Clinical Features and Therapeutic Outcomes of Post-colectomy Enteritis with Ulcerative Colitis.

OBJECTIVES: Few reports are available on post-colectomy enteritis (PCE) with ulcerative colitis (UC), which can be severe and sometimes fatal. The clinical characteristics are unclear, and treatment and diagnosis protocols have not been established. We aimed to investigate the incidence, clinical characteristics, diagnostic criteria, and therapeutic outcomes of PCE in this study. METHODS: Patients with UC who underwent colectomy between April 2010 and December 2019 were included in this study. We retrospectively analyzed patients who developed PCE and excluded patients with other forms of enteritis. RESULTS: We performed 829 colectomies because of a preoperative diagnosis of UC. Eleven and four patients were diagnosed with Crohn's disease and indeterminate colitis after surgery, respectively; 22 patients developed enteritis in the perioperative period. We excluded six patients with backwash ileitis, five with prepouch ileitis, three with infectious enteritis, and one with ischemic enteritis. In total, 7/814 (0.8%) patients developed PCE. All patients with PCE had pancolitis. PCE was observed a median of 33 (12-248) days after surgery. Endoscopy showed friable and granular mucosa. The extent of disease included various types such as pan-enteritis with diffuse type, pan-enteritis and mild inflammation in the middle ileum, and only ileitis. Gastroduodenitis-associated UC developed in 6/7 cases. All patients improved with tumor necrosis factor alpha (TNFα) antagonists even if TNFα antagonists had not been effective for colitis. CONCLUSIONS: PCE was rare. The mucosal endoscopic findings were similar to those of UC, and the extent of disease varied. TNFα antagonist administration for PCE was effective.

Clinical Characteristics and Risk Factors for Pneumocystis Jirovecii Pneumonia during Immunosuppressive Treatment in Patients with Ulcerative Colitis: A Retrospective Study.

AIMS: This study aimed to clarify the clinical characteristics of Pneumocystis jirovecii pneumonia (PJP) infection in patients with ulcerative colitis (UC) and to identify risk factors for PJP using a retrospective case-control study. METHODS: Of 4,525 patients with UC treated between 2007 and 2019, we identified those who satisfied the criteria for PJP. The Lichtiger clinical activity index (LCI) was compared between the initiation of immunosuppressive drug treatment and the onset of PJP. A retrospective case-control study was conducted using a PJP group and a non-PJP group. RESULTS: Nine patients experienced PJP, of whom two died. Since October 2014, there were no cases of PJP among UC patients aged ≥50 years who were prescribed three or more immunosuppressive agents given prophylactic sulfamethoxazole-trimethoprim (TPM-SMX). The median LCI (range) was 13 (8-17) at the initiation of treatment versus 2 (1-8) at PJP onset (p = 0.016). The median time to PJP onset was 83 days after treatment initiation. In the PJP group the median age was significantly greater (p = 0.022), three immunosuppressants were used significantly more frequently (p = 0.004), and the lymphocyte counts during treatment were significantly lower (p < 0.01) than in the non-PJP group. The cut-off lymphocyte count that distinguished PJP patients from non-PJP patients was 570/µL according to a receiver-operating curve analysis. CONCLUSIONS: Prophylactic administration of TPM-SMX prevented further cases of PJP. The onset of PJP occurred at the same time as the symptoms of UC were stabilizing and the immunosuppressive drugs were being reduced. Greater age, lower lymphocyte count, and treatment with three immunosuppressive drugs were risk factors for PJP.

NUDT15, FTO, and RUNX1 genetic variants and thiopurine intolerance among Japanese patients with inflammatory bowel diseases.

