Clinicopathological Features of Autoimmune Hepatitis with IgG4-Positive Plasma Cell Infiltration.

BACKGROUND: We aimed to elucidate the characteristics and prognosis of autoimmune hepatitis (AIH) patients with immunoglobulin (Ig) G4-positive plasma cell infiltration. METHODS: We enrolled 84 AIH patients. The number of IgG- and IgG4-positive plasma cells was immunohistochemically counted per high-power field in the portal area. Patients with 3 or more IgG4-positive plasma cells on average and a ratio of IgG4 to IgG-positive plasma cells ≥5% were defined as IgG4-associated AIH (IgG4-AIH), and their clinicopathological characteristics and prognosis were compared to those of the remaining classical-AIH patients. RESULTS: Ten (11.9%) and 74 patients (88.1%) were categorized as IgG4-AIH and classical-AIH patients, respectively. The median age of the IgG4-AIH patients was 67 years, the majority was female (80.0%), and the distribution was similar to that of the classical-AIH patients. The IgG4-AIH patients exhibited significantly more severe phenotypes in portal inflammation, interface hepatitis, fibrosis, and rosette formation. All clinical laboratory data were similar except for serum IgG4 levels, which were higher in IgG4-AIH patients (168.5 vs. 22.9 mg/dL, p = 0.014). During a median follow-up period of 139 months, the relapse rate was significantly lower in the IgG4-AIH group than in the classical-AIH group (11.1 vs. 49.2%; p = 0.048). Twelve (16.2%) and 6 (8.1%) classical-AIH patients underwent liver-related events and liver-related deaths, respectively. In contrast, none of the IgG4-AIH patients progressed to severe liver disease. CONCLUSIONS: The IgG4-AIH patients had more severe inflammation and advanced fibrosis in the liver. However, their prognosis was not poor compared to that of classical-AIH patients. IgG4-AIH may have a phenotype distinct from classical-AIH.

Use of Endoscopy to Remove Fish Bone that Caused Sigmoid Colon Perforation.

An 87-year-old man experiencing lower abdominal discomfort resulting from the ingestion of a fish bone underwent conservative management involving endoscopic extraction of the fish bone lodged in the sigmoid colon. Most patients with lower gastrointestinal tract perforations typically develop peritonitis or abscesses, necessitating surgical intervention. Notably, endoscopic management of lower gastrointestinal tract perforations is infrequently employed. Patients presenting with localized abdominal symptoms along with a stable overall health condition may benefit from conservative therapeutic approaches that utilize endoscopic methods. Notably, the transition from endoscopic procedures for foreign body removal to surgical intervention requires close collaboration with a surgeon and must be executed judiciously.

Low-grade Appendiceal Mucinous Neoplasm with Appendiceal Reduction and Re-expansion Over a Two-year Period: A Case Report.

A 71-year-old woman was found to have submucosal tumor-like lesion on colonoscopy (CS) before gastric surgery, and computed tomography (CT) showed a 12-mm structure at the base of the appendix. The lesion could not be clearly detected on CT nine months later, but it had enlarged again on CT one year later; therefore, CS and endoscopic ultrasound (EUS) were performed. The lesion was determined to be cystic with viscous contents, and laparoscopic appendicectomy was performed. This is the first report of low-grade appendiceal mucinous neoplasm (LAMN) diagnosed by a histopathologic examination of a resected specimen showing shrinkage and re-expansion of the appendix.

Helicobacter pylori Eradication Therapy for Colorectal Mucosa-associated Lymphoid Tissue Lymphoma: Report of Two Cases.

Two cases of colorectal mucosa-associated lymphoid tissue lymphoma (cMALT) are presented and discussed with the reports from 1997 to the present. Helicobacter pylori (HP)-negative cases showed tumor resolution 2 months after eradication therapy. HP-positive cases were successfully eradicated and tumor resolution was confirmed 16 months later. Analysis of the data reported to date shows that cMALT resolution rates were 68.4% (13/19) in the HP-negative group and 33.3% (7/21) in the HP-positive group. HP eradication should be considered the primary treatment for cMALT regardless of HP infection, especially in untreated patients under follow-up.

Ectopic Adrenocorticotropic Hormone Syndrome due to Pancreatic Neuroendocrine Carcinoma: A Case Report.

