Endoscopic and histological risk stratification for gastric cancer using gastric intestinal metaplasia.

BACKGROUND AND AIM: Intestinal metaplasia (IM) of the gastric mucosa is strongly associated with the risk of gastric cancer (GC). This study was performed to investigate the usefulness of endoscopic and histological risk stratification for GC using IM. METHODS: This was a post-hoc analysis of a multicenter prospective study involving 10 Japanese facilities (UMINCTR000027023). The ridge/tubulovillous pattern, light blue crest (LBC), white opaque substance (WOS), endoscopic grading of gastric IM (EGGIM) score using non-magnifying image-enhanced endoscopy, and operative link on gastric IM assessment (OLGIM) were evaluated for their associations with GC risk in all patients. RESULTS: In total, 380 patients (115 with GC and 265 without GC) were analyzed. The presence of an LBC (limited to antrum: odds ratio [OR] 2.4 [95% confidence interval 1.1-5.0], extended to corpus: OR 3.6 [2.1-6.3]), the presence of WOS (limited to antrum: OR 3.0 [1.7-5.3], extended to corpus: OR 4.2 [2.1-8.2]), and histological IM (limited to antrum: OR 3.2 [1.4-7.4], extended to corpus: OR 8.5 [4.5-16.0]) were significantly associated with GC risk. Additionally, the EGGIM score (5-8 points: OR 8.8 [4.4-16.0]) and OLGIM (stage III/IV: OR 12.5 [6.1-25.8]) were useful for stratification of GC risk. The area under the receiver operating characteristic curve value for GC risk was 0.740 for OLGIM and 0.706 for EGGIM. CONCLUSIONS: The LBC, WOS, EGGIM, and OLGIM were strongly associated with GC risk in Japanese patients. This finding can be useful for GC risk assessment in daily clinical practice.

Kyoto classification risk scoring system and endoscopic grading of gastric intestinal metaplasia for gastric cancer: Multicenter observation study in Japan.

OBJECTIVES: The usefulness of endoscopic and histological risk assessment for gastric cancer (GC) has not been fully investigated in Japanese clinical practice. METHODS: In this multicenter observation study, GC and non-GC patients were prospectively enrolled in 10 Japanese facilities. The Kyoto classification risk scoring system, the Kimura-Takemoto endoscopic atrophy classification, the endoscopic grading of gastric intestinal metaplasia (EGGIM), the operative link on gastritis assessment (OLGA) and the operative link on gastric intestinal metaplasia assessment (OLGIM) were applied to all patients. The strength of an association with GC risk was compared. In addition, important endoscopic findings in the Kyoto classification were identified. RESULTS: Overall, 115 GC and 265 non-GC patients were analyzed. Each risk stratification method had a significant association with GC risk in univariate analysis. In multivariate analysis, OLGIM stage III/IV (odds ratio [OR] 2.8 [95% CI 1.5-5.3]), high EGGIM score (OR 1.8 [1.0-3.1]) and opened-type Kimura-Takemoto (OR 2.5 [1.4-4.5]) had significant associations with GC risk. In the Kyoto classification, opened-type endoscopic atrophy, invisible regular arrangement of collecting venules (RAC), extensive (>30%) intestinal metaplasia in the corpus in image-enhanced endoscopy, and map-like redness in the corpus were independent high-risk endoscopic findings. The modified Kyoto classification risk scoring system using these four findings demonstrated a better area under the receiver operating characteristic curve value (0.750, P = 0.052) than that of the original Kyoto classification (0.706). CONCLUSIONS: The OLGIM stage III/IV, high EGGIM score and open-typed Kimura-Takemoto had strong association with GC risk in Japanese patients. The modified Kyoto classification risk scoring system may be useful for GC risk assessment, which warrants further validation. (UMIN000027023).

Risk Factors for Delayed Bleeding after Therapeutic Gastrointestinal Endoscopy in Patients Receiving Oral Anticoagulants: A Multicenter Retrospective Study.

