Importance of Bowel Habits in Predicting Inadequate Bowel Preparation: A Prospective Observational Study.

OBJECTIVES: Inadequate bowel preparation (BP) negatively affects the efficacy and quality of colonoscopy. Although constipation has already been reported as one of the most important predictors of inadequate BP, there is limited information on the relation between inadequate BP and bowel habits including constipation-related symptoms, medications, and severity of constipation. METHODS: This single-center, prospective observational study was conducted between August 2019 and May 2020. All participants answered questionnaires regarding personal bowel habits and received low-volume polyethylene glycol plus ascorbic acid for outpatient colonoscopy. Severity of constipation was evaluated by constipation scoring system. Bowel preparation cleansing was evaluated using Boston Bowel Preparation Scale (BBPS). Potential predictors of inadequate BP were analyzed using multivariate logistic regression models. RESULTS: Overall, 1054 patients were enrolled, of which, 105 (10%) had inadequate BP (total BBPS ≤ 6 or any segmental BBPS < 2). The risk of inadequate BP increased with constipation severity (P = 0.01). Multivariate analysis showed that frequent straining (> 25% of defecations) (OR 2.09, 95% CI: 1.33-3.28) and chronic use of stimulant laxatives (OR 2.57, 95% CI: 1.59-4.17) were significant predictors of inadequate BP, among personal bowel habits. CONCLUSION: Frequent straining and chronic use of stimulant laxatives were predictors of inadequate BP. An intensified preparation regimen should be considered for severely constipated patients with straining and chronic use of stimulant laxatives.

Predictors of Improvement in Exercise Capacity After Cardiac Rehabilitation Differ Between Octogenarian and Young-Old Patients With Acute Myocardial Infarction.

BACKGROUND: Whether the magnitude and predictors of improvement in exercise capacity after cardiac rehabilitation (CR) are the same between young-old (YO) and octogenarian (OCT) patients with acute myocardial infarction (AMI) is unknown.Methods and Results: We studied 284 YO (age range 65-69 years; mean [±SD] 67±1 years) and 65 OCT (age range ≥80 years; mean [±SD] 83±2 years) patients who participated in a post-AMI CR program. After 3 months of CR, peak oxygen uptake (PV̇O2) measured during cardiopulmonary exercise testing improved significantly in both age groups (P<0.01), although the percentage increase in PV̇O2(%∆PV̇O2) was significantly smaller in the OCT than YO group (5.4±13.7% vs. 10.0±12.8%; P<0.01). Multiple regression analysis demonstrated that independent predictors of %∆PV̇O2were the number of outpatient CR (OPCR) sessions attended (P=0.015), left ventricular ejection fraction (P=0.028), and baseline PV̇O2(P=0.0007) in the YO group; and the number of sessions attended (P=0.018), atrial fibrillation (P=0.042), and the presence of nutritional risk (Geriatric Nutritional Risk Index ≤98; P=0.036) in the OCT group. CONCLUSIONS: The predictors of improvement in exercise capacity after CR differed between the YO and OCT patients with AMI. To obtain a greater improvement in PV̇O2in CR, frequent OPCR session attendance may be necessary in both groups; in addition, particularly in OCT patients, better nutritional status may be important.

Exercise-Based Cardiac Rehabilitation Improves Exercise Capacity Regardless of the Response to Cardiac Resynchronization Therapy in Patients With Heart Failure and Reduced Ejection Fraction.