BACKGROUND/AIMS: Recent genome-wide analyses have provided strong evidence concerning adverse events caused by thiopurine drugs such as azathioprine (AZA) and 6-mercaptopurine. The strong associations identified between NUDT15 p.Arg139Cys and thiopurine-induced leukopenia and severe hair loss have been studied and confirmed over the last 2 years. However, other coding variants, including NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, and FTO p.Ala134Thr, and a noncoding variation in RUNX1 (rs2834826) remain to be examined in detail in this respect. Therefore, we investigated the correlation between these adverse events and the 5 recently identified variants mentioned above among Japanese patients with inflammatory bowel diseases (IBD). METHODS: One hundred sixty thiopurine-treated patients with IBD were enrolled. Genotyping was performed using TaqMan SNP Genotyping Assays or Sanger sequencing. RESULTS: None of the 5 variants were associated with gastrointestinal intolerance to AZA. However, NUDT15 p.Arg139Cys was significantly associated with the interval between initiation and discontinuation of AZA among patients with gastrointestinal intolerance. This variant was strongly associated with early (<8 weeks) and late (≥8 weeks) leukopenia and severe hair loss. Moreover, it correlated with the interval between initiation of thiopurine therapy and leukopenia occurrence, and average thiopurine dose. NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, FTO p.Ala134Thr, and RUNX1 rs2834826 exhibited no significant relationship with the adverse events examined. CONCLUSIONS: Of the 5 variants investigated, NUDT15 p.Arg139Cys had the strongest impact on thiopurine-induced leukopenia and severe hair loss; therefore, its genotyping should be prioritized over that of other variants in efforts to predict these adverse events in Japanese patients with IBD.

Safety of One-Week, First-Line, Standard Triple Therapy for Helicobacter Pylori Eradication in a Japanese Population.

BACKGROUND: Standard triple therapy with the proton pump inhibitors, clarithromycin and amoxicillin for Helicobacter pylori infection is considered to be safe; however, the development of significant adverse events (AEs), such as skin rashes, has been reported. OBJECTIVE: To reconfirm the safety of this treatment. METHODS: This was a retrospective cohort study. After the exclusion of patients allergic to penicillin, 322 consecutive patients, consisting of 305 outpatients and 17 inpatients, had received the first-line eradication treatment with lansoprazole (30 mg), clarithromycin (200 mg), and amoxicillin (750 mg) twice daily for 7 days. Their medical charts were reviewed, and data were collected. RESULTS: Three patients discontinued the treatment because of the development of a skin rash, mild diarrhea, and heat sensation, respectively. The main AE observed was mild diarrhea in 50 patients. One patient had frequent diarrhea, but it was readily resolved by a probiotic treatment. On the second or third day after the conclusion of the treatment, a skin rash also occurred in six patients (2%). Two of these patients and one patient who discontinued the treatment were administered steroids as outpatients. They recovered within 1 month. CONCLUSION: Most AEs that developed were mild, except for some cases of a rash. Rashes developed in spite of the exclusion of penicillin-allergic patients and mainly after the completion of the one-week treatment. As a consequence of little previous exposure to penicillin in the Japanese population, the development of delayed rashes after this exclusion may represent first sensitization to penicillin.

What types of early gastric cancer are indicated for endoscopic ultrasonography staging of invasion depth?

AIM: To clarify the diagnostic efficacy and limitations of endoscopic ultrasonography (EUS) and the characteristics of early gastric cancers (EGCs) that are indications for EUS-based assessment of cancer invasion depth. METHODS: We retrospectively investigated the cases of 153 EGC patients who underwent conventional endoscopy (CE) and EUS (20 MHz) before treatment. RESULTS: We found that 13.7% were "inconclusive" cases with low-quality EUS images, including all nine of the cases with protruded (0-I)-type EGCs. There was no significant difference in the diagnostic accuracy between CE and EUS. Two significant independent risk factors for misdiagnosis by EUS were identified-ulcer scarring [UL(+); odds ratio (OR) = 4.49, P = 0.003] and non-indication criteria for endoscopic resection (ER) (OR = 3.02, P = 0.03). In the subgroup analysis, 23.1% of the differentiated-type cancers exhibiting SM massive invasion (SM2) invasion (submucosal invasion ≥ 500 µm) by CE were correctly diagnosed by EUS, and 23.1% of the undifferentiated-type EGCs meeting the expanded-indication criteria for ER were correctly diagnosed by EUS. CONCLUSION: There is no need to perform EUS for UL(+) EGCs or 0-I-type EGCs, but EUS may enhance the pretreatment staging of differentiated-type EGCs with SM2 invasion without UL or undifferentiated-type EGCs revealed by CE as meeting the expanded-indication criteria for ER.

