Risk factors for intraoperative and delayed perforation related with gastric endoscopic submucosal dissection.

BACKGROUND AND AIM: Perforation is one of the most important complications of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Several studies have examined risk factors for intraoperative and delayed perforations, but most were retrospective analyses with small numbers of patients. METHODS: This study represents a secondary analysis of a Japanese multicenter prospective cohort study. We investigated the factors associated with each type of perforation using 9015 patients with 9975 EGCs undergoing ESD between July 2010 and June 2012. RESULTS: Intraoperative perforation occurred in 198 patients (2.2%) with 203 lesions (2.0%), necessitating emergency surgery for four lesions (0.04% [2.0%, 4/203]). Delayed perforation occurred in another 37 patients (0.4%) with 42 lesions (0.4%), requiring emergency surgery for 12 lesions (0.12% [28.6%, 12/42]). Factors showing significant independent correlations with intraoperative perforation were upper or middle third of the stomach; remnant stomach or gastric tube; procedure time ≥100 min; tumor size >35 mm; body mass index (BMI) < 18.5 kg/m2; and ≥72 years. Factors showing significant independent correlations with delayed perforation were procedure time ≥60 min; BMI < 18.5 kg/m2; ≥75 years; ulceration; and tumor size >20 mm. Intraoperative perforation occurred most frequently at the greater curvature in the upper third of the stomach (7.9%), whereas delayed perforation occurred most frequently at the greater curvature in the middle third (1.2%). CONCLUSION: This multicenter prospective cohort study clarified the risk and risk factors of intraoperative and delayed perforation related to ESD for EGCs, providing information to help endoscopists reduce perforation.

Treatment strategy after noncurative endoscopic resection for early gastric cancers in patients aged ≥ 85 years: a multicenter retrospective study in a highly aged area of Japan.

BACKGROUND: The guidelines recommend additional gastrectomy after noncurative endoscopic resection for early gastric cancers (EGCs). However, no additional treatment might be acceptable in some patients aged ≥ 85 years. We aimed to identify this patient group using the data in a highly aged area. METHODS: We enrolled patients aged ≥ 85 years after noncurative endoscopic resection for EGCs at 30 institutions of the Tohoku district in Japan between 2002 and 2017. Treatment selection and prognosis after noncurative endoscopic resection were investigated. Fourteen candidates were evaluated using the Cox model to identify risk factors for poor overall survival (OS) in patients with no additional treatment. RESULTS: Of 1065 patients aged ≥ 85 years, 143 underwent noncurative endoscopic resection. Despite the guidelines' recommendation, 88.8% of them underwent no additional treatment. The 5-year OS rates in those with additional gastrectomy and those with no additional treatment were 63.1 and 65.2%, respectively. Multivariate analysis showed independent risk factors for poor OS in patients with no additional treatment were the high-risk category in the eCura system (hazard ratio [HR], 2.91), Charlson comorbidity index (CCI) ≥ 3 (HR, 2.78), and male (HR, 2.04). In patients with no additional treatment, nongastric cancer-specific survival was low (69.0% in 5 years), whereas disease-specific survival rates were very high in the low- and intermediate-risk categories of the eCura system (100.0 and 97.1%, respectively, in 5 years). CONCLUSIONS: No additional treatment may be acceptable in the low- and intermediate-risk categories of the eCura system in patients aged ≥ 85 years with noncurative endoscopic resection for EGCs.

Prediction model of 3-year survival after endoscopic submucosal dissection for early gastric cancer in elderly patients aged ≥ 85 years: EGC-2 model.

