Background factors of idiopathic peptic ulcers and optimal treatment methods: a multicenter retrospective Japanese study.

This study investigated the trends in idiopathic peptic ulcers, examined the characteristics of refractory idiopathic peptic ulcer, and identified the optimal treatment. The characteristics of 309 patients with idiopathic peptic ulcer were examined. We allocated idiopathic peptic ulcers that did not heal after 8 weeks' treatment (6 weeks for duodenal ulcers) to the refractory group and those that healed within this period to the healed group. The typical risk factors for idiopathic peptic ulcer (atherosclerosis-related underlying disease or liver cirrhosis complications) were absent in 46.6% of patients. Absence of gastric mucosal atrophy (refractory group: 51.4%, healed group: 28.4%; p = 0.016), and gastric fundic gland polyps (refractory group: 17.6%, healed group: 5.9%; p = 0.045) were significantly more common in the refractory group compared to the healed group. A history of H. pylori eradication (refractory group: 85.3%, healed group: 66.0%; p = 0.016), previous H. pylori infection (i.e., gastric mucosal atrophy or history of H. pylori eradication) (refractory group: 48.5%, healed group: 80.0%; p = 0.001), and potassium-competitive acid blocker treatment (refractory group: 28.6%, healed group, 64.1%; p = 0.001) were significantly more frequent in the healed group compared to the refractory group. Thus, acid hypersecretion may be a major factor underlying the refractoriness of idiopathic peptic ulcer.

Phase II Study of Intraperitoneal Administration of Paclitaxel Combined with S-1 and Cisplatin for Gastric Cancer with Peritoneal Metastasis.

BACKGROUND: Intraperitoneal chemotherapy is promising for gastric cancer with peritoneal metastasis. Although a phase III study failed to show a statistically significant superiority of intraperitoneal paclitaxel combined with S-1 and intravenous paclitaxel, the sensitivity analysis suggested clinical efficacy. Thus, attempts to combine intraperitoneal paclitaxel with other systemic therapies with higher efficacy have been warranted. We sought to explore the efficacy of intraperitoneal paclitaxel with S-1 and cisplatin. PATIENTS AND METHODS: Gastric cancer patients with peritoneal metastasis were enrolled in the phase II trial. In addition to the established S-1 and cisplatin regimen every 5 weeks, intraperitoneal paclitaxel was administered on days 1, 8, and 22 at a dose of 20 mg/m2. The primary endpoint was overall survival rate at 1 year after treatment initiation. Secondary endpoints were progression-free survival and toxicity. RESULTS: Fifty-three patients were enrolled and fully evaluated for efficacy and toxicity. The 1-year overall survival rate was 73.6% (95% confidence interval 59.5-83.4%), and the primary endpoint was met. The median survival time was 19.4 months (95% confidence interval, 16.1-24.6 months). The 1-year progression-free survival rate was 49.6% (95% confidence interval, 34.6-62.9%). The incidences of grade 3/4 hematological and non-hematological toxicities were 43% and 47%, respectively. The frequent grade 3/4 toxicities included neutropenia (25%), anemia (30%), diarrhea (13%), and anorexia (17%). Intraperitoneal catheter and implanted port-related complications were observed in four patients. There was one treatment-related death. CONCLUSIONS: Intraperitoneal paclitaxel combined with S-1 and cisplatin is well tolerated and active in gastric cancer patients with peritoneal metastasis.

Pegfilgrastim for the management of neutropenia during neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil in esophageal cancer patients.