Long-term outcomes and sex differences after restorative proctocolectomy in pediatric patients with ulcerative colitis.

BACKGROUND: Restorative proctocolectomy (RPC) for ulcerative colitis (UC) could result in a higher patient quality of life, avoiding frequent disease flares; however, pouch failures and pouch-related complications (PRCs) can develop. PURPOSE: No cohort studies have examined pouch failure and the differences between adult and pediatric patients or the sex differences in pediatric UC. Therefore, the pouch failure rates were compared between adults and pediatric patients, and pouch failure and PRCs in pediatric UC were evaluated. METHODS: UC patients who underwent RPC between January 1987 and June 2014 at Hyogo College of Medicine were included. Patient background characteristics, PRCs, and pouch failure were reviewed. RESULTS: A total of 1347 adult UC patients and 90 (51 boys, 39 girls) pediatric UC patients were included in the study. The cumulative rate of pouch failure at 10years after RPC was significantly higher in pediatric UC (9.5%) than in adult UC (2.1%; p<0.01). In pediatric UC, the independent risk factors for pouch failure were pouchitis (hazard ratio (HR) 19.3) and anal fistula (HR 5.5). Although a sex difference was not seen in pouch failure, an independent risk factor for PRCs was being a girl (HR 2.5). CONCLUSIONS: Pouch failure was more common in pediatric than in adult UC. PRCs after RPC were more common in girls in pediatric UC.

Morphological Characteristics of Early Gastric Neoplasms Detected After Helicobacter pylori Eradication.

BACKGROUND: Previous morphological studies indicated that the eradication of Helicobacter pylori (H. pylori) made gastric neoplasms endoscopically indistinct through the flattening and covering of tumors with a non-neoplastic epithelium (NE). AIM: To validate these alterations. METHODS: We reviewed and compared the endoscopic and histological findings of early gastric carcinomas and high-grade dysplasias resected endoscopically from H. pylori-infected and H. pylori-eradicated patients. The extent of NE covering a tumor was expressed as the histological length ratio of NE to the tumor. Tumor morphology was compared before and after therapies in patients who received H. pylori eradication treatments during the period from tumor discovery to endoscopic resection. RESULTS: NE-covered ratios were higher in the 59 tumors detected after the eradication of H. pylori than in the 152 tumors detected during the infection (median 8 vs. 0 %, respectively), whereas the frequency at which an elevated morphology and whitish discoloration of a tumor were observed was less (14 vs. 56 %, and 14 vs. 43 %, respectively). These were also independent characteristics for tumors detected after the eradication of H. pylori. Two elevated tumors showing whitish discoloration out of 16 tumors became endoscopically indistinct following H. pylori eradication treatments through the flattening of tumors and muting of the discoloration. CONCLUSION: The eradication of H. pylori promoted covering with NE, the flattening of tumors, and muting of the whitish discoloration, which may make a subset of tumors, potentially including whitish elevated neoplasms, indistinct.

Does Pre-Operative Multiple Immunosuppressive Therapy Associate with Surgical Site Infection in Surgery for Ulcerative Colitis.