PURPOSE: Little is known about the prognostic factors for survival after endoscopic submucosal dissection (ESD) in elderly patients with early gastric cancer (EGC). The aim of this study is to determine prognostic factors and a prediction model of 3-year survival after ESD for EGC in patients aged ≥ 85 years. METHODS: We retrospectively evaluated the clinical outcomes of 740 patients with EGC aged ≥ 85 years, who were treated by ESD at 30 institutions in Japan. Overall survival (OS) and disease-specific survival (DSS) were calculated with the Kaplan-Meier method. Prediction models for 3-year OS after ESD were estimated using the Cox proportional hazards model based on Uno's C-statistics. RESULTS: During the follow-up period, 309 patients died of any cause and 10 patients died of gastric cancer. OS and DSS after 3 years were 82.7% and 99.2%, respectively. No significant differences in OS were found among curability categories. The Cox proportional hazards model revealed the geriatric nutritional risk index (GNRI) and the Charlson comorbidity index (CCI) to be predictors of 3-year survival. We established a final model (EGC-2 model) expressed by GNRI - (2.2×CCI) with a cutoff value of 96. The overall survival rate was significantly lower in the model value < 96 group than in the model value ≥ 96 group (P < 0.001). CONCLUSIONS: The prediction model using GNRI and CCI will be useful to support decision-making for the treatment of EGC in elderly patients aged ≥ 85 years.

Risk factors for short-term re-bleeding in patients with colonic diverticular bleeding: a multicenter retrospective study.

BACKGROUND AND AIM: Few studies have evaluated risk factors for short-term re-bleeding in patients with colonic diverticular bleeding (CDB). We aimed to reveal risk factors for re-bleeding within a month in patients with CDB. METHODS: We retrospectively analyzed clinical course of patients with CDB diagnosed at 10 institutions between 2015 and 2019. Risk factors for re-bleeding within a month were assessed by Cox proportional hazards models. RESULTS: Among 370 patients, 173 (47%) patients had been under the use of antithrombotic agents (ATs) and 34 (9%) experienced re-bleeding within a month. Multivariate analysis revealed that the use of ATs was an independent risk factor for re-bleeding within a month (HR 2.38, 95% CI 1.10-5.50, p = .028). Furthermore, use of multiple ATs and continuation of ATs were found to be independent risk factors for re-bleeding within a month (HR 3.88, 95% CI 1.49-10.00, p = .007 and HR 3.30, 95% CI 1.23-8.63, p = .019, respectively). Two of 370 patients, who discontinued ATs, developed thromboembolic event. CONCLUSIONS: Use of ATs was an independent risk factor for short-term re-bleeding within a month in patients with CDB. This was especially the case for the use of multiple ATs and continuation of ATs. However, discontinuation of ATs may increase the thromboembolic events those patients.

Mesenteric phlebosclerosis complicating colonic cancer treated by endoscopic submucosal dissection.

A 67-year old woman with a history of long-term Chinese herb use was admitted to our institution complaining of abdominal pain. Barium enema disclosed rigidity of throughout the proximal colon and a slightly elevated lesion in the transverse colon. Colonoscopy showed diffuse and bronze mucosa in the proximal colon, which was compatible with mesenteric phlebosclerosis. There was also a reddish, elevated lesion in the transverse colon. Magnifying colonoscopy revealed irregular microsurface and microvessels on the surface of the lesion. Under a diagnosis of intramucosal cancer, the elevated lesion was treated by endoscopic submucosal dissection. Histological examination of the resected specimen showed intramucosal well-differentiated adenocarcinoma, and fibrous thickening of the vascular wall together with collagen deposition in the submucosa. The final diagnosis was an intramucosal cancer occurring in mesenteric phlebosclerosis.

Long-term outcomes of endoscopic submucosal dissection for early gastric cancer: a single-center retrospective study.

BACKGROUND: The aim of the present study was to examine the safety and efficacy of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) based on the long-term outcomes. PATIENTS AND METHODS: From June 2002 to March 2007, ESD was carried out in 472 cases and 570 lesions of EGC. Post-surgical cases and status-unknown cases were excluded. The following long-term outcomes were examined in 438 patients who were reliably followed up for at least 5 years after treatment (range: 5 years [60 months] to 9 years, 9 months [117 months]): local recurrence, metachronous recurrences, and the survival rate. RESULTS: The overall en bloc resection rate was 97.7% for all lesions treated by ESD. The median procedure time was 47.0 min (range 8-345 min). The incidence of positive horizontal andvertical margins was 3.7% and 3.4%, respectively. The incidence of perforation and postoperative bleeding was 5.3% and 4.3%, respectively. There were no deaths related to ESD. Local recurrence was observed in five patients (1.1%), and metachronous recurrences in 7.8% of the patients. The post-treatment 5-year survival was 83.1%. There were no deaths as a result of gastric cancer associated with sites treated by ESD. CONCLUSION: ESD can be considered a standard treatment for EGC based on its expanded indications and low incidences of local recurrence and lymph node metastasis.