BACKGROUND: Neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy is a new standard for locally advanced esophageal squamous cell carcinoma. The optimal timing of pegfilgrastim with the DCF regimen to prevent febrile neutropenia (FN) remains controversial. The effectiveness of concomitant pegfilgrastim administration with continuous 5-fluorouracil (5-FU) infusion in the DCF regimen was therefore assessed. METHODS: All patients who received neoadjuvant DCF for esophageal cancer were retrospectively assessed. Patients who had been scheduled to receive pegfilgrastim on days 3-5 (early group) or days 7-9 (regular group) of the DCF regimen were included. Uni- and multivariate analyses were used to assess risk factors for FN. RESULTS: Eighty-eight patients were included in the analysis. The 26 patients in the early group received pegfilgrastim as scheduled. In the 62 patients of the regular group, 51 received pegfilgrastim at a median of 7 days after starting DCF chemotherapy. However, 11 patients in the regular group could not receive pegfilgrastim. Twenty-two patients of the regular group and 2 patients of the early group developed FN after the first session of DCF. Early administration of pegfilgrastim and grade 4 neutropenia were significantly associated with onset of FN, with multivariate analysis identifying early administration of pegfilgrastim as an independent preventive factor and grade 4 neutropenia as a risk factor, after adjusting for sex and age. CONCLUSION: Early pegfilgrastim administration is a safe approach that reduces the incidence of FN in DCF therapy. Using pegfilgrastim with continuous 5-FU infusion in the DCF regimen represents a reasonable option to prevent FN.

Treatment strategy for successful conversion surgery in clinical stage IVB gastric cancer.

INTRODUCTION: Recent advances in chemotherapy have resulted in successful conversion surgery (CS) for clinical stage (cStage) IVB gastric cancer (GC). This study aimed to evaluate the success rate of CS in clinical practice and determine optimal treatment strategies. METHODS: Totally, 166 patients with cStage IVB gastric and gastroesophageal junction adenocarcinoma, who underwent chemotherapy at Hyogo Medical University Hospital between January 2017 and June 2022, were included. CS was performed after confirming tumor to be M0 based on imaging and/or staging laparoscopy, except for resectable liver metastases. Preoperative chemotherapy was continued for at least 6 months provided that adverse events were manageable. RESULTS: Of 125 eligible patients, 23 were treated with CS, achieving a conversion rate of 18.4% and an R0 resection rate of 91.3%. The median duration of preoperative chemotherapy was 8.5 months; the median number of cycles was eight. The highest conversion rate was observed in patients receiving first-line treatment (14.4%), followed by those receiving second and third lines (5.8% and 2.3%, respectively). The median survival time in patients who received CS was significantly longer than that in patients who continued chemotherapy alone (56.7 versus 16 months, respectively, P < 0.0001). There was no significant difference in the 3-year overall survival between the patients who achieved CS after first-line treatment (63.2%, n = 18) and those who achieved CS after second- or third-line treatment (66.7%, n = 5). CONCLUSION: Consistent chemotherapy strategies could lead to successful CS and improved prognosis in a greater number of patients with cStage IVB GC, regardless of line of treatment.

Proposal for T3 classification of esophagogastric junction carcinoma based on the interconnection of extramural anatomical structures.

Classification of extramural invasion of esophagogastric junction carcinoma (EGJC) is not yet established. The anatomy surrounding the EGJ alters between the mediastinum and the abdominal cavity. This review proposed a T3 classification of EGJC based on anatomical continuity. Analysis of endoscopic ultrasound images, review of intraoperative images, and detailed observation of surgical specimens were followed by a review of the literature. In the EGJ, the muscularis propria of the esophagus is enclosed in mediastinal adipose tissue called the adventitia, which is surrounded by the diaphragmatic crus and contains the paraesophageal lymph nodes (LNs). After passing through the esophageal hiatus along with the vagus nerves and blood vessels, the adventitia joins the adipose tissue containing the paracardial LNs, which is covered by the peritoneum, and then further divides into the lesser and greater omentum. The connective tissue outside the muscularis propria of the stomach, including the adipose tissue of the omentum, is called the subserosa. According to the TNM classification, T3 esophageal and gastric cancer is defined as invasion of the adventitia and subserosa, respectively. Given that the adventitia is anatomically continuous with the subserosa, T3 tumors of the EGJ can be described as those that extend through the muscularis propria but do not invade the peritoneum or diaphragmatic crus. We propose classifying T3 EGJC as "tumor extends through muscularis propria" rather than using the separate terms "adventitia" and "submucosa". T4 could be "tumor perforates serosa or invades adjacent structures", as per the current gastric cancer classification.