BACKGROUND: Almost all surgeries for ulcerative colitis (UC) are performed under immunosuppressive conditions. Immunomodulators or biologics, with the exception of corticosteroids, do not appear to be risk factors for post-operative infectious complications. However, many patients are on multiagent immunosuppressive therapy at the time of surgery. Therefore, we evaluated the influence of pre-operative multiple immunosuppressives on the occurrence of surgical site infection (SSI) in UC. METHODS: We reviewed surveillance data from 181 patients who underwent restorative proctocolectomy between January 2012 and March 2014. The incidences of SSI and the possible risk factors among patients receiving different immunosuppressive therapies were compared and analyzed. RESULTS: The incidence of incisional (INC) SSI was 13.3% and that of organ/space (O/S) SSI was 7.2%. The number of immunosuppressives did not significantly correlate with each incidence. Total prednisolone administration ≥12,000 mg (OR 2.6) and an American Society of Anesthesiologists score ≥3 (OR 2.8) were shown to be independent risk factors for overall SSI, whereas corticosteroid use in INC SSI (OR 17.4) and severe disease (OR 5.2) and a large amount of blood loss (OR 3.9) in O/S SSI were identified as risk factors. CONCLUSION: Although a correlation between multiple immunosuppressive therapy and SSIs was not found, it is not recommended that all patients be treated with multiple immunosuppressive therapy. Treatment strategy should be applied based on the patient's condition.

Clinical Features of Refractory Pouchitis with Penetrating Lesions and the Efficacy of Infliximab Treatment for Patients with Ulcerative Colitis after Restorative Proctocolectomy.

BACKGROUND: Chronic pouchitis with penetrating anal lesions often leads to pouch failure after restorative proctocolectomy. The aim of this study was to analyze those predictors and to evaluate the effects of infliximab (IFX). METHODS: We reviewed patients' backgrounds and performed a prospective trial of IFX treatment. Possible pre-operative factors were analyzed. Efficacy was assessed by comparing the pouchitis disease activity index (PDAI) and peri-anal DAI. Long-term efficacy was assessed via the rate of pouch failure. RESULTS: A total of 41 patients with refractory pouchitis were included. Although the patients with penetrating lesions were younger than those without, neither predictive pre-operative factors nor a correlation of C-related protein levels were observed. A total of 10 patients with penetrating lesions were enrolled for IFX treatment. Although the PDAI and peri-anal DAI decreased significantly (p = 0.04 and p = 0.02, respectively), the primary non-responders during the induction of IFX were 3 patients with obvious abscesses. The 1-year cumulative pouch failure rate was 0% in patients without abscesses and 50% in patients with abscesses under IFX maintenance. CONCLUSIONS: IFX treatment for refractory pouchitis with penetrating complications appears to be effective. However, once penetrating lesions develop to abscesses, these lesions are difficult to heal.

Occurrence of colon tumors in a 16-year-old Japanese boy after hematopoietic stem cell transplantation for Diamond Blackfan anemia at age of 4: a case report.

Diamond Blackfan anemia (DBA) is a congenital pure red cell aplasia mainly caused by a mutation in ribosomal protein genes. One of the proposed mechanisms for red cell aplasia in DBA is apoptosis caused by constitutive activation of tumor suppressor TP53 protein following defective ribosome biogenesis. Because of this close relationship between ribosome biogenesis and TP53 activation, patients with DBA are considered to be cancer-prone. The association between bone marrow failure and tumor susceptibility in DBA appears paradoxical. Also, the detailed information is lacking on malignancy occurring in patients with DBA. Here, we report a case of a 16-year-old Japanese boy suffering from multiple colon tumors during the follow-up after hematopoietic stem cell transplantation for DBA at the age of 4. Well differentiated tubular adenocarcinoma was detected at the rectum 12 years after the transplantation, followed by multiple tubular adenomas of low to high grade throughout the colon. Endoscopic submucosal dissection was performed for these tumors and the lesions were completely resected. These tumors did not show diffuse and strong TP53 positivity by immunohistochemistry, suggesting that TP53 mutation was not involved in the tumorigenesis as observed in conventional colorectal cancers. Microsatellite instability test and immunohistochemical examination of ß-catenin and MLH1 proteins of these tumors showed that WNT signaling or microsatellite instability was less likely to be involved in the present tumors as observed in conventional left-sided or right-sided colon cancers, respectively. To our knowledge, this is the first case report of colon tumors associated with DBA.

