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Background: Patients with duodenal ulcer have a reduced risk of developing gastric cancer compared to those without. Recently, the prostate stem cell antigen (PSCA) rs2294008 C>T polymorphism was found to be associated with different pathogenesis of duodenal ulcer and gastric cancer developments. However, whether PSCA rs2294008 C>T polymorphism is associated with severity of gastric mucosal atrophy is unclear. We examined the influence of the PSCA rs2294008 C>T polymorphism on susceptibility to H. pylori-related diseases and the relationships between PSCA polymorphism and gastric mucosal atrophy., Methods: PSCA rs2294008 C>T polymorphism was assessed in H. pylori-positive Japanese patients (n = 488) with noncardia gastric cancer (n = 193), gastric ulcer (n = 84), duodenal ulcer (n = 61), and atrophic gastritis (n = 150), as well as in H. pylori-negatives (n = 266)., Results: Frequency of PSCA rs2294008 C/C genotype in duodenal ulcer was 36.1%, which was significantly higher than those with gastric cancer (12.4%), gastric ulcer (19.0%), gastritis (10.7%), and H. pylori-negatives (19.5%) (p < .001). Compared with duodenal ulcer, having the T allele significantly increased the risk of gastric cancer (OR: 3.97, 95% CI: 2.02-7.80; p < .001), gastric ulcer (2.40, 1.13-5.10; p = .023), and gastritis (4.72, 2.26-9.86; p < .001). Mean pepsinogen (PG) I/PG II ratio in T allele carriers (2.17 ± 0.75) was significantly lower than that in C/C genotype (3.39 ± 1.27, p < .001)., Conclusions: The PSCA rs2294008 C>T polymorphism is associated with differing susceptibilities to H. pylori-associated diseases. The PSCA rs2294008 C>T polymorphism may be acting through induction of gastric mucosal atrophy, finally leading to development of gastric ulcer and gastric cancer in PSCA rs2294008 T allele carriers, but not duodenal ulcer., (© 2014 John Wiley & Sons Ltd.)

Introduction: Primary malignant melanoma of the vagina is an extremely rare disease affecting 3% of patients with malignant vaginal tumors. It is rare compared to primary malignant melanoma of the skin and its prognosis is unfavorable even in patients with Stage I disease. Here, we report a case of primary malignant melanoma of the vagina and discuss our experience with regard to previously published literature., Case Description: The patient was a 59-year-old female with 2 prior pregnancies and child births. She was examined by a local doctor for swelling of the genitalia, and a 1.8 × 1.0 cm large tumor was detected on the left side of the vaginal wall. A biopsy indicated leiomyosarcoma, and she was referred to our hospital. The tumor was resected, and histopathology of the resected sample confirmed the diagnosis of malignant melanoma based on a positive surgical margin. Additional courses of treatment included left inguinal sentinel lymph node biopsy using an isotope and extended vaginectomy. Although the sentinel node was negative, we performed a modified radical hysterectomy and left vaginectomy during the third operation because the surgical margin was positive. We could not confirm whether the lesion in the extracted sample was malignant, and the final diagnosis was primary malignant melanoma of the vagina T4bN0M0 Stage IIc (UICC 2009). Postoperative adjuvant therapy consisted of 6 cycles of DAV-Feron therapy (dacarbazine, ACNU, vincristine, IFN- β). After 5 months of postoperative adjuvant therapy, a 2 cm single lung metastasis was detected in the lower left lung. We performed a laparoscopic lower left lobectomy and are planning additional chemotherapy., Discussion and Evaluation: Currently, surgical resection has the highest probability of improving the prognosis of patients when used as initial treatment for Stage I disease. By combining treatment with sentinel lymph node biopsy, we were able to accurately determine the stage of disease and thus avoid systematic lymph node dissection and further surgical treatments., Conclusion: Malignant melanoma of the vagina is very rare tumor so it is necessary to requires the integration of further cases.