BACKGROUND/AIMS: Delayed bleeding is among the adverse events associated with therapeutic gastrointestinal endoscopy. The aim of this study was to evaluate risk factors for delayed bleeding after gastrointestinal endoscopic resection in patients receiving oral anticoagulants as well as to compare the rates of occurrence of delayed bleeding between the oral anticoagulants used. METHODS: We retrospectively analyzed a total of 772 patients receiving anticoagulants. Of these, 389 and 383 patients were receiving direct oral anticoagulants (DOACs) and warfarin, respectively. Therapeutic endoscopic procedures performed included endoscopic submucosal dissection (ESD), endoscopic mucosal resection, polypectomy, and cold polypectomy. RESULTS: Delayed bleeding occurred in 90 patients (11.7%) with no significant difference between the DOAC and warfarin groups (9.5 and 13.8%, respectively). Delayed bleeding occurred significantly more frequently with apixaban than with rivaroxaban (13.5 vs. 6.4%; p < 0.05). A multivariate analysis identified continued anticoagulant therapy (OR 2.29), anticoagulant withdrawal with heparin bridging therapy (HBT; OR 2.18), anticoagulant therapy combined with 1 antiplatelet drug (OR 1.72), and ESD (OR 3.87) as risk factors for delayed bleeding. CONCLUSION: This study identified continued anticoagulant therapy, anticoagulant withdrawal with HBT, anticoagulant therapy combined with 1 antiplatelet drug, and ESD as risk factors for delayed bleeding after therapeutic endoscopy in patients receiving oral anticoagulants. Delayed bleeding rates were not significantly different between those receiving DOACs and warfarin. It was also suggested that the occurrence of delayed bleeding may vary between different DOACs and that oral anticoagulant withdrawal should be minimized during therapeutic gastrointestinal endoscopy, given the thromboembolic risk involved.

Strong Intra-Esophageal Reflux May Contribute to the Development of Barrett's Adenocarcinoma and Affect the Localization.

BACKGROUND: There has been no study that has directly measured the esophageal reflux factors in Barrett's adenocarcinoma (BA) using 24-h multichannel intraluminal impedance-pH monitoring (24-h MII-pH). We aimed to clarify the esophageal reflux factors in Barrett's esophagus (BE) and BA and the factors that determine the location of BA with 24-h MII-pH. METHODS: We performed 24-h MII-pH in 26 patients with superficial BA treated endoscopically (BA group) and 13 patients with BE (BE group) and examined the esophageal reflux factors (esophageal acid exposure time [AET], bolus exposure (acid, weakly acid, and alkaline), and number of reflux episodes. In the BA group, there were 16 cases in which the lesions were localized in an area in contact with the esophagogastric junction (EGJ; EGJ group), and 10 cases in which the lesions were proximal to the BE and separated from the EGJ (non-EGJ group). RESULTS: Total reflux in the bolus exposure in the BA group showed higher values compared to that in the BE group. The total of acid and weakly acid reflux of bolus exposure was significantly higher in the BA group than that in the BE group. The BA group also had greater numbers of total reflux episodes than the BE group. As for the cancer locations in BE, the cases in which the lesions were located proximally and separated from the EGJ had more AET and total reflux and acid reflux indicated by bolus exposure compared to the lesions adjacent to the EGJ. CONCLUSIONS: Stronger gastro-esophageal reflux appeared to be an important factor in the development of adenocarcinoma from BE. In addition, the cancer location in BE may be related to the intensity of esophageal reflux.

Continuous liquid-suction catheter attachment for endoscope reduces volume of liquid reflux to the mouth in esophageal endoscopic submucosal dissection.

