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BACKGROUND AND AIM This study aimed to reveal the timing of bleeding and thromboembolism associated with endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). METHODS We retrospectively reviewed 10,320 patients who underwent ESD for EGC during November 2013-October 2016. We evaluated overall bleeding rates and their inter-group differences. Factors associated with early/late (cut-off 5 days) bleeding and thromboembolism frequency and its association with the intake of antithrombotic agents were investigated. RESULTS Overall, the post-ESD bleeding rate was 4.7% (489/10 320); the median time to post-ESD bleeding was 4 days. The post-ESD bleeding rates were 3.2%, 8.7%, 15.5%, and 29.9% in those not taking antithrombotic agents, those taking antiplatelet agents, those taking anticoagulants (ACs), and those taking antiplatelet agents and ACs. Warfarin (odds ratio [OR], 9.16), direct oral ACs (OR, 4.16), chronic kidney disease with hemodialysis (OR, 2.93), thienopyridine (OR, 2.25), aspirin (OR, 1.66), tumor size >30 mm (OR, 1.86), multiple tumors' resection (OR, 1.54), and tumor in the lower third of the stomach (OR, 1.40) were independent risk factors for early bleeding. The independent risk factors for late bleeding were direct oral ACs (OR, 7.42), chronic kidney disease with hemodialysis (OR, 4.99), warfarin (OR, 3.90), thienopyridine (OR, 3.09), liver cirrhosis (OR, 2.43), cilostazol (OR, 1.93), aspirin (OR, 1.92), ischemic heart disease (OR, 1.77), and male sex (OR, 1.65). There were three (0.03%) thromboembolic events (cerebral infarction = 2, transient ischemic attack = 1). CONCLUSION We revealed the timing of bleeding and risk factors for early/late bleeding and showed the thromboembolism frequency associated with ESD for EGC.

OBJECTIVES Duodenal endoscopic submucosal dissection (ESD) for superficial non-ampullary duodenal epithelial tumors has a significant incidence rate of delayed perforation. Although several methods have been proposed to prevent delayed perforation, the most appropriate methods remain unclear. Currently, there is no appropriate animal model to validate methods for preventing duodenal delayed perforation. This study aimed to establish an in-vivo porcine delayed perforation model after duodenal submucosal dissection. METHODS Two porcine models underwent either ESD or surgical submucosal dissection. In the surgical dissection model, an inverted duodenal mucosa was resected with electrosurgical energy. In the ESD model, a gauze was placed behind the duodenum with grasped transverse part to improve endoscopic maneuverability. The mucosal defects after dissection were treated with omental coverage without suture in both models. All models were euthanized 0-5 days after procedure. Body weight; resection size; procedure dissection time; presence of intraoperative perforation and delayed perforation; and adhesion score were assessed. RESULTS There were no significant differences in body weight and adhesion score between the two models. Resection size was significantly larger in the surgical dissection models than in the ESD models (19 mm vs 14.3 mm, P

Objective Bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is a frequent adverse event after ESD. We aimed to develop and externally validate a clinically useful prediction model (BEST-J score: Bleeding after ESD Trend from Japan) for bleeding after ESD for EGC. Design This retrospective study enrolled patients who underwent ESD for EGC. Patients in the derivation cohort (n=8291) were recruited from 25 institutions, and patients in the external validation cohort (n=2029) were recruited from eight institutions in other areas. In the derivation cohort, weighted points were assigned to predictors of bleeding determined in the multivariate logistic regression analysis and a prediction model was established. External validation of the model was conducted to analyse discrimination and calibration. Results A prediction model comprised 10 variables (warfarin, direct oral anticoagulant, chronic kidney disease with haemodialysis, P2Y12 receptor antagonist, aspirin, cilostazol, tumour size >30 mm, lower-third in tumour location, presence of multiple tumours and interruption of each kind of antithrombotic agents). The rates of bleeding after ESD at low-risk (0 to 1 points), intermediate-risk (2 points), high-risk (3 to 4 points) and very high-risk (≥5 points) were 2.8%, 6.1%, 11.4% and 29.7%, respectively. In the external validation cohort, the model showed moderately good discrimination, with a c-statistic of 0.70 (95% CI, 0.64 to 0.76), and good calibration (calibration-in-the-large, 0.05; calibration slope, 1.01). Conclusions In this nationwide multicentre study, we derived and externally validated a prediction model for bleeding after ESD. This model may be a good clinical decision-making support tool for ESD in patients with EGC.

When a lesion does not meet the curative criteria of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC), referred to as non-curative resection or curability C-2 in the guidelines, an additional surgery is the standard therapy because of the risk of lymph node metastasis (LNM). This study aimed to identify high-risk patients for recurrence after additional surgery for curability C-2 ESD of EGC. This multicenter retrospective cohort study enrolled 1064 patients who underwent additional surgery after curability C-2 ESD for EGC. We evaluated the recurrence rate and the risk factors for recurrence after additional surgery in these patients. The 5-year recurrence rate after additional surgery was 1.3%. Multivariate Cox analysis revealed that the independent risk factors for recurrence after additional surgery were LNM (hazard ratio [HR] 32.47; p

Background and aims Recurrence of ampullary neoplasms after endoscopic papillectomy (EP) has not been well elucidated. This study aimed to clarify the predictive factors for recurrences after EP. We also aimed to investigate the retreatment of the recurrent lesions and their outcomes. Methods This multicenter, retrospective cohort study included 96 patients with ampullary neoplasms who underwent EP at four tertiary centers between January 2000 and October 2018. Results The pathological diagnoses of resected specimens confirmed adenoma in 62 and adenocarcinoma in 34 patients (six Tis, 24 T1a, three T1b, one inconclusive). Complete resection was confirmed for 79 patients (82.3%). Recurrent lesions were observed in 13 patients (13.5%) during a median follow-up of 3 months (1-36 months) after EP. The predictive factors of recurrence were piecemeal resection, and non-negative horizontal or vertical margin in univariate analysis. Non-negative vertical margin was the only independent predictive factor of recurrence in the multivariate analysis. The recurrent lesions were treated endoscopically in 11 patients. Recurrence after the endoscopic retreatments was observed in one patient. Conclusions Complete resection with negative vertical margin is important factor in preventing the recurrence of ampullary neoplasms after EP. Endoscopic retreatments are also feasible for recurrent lesions.