Atypical symptoms and health-related quality of life of patients with asymptomatic reflux esophagitis.

BACKGROUND AND AIM: Asymptomatic reflux esophagitis (RE) is simply regarded as RE without the typical reflux symptoms, but it is unknown whether patients with asymptomatic RE have atypical symptoms. The aim of this study was to examine the clinical characteristics and health-related quality of life (HRQOL) of patients with asymptomatic RE. PATIENTS AND METHODS: Consecutive patients with RE were enrolled during January 2010 to August 2012, and of them, 41 who had taken acid-suppressing drugs were excluded, leaving 280 patients as the study group. The patients' symptoms were evaluated using a self-completed questionnaire (modified Frequency Scale for the Symptoms of gastroesophageal reflux disease [FSSG]), as well as an HRQOL questionnaire (SF-8). We defined the typical symptoms of RE as heartburn and regurgitation. Asymptomatic RE was defined if the total symptom score was 0 or the minimum (1 point) for typical reflux symptoms in the modified FSSG. RESULTS: Of the 280 RE patients, 71.8% (n = 201) were symptomatic and 28.2% (n = 79) were asymptomatic. The atypical symptom scores were significantly lower in asymptomatic RE (2.2 ± 2.2) than in symptomatic RE patients (6.9 ± 5.2) (P < 0.0001), and the HRQOL scores were significantly higher in asymptomatic RE than in symptomatic RE (P < 0.0001). Sleep was significantly less disturbed and chronic cough less frequent in asymptomatic RE than in symptomatic RE. CONCLUSION: Frequency and severity of atypical symptoms in patients with asymptomatic RE were significantly less than in patients with symptomatic RE, and the HRQOL score was significantly higher in those patients. These observations suggest a specific patient cohort that is truly unlikely to manifest symptoms.

Evaluation of discomfort during colonoscopy with conventional and ultrathin colonoscopes in ulcerative colitis patients.

BACKGROUND AND AIM: In patients with ulcerative colitis (UC), colonoscopy is an essential procedure for evaluating mucosal damage, and treatment outcomes. A new flexible ultrathin colonoscope (PCF-PQ260) has been developed to readily pass through tortuous and narrow lesions of the colon and cause minimum patient discomfort. The objective of the present study was to evaluate the comfort and performance of this new type of scope in UC patients who underwent colonoscopy for estimation of mucosal inflammation, basically without sedation. METHODS: In a prospective, single-center setting, among 107 UC patients who were to undergo colonoscopy, 84 eligible cases were randomly assigned to the new ultrathin flexible colonoscope, PCF-PQ260 (n = 42) or to a conventional colonoscope, PCF-Q260A (n = 42). Main outcome measure was patient pain level determined by visual analogue scale (VAS) with 0 = none, and 100 = extremely painful. Other outcomes were cecal intubation time, rate of complete intubation (to reach the cecum) and rate of procedural complications. RESULTS: VAS score was significantly lower in the new-scope group as compared with the conventional-scope group: mean ± SD, median (range): 19.3 ± 16.9, 14 (0-62) vs 32.0 ± 21.6, 31.8 (0-100, P = 0.005). However, cecal intubation rate (97.6%) and time (4 min) were similar in the two groups. There was no procedure-related serious complication in either group. CONCLUSION: The findings indicated that the flexible ultrathin colonoscope PCF-PQ260 has significantly better tolerability in UC patients compared to a conventional colonoscope.

Xilei san ameliorates experimental colitis in rats by selectively degrading proinflammatory mediators and promoting mucosal repair.