BACKGROUND: In patients with chronic heart failure with reduced ejection fraction (HFrEF), cardiac resynchronization therapy (CRT) improves left ventricular ejection fraction (LVEF) and exercise-based cardiac rehabilitation (ECR) enhances exercise capacity. This study examined the relationship between the 2 responses.Methods and Results:Sixty-four consecutive HFrEF patients who participated in a 3-month ECR program after CRT were investigated. Patients were categorized according to a median improvement in peak oxygen uptake (PV̇O2) after ECR of 7% as either good (n=32; mean percentage change in PV̇O2[%∆PV̇O2]=23.2%) or poor (n=32; mean %∆PV̇O2=2.5%) responders. There was no significant difference in baseline characteristics between the good and poor responders, except for PV̇O2(51% vs. 59%, respectively; P=0.01). The proportion of good CRT responders was similar between the good and poor responders (%∆LVEF ≥10%; 53% vs. 47%, respectively; P=NS). Overall, there was no significant correlation between %∆LVEF after CRT and %∆PV̇O2after ECR. Notably, among poor CRT responders (n=32), the prevalence of atrial fibrillation (0% vs. 29%; P<0.03) and baseline PV̇O2(48% vs. 57%; P<0.05) were significantly lower among those with a good (n=15) than poor (n=17) response to ECR. CONCLUSIONS: In patients with HFrEF, good ECR and CRT responses are unrelated. A good PV̇O2response to ECR can be achieved even in poor CRT responders, particularly in those with a sinus rhythm or low baseline PV̇O2.

Combination of Peak Exercise Systolic Blood Pressure and Left Atrial Diameter as a Novel Non-Spirometry Prognostic Predictor Comparable to Peak Oxygen Uptake for Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Although peak oxygen uptake (pV̇O2) is a well-established powerful prognostic predictor in heart failure (HF) patients, implementation of cardiopulmonary exercise testing (CPX) is limited by its complex analysis. We aimed to develop a new bivariate predictor obtained without respiratory gas measurement, comparable to pV̇O2.Methods and Results:We studied 560 consecutive HF patients with ejection fraction (EF) <45% who underwent CPX. During a median follow-up of 49.0 months, the composite of all-cause death or HF hospitalization occurred in 228 patients (40.7%) and all-cause death in 111 (19.8%). pV̇O2was the strongest single predictor of the composite outcome (chi-square, 99.3). Among the bivariate non-spirometry parameters, the ratio of systolic blood pressure at peak exercise to left atrial diameter (pSBP/LAD) was the strongest predictor (chi-square, 112.4). Patients with pSBP/LAD <2.8 mmHg/mm, compared with those with pSBP/LAD ≥2.8 mmHg/mm, had a hazard ratio of 3.84 (95% confidence interval, 2.95-5.04) for the composite outcome and 3.66 (2.50-5.37) for all-cause death. In the subgroup with pV̇O2<14 mL/kg/min (n=149), where pV̇O2had no further predictive value, pSBP was the strongest single predictor, and the predictive power of pSBP/LAD was more enhanced. CONCLUSIONS: pSBP/LAD was a new powerful predictor of HF hospitalization and death, comparable to pV̇O2, in HF with reduced EF. Because of its simplicity and high availability, this index has the potential for more widespread use than pV̇O2.

Efficacy of Cardiac Rehabilitation in Heart Failure Patients With Low Body Mass Index.

BACKGROUND: Low body mass index (BMI) is a relevant prognostic factor for heart failure (HF), but HF patients with low BMI are reported to be at risk of not receiving optimal drug treatment. We sought to evaluate the efficacy of cardiac rehabilitation (CR) in patients with low vs. normal BMI. Methods and Results: We studied 152 consecutive patients (low BMI, n=32; normal BMI, n=119) who participated in a 3-month CR program. Low BMI was defined as <18.5 kg/m2and normal BMI, as 18.5≤BMI<25 kg/m2. All patients underwent cardiopulmonary exercise testing and muscle strength testing at the beginning and end of the 3-month CR program. After CR, a significantly greater proportion of HF patients with low BMI had a positive change in peak V̇O2than in the normal BMI group (91% vs. 70%; P=0.010). Average percent change in peak V̇O2was significantly greater in patients with low vs. normal BMI (17.1±2.8% vs. 7.8±1.5%; P<0.001). In addition, on multivariable logistic regression, low BMI was an independent predictor of a positive change in peak V̇O2after CR (OR, 3.97; 95% CI: 1.10-14.31; P=0.035). CONCLUSIONS: CR has a greater effect in patients with low than normal BMI, and low BMI is an independent predictor of a positive change in peak V̇O2. Thus, CR should be strongly recommended for HF patients with low BMI.