Background: Esophageal metastasis of renal cell carcinoma (RCC) is extremely rare. We have described herein a case of a 59-year-old man with esophageal metastasis of RCC that was endoscopically resected. Case presentation: The case was a 59-year-old man who had undergone left nephrectomy for renal clear cell carcinoma 17 years ago and splenectomy for splenic metastasis 3 years ago. Esophagogastroduodenoscopy (EGD) performed 9 years ago revealed a small reddish elevated lesion with a smooth surface in the middle esophagus; this lesion increased in size 4 years ago. However, no biopsy was performed. The lesion continued to grow in size and was found to have become nodular during the present observation. Biopsy revealed clear cell carcinoma. Endoscopic ultrasound (EUS) revealed that the lesion had not invaded the submucosa, and contrast-enhanced computed tomog-raphy did not reveal any other metastasis. The lesion was successfully removed en bloc via endoscopic submucosal dissection (ESD). Pathologically, the tumor was detected in the subepithelium with focal infiltration of the muscularis mucosa. It consisted of monotonous cells with small nuclei and a clear cytoplasm. Immunohistological findings indi-cated that the tumor was a metastasis of RCC. The lateral and vertical margins were noted to be free. Conclusions: We have presented herein a case of esophageal metastasis of RCC that had progressed over 9 years and was then resected en bloc through endoscopic submucosal dissection., BMC Gastroenterology, 21, art. no. 348; 2021

Introduction:As the aging of people in a society advances, the number of elderly patients older than 80 years in Japan with gastric cancer continues to increase. Although delayed ulcer bleeding is a major adverse event after endoscopic submucosal dissection (ESD), little is known about characteristic risk factors for bleeding in elderly patients undergoing ESD. This study aimed to evaluate risk factors for delayed bleeding after ESD for gastric cancer in elderly patients older than 80 years., Methods:We retrospectively evaluated the incidence of delayed bleeding after ESD in 10,320 patients with early-stage gastric cancer resected by ESD between November 2013 and January 2016 at 33 Japanese institutions and investigated risk factors for delayed bleeding in elderly patients older than 80 years., Results:The incidence of delayed bleeding in elderly patients older than 80 years was 5.7% (95% confidence interval [CI]: 4.6%-6.9%, 95/1,675), which was significantly higher than that in nonelderly (older than 20 years and younger than 80 years) patients (4.5%, 4.1%-5.0%, 393/8,645). Predictive factors for ESD-associated bleeding differed between nonelderly and elderly patients. On multivariate analysis of predictive factors at the time of treatment, risk factors in elderly patients were hemodialysis (odds ratio: 4.591, 95% CI: 2.056-10.248, P < 0.001) and warfarin use (odds ratio: 4.783, 95% CI: 1.689-13.540, P = 0.003)., Discussion:This multicenter study found that the incidence of delayed bleeding after ESD in Japanese patients older than 80 years was high, especially in patients receiving hemodialysis and taking warfarin. Management of ESD to prevent delayed bleeding requires particular care in patients older than 80 years.

Sufficient information is not available on the extent to which lymph node metastasis (LNM) and prognosis are affected by submucosal manipulation during endoscopic submucosal dissection (ESD) for submucosal invasive gastric cancer (SMGC). We aimed to identify the effects of submucosal manipulation during ESD on LNM and prognosis in patients with SMGC. From 19 institutions in Japan, 2526 patients who failed to meet the current curative criteria for ESD between 2000 and 2011 were recruited. After exclusion, 1969 patients were remained. Based on the treatment strategy after ESD, 1064 patients underwent additional radical surgery. A total of 890 of 1064 patients with SMGC, LNM and cancer recurrence, and prognosis were retrospectively reviewed. The median follow-up duration was 67 months. A total of 214 patients had SM1 (depth of tumor invasion from the muscularis mucosae

Background/Aims: The outcomes of salvage surgery for recurrence after non-curative endoscopic submucosal dissection (ESD) without additional radical surgery for early gastric cancer (EGC) remain unclear. We determined the recurrence patterns and outcomes of salvage surgery in such cases using data from a multicenter, retrospective study. Methods: Of 15,785 patients who underwent ESD for EGC at 19 participating institutions between January 2000 and August 2011, 1,969 failed to meet the current curative criteria after ESD. Of these, 905 patients received no additional treatment. We evaluated the pattern of recurrence, clinical course after salvage surgery, and long-term survival rate for these patients. Results: Over a median 64-month follow-up period, recurrence was detected in 27 patients. Two patients with missing data were excluded. Three, seven, and 15 (60%) patients showed intragastric relapse, regional lymph node metastasis, and distant metastasis, respectively. The first line of treatment for recurrence in 1, 7, 6, and 11 patients was endoscopic treatment, salvage surgery, chemotherapy, and best supportive care, respectively. One patient survived without recurrence for 31 months after salvage surgery, one died of acute myocardial infarction 1 month after salvage surgery, and 5 showed recurrence at 0, 2, 3, 5, and 30 months after salvage surgery and eventually succumbed to the disease. The median survival times for all patients with recurrence and the 7 patients who underwent salvage surgery were 5 months after recurrence and 7 months after salvage surgery, respectively. Conclusion: The survival rate after salvage surgery for recurrence after non-curative ESD without additional radical surgery for EGC is quite low, with distant metastasis being the most common recurrence pattern in these cases.

Background: Refractory gastroesophageal reflux disease (GERD) may deteriorate patient quality of life (QOL) despite proton pump inhibitor (PPI) therapy. Material/Methods: Nineteen Japanese institutions were surveyed to determine the clinical characteristics and QOL of patients with refractory GERD. Those patients treated with a conventional PPI were switched to 20 mg esomeprazole for 4 weeks. Symptoms and QOL were assessed using Global Overall Symptom and Gastrointestinal Symptom Rating Scale (GSRS) questionnaires at baseline and at 2 and/or 4 weeks of esomeprazole treatment. Results: Of 120 patients who completed the survey, 58 (48.3%) had refractory GERD. Of these, 69.0% were aged >65 years, 79.3% were prescribed a PPI at a standard or high dose, and 22.4% were prescribed a PPI together with another drug. After switching to esomeprazole, patients reported significant improvements in heartburn, acid regurgitation, and excessive belching at 2 weeks using a symptom diary, as well as the total score, reflux, ab dominal pain, and indigestion, which were assessed using the GSRS at 4 weeks. Conclusions: About half of Japanese patients with GERD may be refractory to conventional PPIs. Their reflux-related symp toms are often severe and may impair QOL. Switching to esomeprazole could be used to improve their symptoms and QOL., Medical Science Monitor, 21, pp.4111-4121; 2015