Xilei san (XLS), a herbal preparation widely used in China for erosive and ulcerative diseases, has been shown to be effective in ulcerative colitis (UC). The present experiments were conducted to assess its efficacy and determine its mechanism of action in a rat model that resembles human UC. The model was induced by adding 4% dextran sulfate sodium (DSS) to the rats' drinking water for 7 days. XLS was administered daily by retention enema from day 2 to day 7; the rats were sacrificed on day 8. The colon tissues were obtained for further experiments. A histological damage score and the activity of tissue myeloperoxidase were used to evaluate the severity of the colitis. The colonic cytokine levels were detected in a suspension array, and epithelial proliferation was assessed using Ki-67 immunohistochemistry. Intrarectal administration of XLS attenuated the DSS-induced colitis, as evidenced by a reduction in both the histological damage score and myeloperoxidase activity. It also decreased the levels of proinflammatory cytokines, but increased the mucosal repair-related cytokines. In addition, the epithelial Ki-67 expression was upregulated by XLS. These results suggest that XLS attenuates DSS-induced colitis by degrading proinflammatory mediators and promoting mucosal repair. XLS could be a potential topical treatment for human UC.

A randomized, double-blind, placebo-controlled study of rebamipide for gastric mucosal injury taking aspirin with or without clopidogrel.

INTRODUCTION: Antithrombotic drugs, such as low-dose aspirin (LDA) and clopidogrel, can cause upper gastrointestinal complications. AIM: The goal of the present study was to investigate whether a mucosal-protective agent, rebamipide, could prevent gastric mucosal injuries induced by LDA with or without clopidogrel in healthy subjects. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled trial was performed with 32 healthy male volunteers. Subjects were randomly assigned to a 14-day course of one of the following regimens: group A, placebo (tid) + LDA; group B, rebamipide (100 mg tid) + LDA (100 mg once-daily); group C, placebo + LDA + clopidogrel (75 mg once-daily); or group D, rebamipide + LDA + clopidogrel. The grade of gastric mucosal injuries was evaluated by esophagogastroduodenoscopy before and after dosing (on day 0 and day 14), and the grade of gastric mucosal injury was assessed according to the modified Lanza score. Subjective symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS). A rapid urease test was performed on day 0, and blood tests were performed on day 0 and day 14. RESULTS: Rebamipide significantly inhibited gastric mucosal injury induced by LDA alone or by LDA plus clopidogrel when compared with placebo in healthy subjects. GSRS score and hemoglobin level were not significantly different among the four groups. CONCLUSIONS: Rebamipide is useful for the primary prevention of gastric mucosal injury induced by LDA alone or by LDA plus clopidogrel in healthy subjects.

Prospective postsurgical capsule endoscopy in patients with Crohn's disease.

AIM: To clarify the usefulness of postsurgical capsule endoscopy (CE) in the diagnosis of recurrent small bowel lesions of Crohn's disease (CD). METHODS: This prospective study included 19 patients who underwent ileocolectomy or partial ileal resection for CD. CE was performed 2-3 wk after surgery to check for the presence/absence and severity of lesions remaining in the small bowel, and for any recurrence at the anastomosed area. CE was repeated 6-8 mo after surgery and the findings were compared with those obtained shortly after surgery. The Lewis score (LS) was used to evaluate any inflammatory changes of the small bowel. RESULTS: One patient was excluded from analysis because of insufficient endoscopy data at the initial CE. The total LS shortly after surgery was 428.3 on average (median, 174; range, 8-4264), and was ≥ 135 (active stage) in 78% (14 of 18) of the patients. When the remaining unresected small bowel was divided into 3 equal portions according to the transition time (proximal, middle, and distal tertiles), the mean LS was 286.6, 83.0, and 146.7, respectively, without any significant difference. Ulcerous lesions in the anastomosed area were observed in 83% of all patients. In 38% of the 13 patients who could undergo CE again after 6-8 mo, the total LS was higher by ≥ 100 than that recorded shortly after surgery, thus indicating a diagnosis of endoscopic progressive recurrence. CONCLUSION: Our pilot study suggests that CE can be used to objectively evaluate the postoperative recurrence of small bowel lesions after surgery for CD.