BACKGROUND AND AIM: Pooling of liquid in the esophageal lumen can worsen the field of vision and cause liquid reflux to the mouth, which leads to aspiration pneumonia, in esophageal endoscopic submucosal dissection (ESD). We developed a continuous liquid-suction catheter attachment for the endoscope (CLCA) that has multiple tiny holes and can suction the liquid without causing mucosal injury. Thus, we aim to show the efficacy of CLCA in esophageal ESD. METHODS: This was a single-blinded, randomized controlled trial involving patients with superficial esophageal cancer. The enrolled patients were randomly assigned to the conventional ESD (C-ESD) or ESD with CLCA (CLCA-ESD) groups. Primary endpoint was volume of liquid reflux to the mouth during the ESD procedure. Secondary endpoints were incidence of aspiration pneumonia and procedure time. RESULTS: Fifty patients were enrolled in this trial. Volume of liquid reflux to the mouth was significantly lower in the CLCA-ESD group than in the C-ESD group (mean: 10 vs 73 mL, P = 0.010). Furthermore, the incidence of aspiration pneumonia on computed tomography (CT) scan between the two groups was also significantly different (4.0% vs 32.0%, P = 0.023), although no significant difference was observed through chest radiography. In addition, procedure time tended to be shorter in the CLCA-ESD group (P = 0.054). CONCLUSION: This study first showed that use of CLCA in esophageal ESD reduced the volume of liquid reflux to the mouth and contributed to decreased incidence of aspiration pneumonia on CT scan (UMIN000018167).

Leptin Aggravates Reflux Esophagitis by Increasing Tissue Levels of Macrophage Migration Inhibitory Factor in Rats.

Leptin, produced primarily by the adipose tissue, acts as a pro-inflammatory modulator, thereby contributing to the development of obesity-related disease. Although high levels of leptin in the obese are closely related to gastroesophageal reflux disease, the mechanism by which leptin influences esophageal inflammation remains unknown. Macrophage migration inhibitory factor (MIF) is produced by immune cells, such as T lymphocytes and macrophages, and MIF is known to induce the production of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and interleukin 6 (IL-6). We therefore investigated the mechanism whereby leptin aggravates reflux esophagitis, by focusing on esophageal tissue levels of MIF and CD3+ T lymphocytes, both of which are crucial for the reflux-induced epithelial damage. Esophageal inflammation was surgically induced in male Wistar rats by ligating the forestomach and narrowing the duodenum to facilitate gastroesophageal reflux, followed by administration of leptin or vehicle with an osmotic pump system for 1 week. We demonstrated that the administration of leptin exacerbated the reflux esophagitis with the apparent infiltration of CD3+ T lymphocytes and caused the significant increase in the esophageal tissue levels of MIF. Moreover, the leptin caused increases in the esophageal tissue levels of TNF-α, IL-1ß and IL-6, downstream targets of MIF. Importantly, the increases in these pro-inflammatory cytokines were accompanied by increased protein levels of phospho-STAT3 and phospho-AKT, pivotal molecules of leptin signaling pathways. In conclusion, through enhancing the MIF-induced inflammatory signaling, leptin could contribute to the development of gastroesophageal reflux disease.

Factors Associated With Metachronous Gastric Cancer Development After Endoscopic Submucosal Dissection for Early Gastric Cancer.

GOALS: To clarify the factors associated with metachronous gastric cancer development after endoscopic submucosal dissection (ESD) for early gastric cancer. BACKGROUND: Patients who undergo ESD for early gastric cancer have an appreciable risk of developing metachronous gastric cancer. However, there have been few reports on the association between life style and the development of such cancer. STUDY: Patients with early gastric cancer who underwent ESD at our institution between 2003 and 2012 were enrolled. Metachronous gastric cancer was defined as secondary gastric cancer detected >1 year after initial ESD. Factors, including age, gender, body mass index, eradication of Helicobacter pylori, cigarette smoking, drinking, and continuous use of a proton pump inhibitor, associated with metachronous gastric cancer development were evaluated by Cox proportional hazard regression analysis. RESULTS: A total of 539 patients with a mean 53.6-month follow-up period were analyzed. The 5-year cumulative incidence of secondary gastric cancer was 13.0%. Multivariate analysis exhibited that age of 60 years and above [hazard ratio (95% confidence interval)=4.05 (1.23-13.4)] and cigarette smoking [2.12 (1.19-3.78)] were independent risk factors for metachronous gastric cancer development. Furthermore, ≥20 pack-years of smoking [1.51 (1.03-2.24)] was a significant risk factor with a dose-response relationship (P for trend=0.042). There was no significant association between Helicobacter pylori eradication and metachronous gastric cancer development. CONCLUSIONS: This is the first study to demonstrate the detailed association between cigarette smoking and metachronous gastric cancer development.