Marked improvement of severe reflux esophagitis following proximal gastrectomy with esophagogastrostomy by the right gastroepiploic vessels-preserving antrectomy and Roux-en-Y biliary diversion.

Duodenogastroesophageal reflux (DGER) following esophagectomy or gastrectomy can cause severe esophagitis, which impairs patients' quality of life and increases the risk of esophageal carcinogenesis. It is sometimes resistant to medical treatment, and surgical treatment is considered effective in such cases. However, an optimal operative procedure for medical treatment-resistant reflux esophagitis (RE) after proximal gastrectomy (PG) with esophagogastrostomy (EG) has not yet been established. We performed the right gastroepiploic vessels-preserving antrectomy and Roux-en-Y biliary diversion in a 70-year-old man with medical treatment-resistant severe esophagitis caused by DGER following PG with EG for esophagogastric junction cancer. The postoperative course was uneventful, and esophagogastroduodenoscopy performed on the 19th postoperative day showed marked improvement in the esophageal erosions. The patient reported symptomatic relief. The right gastroepiploic vessels-preserving antrectomy and Roux-en-Y biliary diversion were considered safe and feasible for medical treatment-resistant RE following PG with EG.

Duodenal cholinergic tuft cell number is increased in functional dyspepsia.

BACKGROUND: Low-grade duodenal inflammation has recently been identified in patients with functional dyspepsia (FD). Chemosensory tuft cells were reported to be associated with gastrointestinal diseases. We therefore assessed duodenal tuft cell density and microinflammation in patients with FD to determine whether these measures could serve as useful biomarkers, and also correlated tuft cell density and microinflammation in FD patients. METHODS: Duodenal biopsy specimens were obtained from patients with FD and from controls. Tuft cells, eosinophils, and mast cells were immunochemically stained with specific antibodies. Tuft cells were identified by immunostaining for doublecortin-like kinase 1 (DCLK1); cholinergic tuft cells were assessed by double staining for choline acetyltransferase (ChAT) and DCLK1. Immune-type tuft cells were assessed by IL-25 mRNA expression using real-time PCR. KEY RESULTS: The density of intramucosal eosinophils and mast cells was significantly higher in the duodenum of FD patients than in controls. The density of tuft cells was significantly higher in the duodenum of FD patients compared with controls, and significantly correlated with eosinophil density in the duodenum of FD patients and controls. Moreover, a fraction of ChAT-positive cells was DCLK1 positive; all duodenal DCLK1+ tuft cells were ChAT-immunoreactive in FD and in control subjects. CONCLUSIONS AND INFERENCES: Cholinergic tuft cell density was higher in the duodenum of patients with FD and significantly correlated with eosinophil density. Further studies are needed to investigate the pathophysiological significance of tuft cells in FD and may provide valuable clues to the pathophysiology of FD.

Microinflammation in the intestinal mucosa and symptoms of irritable bowel syndrome.

BACKGROUND: Potential etiological mechanisms of irritable bowel syndrome (IBS) have been reported, and emerging data suggest that immune activation is present in a major subset of IBS, especially in those with diarrhea. Intestinal mucosal mast cell and intraepithelial lymphocyte (IEL) infiltration and related factors were examined in patients with IBS. In addition, the correlations of symptoms and micro-inflammation were assessed. METHODS: Intestinal biopsy specimens were obtained from patients with IBS and controls. Mast cells and IELs were stained with specific antibodies. The mRNA levels of cytokines and chemokines were assessed by quantitative reverse transcription polymerase chain reaction. RESULTS: Infiltration of mast cells in the duodenum was significantly higher in IBS patients than in control subjects. The infiltration of IELs was higher in the duodenum and terminal ileum of IBS patients compared to the control subjects. The numbers of duodenal and ileal IELs were significantly correlated. The number of IELs but not mast cells in the duodenum and terminal ileum was significantly correlated with diarrhea frequency in control subjects and IBS patients. The expression level of the chemotactic chemokine CXCL11 was significantly higher in the duodenum of IBS patients. CONCLUSION: Duodenal mast cells and IELs were increased in IBS patients. In addition, a positive correlation was found between the number of duodenal and ileal IELs and the frequency of diarrhea. Given that the present study was strictly observational, further studies are needed to clarify the pathophysiological functions associated with micro-inflammation in IBS.