Do endoscopic features suggesting eosinophilic esophagitis represent histological eosinophilia?

BACKGROUND: Esophageal linear furrows, corrugated rings, and/or white exudates are often seen in patients with eosinophilic esophagitis (EoE); however, whether these are specific to EoE remains unclear. Endoscopic surveillance of these features was conducted to determine whether these represent esophageal eosinophilia, which is essential for the diagnosis of EoE. PATIENTS AND METHODS: Two thousand seven hundred and sixty-three patients were enrolled consecutively. Target biopsy was carried out when the above features were seen. Histological eosinophilia was defined as 24 or more eosinophils per high-power field (HPF). Associations between features and eosinophilia were analyzed statistically. RESULTS: Two thousand five hundred and forty-five patients completed the study. Linear furrows, corrugated rings and white exudates were seen in 24, 15 and 45 patients, respectively. These findings somewhat overlapped. Among 58 biopsied patients withany of the above features, these features represented eosinophilia in 14% (3/21), 23% (3/13), and 5% (2/43), respectively. None of the 199 patients who received biopsy for other features had eosinophilia. Two of five eosinophilia patients were diagnosed with EoE. Multiple comparisons revealed that eosinophil counts in linear furrows and corrugated rings but not white exudates were significantly greater than those in other features (12, 9, 1, and <1 eosinophils/HPF on average, respectively). CONCLUSIONS: An endoscopic feature suggesting EoE does not always represent esophageal eosinophilia and is non-specific for EoE, although it reminds endoscopists of the presence of EoE. The diagnostic utility of linear furrows or corrugated rings for esophageal eosinophilia is superior to that of white exudates.

Down-regulation of claudin-18 is associated with the proliferative and invasive potential of gastric cancer at the invasive front.

BACKGROUND: Claudins are known as tight junction proteins, and their expression pattern in gastric cancer is still controversial. The relationship between the expression patterns of tight junction proteins and tumor proliferation in early gastric cancer is still far from clear. AIMS: To investigate the expression patterns of claudin-18 and Ki-67 in early gastric cancer at the invasive front and surrounding normal gastric mucosa and to investigate the biological function of claudin-18 in the proliferation and invasion of cancer cells. METHODS: Seventy-five early gastric cancer lesions removed via endoscopic mucosal resection or endoscopic submucosal resection were evaluated. All gastric cancer lesions were diagnosed as differentiated adenocarcinoma using the Japanese Classification of Gastric Carcinoma. To assess epithelial proliferation, immunostaining with Ki-67 was performed, and the labeling index was calculated. To assess the expression of epithelial tight junction proteins, immunofluorescent staining of claudin-18 was performed. The immunoreactivity of claudin-18 was graded according to the number of stained cells. Correlation analysis was performed by Spearman's rank correlation coefficient. Transfection of claudin-18 small interfering RNA (siRNA) was accomplished in MKN74, a claudin-18-positive gastric cancer cell line, to investigate the effect of claudin-18 on proliferation and invasion of cancer cells. RESULTS: Claudin-18 was significantly down-regulated in gastric cancer compared to surrounding gastric normal mucosa or intestinal metaplasia. The Ki-67 labeling index of gastric cancer at the invasive front was inversely correlated with the claudin-18 level, but that at the mucosal lesion was not correlated. Claudin-18 knockdown significantly promoted the proliferation of MKN74 compared with control siRNA-transfected cells. MKN74 invasion increased significantly with claudin-18 siRNA transfection compared with control siRNA transfection. CONCLUSIONS: Down-regulation of claudin-18 is associated with the proliferative potential at the invasive front of gastric cancer, suggesting that it has a pivotal role in gastric cancer progression.