Helicobacter pylori (H. pylori) is a major human pathogen which causes progressive gastroduodenal damage. Guidelines recommend that, unless there are compelling reasons to delay, treatment is indicated for all patients in whom the infection is diagnosed. The rapid urease test (RUT) is a popular diagnostic test in that it is a rapid, cheap and simple test that detects the presence of urease in or on the gastric mucosa. The sensitivity and specificity are generally high and many versions have been approved for use in humans. Best results are obtained if biopsies are obtained from both the antrum and corpus. The tissue sample embedded in the RUT gel can also be utilized for other tests such as for molecular based tests of microbial susceptibility or for host factors. False-positive results are rare if the RUT contains an antibacterial agent to prevent growth of urease-containing contaminants and the tests are discarded at 24 hours. The use of antimicrobial drugs and proton pump inhibitors as well as the presence of intestinal metaplasia may result in false-negative results. A negative test should not be used as the criteria for cure or in cases where accuracy is important for patient management such as in upper gastrointestinal bleeding. Interpretation of the test should take into account the pretest probability and the prevalence of H. pylori in the population. The test can also be used to provide an informal assessment of the accuracy of the histopathology result and discrepancies should prompt a review of the histopathology and discussions with the pathologist.

Introduction: A clearer understanding of the factors affecting the cure rate of Helicobacter pylori infection might lead to the development of novel prevention strategies and therapeutic targets., Areas Covered: This review covers two important issues that affect the eradication of H. pylori: bacterial and host factors. Several virulence factors have been shown to be predictors for gastroduodenal diseases. Successful treatment of H. pylori infection also depends on host genetic factors such as CYP2C19 and IL-1B. The latest evidence on host genetic factors is discussed., Expert Opinion: The authors identify three main targets for achieving effective eradication therapy. The first therapeutic target is to identify counter measures for antibiotic-resistant H. pylori strains. Thus, antibiotic susceptibility should be checked in all patients, ideally, before the start of eradication treatment. The second therapeutic target is the inhibition of acid suppression. Maintaining a high intragastric pH for 24 h increases the effectiveness of some antibiotics and the eradication effects for H. pylori. The third therapeutic target is to identify high-risk groups; the CYP2C19 and IL-1B polymorphisms are candidates for significant risk factors. A personalized medical approach will likely increase the cure rate of H. pylori infection.

Preoperative diagnosis of uterine sarcoma is very difficult, and currently, its diagnostic accuracy is not satisfactory. It is therefore important to perform surgery and establish the pathological diagnosis if the clinical findings and various examination findings indicate possible uterine sarcoma. We investigated the accuracy of the combination of various types of predictors of uterine sarcoma and the novel PREoperative Sarcoma Score (PRESS) for avoiding unnecessary surgery while diagnosing uterine sarcoma. We retrospectively analyzed the clinical findings, blood tests, imaging studies (ultrasonography and magnetic resonance imaging [MRI]), and endometrial cytology of 63 suspected uterine sarcoma cases that underwent surgery from 2006 to 2012. These cases were also scored retrospectively using PRESS. We analyzed the number of unnecessary surgeries that could be avoided using PRESS. Of 63 cases, 15 were diagnosed with uterine sarcoma (sarcoma group), and 48 had benign tumors (benign group). Univariate analysis indicated age, serum lactate dehydrogenase (LDH) values, and MRI and endometrial cytology findings as significant predictors of uterine sarcoma in both groups. In contrast, multivariable analysis identified only age, serum LDH value, and endometrial cytology findings as significant predictors. Accordingly, the latter were placed as 2 points, and the remaining MRI finding as 1 point. The accuracy rate of prediction was 84.1%, and the positive and negative predictive values were 63.2% and 93.2% respectively when the PRESS was interpreted as "positive" when it was 3 points or higher. Using multiple predictors for the preoperative diagnosis of uterine sarcoma, our proposed PRESS score is beneficial in the clinical setting while making treatment decisions in suspected uterine sarcoma cases as well as avoiding unnecessary surgery.