Background and aims A high serum level of saturated free fatty acids (FFAs) is associated with the development of nonalcoholic fatty liver disease (NAFLD). X-box binding protein-1 (XBP-1) is activated by FFA treatment upon splicing. XBP-1 is a transcription factor induced by the endoplasmic reticulum (ER) stress sensor endoribonuclease inositol-requiring enzyme 1 alpha (IRE1α). However, the role of XBP-1 in NAFLD remains relatively unexplored. Toyocamycin was recently reported to attenuate the activation of XBP-1, possibly by inducing a conformational change in IRE1α. In this study, we examined the effect of toyocamycin on hepatocyte lipoapoptosis and steatosis. We also explored the effects of toyocamycin in a mouse model of NAFLD. Methods Huh-7 cells and isolated rat primary hepatocytes were treated with palmitic acid (PA), which is a saturated FFA, in the presence or absence of toyocamycin. In addition, male C57BL/6J mice were fed a diet rich in saturated fat, fructose, and cholesterol (FFC) for 4 months, after which the effect of toyocamycin was assessed. Results Toyocamycin attenuated FFA-induced steatosis. It also significantly reduced PA-induced hepatocyte lipoapoptosis. In addition, toyocamycin reduced the expression of cytosine-cytosine- adenosine-adenosine-thymidine enhancer-binding protein homologous protein (CHOP), which is a key player in ER stress-mediated apoptosis, as well as its downstream cell death modulator, death receptor 5. In the in vivo study, toyocamycin ameliorated the liver injury caused by FFC-induced NAFLD. It also reduced hepatic steatosis and the expression of lipogenic genes. Conclusions The data we obtained suggest that toyocamycin attenuates hepatocyte lipogenesis and ameliorates NAFLD in vivo and may therefore be beneficial in the treatment of NAFLD in humans., PLOS ONE, 12(3), e0170591; 2017

There is a lack of data regarding the long-term outcomes of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) without curative resection, and the relationship of these outcomes with hospital volumes remains unclear. This study evaluated long-term outcomes of patients who underwent ESD for EGC without curative resection according to hospital volumes in Japan. This multicenter retrospective study evaluated 1,969 patients who did not meet the criteria of the Japanese Gastric Cancer Association for curative resection between January 2000 and August 2011. Hospitals were classified according to the annual number of ESD procedures: low- and medium-volume group (LMVG), high-volume group (HVG), and very high-volume group (VHVG). Clinicopathological features, overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were compared across groups after a generalized propensity score matching analysis. In 495 pairs of generalized propensity score-matched patients, the 5-year OS, DSS, and RFS rates were 81.5%, 97.9%, and 97.6% for LMVG; 86.9%, 98.2%, and 97.0% for HVG; and 85.4%, 98.5%, and 97.6% for VHVG, respectively. The 5-year DSS and RFS rates did not significantly differ among the three groups. However, 5-year OS was significantly worse in the LMVG than in the HVG and VHVG (P

Background: Maintenance of mucosal healing is recommended during the treatment of ulcerative colitis (UC). However, symptoms of UC often do not reflect mucosal disease activity. Fecal markers such as calprotectin, lactoferrin, and hemoglobin have been reported to correlate well with the Mayo endoscopic subscore (MES) and are being considered alternative monitoring tools in endoscopy. Ulcerative Colitis Endoscopic Index of Severity (UCEIS) is a new and more detailed endoscopic scoring system compared to MES. Furthermore, magnifying endoscopic stratification (ME) based on alterations in the mucosal surface pit patterns is noted in UC. However, the association between fecal markers and UCIES and magnifying endoscopy is relatively unexplored. Summary: This study investigated the association between the aforementioned fecal markers and MES, UCEIS, and ME in patients with UC in clinical remission. This prospective study included 60 patients with UC in clinical remission who underwent colonoscopy at the Nagasaki University Hospital between June 2015 and November 2016. A significant correlation was observed between MES and all fecal markers. Notably, the fecal markers correlated well with UCEIS (calprotectin Spearman’s correlation coefficient [r] = 0.54, p < 0.0001; lactoferrin r = 0.56, p < 0.0001; and hemoglobin r = 0.43, p < 0.001). Furthermore, ME findings correlated significantly with calprotectin (r = 0.50, p = 0.0002) and lactoferrin (r = 0.46, p = 0.0006) levels and slightly with hemoglobin (r = 0.28, p = 0.043) levels. Moreover, each cutoff level of fecal calprotectin, lactoferrin, or hemoglobin had a high sensitivity and specificity for the detection of MES = 0, UCEIS = 0, ME = A, for predicting mucosa healing. Key Messages: Fecal markers correlated not only with MES but also with UCEIS and ME and should be useful for monitoring patients with UC in clinical remission.

Adult T-cell Leukemia/Lymphoma (ATL) is a rare disease, related to human T-lymphotropic virus-1 (HTLV-1) and presented mainly in adulthood by generalised lymphadenopathy, hepatosplenomegaly, skin lesions and hypercalcaemia, with rare gastrointestinal and/or oral manifestations. We reported this case to raise awareness and demonstrate the therapeutic challenges of this rare disease. A 49-year-old Japanese female presented with skin papules on both forearms, painful mouth ulcers and multiple neck swellings since early February 2017. Initial clinical examination and laboratory investigations were misleading and her condition was diagnosed as candidiasis. Because of un-improvement of the case, a screening upper endoscopy was requested 2 months later and revealed characteristic oropharyngeal ulcers which were biopsied, and its pathologic examination confirmed smouldering type ATL. This case report should raise awareness of doctors and endoscopists about this disease especially in HTLV-1 endemic areas to avoid late diagnosis and help achieve earlier therapeutic decisions., ecancermedicalscience, 12, 801; 2018

Background and aim: pancreatic juice cytology (PJC) is an important predictor of malignant intraductal papillary mucinous neoplasm (IPMN). This study aimed to determine the role of PJC for the prediction of malignant IPMN (intraductal papillary mucinous cancer [IPMC]). Methods: medical records of IPMN patients who underwent surgery between 2012 and 2016 at the Nagasaki University Hospital were reviewed. Patients who underwent preoperative PJC were classified as high risk stigmata (HRS), worrisome features (WF) and no-criteria, based on imaging criteria. PJC class III or higher was considered as positive and only invasive IPMN was defined as IPMC. PJC was validated in each group with regard to sensitivity, specificity, accuracy with the corresponding 95% confidence intervals (95% CI) and area under receiver operating curve (AUROC) analysis. A p-value of < 0.05 was considered as statistically significant. Results: preoperative pancreatic juice was obtained in 33/52 IPMN patients; only patients with adequate aspirate for cytology (n = 29) were included. In the HRS group (n = 9), 4/6 non-IPMC had a negative PJC and 3/3 IPMC had a positive PJC. In the WF group (n = 17), 9/11 non-IPMC had a negative PJC and 3/6 IPMC had a positive PJC. Adding PJC to imaging results improved the AUROCs of HRS and WF from 0.63 and 0.62 to 0.83 and 0.66, respectively. PJC was negative in all no-criteria cases (n = 3; one IPMC and two non-IPMC). In all 29 patients, PJC sensitivity was 60% (95% CI: 26%-88%), specificity was 79% (95% CI: 54%-94%), accuracy was 72% (95% CI: 63%-89%) and the AUROC was 0.69 (p = 0.03). Conclusion: PJC is a statistically significant IPMC predictor that can improve the validity of imaging for IPMC prediction.