Estrogen Enhances Esophageal Barrier Function by Potentiating Occludin Expression.

BACKGROUND: We recently demonstrated that a female sex hormone, estrogen, suppressed esophageal epithelial injury in a reflux esophagitis model of rat, suggesting that estrogen may play an important role in controlling the progress of the gastro-esophageal reflux disease spectrum. However, the precise mechanism of the action is unclear. AIM: To investigate the potential role of estrogen in the esophageal barrier function. METHODS: Male rabbits were pretreated with either continuous release 17ß-estradiol or placebo, and the excised esophageal mucosa was subjected to Ussing chamber experiments after the 2-week pre-treatment. The mucosal side of the chamber was perfused with luminal irritants (HCl or acidified sodium nitrite), while the basal side was perfused by modified Krebs buffer. The epithelial barrier function was evaluated by the transmembrane resistance and the epithelial permeability. The intercellular space of the epithelium was investigated with transmission electron microscopy and the expression of tight junction protein, occludin, claudin-1, and claudin-4, with immunoblotting. RESULTS: Estrogen pre-treatment significantly attenuated the decrease in the transmembrane resistance and the increase in the epithelial permeability induced by luminal irritants. Furthermore, the dilation of the intercellular space induced by luminal HCl was significantly alleviated by 17ß-estradiol administration. The baseline occludin expression was significantly potentiated by 17ß-estradiol administration. CONCLUSIONS: This is the first study showing an enhancement of the esophageal barrier function by 17ß-estradiol administration. The lack of the protective effect of estrogen could be responsible for the male predominance of erosive reflux esophagitis.

Feasibility of optical coherence tomography for the evaluation of Barrett's mucosa buried underneath esophageal squamous epithelium.

OBJECTIVES: The evaluation of Barrett's glands buried underneath esophageal squamous epithelium becomes increasingly important to achieve curative treatments. However, clinically available endoscopies have critical limitations in depicting the subsurface structure, resulting in non-curative treatments. Optical coherence tomography (OCT) can acquire a high-resolution cross-sectional image, equivalent to an 'optical biopsy'. We aimed to assess the feasibility of the in vivo use of probe-type OCT imaging to evaluate Barrett's mucosa buried underneath esophageal squamous epithelium METHODS: We conducted a single-center prospective study with 14 consecutive patients with Barrett's adenocarcinoma from 2008 to 2014. The enrolled patients were examined by a probe-type OCT in vivo, followed by en bloc endoscopic submucosal dissection (ESD) with electric marking. Then, the one-to-one correlations between the OCT images of the buried mucosa and their histological assessment were examined. RESULTS: The overall accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the buried mucosa in the OCT imaging were 85.7% (12/14), 77.8% (7/9), 100% (5/5), 100% (7/7) and 71.4% (5/7), respectively. However, OCT could not easily distinguish non-dysplastic glands from dysplastic glands. Additionally, the linear distance from the histological squamo-columnar junction in correct cases tended to be longer than that in incorrect cases (mm, median [range]: 2.0 [0.7-7.5] vs. 0.5 [0.5-0.5]). CONCLUSIONS: We demonstrated, for the first time, that pre-operative OCT imaging might be feasible for detecting the oral side extension of buried Barrett's mucosa to remove the entire area with malignant potential by ESD. This article is protected by copyright. All rights reserved.

A Japanese case of lymphocytic esophagitis.

We report the case of a 68-year-old Japanese man diagnosed with lymphocytic esophagitis (LE), a rare disease associated with refractory dysphagia. He has had severe dysphagia and heartburn since 2007. Findings of esophagogastroduodenoscopy (EGD) carried out by a local physician in 2010 showed pale mucosa with white exudate and lateral furrows in the esophagus. He was referred to Tohoku University Hospital in 2012, because the symptoms did not improve, despite regular use of a proton pump inhibitor (PPI). At that time, EGD revealed the coexistence of a slight stricture in the upper esophagus, the histopathological findings of which included a predominantly peri-papillary distribution of abundant, infiltrating CD3+ /CD4+ /CD8+ /CD20- lymphocytes without any granulocytes (CD4+  : CD8+  = 3.3:1). These were consistent with a diagnostic criteria of LE. Thereafter, severe dysphagia with food impaction occurred twice a month, despite the long-term use of a PPI, and EGD showed worsened strictures, where endoscopic ultrasonography findings showed marked circumferential thickness of the mucosal and submucosal layers. Then, one session of endoscopic balloon dilatation dramatically improved the dysphagia. Accordingly, LE should be considered an important differential diagnosis of refractory dysphagia based on the characteristic features of endoscopic and pathological findings.