Gastric Xanthoma Is Related to the Rapid Growth of Gastric Cancer.

Early detection of gastric cancer is important. However, rapid growth of gastric cancers that cannot be resected endoscopically occurs even with periodic check-ups. Accordingly, we assessed factors associated with the speed of gastric cancer growth by examining historical endoscopic images. A total of 1996 gastric cancer cases were screened, and characteristics of lesions with slow and rapid growth were assessed. A total of 114 lesions from 114 patients were included in the assessment. Sixty slow-growing and fifty-four rapidly growing gastric cancers were compared. Female sex and incidence of lesions in the lower part of the stomach were significantly less frequent in the rapid-growth group than in the slow-growth group. History of endoscopic treatment tended to be more frequent in the rapid-growth group. Age, body mass index, histology, Helicobacter pylori status, and medications did not differ significantly between groups. Xanthoma was significantly related to rapid growth of gastric cancer, and map-like redness tended to be more frequent in the rapid-growth group in univariate analysis. Xanthoma was significantly related to rapid growth of gastric cancer on multivariate analysis. Further studies are warranted to clarify the pathophysiological mechanisms involved in the speed of gastric cancer growth.

A case of ectopic pancreas of the stomach accompanied by intraductal papillary mucinous neoplasm with GNAS mutation.

BACKGROUND: Ectopic pancreas is basically a benign disease and is not always necessary to be removed. However, all types of neoplasms occurring in the normal pancreas such as ductal adenocarcinomas and intraductal papillary mucinous neoplasms (IPMNs) may develop even within ectopic pancreas. We recently encountered an extremely rare case of ectopic pancreas in the gastric antrum associated with IPMN possessing a GNAS mutation. CASE PRESENTATION: A 71-year-old Japanese woman complained of epigastric pain. Computed tomography and upper gastrointestinal endoscopy showed an intramural cystic mass in the antrum of the stomach. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy did not give a definitive diagnosis, and the patient underwent resection of the lesion. Histology of the resected specimen showed that the gastric intramural lesion was ectopic pancreas. Moreover, the lesion contained dilated duct components with tubulo-villous epithelial proliferation consistent with pancreatic IPMN. Since the covering epithelial cells had highly atypical nuclei, the lesion was diagnosed as IPMN with high grade dysplasia. Immunohistochemistry showed that the IPMN component showed to be MUC2-, MUC5AC-, and CDX2-positive but MUC1- and MUC6-negative. Mutational analyses using genomic DNA revealed that the IPMN component had a mutation of GNAS at exon 8 (Arg201Cys). CONCLUSION: We finally diagnosed this case as gastric ectopic pancreas accompanied by intestinal type IPMN with high grade dysplasia possessing GNAS mutation. Although there were 17 cases of ectopic pancreas with IPMN including 6 cases of gastric ones reported in the English literature, this is the first case of ectopic pancreas with IPMN which was proved to have GNAS mutation. Intimate preoperative examinations including imaging analyses and EUS-FNA biopsy/cytology are recommended to decide whether the lesion has to be resected or not even if they are not effective for getting the right diagnosis.

Successful revision surgery for very late-onset stomal obstruction following Gomez gastroplasty: a case report.