Background: Insufficient acid inhibition during Helicobacter pylori eradication treatment and bacterial resistance to antibiotics often causes eradication failure. Four times daily dosing (q.i.d.) of a proton-pump inhibitor (PPI) achieves potent acid inhibition, suggesting its potential usefulness as a regimen for eradicating H. pylori infection. Therefore, a tailored eradication regimen based on antibiotic susceptibility and maintenance of acid inhibition should have a high success rate. We investigated the efficacy of such treatment based on clarithromycin (CAM) susceptibility., Methods: Using 153 H. pylori-positive Japanese patients, we investigated the efficacy of tailored eradication strategy: (1) Patients infected with CAM-sensitive H. pylori were treated with a PPI (rabeprazole 10 mg q.i.d.), amoxicillin 500 mg q.i.d., and CAM 200 mg b.i.d. (n = 89), and (2) patients infected with CAM-resistant were given the same doses of rabeprazole and amoxicillin and metronidazole 250 mg b.i.d. (n = 64) for 1 week., Results: In the tailored regimen group, the overall eradication rate was 96.7% (95% CI: 92.5-98.9%, 148/153) in the intention-to-treat (ITT) analysis and 97.4% (93.4-99.3%, 148/152) in the PP analysis. The eradication rates for the CAM- and metronidazole-based treatments were similar (95.5% and 98.4%, respectively, p = .400). The tailored treatment achieved a high eradication rate in CYP2C19 rapid metabolizers who were a resistance genotype for PPI treatment (94.3% (86.0-98.4%, 66/70))., Discussion: A tailored H. pylori eradication regimen based on CAM susceptibility and maintaining acid secretion (rabeprazole 10 mg q.i.d.) is useful because it can achieve an eradication rate exceeding 95%, irrespective of eradication history, thus overcoming differences among CYP2C19 genotypes., (© 2014 John Wiley & Sons Ltd.)

Anti-platelet drug-induced gastric mucosal injury correlates with intragastric pH. Our aim was to investigate prophylaxis effects of famotidine, one of the representative histamine-2 receptor antagonists (H2RA), on gastric mucosal injury induced by dual therapy with low-dose aspirin and clopidogrel in relation to Helicobacter pylori (H. pylori) infection and CYP2C19 genotypes. This study was conducted for 20 healthy Japanese volunteers (10 H. pylori-positive and 10-negative subjects) with 100 mg aspirin plus 75 mg clopidogrel (AC) once-daily dosing and AC plus 20 mg famotidine twice-daily dosing (ACH). Mucosal injury was endoscopically assessed on day 3 and 7 and 24-hour intragastric pH and antiplatelet-function test was performed on day 7. Median pH in ACH was similar between CYP2C19 extensive metabolizer (EM) and intermediate metabolizer (IM)/poor metabolizer (PM) and was significantly higher in H. pylori-positive than negative subjects (P < .05). Mucosal injury with ACH significantly decreased in both day 3 and 7 compared with AC, irrespective with H. pylori and CYP2C19 genotypes (P < .05). Although antiplatelet effect of clopidogrel in EM was significantly higher than that in IM/PM, the additional famotidine did not affect the effect. Anti-platelet drug-induced gastric injury was alleviated by famotidine without attenuation of anti-platelet functions irrespective of H. pylori and CYP2C19 genotypes., (© 2014, The American College of Clinical Pharmacology.)