Misoprostol Heals Small Bowel Ulcers in Aspirin Users With Small Bowel Bleeding.

BACKGROUND & AIMS: There is no effective treatment for aspirin-induced small bowel ulcer bleeding. We performed a double-blind, randomized, placebo-controlled trial to determine whether misoprostol can heal small bowel ulcers in patients with small bowel bleeding who require continuous aspirin therapy. METHODS: We performed a prospective study of 84 aspirin users with small bowel bleeding who required continued aspirin therapy in Hong Kong and Japan. Patients with small bowel ulcers or multiple erosions, detected by capsule endoscopy, were randomly assigned to groups that received either misoprostol (200 µg, 4 times daily; n = 42) or placebo (n = 42) for 8 weeks. All patients continued taking aspirin (100 mg, once daily). The primary end point was complete ulcer healing at follow-up capsule endoscopy. Secondary end points included changes in hemoglobin level and number of ulcer/erosions from baseline. RESULTS: Complete healing of small bowel ulcers was observed in 12 patients in the misoprostol group (28.6%; 95% CI, 14.9%-42.2%) and 4 patients in the placebo group (9.5%; 95% CI, 0.6%-18.4%), for a difference in proportion of 19.0% (95% CI, 2.8%-35.3%; P = .026). The misoprostol group had a significantly greater mean increase in hemoglobin than the placebo group (mean difference, 0.70 mg/dL; 95% CI, 0.05-1.36; P = .035). The reduction in medium number of ulcers or erosions was significantly greater in the misoprostol group (from 6.5 [range, 1-85] to 2 [range, 0-25]) than in the placebo group (from 7 [range, 1-29] to 4 [range, 0-19] (P = .005). CONCLUSIONS: In a double-blind, randomized, placebo-controlled trial, we found misoprostol to be superior to placebo in promoting healing of small bowel ulcers among aspirin users complicated by small bowel ulcer bleeding who require continuous aspirin therapy. However, use of misoprostol alone would provide only limited protection against aspirin on the small bowel. ClinicalTrials.gov ID NCT01998776.

Effect of eicosapentaenoic acid/docosahexaenoic acid on coronary high-intensity plaques detected with non-contrast T1-weighted imaging (the AQUAMARINE EPA/DHA study): study protocol for a randomized controlled trial.

BACKGROUND: Despite the success of HMG-CoA reductase inhibitor (statin) therapy in reducing atherosclerotic cardiovascular events, a residual risk for cardiovascular events in patients with coronary artery disease (CAD) remains. Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are promising anti-atherosclerosis agents that might reduce the residual CAD risk. Non-contrast T1-weighted imaging (T1WI) with cardiac magnetic resonance (CMR) less invasively identifies high-risk coronary plaques as high-intensity signals. These high-intensity plaques (HIPs) are quantitatively assessed using the plaque-to-myocardium signal intensity ratio (PMR). Our goal is to assess the effect of EPA/DHA on coronary HIPs detected with T1WI in patients with CAD on statin treatment. METHODS/DESIGN: This prospective, controlled, randomized, open-label study examines the effect of 12 months of EPA/DHA therapy and statin treatment on PMR of HIPs detected with CMR and computed tomography angiography (CTA) in patients with CAD. The primary endpoint is the change in PMR after EPA/DHA treatment. Secondary endpoints include changes in Hounsfield units, plaque volume, vessel area, and plaque area measured using CTA. Subjects are randomly assigned to either of three groups: the 2 g/day EPA/DHA group, the 4 g/day EPA/DHA group, or the no-treatment group. DISCUSSION: This trial will help assess whether EPA/DHA has an anti-atherosclerotic effect using PMR of HIPs detected by CMR. The trial outcomes will provide novel insights into the effect of EPA/DHA on high-risk coronary plaques and may provide new strategies for lowering the residual risk in patients with CAD on statin therapy. TRIAL REGISTRATION: The University Hospital Medical Information Network (UMIN) Clinical Trials Registry, ID: UMIN000015316 . Registered on 2 October 2014.