Mohammed Tag-Adeen,1,2 Ahlam Mohamed Sabra,1 Yuko Akazawa,2 Ken Ohnita,2 Kazuhiko Nakao2 1Department of Internal Medicine, Qena School of Medicine, South Valley University, Qena, Egypt; 2Department of Gastroenterology and Hepatology, Nagasaki School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan Background: Liver fibrosis is the most important prognostic factor in chronic hepatitis C virus (HCV) patients, and Egypt shows the highest worldwide HCV prevalence with genotype-4 predominance. The aim of this study was to investigate the degree of liver stiffness measurement (LSM) improvement after successful HCV eradication.Patients and methods: The study included 84 chronic HCV Egyptian patients, and was conducted at Qena University Hospital from November 1, 2015 till October 31, 2016. LSM was obtained by FibroScan® before starting direct acting antiviral (DAA) treatment and after achieving sustained virologic response-24 (SVR-24). Based on baseline LSM, patients were stratified into F0–F1, F2, F3 and F4 groups (METAVIR). LSM and laboratory data after achieving SVR-24 was compared with that before starting therapy in each fibrosis group (F0-F4), p-value

Background 5-Aminolevulinic acid is a precursor of photosensitizing protoporphyrin IX and has been applied for photodynamic diagnosis of brain and bladder tumors with few side effects. Although most upper gastrointestinal tumors can be detected during photodynamic diagnosis, some tumors containing signet-ring cells cannot be visualized. Here, we aimed to assess whether proteins involved in the absorbance, activation, and turnover of protoporphyrin IX altered the fluorescence signal in gastric cancer. Methods Aminolevulinic acid-mediated photodynamic diagnosis was performed in 23 lesions from 20 patients using an endoscope equipped with a blue laser light that caused red fluorescence emission of photosensitizing protoporphyrin IX. Red fluorescence signal and intensity was assessed during photodynamic diagnosis procedures. Lesions were resected by endoscopic and/or laparoscopic surgery, and specimens were immunostained and assessed for the expression of ATP-binding cassette sub-family G member 2, oligopeptide transporter-1, and coproporphyrinogen oxidase. Results Photodynamic diagnosis was negative in four cases (17.4%). Three cases of photodynamic diagnosis-negative lesions were signet-ring cell carcinomas, and only one case was differentiated adenocarcinoma (intestinal type). Twenty intestinal type, photodynamic diagnosis-positive lesions showed high expression of coproporphyrinogen oxidase, whereas signet-ring cell carcinomas were all negative. Oligopeptide transporter-1 immunoreactivity was significantly higher in tumors of intestinal type. ATP-binding cassette sub-family G member 2 expression tended to be higher in luminal surface tumors than in intestinal type tumors. Conclusion Aminolevulinic acid-mediated photodynamic diagnosis provided good detection of upper gastrointestinal tumors of intestinal type but not diffuse type tumors, such as signet-ring cell carcinomas, possibly owing to coproporphyrinogen oxidase expression.

Esophageal achalasia is a benign esophageal motility disorder resulting from an impaired relaxation of the lower esophageal sphincter. The principles of treatment involve disruption of the sphincter at the esophagogastric junction. Treatment techniques include balloon dilatation, botulinum toxin injection, and surgical myotomy. In 2008, per-oral endoscopic myotomy (POEM) was introduced by Inoue et al. as an endoscopic myotomy with no skin incision. The procedure has been well accepted and widely applied owing to its minimal invasiveness and high cure rates. Moreover, there have been discussions on wider indications for POEM and new technical developments have been reported. The present article reviews the historical background and present status of POEM, as well as future prospects for its application in the treatment of esophageal achalasia.

Endoscopic submucosal dissection (ESD) enables the curative resection of early gastric cancer (EGC); however, little information is available on the long-term outcomes of ESD. This study was conducted to clarify the clinical outcomes of a large number of patients with EGC who underwent ESD. The early outcomes were assessed in 1,209 patients and the long-term outcomes were assessed in 300 patients at a follow-up >5 years after the ESD procedure. The overall survival rates were compared between indication and expanded-indication groups, and between the patients who did or did not undergo additional surgery in an out-of-indication group. Overall survival rates were also compared among different age groups. In total, 617 lesions were classed as the indication group, 507 as the expanded-indication group and 208 as the out-of-indication group. Curative resection rates were 96.6% and 91.5% in the indication and expanded-indication groups, respectively. In terms of the long-term outcomes, 20 of the 146 patients in the indication group, 15 of the 105 patients in the expanded-indication group and one of the 23 patients who underwent additional surgery in the out-of-indication group succumbed due to causes other than gastric cancer. Among the 26 patients who did not undergo additional surgery in the out-of-indication group, 10 mortalities occurred, including one due to gastric cancer. The five-year survival rates were not significantly different between the indication and expanded-indication groups. In the out-of-indication group, the five-year survival rate for the patients who did not undergo additional surgery (65.0%) was significantly lower than that for those who did undergo additional surgery (100%) (P80 years (67.1%) was significantly lower than that of the younger patients (, Experimental and Therapeutic Medicine, 7(3), pp.594-598; 2014

Endoscopic diagnostics of early squamous cell carcinoma (SCC) in the laryngo-esophageal region have dramatically improved together with development of less invasive endoscopic treatment. It is essential for gastrointestinal endoscopists to detect lesions when they are still endoscopically treatable, especially in this region since surgical approach can still be extremely invasive. Pioneers have found some notable fundamental alterations in early SCC and created several classifications. Inoue [Dig Endosc 2001;13(suppl): 40-41] proposed the intrapapillary capillary (IPCL) classification, which focused on the microvascular change of the mucosal surface. One of the significances of this classification is that it clearly distinguished the lesions that require further pathological evaluation by categorizing the diameter change of the IPCLs. On the other hand, Arima et al. [Esophagus 2005;2:191-197] advocated the alteration of microvessels as well as change of the vascular arrangement in the area. Most recently, the Japan Esophageal Society constructed a new classification uniting these two exemplary classifications as the 'Japanese Classification of Magnifying Endoscopy for Early Squamous Cell Carcinoma'. This classification was intended to be simple and easily applicable in general clinical practice. Brownish color change between the IPCLs has reported to be one of the useful findings in distinguishing early SCC from benign changes such as inflammatory change and low-grade intraepithelial neoplasia. Nevertheless, the exact cause of this phenomenon remains unclear. We recently examined the association of color change with hemoglobin (Hb) in cancer tissue, since NBI exclusively detects the wavelength of Hb in superficial vessels in the gastrointestinal tract. This review article also describes our examination of a distinct finding in esophageal cancer, namely, 'background coloration'., Digestion, 89(1), pp.6-11; 2014