Multiple carcinoid tumors of the rectum: report of two cases suggesting the origin of carcinoid tumors.

Two cases of multiple carcinoid tumors of the rectum with numerous micronests of carcinoid tumors are reported. The patients were 51- and 58-year-old males. Many carcinoid tumors and numerous carcinoid micronests were found in the resected rectum; the total number of carcinoid tumors, groups of micronests, and solitary micronests was 69 in the first case and 62 in the second case. The micronests, consisting of a few to many endocrine cells, were observed in the lamina propria, muscularis mucosa, and/or submucosa. Micronests increased in number, gathered and formed carcinoid tumors, which were up to 8 mm in diameter. It was found that a nest of the carcinoid tumors in the lamina propria showed continuity with the endocrine cells of a crypt in the different carcinoid tumors in both cases. The carcinoid tumor and micronest infiltrated the nerves and ganglions in the muscularis mucosa and submucosa. Nests of the carcinoid tumors and micronests were surrounded by S-100-positive cells. Lymph node metastases of the carcinoid tumor were found in both cases. Rectal carcinoid tumors may originate from endocrine cells of the crypts, and multiple carcinoid tumors may occur heterogeneously.

Gastric motility and emptying in cirrhotic patients with portal hypersensitive gastropathy.

BACKGROUND/AIMS: Our aim was to clarify gastric motility and emptying in LC patients with PHG. METHODOLOGY: A total of 30 LC patients (18 with mild gastropathy type, 12 with severe gastropathy type) with a mean age with 65.8 yr were enrolled and 17 healthy participants were recruited as the control group. Electrogastrography was performed to examine gastric motility in the fasting, nocturnal and 2 hr postprandial phase. Subsequently, patients with LC and control were performed to measure gastric emptying of solids with the breath test using 13C for labeling the octanoic acid. Breath samples were obtained every 15 to 30 minutes for 5 hours. RESULTS: The mean frequency of the EGG while fasting with severe PHG was significantly increased compared to mild PHG (p<0.05). The mean frequency of the EGG at 1-hr and 2-hr postprandially with severe PHG was significantly increased compared to mild PHG. The half time of GE with both mild and severe PHG was significantly increased compared to controls. CONCLUSIONS: Postprandial EGG and GE in LC patients would be affected by PHG.

Usefulness of double-balloon endoscopy in the postoperative gastrointestinal tract.

Background. The small intestine has been considered to be a highly difficult organ to visualize in imaging examinations due to its anatomical location compared with the stomach and the colon. In recent years, many imaging modalities have become available, such as CT enterography, MR enterography, capsule endoscopy (CE), and double-balloon endoscopy (DBE). Patients and Methods. DBE was performed in the postoperative intestines of 91 patients (128 DBE examinations) at Iwate Medical University between 2004 and 2010. There were 61 male and 30 female patients, and their mean age was 69.7 years (range: 30-80 years). Results. A total of 124 DBE examinations were performed with endoscope insertion into the reconstructed intestines. The endoscope reached the blind end in 115 of 124 examinations, (92.7%). There were 17 patients with obscure gastrointestinal bleeding in whom 30 DBE examinations were performed. The bleeding site was identified in 12 patients (70.6%). Nine patients underwent endoscopic treatment. Hemostasis was achieved in all patients. Conclusion. DBE is very useful modality for the assessment and application of endotherapy to areas of the small bowel which have been altered by surgery.

Serial changes in cytokine expression in irritable bowel syndrome patients following treatment with calcium polycarbophil.