Endoscopic balloon dilatation for pharyngo-upper esophageal stricture after treatment of head and neck cancer.

BACKGROUND AND AIM: Dysphagia caused by pharyngo-upper esophageal stricture is a complication of treatment for head and neck cancer. Endoscopic balloon dilation (EBD) is in widespread use as an effective and safe treatment for stricture in many areas of the gastrointestinal tract. In the present study, we investigated the efficacy and safety of EBD for pharyngo-upper esophageal strictures that developed after treatment for head and neck cancer. METHODS: From January 2010 to December 2013, the medical records and endoscopic findings of 19 consecutive patients with pharyngo-upper esophageal strictures occurring after surgery and/or chemoradiotherapy for head and neck cancer were retrospectively examined. RESULTS: Mean number of EBD sessions per patient was 6.6 (1-30), and mean maximum diameter of dilation was 15.8 (11-20) mm. Technical success was achieved in 16 of 19 (84.2%) patients, and only two major complications (bleeding and pha ryngeal edema) occurred in a total of 125 dilatation sessions (1.6%). Regarding the influence of chemoradiotherapy on the outcome of EBD, patients who had undergone chemoradiotherapy plus surgery experienced significantly more restenosis during the follow-up period compared to those who had undergone surgery alone (50% vs 0%, P < 0.05). CONCLUSIONS: This retrospective analysis demonstrated the efficacy and safety of exclusive EBD for pharyngo-upper esophageal strictures occurring after treatment for head and neck cancer, indicating that the therapeutic application of EBD could be extended to such strictures. Patients who underwent chemoradiotherapy and surgery experienced more restenosis; hence, such patients should be carefully followed up after EBD treatment.

Prospective analysis of risk for bleeding after endoscopic biopsy without cessation of antithrombotics in Japan.

BACKGROUND AND AIM: In Japan, after the revision of the gastrointestinal endoscopic guidelines for patients taking antithrombotics, endoscopic biopsies were permitted while continuing antithrombotic treatment. However, the risk of bleeding after the biopsy with or without cessation of antithrombotics has not been fully evaluated because bleeding events are very rare. The aim of this prospective study was to evaluate the risk for bleeding after upper gastrointestinal biopsy without cessation of antithrombotics. METHODS: Consecutive patients who underwent upper gastrointestinal endoscopic biopsy from December 2011 to March 2014 were enrolled in this study. Antithrombotic medication and its cessation status was checked at enrollment. To confirm bleeding events associated with biopsy, medical examination at the hospital or direct confirmation by telephone was done within 1 month after the biopsy. RESULTS: Among the 3758 patients who underwent endoscopic biopsies, 394 patients (10.5%) were medicated with antithrombotics, and 286 of them (72.6% of the total antithrombotics users) did not undergo cessation. Bleeding after the biopsy occurred in six cases (0.15%, 95% CI; 0.09%∼0.22%), but there was only one case that had continued taking antithrombotics. The incidence of bleeding after biopsy was not significantly higher in the patients who had continued taking antithrombotics compared with the others (0.35% vs 0.14%, P = 0.38). CONCLUSION: This prospective study showed that continuation of antithrombotics did not increase the bleeding risk after upper gastrointestinal endoscopic biopsy.

Endoscopic findings for predicting gastric acid secretion status.

