) and invasive IPMN were investigated in this study to determine the optimal indicators of surgical resection for IPMN. BACKGROUND: Recently, international consensus guidelines have described the standard indicators of resection for IPMN. However, the indicators of surgical resection for IPMN, especially for branch duct IPMN, still remain controversial. STUDY: Eighty-two patients with IPMN who underwent surgical resection during April 1998 to January 2009, were retrospectively reviewed and examined with regard to their preoperative factors and pathologic diagnosis. RESULTS: Multivariate analysis showed that main duct IPMN (P<0.01) and earlier diabetes (P=0.03) were independent predictors of malignant IPMN. In branch duct IPMN, the diameter of the main pancreatic duct (MPD) was found to be significantly associated with malignancy by univariate analysis (P=0.034). An elevated serum CA19-9 level (P<0.01) was an independent predictor of invasive IPMN. CONCLUSIONS: Our observations suggest that main duct IPMN, branch duct IPMN with MPD dilatation, and IPMN with an elevated serum CA19-9 level should be considered as indications for surgical resection.

Role of metallothionein in Helicobacter pylori-positive gastric mucosa with or without early gastric cancer and the effect on its expression after eradication therapy.

BACKGROUND AND AIM: Metallothionein (MT) has a proven relationship with various kinds of cancer and reduces tissue damage. Helicobacter pylori (H. pylori) infection is associated with the alteration of gastric epithelial cell cycle events, a condition implicated in the initiation and development of gastric cancer. This study investigates the role of MT in H. pylori-induced gastritis with or without early gastric cancer (ECG) and evaluates the effect on MT expression after eradication therapy. METHODS: Gastric biopsy samples were immunohistochemically examined for MT expression in 36 H. pylori-negative patients without ECG and 98 positive patients with or without ECG. Real time polymerase chain reaction was performed in 14 antral biopsy samples with or without H. pylori. The severity of gastritis was also evaluated according to the updated Sydney System. In 31 successfully eradicated patients, the above assessment was repeated for two consecutive years. RESULTS: MT expression was higher in H. pylori-negative patients than in positive patients (P < 0.01). Moreover, in the corpus it was higher in H. pylori-positive patients without ECG compared to those with ECG (P < 0.05). The MT labeling index had a negative correlation with the severity of gastritis (P < 0.01). A positive correlation was shown between the MT labeling index and apoptosis: proliferation ratio (r = 0.41, P < 0.01). The MT labeling index in H. pylori-positive patients was gradually recovered after eradication (P < 0.05). CONCLUSION: The decrease of MT expression cannot prevent tissue damage in H. pylori-positive gastric mucosa and leads to more severe gastritis. This phenomenon may be attributed to gastric carcinogenesis. H. pylori eradication increases MT expression and may reduce the risk of ECG.

Relationship of BRAF mutation, morphology, and apoptosis in early colorectal cancer.

BACKGROUND AND AIMS: Many investigators have reported flat and depressed lesions as a new type of precursor of colorectal cancer. In our previous study, we determined that mutations in the BRAF gene may contribute to colorectal carcinogenesis by inhibiting apoptosis. However, the relationship among BRAF mutations, morphology and apoptosis in early colorectal cancer has not been clear. Therefore, gene alternation, morphology, and apoptosis in early colorectal cancer were investigated. MATERIALS AND METHODS: Forty-five flat and depressed early colorectal cancer samples and 43 polypoid early colorectal cancer samples were analyzed. Mutations in the BRAF gene and the K-ras gene were examined by direct sequence analysis, and proliferative activity and induction of apoptosis were evaluated using immunohistochemical examination. RESULTS FINDINGS: BRAF mutations were found in 5 (11.1%) of 45 flat and depressed early colorectal cancer samples. No BRAF alteration was found in polypoid early colorectal cancer samples. Mutations in the K-ras gene were detected in 13 (30.2%) of 43 polypoid early colorectal cancer samples. The rate of submucosal invasion of the samples with BRAF mutations was significantly higher than that of the samples with K-ras mutations (p<0.05). INTERPRETATION/CONCLUSIONS: BRAF and K-ras mutations were independent factors that influenced morphology in early colorectal cancer. In this study, the relationship between BRAF mutation and apoptosis is not so clear, but BRAF mutations and inhibition in apoptosis may play an important role in the developmental process of flat and depressed early colorectal cancer.