Bowel preparation with linaclotide and 1 L polyethylene glycol plus ascorbic acid prior to colonoscopy in chronic constipated patients.

BACKGROUND AND AIMS: Information on effective bowel preparation (BP) methods for patients with constipation is limited. We recently reported the efficacy of 1 L polyethylene glycol plus ascorbic acid (PEG-Asc) combined with senna for BP; however, this regimen was insufficient in patients with constipation. We hypothesized that the addition of linaclotide, which is approved for the treatment of chronic constipation, to 1 L PEG-Asc would yield results superior to those of senna in patients with constipation. METHODS: This was a retrospective, single-center study that included outpatients with constipation who underwent BP prior to colonoscopy between March and December 2019 (receiving 1 L PEG-Asc with 24 mg senna) and between January and October 2020 (receiving 1 L PEG-Asc with 500 mg linaclotide). RESULTS: A total of 543 patients with constipation were included, of whom 269 received linaclotide and 274 received senna. The rate of inadequate BP was significantly lower (11% vs 20%, p < 0.01) and the adenoma detection rate was significantly higher (54% vs 45%, p = 0.04) in the linaclotide group than in the senna group. Multivariate analysis revealed that the linaclotide regimen significantly reduced the risk of inadequate BP (odds ratio = 0.36, 95% confidence interval = 0.21-0.60, p < 0.01). CONCLUSIONS: The linaclotide regimen significantly increased BP efficacy and the adenoma detection rate compared with the senna regimen without reducing tolerability and is therefore a promising new option for BP in patients with constipation.

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.

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.

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.

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.

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.

NLRP3 inflammasome has a protective effect against oxazolone-induced colitis: a possible role in ulcerative colitis.

The inflammasomes induce maturation of pro-interleukin-1ß (IL-1ß) and pro-IL-18. We investigated roles of the NLRP3 inflammasome in the pathogenesis of ulcerative colitis (UC). After induction of oxazolone-induced colitis, a mouse UC model, colonic tissues were assayed for inflammatory mediators. Histological studies were performed on inflamed colonic tissue from mice and UC patients. Histological severity of murine colitis peaked on day 1, accompanied by an increase in the expression of Th2 cytokines including IL-4 and IL-13. Oxazolone treatment stimulated maturation of pro-caspase-1 and pro-IL-1ß, while it reduced IL-18 expression. Either exogenous IL-1ß or IL-18 ameliorated the colitis with or without reduction in Th2 cytokine expression, respectively. Induction of colitis decreased MUC2 expression, which was reversed by administration of IL-18, but not IL-1ß. Compared to wild-type mice, NLRP3-/- mice exhibited higher sensitivity to oxazolone treatment with enhancement of Th2 cytokine expression and reduction of mature IL-1ß and IL-18 production; this phenotype was rescued by exogenous IL-1ß or IL-18. Immunofluorescent studies revealed positive correlation of NLRP3 expression with disease severity in UC patients, and localization of the inflammasome-associated molecules in macrophages. The NLRP3 inflammasome-derived IL-1ß and IL-18 may play a protective role against UC through different mechanisms.

Concentration of Glial Cell Line-Derived Neurotrophic Factor Positively Correlates with Symptoms in Functional Dyspepsia.

BACKGROUND: In patients with functional dyspepsia (FD), mild duodenal inflammation correlates with increased mucosal permeability. Enteric glial cells can produce glial cell line-derived neurotrophic factor (GDNF) to repair disrupted epithelial barrier function. AIMS: We examined the role of duodenal GDNF in FD pathophysiology and its association with dyspeptic symptoms. METHODS: Duodenal biopsies taken from FD patients and control subjects were used for analysis. GDNF protein expression and localization were examined. Cellular infiltration of eosinophils and mast cells was measured. We also examined the intercellular space between the adjacent epithelial cells at the apical junction complex using transmission electron microscopy. RESULTS: In FD patients, expression of GDNF protein was significantly increased compared with controls, 107.3 (95.3-136.7) versus 49.3 (38.0-72.6) pg/mg protein (median (interquartile range), p = 0.006), respectively. GDNF was localized in enteric glial cells, eosinophils, and epithelial cells. The number of eosinophils was significantly greater in FD patients than in controls, 1039 (923-1181) versus 553 (479-598) cells/mm2 (p = 0.021), respectively. The intercellular space was dilated at the adherent junction in FD patients compared to control patients, 32.4 (29.8-34.8) versus 22.0 (19.9-26.1) nm (p = 0.002), respectively. Intercellular distance positively correlated with the frequency of postprandial fullness and early satiation (p = 0.001, r = 0.837 and p = 0.009, r = 0.693, respectively). Expression of GDNF correlated with epigastric burning (p = 0.041, r = 0.552). CONCLUSIONS: Increased expression of duodenal GDNF might be involved in FD pathophysiology and symptom perception.

NOD-Like Receptor Protein 3 Inflammasome Priming and Activation in Barrett's Epithelial Cells.