BACKGROUND AND AIM: Gastric acidic abnormalities are related to various types of diseases in Helicobacter pylori (H. pylori) infection status. However, no studies have shown correlations between many tiny endoscopic findings and the acid secretion level simultaneously. In the present study, we investigated predictive tiny endoscopic findings of hyperchlorhydria and hypochlorhydria. METHODS: A total of 223 subjects without organic diseases who underwent esophagogastroduodenoscopy and endoscopic gastrin test (EGT) for estimating gastrin-stimulated gastric acid secretory response between 1999 and 2012 at our institution were retrospectively analyzed. Two blinded expert endoscopists reviewed the images independently and recorded the endoscopic findings. RESULTS: According to the EGT values, the enrolled subjects were categorized into hyperchlorhydria, normal acid secretion, and hypochlorhydria groups. In all subjects, hematin (odds ratio [95% confidence interval] = 3.32 [1.40-7.84]) and antral erosion(2.88 [1.24-6.70]) were the predictive endoscopic findings for hyperchlorhydria, and swelling of areae gastricae (14.4 [5.74-36.1]) and open-type atrophy (15.1 [7.35-31.1]) were those for hypochlorhydria. In addition, the predictive endoscopic findings for hyperchlorhydria differed according to the H. pylori infection status, hematin in H. pylori-positive subjects and antral erosion in H. pylori-negative subjects, in contrast to those for hypochlorhydria, which were the same irrespective of the H. pylori infection status. CONCLUSIONS: We could predict the acid secretion status based on the endoscopic findings regardless of H. pylori infection status, which would be of some help for evaluating the risk for acid-related diseases.

Comparison of the long-term outcomes of endoscopic resection for superficial squamous cell carcinoma and adenocarcinoma of the esophagus in Japan.

OBJECTIVES: Few studies have simultaneously evaluated the long-term outcomes of endoscopic resection (ER) for squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus in Japan. The objective of this study was to evaluate the long-term outcomes of ER for superficial esophageal cancer in consecutive patients. METHODS: This was a retrospective study from a single institution. From April 2001 to June 2012, 204 patients with SCC and 26 patients with AC were included from a total of 355 consecutive patients who were treated by esophageal ER at the Tohoku University Hospital. Patients with submucosal invasion deeper than 200 µm and lymphovascular involvement were excluded. The intervention followed was endoscopic therapy. RESULTS: Overall survival, disease-free survival, and recurrence rates were evaluated as long-term outcomes. In the SCC group, during the median observation time of 36.5 months (range, 6-120 months), 22 (10.8%) patients experienced metachronous recurrence, 4 (2.0%) patients experienced local recurrence, and 27 (13.2%) patients died from causes unrelated to SCC. In the AC group, during the median observation time of 45.5 months (range, 6-131 months), one patient (3.8%) experienced metachronous recurrence and two (7.7%) died from causes unrelated to AC. The cumulative 5-year overall survival rates were not significantly different between SCC (75.9%) and AC (88.9%) (P=0.120). The cumulative 5-year disease-free survival rates of SCC (57.1%) were significantly lower than those of AC (85.2%; P=0.017). The cumulative 5-year recurrence rates of SCC (32.0%) were significantly higher than those of AC (4.2%; P=0.023). CONCLUSIONS: The rate of recurrence after ER was higher in patients with SCC than that in patients with AC. These findings suggest that, by detecting AC of the esophagus earlier, a satisfactory prognosis without recurrence can be expected after ER in Japan, and more rigorous endoscopic follow-up is necessary after ER in patients with SCC than in those with AC.

Calcium carbonate breath test for non-invasive estimation of gastric acid secretion.

Gastric acid measurement is useful in assessing the effectiveness of antisecretory drugs, however, the conventional tests involve invasive nasogastric intubation. Orally administered ¹³C-labeled calcium carbonate (Ca¹³CO3) reacts with gastric acid to produce ¹³C-labeled carbon dioxide (¹³CO2), which is then excreted in the breath. The objective of this study was to evaluate the suitability of Ca¹³CO3 breath test for estimating gastric acid secretion in human noninvasively. First, the Ca¹³CO3 breath test and the measurement of pooled gastric acid under a fasting condition were performed in 6 healthy volunteers to evaluate the correlation between the two parameters. Next, endoscopic gastric acid collection and the Ca¹³CO3 breath test were performed on different days after pentagastrin injection in 20 subjects to evaluate the correlation between the tests and the reproducibility. Finally, the same studies were repeated in 4 subjects before and after 1-week rabeprazole, a proton pump inhibitor, administration. The maximum CO2 concentration (Cmax) correlated very well with the amount of pooled gastric acid (r = 0.95), suggesting that Ca¹³CO3 breath test values well reflected the fasting intragastric acidity. The ¹³CO2 concentration after pentagastrin injection correlated well with pentagastrin-stimulated maximal acid output (r = 0.79 at 20 min). The reproducibility of the Ca¹³CO3 breath test under pentagastrin-stimulation was good (coefficient of variation = 0.11). Rabeprazole administration markedly reduced the values of the Ca¹³CO3 breath test, suggesting that it can sensitively assess the efficacy of rabeprazole. The Ca¹³CO3 breath test can potentially be a useful method for non-invasive estimation for gastric acid secretion in human.