BACKGROUND: Gomez gastroplasty, which was developed in the 1970s as one of the gastric restrictive surgeries for severe obesity, partitions the stomach using a stapler from the lesser towards the greater curvature at the upper gastric body, leaving a small channel. This procedure is no longer performed due to poor outcomes, but surgeons can encounter late-onset complications even decades after the surgery. Here, we report a case of very late-onset stomal obstruction following Gomez gastroplasty which was successfully treated by revision surgery. CASE PRESENTATION: A 58-year-old man was referred to our institution with sudden-onset nausea and vomiting. He underwent weight loss surgery in the USA in 1979, but the details of the surgery were unclear. Esophagogastroduodenoscopy demonstrated a stoma at the greater curvature of the upper gastric body, and fluoroscopy showed retention of contrast medium in the fundus and poor outflow through the stoma. Abdominal computed tomography revealed a staple line partitioning the stomach. Considering these preoperative investigation findings and the period during which the surgery was performed, the patient was diagnosed with very late-onset stomal obstruction following Gomez gastroplasty. Supporting the preoperative diagnosis, the surgical findings revealed a staple line extending from the lesser towards the greater curvature of the upper gastric body and a channel reinforced by a running seromuscular suture on the greater curvature. Moreover, gastric torsion caused by the enlarged proximal gastric pouch was found. Re-gastroplasty involving wedge resection of the original channel was performed followed by construction of a new channel. Postoperative course was uneventful, and the patient no longer had symptoms of stomal obstruction after revision surgery. CONCLUSIONS: Re-gastroplasty was safe and feasible for very late-onset stomal obstruction following Gomez gastroplasty. Accurate preoperative diagnosis based on the patient's interview and the investigation findings was important for surgical planning. A careful follow-up is required to prevent excessive weight regain after revision surgery.

Accuracy of Preoperative Endoscopy in Determining Tumor Location Required for Surgical Planning for Esophagogastric Junction Cancer.

PURPOSE: The surgical strategy for esophagogastric junction (EGJ) cancer depends on the tumor location as measured relative to the EGJ line. The purpose of this study was to clarify the accuracy of diagnostic endoscopy in different clinicopathological backgrounds. METHODS: Subjects were 74 consecutive patients with abdominal esophagus to upper gastric cancer who underwent surgical resection. Image-enhanced endoscopy with narrow-band imaging (NBI) was used to determine the EGJ line, prioritizing the presence of palisade vessels, followed by the upper end of gastric folds, as a landmark. The relative positional relationship between the tumor epicenter and the EGJ line was classified into six categories, and the agreement between endoscopic and pathologic diagnoses was examined to evaluate prediction accuracy. RESULTS: The concordance rate of 69 eligible cases was 87% with a kappa coefficient (K) of 0.81. The palisade vessels were observed in 62/69 patients (89.9%). Of the 37 pathological EGJ cancers centered within 2 cm above and below the EGJ line, Barrett's esophagus was found to be a significant risk factor for discordance (risk ratio, 4.40; p = 0.042); the concordance rate of 60% (K = 0.50) in the Barrett's esophagus group was lower than the rate of 91% (K = 0.84) in the non-Barrett's esophagus group. In five of six discordant cases, the EGJ line was estimated to be proximal to the actual line. CONCLUSION: Diagnostic endoscopy is beneficial for estimating the location of EGJ cancer, with a risk of underestimating esophageal invasion length in patients with Barrett's esophagus.

Pathological Complete Response and Successful Conversion Surgery After Nivolumab Therapy for Stage IV Oesophagogastric Junction Cancer.

BACKGROUND: Multimodality treatment including immune check point inhibitors is required for stage IV oesophagogastric junction cancer (OGJC). CASE REPORT: A 69-year-old man, was diagnosed with advanced OGJC and para-aortic lymph node metastasis (T3N+M1, stage IV), which upon biopsy, was shown to be an adenocarcinoma. After eight courses of nivolumab as third-line chemotherapy, the primary tumour and enlarged regional and para-aortic lymph nodes shrunk markedly, while tumour markers decreased within normal ranges. We performed a minimally invasive Ivor-Lewis oesophagectomy with completion of an abdominal D2 and transhiatal lower mediastinal lymph node dissection. Pathological findings revealed a complete response for the primary tumour and a regional lymph node metastasis. A biopsy of the previous sample revealed microsatellite instability-negativity, Epstein-Barr virus-negativity, and programmed cell death-1-ligand combined positive score of 2. He was followed up for 3 months without recurrence. CONCLUSION: Nivolumab may induce pathological complete response for stage IV OGJC even in cases negative for microsatellite instability and Epstein-Barr virus, besides the programmed cell death-1-ligand combined positive score of <5.

Role of the ß-Catenin/REG Iα Axis in the Proliferation of Sessile Serrated Adenoma/Polyps Associated with Fusobacterium nucleatum.