BACKGROUND/AIMS: Calcium polycarbophil improves abdominal symptoms in patients with irritable bowel syndrome (IBS). We examined cytokine expression in IBS patients before and after administration of calcium polycarbophil. METHODOLOGY: A total of 24 IBS patients (13 diarrhea type, 11 constipation type; median age, 55 years) were enrolled. Serum levels of high sensitive C-reactive protein (CRP) and 17 cytokines (interleukin [IL]-1ß, -2, -4, 5, -6, -7, -8, -10, -12, -13 and -17; tumor necrosis factor-a [TNF-a]; interferon [IFN]-?; granulocyte colony-stimulating factor [G-CSF]; granulocyte macrophage colony-stimulating factor [GM-CSF]; macrophage inflammatory protein [MIP]-1ß; and macrophage chemo-attractant protein [MCP-1]) were simultaneously determined using a Bio-Plex suspension array system before and 12 weeks after administration of calcium polycarbophil 1,500-3,000mg/day. RESULTS: Serum MCP-1 levels in diarrhea type IBS patients were significantly higher than those in constipation type patients (p<0.05). In IBS patients, no significant changes in serum cytokine levels were observed following calcium polycarbophil administration. In constipation type patients, serum high sensitive CRP levels were significantly lower after treatment than before treatment. CONCLUSIONS: Decreases in serum high sensitive CRP levels following calcium polycarbophil treatment may be involved in the relief of abdominal symptoms in IBS patients; diarrhea type IBS is characterized by increased MCP-1 expression.

Effects of proton pump inhibitors in patients with laryngopharyngeal reflux disease.

BACKGROUND/AIMS: The effect of proton pump inhibitors (PPIs) on the health-related quality of life (HRQoL) of patients with laryngopharyngeal reflux disease (LPRD) is not well known. Our aim was to assess the HRQoL before and after administration of a PPI in patients with LPRD. METHODOLOGY: A total of 27 LPRD patients (14 women, 13 men; mean age 54 years) were enrolled. We determined the HRQoL using three different inquiry systems: 1) Frequency Scale for the Symptoms of GERD (FSSG); 2) the 36 item short form of the Medical Outcome Study Questionnaire (SF-36); and 3) the Gastrointestinal Symptom Rating Scale (GSRS). The HRQoL was determined at baseline and after eight weeks of treatment with lansoprazole at a dose of 30mg once daily or rabeprazole at a dose of 10mg once daily. RESULTS: After administration of the PPI, the FSSG, the SF-36 general health scale and mental health scale, GSRS reflux syndrome score, abdominal pain syndrome score and the indigestion syndrome score were significantly improved compared to baseline pretreatment scores (p<0.05). CONCLUSIONS: PPI therapy would be useful for the treatment of LPRD.

Peripheral Blood CD64 Levels Decrease in Crohn's Disease following Granulocyte and Monocyte Adsorptive Apheresis.

Granulocyte and monocyte adsorptive apheresis (GMA) is reportedly useful as induction therapy for Crohn's disease (CD). However, the effects of GMA on CD64 have not been well characterized. We report here our assessment of CD64 expression on neutrophils before and after treatment with GMA in two patients with CD. The severity of CD was assessed with the CD activity index (CDAI). The duration of each GMA session was 60 min at a flow rate of 30 ml/min as per protocol. CD64 expression on neutrophils was measured by analyzing whole blood with a FACScan flow cytometer. In case 1, CD64 levels after each session of GMA tended to decrease compared to pretreatment levels, whereas in case 2, CD64 levels dropped significantly after treatment. The CDAI decreased after GMA in both cases 1 and 2. A significant correlation was noted between CDAI scores and CD64 levels in both cases. In conclusion, GMA reduced blood CD64 levels, which would be an important factor for the decrease of CDAI scores.

Usefulness of endoscopic treatment for duodenal adenoma.