A 55-year-old woman presented to her primary care physician with facial and lower leg edema. After being referred to our hospital because of hypothyroidism and hypokalemia on blood tests, she also had elevated adrenocorticotropic hormone (ACTH) and cortisol levels, but a dexamethasone suppression test showed no cortisol suppression. Ectopic ACTH syndrome due to pancreatic neuroendocrine carcinoma (PNEC) was suspected. endoscopic ultrasound-guided fine-needle aspiration was performed, and a histopathological examination of the obtained specimen revealed multiple liver metastases of the PNEC. Imaging after etoposide and cisplatin therapy showed cystic changes in the primary lesions and shrinkage of the liver metastases, and the ACTH levels were within the normal range.

Effect of pretreatment with Lactobacillus gasseri OLL2716 on first-line Helicobacter pylori eradication therapy.

BACKGROUND AND AIM: Helicobacter pylori eradication clearly decreases peptic ulcer recurrence rates. H. pylori eradication is achieved in 70-90% of cases, but treatment failures due to poor patient compliance and resistant organisms do occur. Lactobacillus gasseri can suppress both clarithromycin-susceptible and -resistant strains of H. pylori in vitro. The aim of this study was to determine the effect of pretreatment with L. gasseri- containing yogurt on H. pylori eradication. We conducted a randomized, controlled clinical trial in patients with H. pylori infection. METHODS: A total of 229 patients were randomized into either a 1-week triple therapy of rabeprazole (10 mg bid), amoxicillin (750 mg bid), and clarithromycin (200 mg bid) or triple therapy plus L. gasseri-containing yogurt. In the yogurt-plus-triple therapy groups, yogurt containing L. gasseri OLL2716 (112 g) was given twice daily for 4 weeks (3 weeks pretreatment and also 1 week during eradication therapy). Clarithromycin resistance was determined by the detection of a mutation in 23S rRNA using nested polymerase chain reaction and the direct sequencing of DNA from pretreatment feces. H. pylori eradication was diagnosed based on the urea breath test and a stool antigen test after 8 weeks of eradication. RESULTS: The status of H. pylori susceptibility to clarithromycin was successively determined in 188 out of 229 samples. The rate of infection with clarithromycin-resistant strains of H. pylori was 27.1%. Overall eradication (intention to treat/per protocol) was 69.3/74.5% for the triple-only group, and 82.6/85.6% for the yogurt-plus-triple group (P = 0.018/P = 0.041). Eradication of primary clarithromycin-resistant strains tended to be higher for yogurt-plus-triple therapy than triple-only therapy (38.5 vs 28.0%, respectively, P = 0.458). CONCLUSION: This study confirmed that the major cause of treatment failure is resistance to clarithromycin. A 4-week treatment with L. gasseri-containing yogurt improves the efficacy of triple therapy in patients with H. pylori infection.

Clinical symptoms of FSSG in gastroesophageal reflux disease are critical for PPI treatment: Japanese multi-centers with 185 patients.

AIM: The main aim of this study was to determine whether questionnaire evaluations of clinical symptoms in gastroesophageal reflux disease were useful to assess proton pump inhibitor therapy. METHODS: A total of 185 Japanese patients (men, 88; women, 97; age: 55.7 ± 16.1 years) with gastroesophageal reflux disease were enrolled. The patients were divided based on the frequency scale for symptoms of gastroesophageal reflux disease: severe symptoms with scores ≥8 and mild symptoms with scores ≤7. Quality of life was evaluated with the Medical Outcomes Study 8-Item Short-Form Health Survey. All patients were treated with a proton pump inhibitor, rabeprazole (10 mg/day), for 8 weeks. RESULTS: Patients were classified into four groups: reflux esophagitis with severe symptoms (n = 92, 49.7%); reflux esophagitis with mild symptoms (n = 17, 9.2%); non-erosive reflux disease with severe symptoms (n = 66, 35.7%); and non-erosive reflux disease with mild symptoms (n = 10, 5.4%). The dysmotility score was high in non-erosive reflux disease with severe symptoms compared with reflux esophagitis with severe symptoms (9.1 ± 0.5 vs 6.8 ± 0.5, P < 0.05). The symptom score and quality of life in the severe symptoms groups for both reflux esophagitis and non-erosive reflux disease were significantly improved by rabeprazole treatment. Only the reflux score was improved by rabeprazole in the reflux esophagitis with mild symptoms group; no therapeutic effect was observed for the non-erosive reflux disease with mild symptoms group. CONCLUSIONS: Low scores on the frequency scale for the symptoms of gastroesophageal reflux disease indicate poor responsiveness to proton pump inhibitor treatment, and high scores indicate good responsiveness.