Background: Adipocytokines are associated with energy homeostasis and mediate various immune responses and inflammatory processes. Vaspin is a novel adipocytokine that is thought to exhibit anti-inflammatory effects. Aim: We aimed to evaluate serum vaspin levels in inflammatory bowel disease (IBD) and determine its possible associations with the course and to clarify its intestinal localization. Methods: Serum samples were obtained from patients with Crohn's disease (CD; n = 30) and ulcerative colitis (UC; n = 33) and from healthy volunteers (controls; n = 26). Enzyme-linked immunosorbent assays were performed for all patients. Vaspin immunohistochemical staining was performed for intestines affected with IBD. Results: Serum vaspin concentrations were significantly higher in patients with UC than in patients with CD and controls (422.9 ± 361.9 vs. 163.4 ± 116.2 vs. 147.5 ± 89.4 pg/mL, respectively; P < 0.01). There was no difference in the serum vaspin concentrations between the patients with CD and controls. There was also no difference in the serum vaspin concentrations between the patients with active IBD and those with inactive IBD. However, the serum vaspin concentrations of most patients with UC increased after remission induction. Vaspin was expressed in the adipocytes of the mesenteric adipose tissues but not in the epithelial or inflammatory cells of large intestines of the patients with IBD. Conclusions: Serum vaspin concentrations are elevated in patients with UC and increase further after remission induction, suggesting that vaspin may aid the auxiliary diagnosis of UC and may be useful for assessing disease activity in patients., Digestive Diseases and Sciences, 59(2), pp.315-321; 2014

Background: There are few reports of the efficacy of adalimumab (ADA) for clinical remission and preventing postoperative recurrence in Crohn's disease (CD) in Asian real practice settings. We conducted a Japanese multicenter retrospective observational study. Methods: We evaluated patients with CD who were treated with ADA at 11 medical institutions in Japan to investigate the clinical efficacy of remission up to 52 weeks and the associated factors to achieve remission with a CD Activity Index (CDAI) < 150. The effects of preventing postoperative recurrence were also evaluated. Results: In 62 patients, the remission rates were 33.9, 74.2, 75.8, 77.4, and 66.1 % at 0, 4, 12, 26, and 52 weeks, respectively. Although 10 patients discontinued treatment due to primary nonresponse, secondary nonresponse, or adverse events, the ongoing treatment rate at 52 weeks was 83.9 %. Comparison of remission and non-remission on univariate analysis identified colonic type and baseline CDAI value as significant associated factors (P < 0.05). In 16 patients who received ADA to prevent postoperative recurrence, the clinical remission maintenance rate was 93.8 % and the mucosal healing rate was 64.3 % during a mean postoperative follow-up period of 32.3 months. Conclusions: ADA effectively induced remission and prevented postoperative recurrence in patients with CD in a real practice setting., BMC Gastroenterology, 16, 82; 2016

A 37-year-old woman was evaluated at our hospital for a treatment-resistant proctosigmoiditis. Fifteen years previously, ulcerative colitis was suspected and she was cured by steroid therapy. Colonoscopy revealed multiple sessile polyps covered with white exudate from the rectum to the sigmoid colon. Histopathological examination revealed a mucosal surface cover of granulation tissue. Based on these findings, cap polyposis was diagnosed. She underwent Helicobacter pylori eradication therapy, and at 1 month after therapy, her symptoms had improved. We present a case of cap polyposis relapsing 15 years after remission with steroid therapy, and that was improved by H. pylori eradication therapy.

The patient was a 74-year-old woman. She visited a dermatology clinic with a complaint of discomfort in the anal region. Erosion was observed in the anal region, and biopsies were performed. She was diagnosed with Bowen's disease and was referred to the dermatology department of our hospital for treatment. At our department, an endoscopic examination was performed for assessing the extent of Bowen's disease in the rectum. A retroflexed view of the anal canal revealed a slightly raised lesion with a faded color and an irregular surface. Narrow-band imaging (NBI) revealed a whitish lesion with a relatively clear margin and brown dots on the inside. Magnifying endoscopy with NBI revealed abnormal microvessels with dilatation, tortuosity, caliber change and various shapes, which were quite similar to the intrapapillary capillary loop patterns of superficial esophageal cancer. A complete transanal resection of the anal mucosa was performed thereafter. The patient was diagnosed with a well-differentiated squamous cell carcinoma on the basis of a pathological examination. An early diagnosis is critical for successful treatment of anal canal cancer. In this regard, magnifying endoscopy with NBI may be useful for determining the presence and extent of anal canal cancer.

Background Using a novel autofluorescence imaging video (AFI) endoscopy system, early esophageal cancers (EECs) appeared purple or brown in green background. However, the factors associated with these color patterns remain unraveled. The aims of this study were to classify the AFI color patterns of EECs and to investigate the correlation between the color patterns and clinicopathologic features of EECs. Patients From April 2008 to April 2010, 32 patients with 42 EECs who underwent endoscopic submucosal dissection at the Nagasaki University Hospital were enrolled in this study. They consisted of 25 men and 7 women, with the mean age of 64.7 years old (range, 52 to 82 y). Methods With AFI endoscopy, we classified 2 color patters in EECs into purple in green patterns (P in G) and brown with purple dots in green patterns (BP in G), and we assessed the association with clinicopathologic factors. These factors included tumor morphology, location, size, histologic depth of invasion, and histologic lymphatic and vessel permeations. Results The color patterns of EECs were classified into 2 groups: purple in green patterns (P in G) (14%) and brown with purple dots in green patterns (BP in G) (86%). Univariate analysis revealed that only macroscopic type was associated with the EECs color pattern. Conclusions This study revealed the association of AFI color patterns with clinicopathologic factors of EECs. Recognition of the color patterns in AFI images might be useful for the detections and diagnosis of EECs as one of the new endoscopic modalities.