Association between obesity and Barrett's esophagus in a Japanese population: a hospital-based, cross-sectional study.

BACKGROUND: The association between obesity and Barrett's esophagus (BE) in the Japanese population remains unclear. The prevalence of BE and its associated risk factors was examined. METHODS: A cross-sectional study of 1581 consecutive individuals who underwent upper gastrointestinal endoscopy was conducted. The prevalence of endoscopically suspected BE (ESBE) was evaluated. Obesity was evaluated by body mass index (BMI, ≥ 25 kg/m2) and waist circumference (WC) (males, ≥ 85 cm; females, ≥ 90 cm). Because endoscopic diagnosis of ultra-short ESBE (<1 cm in extent) is difficult and highly unreliable, this type of ESBE was excluded from the study. RESULTS: In proton pump inhibitor (PPI) non-users, the prevalence of ESBE ≥ 1 cm was 5.6%. In univariate analysis, male sex and reflux esophagitis (RE) were significantly associated with BE, but BMI, WC, and reflux symptoms were not. In multivariate logistic regression analysis, only RE (odds ratio [OR] = 3.48, 95% confidence interval [CI] 1.89-6.41, p < 0.0001) was an independent risk factor for BE; obesity and the other factors were not. In contrast, RE (OR 5.67, p = 0.0004) and large WC (OR 5.09, p = 0.0005) were significant risk factors for ESBE ≥ 1 cm in PPI users. Only male sex, but not obesity or the other risk factors, was associated with an increased risk of RE in patients not taking PPIs. CONCLUSIONS: RE, but not obesity, may have an independent association with the risk of ESBE in the Japanese population. Furthermore, obesity measures were not independent risks for RE. Interestingly, PPI-refractory RE and large WC were risk factors for ESBE ≥1 cm in patients taking PPIs.

The incidence of "silent" free air and aspiration pneumonia detected by CT after gastric endoscopic submucosal dissection.

BACKGROUND: Although endoscopic submucosal dissection (ESD) is feasible as a treatment for early gastric cancer, it requires great skill to perform and may place patients at increased risk of a number of complications, including perforation and aspiration pneumonia. OBJECTIVE: To investigate the incidence of "silent" free air without endoscopic perforation and aspiration pneumonia detected by CT after ESD and risk factors for the development of these 2 conditions. DESIGN: Prospective cohort study. SETTING: Single academic center. PATIENTS: This study involved 87 patients with a total of 91 malignancies. INTERVENTION: All patients underwent chest and abdominal CT and blood biochemistry analysis before and 1 day after ESD. MAIN OUTCOME MEASUREMENTS: The incidence of silent free air and aspiration pneumonia after ESD and the related risk factors. RESULTS: Silent free air was identified in 37.3% of patients without perforation. Tumor location (the upper portion of the stomach), the presence of a damaged muscular layer during ESD, and procedure time, but not specimen size, were significantly associated with silent free air (P = .006, P = .04, P = .02, and P = .53, respectively). According to the receiver-operating characteristic analysis, the resulting cutoff value of the procedure time for silent free air was 105 minutes (67.7% sensitivity, 65.4% specificity). Only procedure time (≥ 105 minutes) was an independent predictor of silent free air development (odds ratio 3.23; 95% confidence interval, 1.21-8.64; P = .02). On the other hand, aspiration pneumonia was seen in 6.6% of patients. Silent free air and aspiration pneumonia did not affect hospitalization. LIMITATIONS: Single center and small number of patients. CONCLUSIONS: Silent free air is frequently observed after ESD, and longer procedure time (≥ 105 minutes) was an independent risk factor for silent free air. However, silent free air and aspiration pneumonia detected by CT are not associated with clinically significant complications.