Comparison of a monoclonal with a polyclonal antibody-based enzyme immunoassay stool test in diagnosing Helicobacter pylori infection after eradication therapy.

BACKGROUND: Recently, a novel Helicobacter pylori stool antigen test (Testmate pylori antigen EIA) using monoclonal antibodies against H. pylori catalase has been developed commercially. This study assessed the diagnostic usefulness of the stool antigen test compared with a polyclonal enzyme immunoassay (HpSA test) after H. pylori eradication. METHODS: A total of 150 patients with H. pylori infection were treated by triple therapy with PPI and amoxicillin with either clarithromycin or metronidazole. H. pylori stool antigen was tested 4 and 8 weeks after eradication. The outcome of H. pylori eradication was assessed by urea breath test (UBT) 8 weeks after the end of therapy. Discordant results were followed by endoscopic examination. RESULTS: Of 150 patients enrolled, H. pylori status was negative in 122 cases and positive in 28 cases, assessed by the 13C-UBT. On the other hand, the monoclonal stool antigen test results were negative in 126 cases and positive in 24. The polyclonal stool test results were negative in 126 cases and positive in 22. The overall sensitivity and specificity of the monoclonal stool antigen test were 91.6% (95% CI 85.9-97.3%) and 98.4% (95% CI 97.3-99.5%). The overall sensitivity and specificity of the polyclonal stool antigen test were 87.0% (95% CI 86.9-94.0%) and 97.5% (95% CI 96.1-98.9%). CONCLUSION: The new stool antigen test using monoclonal antibody is useful for the diagnosis of H. pylori eradication 4 weeks after the end of treatment.

Impaired Renal Function May Not Negate the Efficacy of Tolvaptan in the Treatment of Cirrhotic Patients with Refractory Ascites.

BACKGROUND AND OBJECTIVE: Tolvaptan, an oral vasopressin V2 receptor antagonist, has been widely used for the treatment of patients with cirrhosis and ascites. However, its efficacy in patients with renal dysfunction remains unknown. The objective of this study was to investigate the efficacy and safety of tolvaptan in patients with decompensated cirrhosis and severe chronic kidney disease (s-CKD). METHODS: We studied 43 patients with liver cirrhosis who received tolvaptan (7.5 mg/day) for refractory ascites. s-CKD was defined as an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2. Response to tolvaptan was defined as weight loss ≥ 1.5 kg in 7 days of treatment. RESULTS: Eighteen patients (42%) had s-CKD (s-CKD group), while the other 25 patients (58%) did not have s-CKD (n-CKD group). Rates of response to tolvaptan were similar: 68% in the n-CKD group and 56% in the s-CKD group. Urine volumes increased significantly from baseline to day 7 in both groups. Incidences of adverse events were also similar (P = 0.93). Mean eGFR did not decline even in the s-CKD group (27.3 ± 2.2 mL/min/1.73 m2 at baseline vs. 26.6 ± 2.3 mL/min/1.73 m2 on day 7; P = 0.9). The cumulative survival rate did not differ significantly between the n-CKD and s-CKD groups. In the s-CKD group, responders obtained a better prognosis than non-responders. CONCLUSIONS: Tolvaptan significantly increased urine volumes similarly in patients with s-CKD and n-CKD without affecting renal function. As responders achieved a better prognosis, tolvaptan could be a good option to treat ascites in patients with cirrhosis and s-CKD.

Effect of Sodium Glucose Co-Transporter 2 Inhibitors on Liver Fat Mass and Body Composition in Patients with Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus.