Forkhead Box F2 Suppresses Gastric Cancer through a Novel FOXF2-IRF2BPL-ß-Catenin Signaling Axis.

DNA methylation has been identified as a hallmark of gastric cancer (GC). Identifying genes that are repressed by DNA promoter methylation is essential in providing insights into the molecular pathogenesis of gastric cancer. Using genome-wide methylation studies, we identified that transcription factor forkhead box F2 (FOXF2) was preferentially methylated in gastric cancer. We then investigated the functional significance and clinical implication of FOXF2 in gastric cancer. FOXF2 was silenced in gastric cancer cell lines and cancer tissues by promoter methylation, which was negatively associated with mRNA expression. Ectopic expression of FOXF2 inhibited proliferation, colony formation, G1-S cell-cycle transition, induced apoptosis of gastric cancer cell lines, and suppressed growth of xenograft tumors in nude mice; knockdown of FOXF2 elicited opposing effects. FOXF2 inhibited Wnt signaling by inducing ß-catenin protein ubiquitination and degradation independently of GSK-3ß. FOXF2 directly bound the promoter of E3 ligase interferon regulatory factor 2-binding protein-like (IRF2BPL) and induced its transcriptional expression. IRF2BPL in turn interacted with ß-catenin, increasing its ubiquitination and degradation. Multivariate Cox regression analysis identified FOXF2 hypermethylation as an independent prognostic factor of poor survival in early-stage gastric cancer patients. In conclusion, FOXF2 is a critical tumor suppressor in gastric carcinogenesis whose methylation status serves as an independent prognostic factor for gastric cancer patients.Significance: FOXF2-mediated upregulation of the E3 ligase IRF2BPL drives ubiquitylation and degradation of ß-catenin in gastric cancer, blunting Wnt signaling and suppressing carcinogenesis. Cancer Res; 78(7); 1643-56. ©2018 AACR.

Comparison of propofol with midazolam in endoscopic submucosal dissection for esophageal squamous cell carcinoma: a randomized controlled trial.

BACKGROUND: Interruption of sedation due to a poor response to modified neuroleptanalgesia (m-NLA) with midazolam often occurs during endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) because most patients have a history of heavy alcohol intake. Recently, propofol has been used feasibly and safely during endoscopic procedures. The aim of this study was to clarify the efficacy and safety of propofol compared with that of midazolam during ESD for ESCC. METHODS: This was a single-blind, randomized controlled trial in a single center. Patients with ESCC scheduled for ESD were included in the study. Patients were randomly assigned to one of two groups: the propofol group and the midazolam group. The main outcome was the incidence of discontinuation of the procedure due to a poor response to sedation. Secondary outcomes included risk factors for a poor response to sedation. RESULTS: Between April 2014 and October 2015, 132 patients (n = 66 per group) who underwent ESD for ESCC were enrolled in this study. The incidence of discontinuation due to a poor response to sedation in the propofol and midazolam groups was 0% (0/66) and 37.9% (25/66), respectively (p < 0.01). Multivariate analyses revealed that use of midazolam [Odds ratio (OR), 7.61; 95% confidence interval (CI), 2.64-21.92; p < 0.01] and age (OR, 0.93; 95% CI, 0.86-0.98; p < 0.01) were risk factors for a poor response to sedation. CONCLUSIONS: Our study indicates that, compared with midazolam, propofol is a more efficient sedative for m-NLA during ESD for ESCC.

Efficacy of a concomitant elemental diet to reduce the loss of response to adalimumab in patients with intractable Crohn's disease.