In the field of colorectal cancer and adenoma, Kudo’s classification of pit pattern with magnifying chromocolonoscopy using crystal violet (CV) staining is now accepted. Magnifying endoscopy using narrow band imaging has been used for the diagnosis of gastric carcinoma; the characteristic findings of microvascular patterns have been demonstrated. However, there was limited information on magnified endoscopic findings with CV staining for gastric neoplasms in terms of their pit patterns. Magnifying chromoendoscopy with CV was performed in 175 patients with early gastric cancer and 18 with gastric adenoma, prior to treatment. Surface patterns of gastric tumors were classified into five types: (1) long tubular pit pattern, (2) irregular size pit pattern, (3) small round pit pattern, (4) destroyed pit pattern, and (5) non-structural pattern. Long tubular pit pattern was most common in gastric adenoma. Well differentiated adenocarcinoma and papillary adenocarcinoma tended to show different size of pit pattern or destroyed pit pattern. Small round pit pattern was most commonly seen in moderately differentiated adenocarcinoma. Non-structural pattern was most frequently observed in poorly differentiated adenocarcinoma and signet ring cell carcinoma (P

A 74-year-old man with nausea underwent upper gastrointestinal endoscopy, and a 0-IIb type tumor was found in the middle thoracic esophagus. Histological examination with endoscopic biopsies revealed squamous cell carcinoma (SCC), and chromoendoscopy with iodine staining revealed that the superficial SCC involved nearly the entire circumference of the esophageal lumen. There were neither nodal nor distant metastases. Complete circular endoscopic submucosal dissection (ESD) was successfully achieved with tumor-free margins in an en bloc fashion. The histopathological examination confirmed a diagnosis of intramucosal invasive carcinoma limited to the lamina propria mucosae without angiolymphatic invasion. Oral prednisolone was started with 0.5 mg/kg daily on the 3rd post-ESD day, tapered gradually, and then discontinued 8 weeks later without adverse effects. There were no complaints of dysphagia following ESD. On follow-up endoscopy with iodine staining, which was scheduled at 1, 3 and 6 months after ESD, there was no postprocedural esophageal stricture, and neither recurrent nor metachronous lesions were found. Thus, the patient required no sessions of endoscopic balloon dilatation. At the last outpatient clinic visit 7 months after ESD, he remained well without dysphagia. Oral prednisolone administration may offer an effective therapeutic strategy to prevent the post-ESD esophageal stricture after complete circular ESD.

Peyer's patches (PPs), a major component of the gut-associated lymphoid tissue, serve as important antigen entry sites in mucosal immunity. PPs may play a role in the extension of ulcerative colitis (UC) into the terminal ileum. We sought to clarify the magnified endoscopic findings of the PPs in the terminal ileum of UC patients. Eighteen UC patients underwent magnifying chromoendoscopy before initial treatment to evaluate the follicle-associated epithelium (FAE) on the PPs domes and the surrounding villi. In 8 UC patients, as in healthy controls, the PPs' domes were slightly elevated, covered with the regular FAE lining, and surrounded by dense and bulky villi; however, in 10 UC patients, the PPs' domes were irregular, and the surrounding villi were sparse and atrophic. These abnormal findings within the PPs were associated with minimal mucosal lesions but not with backwash ileitis; both electron microscopy and magnifying endoscopy confirmed that these lesions were reversible following remission with prednisolone-mesalazine therapy. Similar to Crohn's disease patients, UC patients commonly had abnormalities in the FAE on PPs' domes and the surrounding villi on magnifying endoscopy., Journal of clinical biochemistry and nutrition, 46(2), pp.111-118; 2010

Endoscopic submucosal dissection permits removal of colorectal epithelial neoplasms en bloc, but long-term clinical outcomes remain unknown.Endoscopic submucosal dissection was performed in 282 patients having 296 colorectal tumors that fulfilled the inclusion criteria, which included lesions greater than 20 mm in size for which en bloc resection would be difficult with endoscopic mucosal resection, lesions with fibrotic scar due to previous endoscopic treatment or biopsies, locally residual lesions after endoscopic resection, or invasive carcinoma with slight submucosal penetration. En bloc or piecemeal resection, complete (en bloc with tumor-free lateral/basal margins) or incomplete resection, and complications were assessed, and factors related to each were analyzed using logistic regression. Patients with early colon cancer received endoscopic follow-up and metastatic surveys for a median of 34 months.En bloc resection was achieved in 89.2% (264/296) and 234 lesions (79.1%) were deemed to have undergone complete resection. A right-side colonic location was the significant contributor to incomplete resection. Perforation was seen in 24 cases (8.1%) in association with tumor size and the presence of fibrosis. There was 1 case of locally recurrent tumor with incomplete resection, whereas neither recurrence nor residual disease was observed in the complete resection group. Neither cancer-related nor cancer-unrelated death was observed.Precise assessment of curability with successful en bloc resection may reduce tumor recurrence after endoscopic submucosal dissection. The prognosis of early colorectal cancer in patients treated by endoscopic submucosal dissection is likely to be excellent, although further longer follow-up studies are warranted.

A 50-year-old man with a 30-year history of alcohol abuse was admitted because of abdominal pain. Based on an elevated serum amylase level and abdominal computed tomography findings, a diagnosis of alcoholic pancreatitis was made. The pancreatitis improved after 1 month of conservative therapy, but the patient complained of a tender right ankle that showed no abnormal findings on X-ray examination. Two months later, the patient was readmitted for recurrent pancreatitis and a swollen, warm, tender right ankle. Imaging studies, including plain radiographs, magnetic resonance imaging, and a bone scintigram showed the typical findings of intraosseous fat necrosis of the right tibia. We report a rare case of intraosseous fat necrosis associated with alcoholic pancreatitis.

AIM: Cancer death in the early period after hepatectomy still occurs in patients with colorectal liver metastasis (CLM). We examined the relationship between clinicopathological parameters and survival periods in 130 CLM patients who underwent hepatectomy. PATIENTS/METHODS: Patients were divided into four groups: Group 1 (5-year survivors without tumor relapse), Group 2 (survivors at 2-5years), Group 3 (cancer death at 2-5years), and Group 4 (cancer death within 2years). RESULTS: A short surgical margin was frequent in Group 4 compared to Group 1 (31 vs. 78%, P, European Journal of Surgical Oncology, 35(5), pp.504-509; 2009

Endoscopic submucosal dissection (ESD) yields substantially high rates for curative resection of early gastric cancer (EGC). It is suggested that larger, ulcerative, or upper EGCs may prevent successful ESD. A detailed analysis of factors associated with the curability of ESD was performed. Endoscopic submucosal dissection was performed for patients with EGC that fulfilled the expanded criteria, which specified mucosal cancer without ulcer findings irrespective of tumor size, mucosal cancer with ulcers 3 cm in diameter or smaller, and minute submucosal invasive cancer 3 cm or smaller. Resectability (en bloc or by piecemeal resection), curability (curative or non-curative), and complications were assessed, and logistic regression analysis was used to analyze the related factors. Ulcerative EGCs showed a significantly higher risk associated with ESD on multivariate analysis. When the risk factors (tumor size, location, and ulcer findings) were combined, the larger EGCs (>30 mm) located in the upper third or ulcerative tumors located in the upper and middle portion of the stomach were at significantly higher risk of non-curative resection. Such lesions also were associated with increased risk of procedure-related perforation. When risk factors including positive ulcer findings and larger size and upper location of tumors are combined, ESD should be performed more carefully.