In recent years, due to the increasing prevalence of upper gastrointestinal endoscopy, there have been an increasing number of reports on duodenal adenoma and early stage cancer. However, endoscopic techniques for the resection of duodenal adenomas are difficult, due to the anatomical features of the duodenum, and the long distance to the lesion. There have only been a few reports on the use of endoscopic techniques for duodenal adenomas compared to those focused on the stomach and large intestine. For duodenal adenomas, we used a conventional endoscope for lesions proximal to the major duodenal papilla, and a short-type double balloon endoscope for lesions distal to the papilla. The en-bloc resection rate was 93.8%. There was only one case of microperforation. Endoscopic manipulation is considered difficult in the deep areas of the duodenum, but double balloon endoscopy enabled stable manipulation and successful resection of the tumor in the majority of cases.

Gastric emptying and electrogastrography in reflux esophagitis: results in patients showing endoscopically erosive esophagitis under proton pump inhibitor therapy.

BACKGROUND/AIMS: Dynamics of gastric emptying and motility are not fully understood in reflux esophagitis (RE) patients under proton pump inhibitor (PPI) therapy who have endoscopically diagnosed erosive esophagitis (EE). METHODOLOGY: Twenty patients with RE receiving 8 weeks of oral PPI (lansoprazole, 30 mg/day) administration and 17 healthy control subjects were enrolled. After a repeat endoscopy, gastric emptying and electrogastrography were performed. Patients were divided into two groups based on the Los Angeles classification after 8 weeks of PPI treatment--a response RE group (RG: patients with either non-EE or a two-rank improvement by an endoscopic grading system) and a non-response RE group (NRG: patients with EE and only one rank of improvement by endoscopic grading). RESULTS: The rates of RG and NRG were 12/20 and 8/20, respectively. A significantly delayed gastric emptying half-time (t1/2) prior to PPI therapy is shown in RE patients as compared to controls. The t1/2 in the NRG was delayed compared to RG. The frequencies of EGG in the fasting phase of the RE group were significantly lower than in controls. The rate of both fasting and nocturnal phase normogastria in the RE group was also markedly decreased compared to controls. There was no significant difference between the RG and NRG with regard to the frequencies of EGG waves. The rate of normogastria during the fasting phase in the NRG was lower than in the RG. CONCLUSIONS: Abnormalities of gastric motor function are persistently seen in the patients of non-responsive RE undergoing PPI therapy.

Characterization of follicular lymphoma in the small intestine using double-balloon endoscopy.

Follicular lymphomas occur rarely in the gastrointestinal tract, representing only 1-3% of all gastrointestinal tract B-cell non-Hodgkin lymphomas. We describe endoscopic analysis of 3 cases of follicular lymphoma in the small intestine using double-balloon endoscopy. Double-balloon endoscopy revealed multiple nodular lesions and elevated white patches, multiple polypoid lesions, and scattered white polypoid and nodular lesions in the duodenum and small intestine. Fuji Intelligent Chromo Endoscopy demonstrated small, whitish nodules, and narrow-band imaging showed a coiled, elongated vascular pattern within the elevated lesions. These cases are the first follicular lymphomas in the small intestine evaluated using narrow-band imaging or Fuji Intelligent Chromo Endoscopy to be reported.

Evaluation of Infliximab Effects on Gastrointestinal Bleeding in Crohn's Disease Using Double-Balloon Endoscopy.

Tumor necrosis factor α plays an important role in the pathogenesis of Crohn's disease (CD). The effects of infliximab on gastrointestinal bleeding in CD have not yet been fully evaluated. Herein we describe three CD cases who presented with gastrointestinal bleeding and received infliximab treatment. In case 1, double-balloon endoscopy showed a large ulcer with several irregularly shaped ulcers in the terminal ileum; 8 weeks after infliximab administration, complete healing of all lesions was observed. In case 2, double-balloon endoscopy showed linear ulcers and mucosal edema in the jejunum and ileum; 5 weeks after infliximab administration, all lesions were decreased in size and were healed. In case 3, double-balloon endoscopy revealed ulcerations and stenosis in the terminal ileum; 12 weeks after infliximab administration, ulcer healing and an increased diameter of the ileal stenosis were observed. These three cases have been receiving ongoing infliximab maintenance therapy and are currently symptom-free. Infliximab thus appears to be useful for treatment of gastrointestinal bleeding in CD patients.