BACKGROUND AND AIM: Secondary loss of response to adalimumab (ADA-LOR) commonly occurs in patients with Crohn's disease (CD) treated with adalimumab (ADA). We evaluated the efficacy of concomitant elemental diet (ED) therapy to reduce ADA-LOR in adult CD patients. METHODS: Patients were divided into either an ED (≥900 kcal/day) or a non-ED group (<900 kcal/day). Cumulative non-ADA-LOR rates were compared between groups. The effects of ED intake to reduce ADA-LOR were also assessed in antitumor necrosis factor-alpha (TNF-α)-naïve and infliximab (IFX)-intolerant or refractory CD patients. Serum ADA and TNF-α levels were measured. RESULTS: We enrolled 117 CD patients into the ED (n = 25) or non-ED (n = 92) groups. Although the cumulative non-ADA-LOR rate was higher in the ED group than in the non-ED group, ED intake was not an independent reducing factor for ADA-LOR (adjusted hazard ratio = 0.725; 95% confidence interval: 0.448-1.180; P = 0.196) in all patients. ED intake was significantly more effective in reducing ADA-LOR in IFX-intolerant or refractory patients than in anti-TNF-α-naïve patients in a dose-related manner (P for interaction <0.20). Serum ADA levels did not differ between the groups. Serum TNF-α levels were significantly lower in the ED group than in the non-ED group at week 28 (P = 0.044) and week 52 (P = 0.043). CONCLUSIONS: Concomitant ED therapy reduced ADA-LOR in IFX-intolerant or refractory patients in a dose-related manner. Reductions in the TNF-α levels by concomitant ED intake may contribute to reduce ADA-LOR in CD patients.

Predictors of improvements in exercise capacity during cardiac rehabilitation in the recovery phase after coronary artery bypass graft surgery versus acute myocardial infarction.

This study aimed to elucidate the predictors of improvements in exercise capacity during cardiac rehabilitation (CR) in the recovery phase after coronary artery bypass graft surgery (CABG) versus acute myocardial infarction (AMI). We studied 152 patients (91 after AMI and 61 after CABG) who participated in a 3-month CR program. All patients underwent a cardiopulmonary exercise test, blood tests, maximal quadriceps isometric strength (QIS) measurement, and bioelectrical impedance body composition measurement at the beginning and end of the 3-month CR program. At baseline, the percentage of predicted peak oxygen uptake (%pred-PVO2), maximal QIS, and hemoglobin (Hb) were significantly lower, while C-reactive protein (CRP) was significantly higher, in the CABG than the AMI group. After the 3-month CR, %change in PVO2 (%ΔPVO2) was significantly greater in the CABG than the AMI group (18 ± 15% vs 11 ± 12%, P < 0.01). At univariate analysis, baseline plasma brain natriuretic peptide (BNP), %change in maximal QIS after CR (%Δ maximal QIS), and change in plasma hemoglobin (ΔHb) significantly correlated with %ΔPVO2 in the CABG group, whereas only baseline %pred-PVO2 did so in the AMI group. Multiple regression analysis revealed that the same factors were independent and significant predictors of %ΔPVO2 in the CABG and AMI groups. The predictors of improvements in exercise capacity after CR differed between patients after CABG or AMI. Specifically, in CABG patients both enhancing QIS and correcting anemia may contribute to greater improvements in exercise capacity after CR, while a more effective CR program should be designed for CABG patients with high baseline BNP.

A Metastatic Gastric Tumor from Ovarian Cancer.

Gastric metastasis from ovarian cancer has rarely been reported. We herein report the case of a 64-year-old woman with gastric metastasis from ovarian cancer that was diagnosed as surgical stage IA. Diagnostic and staging laparotomy showed mucinous carcinoma of the right ovary. At one month after surgery, bone metastasis was detected via scintigraphy. On esophagogastroduodenoscopy, a 10-mm elevated lesion with ulceration on the top was seen in the stomach. The immunohistochemical analysis of biopsy specimens showed that these metastases arose from ovarian cancer. We recommend that physicians remain aware of the possibility of gastric metastasis in patients with ovarian cancer.

Analysis of the Risk Factors of Surgery after Endoscopic Balloon Dilation for Small Intestinal Strictures in Crohn's Disease Using Double-balloon Endoscopy.