We report magnified endoscopic findings of gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphoma before and after anti-tumor therapies. Magnifying chromoendoscopy with crystal violet was carried out in nine patients with low-grade MALT lymphoma of the gastric corpus with Helicobacter plyori infection. A Wotherspoon histologic score of 5 was used as the criterion to make the histopathologic diagnosis. On conventional endoscopy, each patient was classified as having a superficial spreading type of the lymphoma, varying from gastritis to adenocarcinoma-like appearance. Anti-H. pylori treatment was successful in all cases. Complete regression was observed in six of the nine patients with MALT lymphoma and no regression was seen in three during the median follow-up of 12 months. Magnified endoscopic findings consisted exclusively of irregular and destroyed gastric pits in the lymphoma lesions. Histopathologic examination of targeted biopsies obtained from the affected mucosa with the abnormal pit pattern revealed the characteristic features of lymphoepithelial lesions and centrocyte-like cell infiltration. In six patients who underwent repeat magnifying endoscopy at 6 months or more after anti-tumor therapies (five with complete regression following anti-H. pylori therapy and one who had been treated with radiation), the abnormal pits appeared to have returned to normal. Magnifying endoscopy can reliably identify irregular and destructive pit patterns in the lymphoma lesions, and aid the prediction ofhistopathlogic regression.

Background: Osteopontin (OPN) plays a key role in the progression of T H l-immune-mediated disease in models of multiple sclerosis and rheumatoid arthritis. Aim: To determine whether plasma OPN levels in patients with inflammatory bowel disease are associated with disease activity. Methods: Plasma samples were obtained from patients with ulcerative colitis (UC, n = 30), Crohn's disease (CD, n = 30), and healthy volunteers (controls, n = 30) and enzyme immunoassay was performed. Results: Plasma OPN concentrations were significantly higher in patients with Crohn's disease than in controls (951.9 ± 538.5 ng/ mL and 659.0 ± 163.7ng/mL, respectively). OPN concentrations in patients with UC were also higher than in the controls (1149.6 ± 791.0 and 659.0 ± 163.7, respectively). There was a significant difference in plasma OPN level between active UC and inactive UC (2102.0 ± 552.8 and 649.4 ± 313.0, respectively). Moreover, a significant correlation was observed between plasma OPN concentration and disease activity, as determined by the clinical activity index in patients with UC. Conclusions: Our results indicate that the plasma concentrations of OPN are elevated in patients with UC and that OPN expression is correlated with clinical activity. These results provide insight into UC pathogenesis and suggest that OPN may be a useful tool for assessing disease activity.

An 80-year-old woman was admitted to our hospital with complaints of jaundice and liver dysfunction. She was found to have a high titer of serum IgG4, positive rheumatoid factor and marked elevation of DUPAN-2 (11,148 U/ml). Computed tomography showed swelling of the pancreas, and endoscopic retrograde cholangiopancreatography revealed diffuse irregular narrowing of the main pancreatic duct, which are typical findings of autoimmune pancreatitis. There was no evidence of malignancy. Administration of 30 mg/day of prednisolone was started. Computed tomography showed significant regression in the size of the pancreas, and the stenosis of the main pancreatic duct was improved on ERCP. The serum level of DUPAN-2 was also markedly decreased after the treatment., Internal Medicine, vol.46(7), pp.377-381; 2007

Background and Study Aims Endoscopic diagnosis of esophageal achalasia lacking typical endoscopic features can be extremely difficult. The aim of this study was to identify simple and reliable early indicator of esophageal achalasia. Patients and Methods This single-center retrospective study included 56 cases of esophageal achalasia without previous treatment. As a control, 60 non-achalasia subjects including reflux esophagitis and superficial esophageal cancer were also included in this study. Endoscopic findings were evaluated according to Descriptive Rules for Achalasia of the Esophagus as follows: (1) esophageal dilatation, (2) abnormal retention of liquid and/or food, (3) whitish change of the mucosal surface, (4) functional stenosis of the esophago-gastric junction, and (5) abnormal contraction. Additionally, the presence of the longitudinal superficial wrinkles of esophageal mucosa, “pinstripe pattern (PSP)” was evaluated endoscopically. Then, inter-observer diagnostic agreement was assessed for each finding. Results The prevalence rates of the above-mentioned findings (1–5) were 41.1%, 41.1%, 16.1%, 94.6%, and 43.9%, respectively. PSP was observed in 60.7% of achalasia, while none of the control showed positivity for PSP. PSP was observed in 26 (62.5%) of 35 cases with shorter history < 10 years, which usually lacks typical findings such as severe esophageal dilation and tortuosity. Inter-observer agreement level was substantial for food/liquid remnant (k = 0.6861) and PSP (k = 0.6098), and was fair for abnormal contraction and white change. The accuracy, sensitivity, and specificity for achalasia were 83.8%, 64.7%, and 100%, respectively. Conclusion “Pinstripe pattern” could be a reliable indicator for early discrimination of primary esophageal achalasia.

Background The “Liver damage” classification proposed by the Liver Cancer Study Group of Japan and Child-Pugh classification are both useful classifications for hepatic function. However, the factors responsible for the difference between the two classifications have not been fully investigated. Methods The medical records of 594 admissions of 220 patients with hepatocellular carcinoma (HCC) were retrospectively analyzed for encephalopathy, ascites, serum bilirubin and albumin, plasma retention rate (%) at 15 min after injection of 0.5 mg/kg of indocyanine green (ICG R15), and prothrombin time. Results Of 594 admissions, ICG R15 was tested in 337 (56.7%). The Child-Pugh classification was evaluated in all 594 admissions, but the “Liver damage” could be evaluated in 510 (85.9%) due to the lack of ICG R15 results. Of the 594 admissions, 372 (62.6%), 162 (27.3%), and 60 (10.1%) were Child-Pugh grade A, B, and C, respectively. Of the 510 admissions, 219 (42.9%), 202 (39.6%), and 89 (17.5%) were “Liver damage” grade A, B, and C, respectively. The grade of “Liver damage” was similar to that of Child-Pugh classification in 369 (72.4%), under-evaluated in 138 (27.1%), and over-evaluated in 3 (0.6%). The Child-Pugh classification was statistically a better classification for predicting outcome than “Liver damage”, but the “Liver damage” had better stratification ability than Child-Pugh classification in patients with relatively good liver function. Conclusions Although the “Liver damage” could not be evaluated in some cases due to the lack of ICG R15 results, this classification system is useful in the evaluation and prediction of outcome of patients with early-stage liver diseases.