Endoscopically proven case of rapid esophagogastric variceal progression and rupture as a result of portal hypertension with liver sarcoidosis.

Sarcoidosis is a multi-systemic disease of unknown etiology that results in the development of non-caseating epithelioid granulomas. The liver is the third most frequently involved organ after the lymph nodes and the lungs. Most cases of liver sarcoidosis do not present with symptoms and involve minimal liver dysfunction, but some cases display progression to portal hypertension and liver cirrhosis, and finally to liver failure. The mechanism and the risk of progression in liver sarcoidosis are still unknown because of the diagnostic difficulty associated with this condition, and because follow-up examinations can only be done in an invasive manner. Here, we present an informative case of liver sarcoidosis with rapid progression of esophagogastric varices. Four months prior to the definitive diagnosis, no signs of varices were observed on endoscopy, and developmentof esophagogastric varices, rapid progression, and eventual rupture occurred in a short period of time. A liver biopsy, carried out after endoscopic sclerotherapy, revealed that granulomas primarily affected the portal area without fibrotic and cirrhotic changes, which is considered a primary cause of portal hypertension and esophagogastric varices. Following the liver biopsy, the patient was given systemic steroids and is currently receiving outpatient care. Thus, we should consider the possibility that liver sarcoidosis, even in the absence of cirrhotic changes, can cause serious events such as esophagogastric variceal rupture following rapid progression as a result of portal hypertension.

Gender differences in oesophageal mucosal injury in a reflux oesophagitis model of rats.

OBJECTIVE: There is a strong male predominance of oesophageal adenocarcinoma, which might be related to the higher prevalence of precursor lesions such as erosive reflux oesophagitis in men compared with women. This experiment investigated the gender difference in a reflux oesophagitis model of rats and explored the potential role of oestrogen in controlling oesophageal tissue damage. DESIGN: An acid-reflux oesophagitis model was surgically produced in male and female rats, and ascorbic acid in the diet and sodium nitrite in the drinking water were administered to half of either group to provoke luminal exogenous nitric oxide (NO) as an exacerbating agent. Seven days after the surgery, the oesophagus was excised, and the injury area, myeloperoxidase activity and pro-inflammatory cytokine levels were measured. Furthermore, 17ß-oestradiol was administered to ovariectomised female rats or male rats, which then underwent reflux oesophagitis surgery. RESULTS: While there was no gender difference in oesophageal damage in the baseline model, oesophageal damage was more intensively observed in males than in females in the presence of exogenous NO administration. While oesophageal damage was increased in ovariectomised rats compared with sham ovariectomised, exacerbated oesophageal damage was attenuated by the replacement of 17ß-oestradiol. In addition, exacerbated oesophageal damage in male rats was suppressed by 17ß-oestradiol. CONCLUSION: This is the first study showing the prominent gender difference in the severity of oesophageal tissue damage in a gastro-oesophageal reflux disease-related animal model, highlighting the critical involvement of oestrogen in controlling gastro-oesophageal reflux disease-related oesophageal epithelial injury.

Increased gastric mucus secretion alleviates non-steroidal anti-inflammatory drug-induced abdominal pain.