Objective Balloon-assisted endoscopy enables access to and treatment of strictures in the small intestine using endoscopic balloon dilation (EBD); however, the long-term outcomes of EBD have not been sufficiently evaluated. This study evaluated the long-term outcomes of EBD in Crohn's disease to identify the risk factors associated with the need for subsequent surgical intervention. Methods We retrospectively analyzed patients with Crohn's disease who had undergone EBD with double-balloon endoscopy (DBE) for small intestinal strictures at a single center between 2006 and 2015. The long-term outcomes were assessed based on the cumulative surgery-free rate following initial EBD. Results Seventy-two EBD with DBE sessions and 112 procedures were performed for 37 patients during this period. Eighteen patients (48.6%) required surgery during follow-up. Significant factors associated with the need for surgery in a multivariate analysis were multiple strictures (adjusted hazard ratio, 14.94; 95% confidence interval, 1.91-117.12; p=0.010). One patient (6.7%) required surgery among 15 who had single strictures compared to 17 (77.3%) among 22 patients with multiple strictures. Conclusion In a multivariate analysis, the presence of multiple strictures was a significant risk factor associated with the need for surgery; therefore, a single stricture might be a good indication for EBD using DBE for small intestinal strictures in Crohn's disease patients.

Postprandial Symptoms Felt at the Lower Part of the Epigastrium and a Possible Association of Pancreatic Exocrine Dysfunction with the Pathogenesis of Functional Dyspepsia.

Objective In symptom-dependent diseases such as functional dyspepsia (FD), matching the pattern of epigastric symptoms, including severity, kind, and perception site, between patients and physicians is critical. Additionally, a comprehensive examination of the stomach, duodenum, and pancreas is important for evaluating the origin of such symptoms. Methods FD-specific symptoms (epigastric pain, epigastric burning, early satiety, and postprandial fullness) and other symptoms (regurgitation, nausea, belching, and abdominal bloating) as well as the perception site of the above symptoms were investigated in healthy subjects using a new questionnaire with an illustration of the human body. A total of 114 patients with treatment-resistant dyspeptic symptoms were evaluated for their pancreatic exocrine function using N-benzoyl-L-tyrosyl-p-aminobenzoic acid. Results A total of 323 subjects (men:women, 216:107; mean age, 52.1 years old) were initially enrolled. Most of the subjects felt the FD-specific symptoms at the epigastrium, while about 20% felt them at other abdominal sites. About 30% of expressed as epigastric symptoms were FD-nonspecific symptoms. At the epigastrium, epigastric pain and epigastric burning were mainly felt at the upper part, and postprandial fullness and early satiety were felt at the lower part. The prevalence of patients with pancreatic exocrine dysfunction was 71% in the postprandial fullness group, 68% in the epigastric pain group, and 82% in the diarrhea group. Conclusion We observed mismatch in the perception site and expression between the epigastric symptoms of healthy subjects and FD-specific symptoms. Postprandial symptoms were often felt at the lower part of the epigastrium, and pancreatic exocrine dysfunction may be involved in the FD symptoms, especially for treatment-resistant dyspepsia patients.

Improvement in Exercise Capacity by Exercise Training Associated With Favorable Clinical Outcomes in Advanced Heart Failure With High B-Type Natriuretic Peptide Level.

BACKGROUND: The efficacy of exercise training (ET) programs and its relationship with long-term clinical outcomes in advanced heart failure (HF) patients with high levels of B-type natriuretic peptide (BNP) remain uncertain.Methods and Results:We studied 340 consecutive HF patients with ejection fraction (EF) <45% who completed a 3-month ET program. Patients with BNP ≥200 pg/mL (High-BNP, n=170) had more advanced HF characteristics, including lower EF (25.0±8.6% vs. 28.1±8.0%, P=0.0008), than those with BNP <200 pg/mL. In the High-BNP patients, peak oxygen uptake (V̇O2) was significantly increased by 8.3±16.2% during the ET program, and changes in peak V̇O2inversely correlated with changes in BNP (R=-0.453, P<0.0001) and changes in ventilatory efficiency (V̇E/V̇CO2slope) (R=-0.439, P<0.0001). During a median follow-up of 46 months, patients in the upper tertile of changes in peak V̇O2(≥13.0%), compared with those in the lower tertile (<1.0%), had lower rates of the composite of all-cause death or HF hospitalization (37.9% vs. 54.4%, P=0.036) and all-cause death (8.6% vs. 24.6%, P=0.056). In the multivariate analysis, change in peak V̇O2was a significant independent predictor of the composite outcome and all-cause death. CONCLUSIONS: Even among advanced HF patients with high BNP level, an ET program significantly improved exercise capacity, and a greater improvement in exercise capacity was associated with greater decreases in BNP level and V̇E/V̇CO2slope and more favorable long-term clinical outcomes.