Summary Objective Photodynamic diagnosis (PDD) is an imaging technology that is based on the fundamental biological features of cancer cells. Five-aminolevulinic acid (ALA), a precursor of photosensitizing protoporphyrin IX (PpIX) has been applied. In fact, ALA-mediated PDD provides good visualization for certain tumors. However, there have been few studies on clinical application of PDD for gastrointestinal (GI) cancers. This study was aimed to investigate the feasibility of ALA-mediated PDD for navigation of upper GI tumors. Materials and methods Using a newly developed endoscope equipped with a blue laser light excitation, ALA-mediated PDD was conducted in 27 lesions from 23 patients with upper GI tumors including 2 Barrett's intramucosal cancers. ALA solution was given orally 3 h before PDD. All the adenocarcinomas came under clinical stage I, and the tumors were resected endoscopic submucosal dissection and/or laparoscopic surgery. Red fluorescence signal and intensity was assessed as for clinicopathological features of the cases. Results The laser-based endoscopy could detect upper GI tumors as red fluorescent navigation (PDD-positive) in 23 of the 27 lesions. All but one intestinal typed tumors in histopathology were significantly PDD-positive, whereas each signet ring cell carcinoma was PDD-negative. There was a significant difference in tumor size between the PDD-positive and -negative tumors. The elevated lesions emitted significantly more intense fluorescence. Conclusions Fluorescence navigation by ALA-mediated PDD provided sufficient detection of upper GI tumors in particular for the intestinal typed tumors. Thus, ALA-PDD using the blue laser-equipped endoscope offers a promising diagnostic tool.

We describe a case of pseudomyxoma peritonei (PMP) successfully managed with intraperitoneal hyperthermic chemoperfusion. This case is unique due to the concurrent presence of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. The patient presented with abdominal fullness. Abdominal computed tomography revealed massive ascites, thickened peritoneum, and a cystic lesion of the pancreas. Cytological examination of ascitic fluid sample showed mucin-rich atypical cells. Endoscopic retrograde pancreatography revealed a cystic lesion with the defect probably due to mural nodule and mucin, communicating with the pancreatic duct. At exploratory laparotomy, massive ascites and multiple nodules were identified within the peritoneal cavity. No primary tumour, including mucinous neoplasm of the appendix, was found. Histopathological examination of the omentum showed mucinous adenocarcinoma in pools of mucoid material, consistent with PMP. The relation between PMP and IPMN of the pancreas was possible, but not conclusive. The patient received intraperitoneal perfusion of saline heated to 42 degrees C containing cisplatin, etoposide, and mitomycin C, followed by 24 courses of postoperative chemotherapy with gemcitabine. The patient remains in good general condition with no signs of progression of PMP for 2 years, but with a gradual and progressive enlargement of the pancreatic cystic lesion.

Multiple lymphomatous polyposis is an unusual form of non-Hodgkin's lymphoma characterised by myriad polyps throughout the alimentary tract. Most multiple lymphomatous polyposis cases are derived from B-cell, and there has been little information on multiple lymphomatous polyposis of T-cell origin. A 67-year-old Japanese man presented with lower abdominal pain and diarrhoea of 4-week duration. Colonoscopy revealed numerous small umbilicated polyps and several raised erosions in the colorectum. Biopsy specimens showed diffuse proliferation of lymphoma cells negative for B-cell markers but positive for T-cell markers. Polymerase chain reaction using extracted chromosomal deoxyribonucleic acid from paraffin-embedded samples identified T-cell receptor gamma and delta gene recombination. The patient was treated with combined chemotherapy, leading to complete resolution of the lesions.

A 65-year-old man in the remission stage of ulcerative colitis developed severe bloody diarrhea and high fever. He was treated with imipenem/cilastatin and clindamycin for infectious enterocolitis at a local hospital, but there was no improvement in his condition. Steroid pulse therapy was also ineffective. Colonoscopy revealed pseudomembranous colitis extending from the ascending colon to the cecum, and Clostridium difficile toxin was positive in the feces. The administration of vancomycin in addition to oral steroids resulted in rapid improvement of the condition. Total colonoscopy is recommended for precise diagnosis when patients with ulcerative colitis develop intractable diarrhea during or after antibiotic therapy.

BACKGROUND Gastrointestinal involvement is seen frequently in patients with adult T-cell leukemia/lymphoma (ATLL). The authors previously showed a relatively low prevalence of Helicobacter pylori infection in individuals with human T-cell lymphotropic virus 1 (HTLV-1) infection, including patients with ATLL; however, the correlation between H. pylori infection and ATLL gastric involvement has not been investigated. METHODS The authors studied 71 patients with ATLL. Gastric involvement was confirmed by endoscopy and biopsy. H. pylori infection was detected by serology, rapid urease test, and immunohistochemistry on biopsy samples. The expression of adhesion molecules on ATLL cells or their ligands on the vasculature in gastric mucosa was analyzed immunohistochemically. The expression of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. RESULTS Gastric involvement was detected in 21 patients (30%), including 8 patients with acute clinical subtype ATLL and 13 patients with lymphoma type ATLL. The prevalence of H. pylori infection was 86% (18 of 21 patients) in the patients with gastric involvement but only 38% (19 of 50 patients) in the patients without such involvement (P < 0.001). The expression of lymphocyte function-associated antigen 1 (LFA-1) and its ligand, intercellular adhesion molecule 1 (ICAM-1), was most frequent on ATLL cells infiltrating the stomach and was enhanced substantially on vascular endothelium in H. pylori-infected gastric mucosa. Human mucosal lymphocyte antigen 1 also was expressed on infiltrating ATLL cells in the stomach. The expression of MAdCAM-1 mRNA assessed by RT-PCR also was seen selectively in H. pylori-infected patients. CONCLUSIONS ATLL cells infiltrate gastric tissues infected with H. pylori, probably through the interaction of adhesion molecules on these cells and their ligands on the vasculature, i.e., through the LFA-1/ICAM-1 pathway. Cancer 2002;94:1507–16. © 2002 American Cancer Society. DOI 10.1002/cncr.10367