Backgrounds: Quinolone-based regimens have been used as the rescue for eradication of Helicobacter pylori. Sitafloxacin is known to have low minimum inhibitory concentration for H. pylori. Here, we compared two sitafloxacin-based eradication regimens as rescue for the eradication of H. pylori., Methods: We attempted to eradicate H. pylori in 180 Japanese patients who had never failed in eradication of H. pylori with the triple proton pump inhibitor/amoxicillin/clarithromycin therapy (1st line) and the triple proton pump inhibitor/amoxicillin/metronidazole therapy (2nd line). They were assigned to either the triple therapy with rabeprazole 10 mg b.i.d./q.i.d., amoxicillin 500 mg q.i.d, and sitafloxacin 100 mg b.i.d. (RAS) for 1 or 2 weeks or the triple therapy with rabeprazole 10 mg b.i.d./q.i.d., metronidazole 250 mg b.i.d., and sitafloxacin 100 mg b.i.d. (RMS) for 1 or 2 weeks. Eradication was assessed via the (13) C-urea breath test and rapid urease test., Results: Intention-to-treat and per-protocol analyses of eradication rates were 84.1% (37/44) and 86.4% (37/43) with RAS for 1 week, 88.9% (40/45) and 90.9% (40/44) for RAS for 2 weeks, 90.9% (40/44) and 90.9% (40/44) for 1 week-RMS and 87.2% (41/47) and 91.1% (41/45) with RMS for 2 weeks. We noted no statistical significant differences in eradication rates among four regimens., Conclusion: All of the above-described rescue regimens proved relatively equally useful in the eradication of H. pylori. Of them, RAS for 2 weeks and RMS for 1 or 2 weeks could attain the rescue eradication rates higher than 90% by per-protocol analysis., (© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Objectives: In standard regimens for Helicobacter pylori infection, amoxicillin is dosed twice daily, although the bactericidal effect of amoxicillin depends on the %time-above-MIC. We aimed to examine whether dosing schemes of amoxicillin influenced eradication rates of amoxicillin-based regimens., Methods: One hundred eighty-seven patients infected with clarithromycin-sensitive strains of H. pylori were treated with PPI, clarithromycin 200 mg bid and amoxicillin 750 mg bid, 500 mg tid or 500 mg qid for 1 week and 125 infected with clarithromycin-resistant strains were treated with PPI, metronidazole 250 mg bid and amoxicillin 750 mg bid, 500 mg tid or 500 mg qid for 1 week., Results: Eradication rates (ITT) of the triple PPI/amoxicillin/clarithromycin therapy with bid, tid and qid dosings of amoxicillin were 77.8% (49/63), 93.5% (58/62), and 91.9% (57/62), respectively. Those of the triple PPI/amoxicillin/metronidazole therapy were 80.5% (33/41), 90.5% (38/42), and 95.2% (40/42), respectively. Eradication rates in regimens with tid and qid dosing of amoxicillin were higher than those of regimens with the bid dosing of amoxicillin., Conclusions: The dosing scheme of amoxicillin significantly influenced eradication rates of triple therapies. Although amoxicillin is empirically dosed twice daily, amoxicillin should be dosed at least three times daily in amoxicillin-based triple therapies., (© 2013, The American College of Clinical Pharmacology.)

Recent reports have suggested that the candidates of the third rescue regimens for H. pylori infection in Japan are fluoroquinolone-based regimens and the dual therapy with high doses of proton pump inhibitor and amoxicillin. Of fluoroquinolones, sitafloxacin has the strong anti-H. pylori effect as AMPC has and is effective for strains resistant to levofloxacin. Sitafloxacin-based regimens have been reported to yield relatively sufficient eradication rates as the third line therapy. The dual therapy with high doses of proton pump inhibitor and amoxicillin has also been reported to attain the sufficient rescue rates. To achieve the high rescue eradication rates, the eradication regimens must be designed based on well-understanding of reasons for eradication failure, such as the resistance patterns of the bacteria, and the pharmacological characteristics of agents used for H. pylori eradication therapy.