Production of insulin-like growth factor-II in hepatocellular carcinoma with recurrent hypoglycemia: a case report.

A 35-year-old woman, who was an HBV carrier, complained of fever for 2 weeks, and thus, she was admitted in our hospital. Both serum AFP and PIVKA-II levels were abnormally high, and an abdominal enhanced CT revealed the presence of multiple masses in both lobes of the liver. She was diagnosed with hepatocellular carcinoma (T4, N0, M0, and Vp4) and was treated with transcatheter arterial infusion chemotherapy. On the 4th day of her illness, her serum glucose level was 26mg/dl. Glucose infusion and intravenous hyperalimentation were not effective, and she experienced repeated hypoglycemic attacks. Based on the low levels of both insulin (0.4µU/ml) and insulin-like growth factor (IGF)-I (14ng/ml), we made a diagnosis of non-islet cell tumor hypoglycemia associated with hepatocellular carcinoma. The patient was orally administered prednisolone at a dose of 20mg/day. On the 49th day of illness, the hepatocellular carcinoma ruptured, and 2 days later, she died because of hemorrhage shock. Postmortem immunohistochemical staining for IGF-II was positive in the tumor cells of the liver. Furthermore, Western immunoblotting revealed the presence of high-molecular-weight form of IGF-II in the serum of the patient.

Single Locoregional Triamcinolone Injection Immediately After Esophageal Endoscopic Submucosal Dissection Prevents Stricture Formation.

OBJECTIVES: Although endoscopic submucosal dissection (ESD) is an efficient treatment for superficial esophageal cancer, it is associated with stricture formation after wide-circumference resection that leads to a low quality of life. Although locoregional steroid injections prevent stricture formation, a randomized comparative study did not report any advantages associated with steroid injection. We evaluated the prophylactic efficacy of a single locoregional triamcinolone injection for stricture formation after esophageal ESD. METHODS: This was a retrospective matched case-control study using propensity score matching (PSM). Between April 2006 and July 2015, a total of 602 patients with superficial esophageal neoplasia underwent ESD. Among them, 189 patients with mucosal defects that spanned more than 2/3 of the esophageal circumference were included. After exclusion, 150 patients were enrolled. Triamcinolone acetonide (80 mg) was injected into the residual submucosal layer of the resected region immediately after ESD. PSM was performed to reduce the effects of selection bias for steroid injection. The primary outcome was the incidence of stricture formation. The secondary outcome was the number of balloon dilatation procedures required to resolve the stricture formation. RESULTS: Thirty-seven patients, with and without triamcinolone injection each, were matched after PSM. The incidence of stricture formation decreased from 45.9% (17/37) without triamcinolone injection to 18.9% (7/37) with triamcinolone injection (p=0.016). After matching, the mean number of balloon dilatation procedures required also decreased from 2.8±4.6 to 0.6±1.5 times (P<0.01). CONCLUSIONS: A single locoregional triamcinolone injection efficiently prevented stricture formation after esophageal ESD.