Although sessile serrated adenoma/polyps (SSA/Ps) may arise through a pathway different from the traditional adenoma-carcinoma sequence, details of SSA/P tumorigenesis still remain unclear. Fusobacterium nucleatum (Fn) is frequently detected in colorectal cancer (CRC) tissues and may play a pivotal role in colorectal carcinogenesis. Here, we investigated the relationship between Fn and the ß-catenin/REG Iα axis in SSA/Ps and their involvement in the proliferation of these lesions. Fn was detected in SSA/Ps by fluorescence in situ hybridization using a Fn-targeted probe, and expression of ß-catenin, REG Iα and Ki67 was examined using immunohistochemistry. Sixteen of 30 SSA/P lesions (53.3%) were positive for Fn. Eighteen SSA/P lesions (60%) showed ß-catenin immunoreactivity in the tumor cell nuclei. A significant majority of Fn-positive lesions showed nuclear expression of ß-catenin (87.5%) and higher REG Iα scores and Ki67 labeling indices relative to Fn-negative lesions. The SSA/P lesions expressing ß-catenin in nuclei had significantly higher REG Iα scores and Ki67 labeling indices than those expressing ß-catenin on cytomembranes. The REG Iα score was positively correlated with the Ki67 labeling index in SSA/P lesions. The treatment with Wnt agonist SKL2001 promoted nuclear ß-catenin translocation and enhanced REG Ia expression in Caco2 cells. Fn may play a role in the proliferation of SSA/P lesions through promotion of ß-catenin nuclear translocation and REG Iα expression.

Butyrate Alleviates Cytokine-Induced Barrier Dysfunction by Modifying Claudin-2 Levels.

Gastrointestinal (GI) disorders such as celiac disease and inflammatory bowel disease are attributed to intestinal barrier disruption. Imbalance of cytokines has been reported in the intestinal epithelium of patients with GI disorders. Short-chain fatty acids (SCFAs), derived from the fermentation of dietary fiber in the intestine, have been reported to benefit the intestinal barrier. Accordingly, we evaluated the effect of specific SCFAs on intestinal barrier function under cytokine-stimulated conditions. Caco-2 cells were cultured on insert membranes to generate monolayers, which then were used to investigate the effects of SCFAs. Tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), or interleukin-13 (IL-13) was added to the basolateral side of the membrane while SCFAs were added to the apical side. After a 24 h stimulation, transepithelial electrical resistance (TEER) was measured, and the protein levels of claudin-1, claudin-2, claudin-3, claudin-4, occludin, and zonula occludens-1 (ZO-1) were evaluated by Western blot. Butyrate, but not acetate, propionate, or succinate, ameliorated the TNF-α/IFN-γ-induced decrease in TEER. TNF-α/IFN-γ stimulation significantly increased the protein level of claudin-2 and decreased the level of claudin-3. Butyrate significantly attenuated the upregulation of claudin-2 induced by TNF-α/IFN-γ. Butyrate blocked the decrease in TEER and the upregulation of claudin-2 induced by IL-13 without changing the level of other tight junction proteins. Our results suggested that butyrate is the main component of SCFAs to alleviate barrier dysfunction and that claudin-2 is the major target of this SCFA.

Effect of Instruction on Preventing Delayed Bleeding after Colorectal Polypectomy and Endoscopic Mucosal Resection.

BACKGROUND: The frequency of delayed bleeding after colorectal polypectomy has been reported as 0.6-2.8%. With the increasing performance of polypectomy under continuous use of antithrombotic agents, care is required regarding delayed post-polypectomy bleeding (DPPB). Better instruction to educate endoscopists is therefore needed. We aimed to evaluate the effect of instruction and factors associated with delayed bleeding after endoscopic colorectal polyp resection. METHODS: This single-center, retrospective study was performed to assess instruction in checking complete hemostasis and risk factors for onset of DPPB. The incidence of delayed bleeding, comorbidities, and medications were evaluated from medical records. Characteristics of historical control patients and patients after instruction were compared. RESULTS: A total of 3318 polyps in 1002 patients were evaluated. The control group comprised 1479 polyps in 458 patients and the after-instruction group comprised 1839 polyps in 544 patients. DPPB occurred in 1.1% of polyps in control, and 0.4% in after-instruction. Instruction significantly decreased delayed bleeding, particularly in cases with antithrombotic agents. Hot polypectomy, clip placement, and use of antithrombotic agents were significant independent risk factors for DPPB even after instruction. CONCLUSION: The rate of delayed bleeding significantly decreased after instruction to check for complete hemostasis. Even after instruction, delayed bleeding can still occur in cases with antithrombotic agents or hot polypectomy.