Background & Aims: Low doses of aspirin can injure the gastric mucosa. It is not clear whether other drugs such as the antiplatelet agent clopidogrel also cause gastric mucosal injury or exacerbate aspirin-induced injury, or whether proton pump inhibitors prevent damage., Methods: Twenty Japanese subjects with different CYP2C19 genotypes were randomly assigned to groups that were given a low dose of aspirin (100 mg; A), clopidogrel (75 mg; C), low dose of aspirin and clopidogrel (AC), or low dose of aspirin in combination with clopidogrel and rabeprazole (10 mg; ACR) once daily for 7 days. Subjects underwent gastroduodenoscopy and platelet tests on days 3 and 7; gastric mucosal damage was assessed by using the modified Lanza score (MLS). We performed 24-hour intragastric pH monitoring on day 7 of each regimen. We also analyzed the effects of the AC regimen on 30 patients with different CYP2C19 genotypes., Results: Subjects in groups A, C, and AC had significantly higher levels of gastric mucosal damage on days 3 and 7, compared with baseline. The median MLS for the AC group was similar to that of the A group. Helicobacter pylori-negative subjects in the ACR group with different CYP2C19 genotypes had significant differences in MLS, intragastric pH, and platelet function. Gastric mucosal injury was inhibited equally among H pylori-positive subjects in the ACR group. Rabeprazole did not appear to affect platelet function or intragastric pH in subjects given clopidogrel., Conclusions: Clopidogrel and low doses of aspirin cause a similar degree of gastric mucosal damage. Rabeprazole prevented this damage without reducing the antiplatelet function of clopidogrel. However, its prophylactic effect varies with CYP2C19 genotype in H pylori-negative subjects., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Aim: We investigated the effects of trastuzumab, an anti-HER2 humanized monoclonal antibody, on DNA breaks induced by SN-38, a topoisomerase-1 inhibitor, in gastric cancer cell lines positive or negative for HER2 expression., Materials and Methods: NCI-N87 (HER2+) and MKN74 (HER2-) cells were exposed to SN-38 in the presence or absence of trastuzumab. Trastuzumab was added either prior to or after SN-38. Effects of trastuzumab on the induction of gamma-H2AX, a marker of DNA double-strand breaks, the cytotoxicity of SN-38 and cell cycle progression were determined., Results: When trastuzumab was administered following SN-38, it increased γH2AX levels and cytotoxicity of SN-38 in NCI-N87 cells, but not in MKN74 cells. In contrast, pretreatment with trastuzumab reduced SN-38-induced γH2AX expression and cytotoxicity of SN-38 in NCI-N87 cells, but not in MKN74 cells. Trastuzumab delayed cell cycle progression in NCI-N87 cells only., Conclusion: Trastuzumab has opposing effects on SN-38-induced double-strand breaks and cytotoxicity depending on the order of administration of the two agents.

Background and Aim: As bacterial resistance to clarithromycin limits the efficacy of clarithromycin-based regimens for Helicobacter pylori infection, attention has turned to quinolone-based rescue therapies. Resistance of H. pylori to both clarithromycin and quinolone can be predicted by genetic testing. Here, we used this approach to evaluate the prevalence of clarithromycin- and quinolone-resistant strains of H. pylori in Japan., Methods: DNA was extracted from gastric tissue samples obtained from 153 patients infected with H. pylori (103 naive for eradication therapy and 50 with previous eradication failure following triple proton pump inhibitor/amoxicillin/clarithromycin therapy). Mutations in H. pylori 23S rRNA and gyrA genes associated with resistance to clarithromycin and quinolones, respectively, were determined., Results: Of 153 patients, 85 (55.6%) were infected with clarithromycin-resistant strains. The prevalence of clarithromycin-resistant strains in patients with previous eradication failure (90.0%, 45/50) was significantly higher than that (38.8%, 40/103) of those naive for eradication therapy (P < 0.001). Fifty-nine patients (38.6%) were infected with strains resistant to quinolones. The incidence of quinolone-resistant strains also appeared higher in patients with eradication failure (48.0%, 24/50) than in those who had not undergone therapy (34.0%, 35/103); however, the difference was not statistically significant (P = 0.112). The incidence of quinolone-resistance in clarithromycin-resistant strains (44/85, 51.8%) was significantly higher than that in clarithromycin-sensitive strains (15/68, 22.1%) (P < 0.001)., Conclusions: A high incidence of quinolone-resistance was found in clarithromycin-resistant strains of H. pylori, particularly in patients with previous eradication failure. Our results suggest that testing for susceptibility of H. pylori to quinolones is useful for determining the optimal rescue eradication regimen., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