Non-steroidal anti-inflammatory drugs (NSAIDs) can cause dyspeptic symptoms, including abdominal pain. Gastric mucus is important as the first line of defense against luminal irritants. In the present study, we investigated whether gastric mucus secretion could influence the severity of gastric mucosal injuries or NSAID-induced dyspeptic symptoms. Fifteen Helicobacter pylori-negative, healthy males were administered two types of NSAIDs, a non-selective cyclooxygenase inhibitor, naproxen (300 mg, twice a day), or a cyclooxygenase-2-selective inhibitor, etodolac (200 mg, twice a day), for 1 week in a crossover study, with an interval of ≥ 4 weeks. Study participants underwent endoscopic examinations before and after treatment. Pentagastrin-stimulated gastric secretions were collected for 10 min during endoscopic examinations, and were analyzed for gastric acid levels (mEq/10 min) and mucus output (mg hexose/10 min). The grade of gastric mucosal injury was assessed endoscopically. Among 29 subjects who completed the crossover study, 11 individuals reported abdominal pain following the administration of naproxen or etodolac for 1 week, as judged by elevated pain scores, while 18 individuals did not report abdominal pain. The occurrence of symptoms was not associated with the type of NSAIDs administered or the occurrence of erosive injury visualized by endoscopy. Gastric mucus secretion was significantly increased in subjects without drug-induced abdominal pain (P < 0.05), whereas it was significantly reduced in those with drug-induced abdominal pain (P < 0.05). In conclusion, the occurrence of NSAID-induced abdominal pain is associated with reduced levels of gastric mucus secretion rather than the occurrence of endoscopic mucosal injury.

Collagenous gastritis.

In the present paper, we report a case of rare collagenous gastritis. The patient was a 25-year-old man who had experienced nausea, abdominal distention and epigastralgia since 2005. Esophagogastroduodenoscopy (EGD) carried out at initial examination by the patient's local doctor revealed an extensively discolored depression from the upper gastric body to the lower gastric body, mainly including the greater curvature, accompanied by residual mucosa with multiple islands and nodularity with a cobblestone appearance. Initial biopsies sampled from the nodules and accompanying atrophic mucosa were diagnosed as chronic gastritis. In August, 2011, the patient was referred to Tohoku University Hospital for observation and treatment. EGD at our hospital showed the same findings as those by the patient's local doctor. Pathological findings included a membranous collagen band in the superficial layer area of the gastric mucosa, which led to a diagnosis of collagenous gastritis. Collagenous gastritis is an extremely rare disease, but it is important to recognize its characteristic endoscopic findings to make a diagnosis.

A pilot study of scheduled endoscopic balloon dilation with oral agent tranilast to improve the efficacy of stricture dilation after endoscopic submucosal dissection of the esophagus.

BACKGROUNDS AND AIM: As circumferential or near-circumferential endoscopic submucosal dissection (ESD) for superficial esophageal neoplasms might evoke refractory strictures, multiple sessions of endoscopic balloon dilation (EBD) are required. We aimed to assess the effectiveness and safety of oral agent tranilast with EBD for improving the efficacy of stricture dilation after esophageal ESD. METHODS: In an open-label prospective study at a single institution, 31 asymptomatic consecutive patients with superficial esophageal squamous cell carcinomas were enrolled from April 2007 to October 2010. After ESD, we performed scheduled EBD (twice weekly for 4 wk) with or without administration of oral agent tranilast for 8 weeks. Thereafter, we added additional EBD on the basis of solid criteria-for example, patient's awareness of vomiting >1/wk and inability of passage of routine endoscope through the ESD site. We compared the rates of post-ESD strictures and the numbers of additional EBD sessions for 48 weeks after ESD and the Dysphagia score between tranilast (T)-group and none (N)-group, based on patients' subjective symptoms, at 16, 24, and 48 weeks after ESD. RESULTS: The percentage of post-ESD strictures in T-group was significantly lower than that in N-group (P=0.04). The median numbers of additional EBD sessions and Dysphagia score at 16 and 24 weeks after ESD in T-group were significantly smaller than those in N-group (P=0.0138, 0.002, 0.005, respectively). No adverse events and no recurrence were observed. CONCLUSIONS: We demonstrated for the first time that scheduled EBD combined with oral agent tranilast might be effective and safe for improving the efficacy of stricture dilation after esophageal ESD.