Gastric Xanthelasma, Microsatellite Instability and Methylation of Tumor Suppressor Genes in the Gastric Mucosa: Correlation and Comparison as a Predictive Marker for the Development of Synchronous/Metachronous Gastric Cancer.

A predictive marker for the development of synchronous/metachronous gastric cancer (GC) would be highly desirable in order to establish an effective strategy for endoscopic surveillance. Herein, we examine the significance of gastric xanthelasma (GX) and molecular abnormalities for the prediction of synchronous/metachronous GC. Patients (n = 115) were followed up (range, 12-122; median, 55 months) in whom the presence of GX and molecular alterations, including microsatellite instability (MSI) and methylation of human mutL homolog 1 (hMLH1), cyclin-dependent kinase inhibitor 2A (CDKN2A) and adenomatous polyposis coli (APC) genes, had been confirmed in non-neoplastic gastric mucosa when undergoing endoscopic submucosal dissection (ESD) for early GC. At the start of surveillance, the numbers of positive subjects were as follows: GX, 59 (51.3%); MSI, 48 (41.7%); hMLH1, 37 (32.2%); CDKN2A, 7 (6.1%); APC, 18 (15.7%). After ESD treatment, synchronous/metachronous GCs occurred in patients with the following positive factors: GX, 16 (27.1%); MSI, 7 (14.6%); hMLH1, 6 (16.2%); CDKN2A, 3 (42.9%); APC, 3 (16.7%). The presence of GX had no significant relationship to positivity for MSI or methylation of hMLH1, CDKN2A or APC. GX was significantly (p = 0.0059) and independently (hazard ratio, 3.275; 95% confidence interval, 1.134-9.346) predictive for the development of synchronous/metachronous GC, whereas those genetic alterations were not predictive. GX is a simple and powerful marker for predicting the development of synchronous or metachronous GC.

Glutamine Blocks Interleukin-13-Induced Intestinal Epithelial Barrier Dysfunction.

INTRODUCTION: Impaired intestinal epithelial barrier function is a hallmark of a variety of pathological conditions such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). IBD patients with IBS-like symptoms show higher interleukin-13 (IL-13) serum levels and poor psychological well-being. Supplementary glutamine reduced the daily bowel movement frequency, improved the stool form, and normalized intestinal hyperpermeability. This study was aimed at assessing the effects of IL-13 and supplementary glutamine on human intestinal epithelial function in vitro. METHODS: Caco-2 cells were grown on TranswellTM inserts. -IL-13 was added to the basolateral compartment, and transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC) labeled-dextran permeability measured. Effects of glutamine or the phosphatidylinositol-3-kinase inhibitor LY294002 were assessed. Involvement of tight junction proteins was assessed using Western blotting and immunofluorescence staining. RESULTS: IL-13 significantly decreased TEER and increased FITC labeled-dextran epithelial permeability. IL-13 stimulation decreased the claudin-1 expression and increased the claudin-2 expression. Glutamine alleviated IL-13-induced decrease of TEER and increase of FITC labeled-dextran permeability. Further, the phosphatidylinositol-3-kinase inhibitor showed this alleviating effect while the signal transducer and activator of transcription 6 inhibitor did not. CONCLUSIONS: IL-13 induced barrier integrity impairment by decreasing claudin-1 and increasing claudin-2. Glutamine alleviated IL-13-induced barrier dysfunction by increasing claudin-1 expression, via disruption of the phosphatidylinositol-3-kinase/Akt signaling pathway.