We encountered a very rare case of eosinophilic gastroenteritis accompanied with fasciitis of the extremities. The patient was a 28-year-old woman with epigastralgia, eosinophilia plus leukocytosis, massive pleural effusion and ascites, and thickening of the walls of the intestine. Increase of the eosinophilic fraction in her ascites led to a diagnosis of eosinophilic gastroenteritis. She soon developed resting pain in all limbs and MRI revealed fasciitis. Prednisolone was effective in treating both gastroenteritis and fasciitis.

Gastrointestinal involvement in cytomegalovirus (CMV) infection is well documented among immunocompromised patients and is also observed in immunocompetent individuals. The presentation of this infection can sometimes mimic those of other diseases, thus making accurate diagnosis difficult. We herein report a rare case of an immunocompetent elderly adult with gastrointestinal CMV infection that presented as a vanishing tumor at the cecum. A 76-year old man initially presented with lower abdominal pain. Colonoscopy revealed a tumorous lesion with irregular ulceration observed at the ileocecal valve. Histological findings of a biopsy specimen revealed intranuclear inclusions which were positive for CMV on immunohistochemical staining. However, this tumorous lesion disappeared within 7 wk from the initial hospital visit without any further treatment. Inflammatory pseudotumors associated with CMV infection should be considered as a differential diagnosis of tumorous lesions in the colon, even in immunocompetent adults.

Backgrounds/aims: Most of patients who are refractory to usual standard eradication therapies for H. pylori infection have rapid metabolizer genotype of CYP2C19 and are infected with resistant strains to several antimicrobial agents. However, most of H. pylori strains are sensitive to amoxicillin. We tested whether dual therapy with the 4 times daily dosing of rabeprazole and amoxicillin was effective as the 3rd rescue regimen for eradication of H. pylori., Methodology: 49 patients who failed in eradication of H. pylori after two (1st: proton pump inhibitor (PPI)/amoxicillin/clarithromycin and 2nd: PPI/amoxicillin/metronidazole) were enrolled to the study. They were treated with rabeprazole 10 mg q.i.d. and amoxicillin 500 mg q.i.d. for 2 weeks. At 4 weeks after the treatment, they underwent the [13C]-urea breath test. When the result of [13C]-urea breath test was negative, they underwent the endoscopy and the successful eradication was confirmed by rapid urease test., Results: All patients completed the treatment. The eradication rate was 87.8% (43/49) (95% CI = 75.2%-95.4%). No undesirable severe adverse events were observed during the study period., Conclusions: The dual therapy with 4 times daily dosing of rabeprazole and amoxicillin is well tolerated and effective as the 3rd rescue regimen for eradication of H. pylori.

Gallstone ileus is a rare but important cause of small bowel obstruction in the geriatric population. A 65-year-old man with a twenty year history of cholecystolithiasis was admitted to our hospital with abdominal pain and vomiting. Physical exams showed abdominal defence and rebound tenderness. A plain abdominal X-ray suggested a small bowel obstruction and pneumobilia. CT scan revealed a 2.5-cm gallstone at the jejunum and air in the biliary tree. The patient underwent a emergency laparotomy based on a diagnosis of panperitonitis with a perforation associated with gallstone ileus. Operative findings revealed a jejunal perforation and a impacted stone on the anal side of perforation. Enterolithotomy and jejunal resection were performed with cholecystectomy and repairment of the cholecystoduodenal fistula.