Effects of itopride hydrochloride and ranitidine in patients with functional dyspepsia: comparison between prokinetic and acid suppression therapies.

BACKGROUND/AIMS: The effect of itopride hydrochloride or ranitidine on the health-related quality of life (HRQoL) of functional dyspepsia is not well known. Our aim was to assess the HRQoL before and after administration of itopride hydrochloride or ranitidine in patients with functional dyspepsia. METHODOLOGY: A total of 18 functional dyspepsia patients (12 women, 6 men; mean age 52.5 y.o.) were enrolled. We determined the HRQoL using two different inquiry systems: the 36 item short form of the Medical Outcome Study Questionnaire (SF-36) and the Gastrointestinal Symptom Rating Scale (GSRS). The HRQoL was determined before administration of drug, and two, four, and eight weeks after administration of drug. RESULTS: After administration of itopride hydrochloride, the SF-36 mental health scale and GSRS indigestion syndrome score and constipation syndrome score were significantly improved compared to before administration (p < 0.05). After the administration of ranitidine, the GSRS reflux syndrome score was significantly improved compared to before administration (p < 0.05). CONCLUSIONS: Itopride hydrochloride would be useful for the treatment of dysmotility-type functional dyspepsia, whereas ranitidine would be beneficial for ulcer-type functional dyspepsia.

Effect of a muscarinic M3 receptor agonist on gastric motility.

Muscarinic M3 receptors exist in the gastrointestinal wall in humans and the muscarinic M3 agonist cevimeline hydrochloride (Evoxac) is a candidate therapeutic agent for the treatment of xerostomia in Sjögren's syndrome. However, M3 receptor agonists are not known to show efficacy for diseases associated with abnormal gastrointestinal motility. Herein the effects are reported of cevimeline on gastric motility in two patients with non-ulcer dyspepsia. The patients both received long-term proton pump inhibitor therapy for 6 months, but their symptoms persisted. Then cevimeline was administered orally for 8 weeks at 30 mg three times daily (90 mg/day) and their dyspepsia symptoms improved. Electrogastrography was performed to examine gastric motility before and after administration of the M3 agonist. The fasting or nocturnal wave rate was significantly increased after administration compared with before administration, but no significant postprandial changes were seen. No adverse effects of cevimeline were observed. This drug might be a candidate therapeutic agent for non-ulcer dyspepsia. Because its postprandial effects on gastrointestinal motility are unclear, a dose-finding clinical study should be performed in the future.

Colonic transit, bowel movements, stool form, and abdominal pain in irritable bowel syndrome by treatments with calcium polycarbophil.

BACKGROUND/AIMS: Calcium polycarbophil improves abdominal symptoms in patients with irritable bowel syndrome (IBS). We examined colonic transit times in IBS patients both before and after administration of calcium polycarbophil, and clarified the correlations among colonic transit, bowel movements, stool form and abdominal pain. METHODOLOGY: A total of 26 IBS patients (14 diarrhea-predominant type, 12 constipation-predominant type) with a median age of 51 yr were enrolled. Before administration of calcium polycarbophil, mean colonic transit times were calculated from the number of radiopaque markers in the colon. Bowel movements, the stool form scale score and abdominal pain were also measured. After oral administration of calcium polycarbophil for 8 weeks, the transit times were again measured. RESULTS: In diarrhea type, the mean colonic transit time increased, bowel movements decreased in frequency, the stool form scale score decreased, and the abdominal pain appeared to be diminished after treatment (p<0.05). In constipation type, mean colonic transit time decreased, bowel movements increased in frequency, the stool form scale score increased, the abdominal pain appeared to be diminished after treatment (p<0.05). Colonic transit times were highly correlated with stool form or bowel movements. Stool form was also highly correlated with bowel movements before and after treatment. Abdominal pain was significantly correlated with colonic transit before treatment. CONCLUSIONS: Calcium polycarbophil is useful in improving colonic transit, bowel movements, stool form and abdominal pain in both types of IBS. Improvement in colonic transit might relieve abdominal pain in IBS patients.