Microbiota Plays a Key Role in Non-Steroidal Anti-Inflammatory Drug-Induced Small Intestinal Damage.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) damage the small intestine by causing multiple erosions and ulcers. However, to date, no established therapies and prophylactic agents are available to treat such damages. We reviewed the role of intestinal microbiota in NSAID-induced intestinal damage and identified potential therapeutic candidates. SUMMARY: The composition of the intestinal microbiota is an important factor in the pathophysiology of NSAID-induced small intestinal damage. Once mucosal barrier function is disrupted due to NSAID-induced prostaglandin deficiency and mitochondrial malfunction, lipopolysaccharide from luminal gram-negative bacteria and high mobility group box 1 from the injured epithelial cells activate toll-like receptor 4-signaling pathway and nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 inflammasome; this leads to the release of proinflammatory cytokines such as tumor necrosis factor-α and interleukin-1ß. Proton pump inhibitors (PPIs) are often used for the prevention of NSAID-induced injuries to the upper gastrointestinal tract. However, several studies indicate that PPIs may induce dysbiosis, which may exacerbate the NSAID-induced small intestinal damage. Our recent research suggests that probiotics and rebamipide could be used to prevent NSAID-induced small intestinal damage by regulating the intestinal microbiota. Key Messages: Intestinal microbiota plays a key role in NSAID-induced small intestinal damage, and modulating the composition of the intestinal microbiota could be a new therapeutic strategy for treating this damage.

The five-year survival rate after endoscopic submucosal dissection for superficial esophageal squamous cell neoplasia.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a widely accepted procedure for superficial esophageal squamous cell neoplasia (ESCN) because of a high complete resection rate. However, there were a few reports about the long-term outcomes of these patients due to short follow-up periods. AIMS: We aimed to evaluate the 5-year survival after ESD for superficial ESCN. METHODS: This was a retrospective cohort study performed at a single institution. Between 2006 and 2009, 94 patients with superficial ESCN underwent ESD. Eighty-three patients (93.3%) who had completed an extended period of observation of at least 5 years were enrolled. The main outcomes were the 5-year survival rates. The secondary outcomes were the cumulative incidence rate of metachronous ESCN, and the clinical outcomes. RESULTS: The 5-year relative overall survival rate was 99.0%, whereas the cause specific survival rate was 100% during 72.9 months of median follow up period. Subgroup analysis showed that the 5year survival of patients with EP/LPM and MM/SM1 (submucosal invasion ≤200µm) were 100% and 89.0%, respectively. The cumulative incidence rate of metachronous ESCN at 5 years was 16.8%. CONCLUSION: ESD for superficial ESCN is a curative treatment with a favorable 5-year survival rate.

Long-term prognosis of expanded-indication differentiated-type early gastric cancer treated with endoscopic submucosal dissection or surgery using propensity score analysis.

BACKGROUND AND AIMS: Although endoscopic submucosal dissection (ESD) for expanded-indication lesions of differentiated-type early gastric cancer (EGC) has been widely accepted, no prospective randomized study has been conducted on this subject. This study aimed to evaluate the long-term outcomes of ESD and surgery for expanded-indication lesions of differentiated-type EGC. METHODS: Between 1997 and 2012, 1500 consecutive patients with EGC were treated in Osaka City University Hospital. Using propensity score matching and inverse probability of treatment weighting (IPTW), we retrospectively evaluated the long-term outcomes, risk factors for mortality, and adverse events for patients with expanded-indication lesions of differentiated-type EGC who underwent ESD or surgical treatments. RESULTS: A total of 308 patients with expanded-indication lesions of differentiated-type EGC confirmed by pathologic examination after ESD or surgery met the eligibility criteria. After matching, the 5-year overall survival rate was higher in the ESD group than in the surgery group (97.1% vs 85.8%; P = .01). We also found that surgery was significantly associated with mortality using both the IPTW method (hazard ratio [HR], 10.89; 95% confidence interval [CI], 1.37-86.6; P < .01), and Cox analysis (HR, 8.60; 95% CI, 1.11-66.52; P = .04) after matching. Significantly fewer adverse events were associated with ESD than with surgery (6.8% vs 28.4%; P < .01). No cause-specific mortality was observed in either group. CONCLUSIONS: Our results indicate that ESD might be an alternative treatment modality for expanded-indication lesions of differentiated-type EGC.