BACKGROUND & AIMS: Microbial molecular products incite intestinal inflammation by activating Toll-like receptors (TLRs) and inflammasomes of the innate immune system. This system's contribution to esophageal inflammation is not known. Gram-negative bacteria, which dominate the esophageal microbiome in reflux esophagitis, produce lipopolysaccharide (LPS), a TLR4 ligand. TLR4 signaling produces pro-interleukin (IL)1ß, pro-IL18, and NOD-like receptor protein 3 (NLRP3), which prime the NLRP3 inflammasome. Subsequent NLRP3 inflammasome activation cleaves caspase-1, inducing secretion of proinflammatory cytokines and pyroptosis (inflammatory cell death). We explored LPS effects on NLRP3 inflammasome priming and activation in esophageal cells. METHODS: We exposed esophageal squamous and Barrett's epithelial cells to LPS and measured the following: (1) TLR4, pro-IL1ß, pro-IL18, and NLRP3 expression; (2) caspase-1 activity; (3) tumor necrosis factor-α, IL8, IL1ß, and IL18 secretion; (4) lactate dehydrogenase (LDH) release (a pyroptosis marker); and (5) mitochondrial reactive oxygen species (ROS). As inhibitors, we used acetyl-Tyr-Val-Ala-Asp-CHO for caspase-1, small interfering RNA for NLRP3, and (2-(2,2,6,6,-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride for mitochondrial ROS. RESULTS: Squamous and Barrett's cells expressed similar levels of TLR4, but LPS induced TLR4 signaling that increased tumor necrosis factor-α and IL8 secretion only in Barrett's cells. Barrett's cells treated with LPS showed increased expression of pro-IL18, pro-IL1ß, and NLRP3, and increased mitochondrial ROS levels, caspase-1 activity, IL1ß and IL18 secretion, and LDH release. Acetyl-Tyr-Val-Ala-Asp-CHO, NLRP3 small interfering RNA, and Mito-TEMPO all blocked LPS-induced IL1ß and IL18 secretion and LDH release. CONCLUSIONS: In Barrett's cells, LPS both primes and activates the NLRP3 inflammasome, causing secretion of proinflammatory cytokines and pyroptosis. By triggering molecular events promoting inflammation, the esophageal microbiome might contribute to inflammation-mediated carcinogenesis in Barrett's esophagus.

Prediction of Poor Response to Modified Neuroleptanalgesia with Midazolam for Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIMS: Modified neuroleptanalgesia (m-NLA) with midazolam is often used for sedation and analgesia during endoscopic submucosal dissection (ESD) for gastrointestinal neoplasia. However, interruption due to poor response to midazolam is often experienced during ESD for esophageal squamous cell carcinoma (ESCC) because most patients with ESCC have a history of heavy alcohol intake. We examined the incidence and risk factors for poor response to m-NLA with midazolam and pethidine hydrochloride. METHODS: This retrospective cross-sectional study was conducted at a single institution. Between April 2007 and July 2013, 151 patients with superficial ESCC who underwent ESD under sedation using m-NLA with midazolam and pethidine hydrochloride were enrolled. Poor response to sedation was defined as the use of a second drug when Ramsay Sedation Score 1-2. RESULTS: Poor response to sedation occurred in 66.2% patients. Most cases of poor response were controlled by using additional flunitrazepam. Multivariate logistic regression analysis showed that cumulative alcohol intake and major specimen size were independent risk factors for poor response to sedation (OR 3.63, 95% CI 1.20-10.99, and OR 3.23, 95% CI 1.26-8.25). CONCLUSION: Our study indicated that cumulative alcohol intake and major specimen size were associated with poor response to m-NLA with midazolam and pethidine hydrochloride.

Alteration of Esophageal Microbiome by Antibiotic Treatment Does Not Affect Incidence of Rat Esophageal Adenocarcinoma.

BACKGROUND: Recent studies suggest that chronic inflammation-associated cancer is relevant to microbiome. Esophageal adenocarcinoma arises from an inflammatory condition called Barrett's esophagus, which is caused by gastroesophageal reflux. We hypothesized that esophageal microbiome plays a role in carcinogenesis of esophageal adenocarcinoma. AIM: We investigated whether alteration of microbiome using antibiotics affects the development of esophageal adenocarcinoma in a rat model. METHODS: Seven-week-old male Wistar rats which had undergone esophagojejunostomy were divided into control (n = 21) and antibiotic groups (n = 22) at 21 weeks after surgery. Control animals were given drinking water, while the other group was given penicillin G and streptomycin in drinking water until rats were killed at 40 weeks after operation. Incidence rates of Barrett's esophagus and adenocarcinoma in each group were evaluated by histological analysis. DNA was extracted from a portion of the distal esophagus, and the microbiome was investigated using terminal restriction fragment length polymorphism (T-RFLP) analysis. RESULTS: All rats in both groups developed Barrett's esophagus. Incidence of esophageal adenocarcinoma was similar between both groups with a trend to reduced incidence in the antibiotics group (89 % in the control group, 71 % in the antibiotics group, P = 0.365). T-RFLP analysis showed that esophageal microbiome was different between two groups such as the proportion of Lactobacillales was lower in the antibiotics group and Clostridium cluster XIVa and XVIII was higher in the antibiotics group. CONCLUSIONS: Alteration of microbiome does not affect the incidence of esophageal adenocarcinoma. Microbiome may not contribute to the development of esophageal adenocarcinoma.