BACKGROUND AND OBJECTIVE: Sodium glucose co-transporter 2 inhibitors increase urinary glucose excretion and reduce visceral adiposity and body weight, but their efficacy on patients with nonalcoholic fatty liver disease has not been sufficiently investigated. The aim of this study was to assess the effect of sodium glucose co-transporter 2 inhibitors on liver fat mass and body composition in patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus. METHODS: We retrospectively analyzed 17 patients with nonalcoholic fatty liver disease and type 2 diabetes who received sodium glucose co-transporter 2 inhibitors between November 2016 and July 2017. Changes in liver fat, subcutaneous and visceral fat, body composition, and liver function-related parameters were assessed after 24 weeks of sodium glucose co-transporter 2 inhibitor treatment and compared to baseline values. RESULTS: Ten patients received dapagliflozin at 5 mg/day and seven patients received canagliflozin at 100 mg/day for 24 weeks. All patients completed the study without any serious adverse effects and achieved body weight loss and improved glycated hemoglobin levels. Liver fat mass evaluated by proton magnetic resonance spectroscopy was significantly reduced (19.1% vs. 9.2%, p < 0.01), and so were both subcutaneous and visceral fat mass. The body fat/body weight ratio decreased, whereas the skeletal muscle mass/body weight ratio increased. Liver function (aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transpeptidase) improved significantly. CONCLUSIONS: Sodium glucose co-transporter 2 inhibitor treatment not only improved glycemic control but also reduced liver fat mass in patients with nonalcoholic fatty liver disease and type 2 diabetes. Body weight loss was primarily attributable to a reduction in fat mass, especially visceral fat. Thus, sodium glucose co-transporter 2 inhibitors could potentially serve as a therapeutic agent for patients with nonalcoholic fatty liver disease and type 2 diabetes.

Successful Eradication Therapy for Helicobacter pylori-positive Atrophic Gastritis at the Sixth Attempt: A Case Report.

A 74-year-old woman undergoing outpatient follow-up for reflux esophagitis and atrophic gastritis tested positive for Helicobacter pylori and underwent primary eradication therapy with lansoprazole (LPZ) 30 mg, amoxicillin (AMPC) 750 mg, and clarithromycin (CAM) 200 mg twice daily for 1 week in August 2012. A urea breath test (UBT) after this treatment revealed that eradication had failed. Secondary eradication therapy was carried out with esomeprazole (EPZ) 20 mg, AMPC 750 mg, and metronidazole (MNZ) 250 mg twice daily for 1 week, but this also failed. The third attempt at eradication consisted of EPZ 20 mg, AMPC 750 mg, and sitafloxacin (STFX) 100 mg twice daily for 1 week, but this also ended in failure. A fourth attempt using rabeprazole (RPZ) 20 mg (4 times daily) with MNZ 250 mg and STFX 100 mg twice daily for 2 weeks also failed, as did a fifth attempt in April 2015 using vonoprazan (VPZ) 20 mg, AMPC 750 mg, and MNZ 250 mg twice daily for 1 week. Eradication was finally successful after the sixth attempt, in which the patient was treated with vonoprazan 20 mg, MNZ 250 mg, and STFX 100 mg twice daily for 2 weeks.

Double Common Bile Duct with Ectopic Drainage into the Stomach Found in Asymptomatic.

The case of a patient with asymptomatic double common bile duct that was identified by chance is presented. A 41-year-old man underwent esophagogastroduodenoscopy(EGD) as part of a regular health checkup, during which he was found to have an elevated lesion in the lesser curvature of the upper gastric corpus with bile draining from its tip. Further examination led to a diagnosis of double common bile duct from the left intrahepatic bile duct to the opening into the stomach. Morphological abnormalities of the biliary tree are commonly encountered in everyday gastroenterological practice, but a double common bile duct with an ectopic opening into the stomach is comparatively rare. It is also associated with an increased risk of developing cancer of the stomach or bile duct, and as such is a biliary abnormality that must be treated with caution. This case is reported together with a discussion of the literature.

Relationship between IL-1beta gene polymorphism and gastric mucosal IL-1beta levels in patients with Helicobacter pylori infection.

BACKGROUND: Interkeukin-1 (IL-1) gene cluster polymorphisms that are thought to enhance the production of IL-1beta are associated with an increased risk of gastric cancer. To determine the role of host genetic factors in Helicobacter pylori infection, we examined the relationship between gastric mucosal IL-1beta levels and IL-1B polymorphisms in patients with H. pylori infection. METHODS: Biopsy tissues obtained from 99 patients were homogenized and gastric mucosal IL-1beta levels were measured by enzyme-linked immunosorbent assay (ELISA). Single-base polymorphisms at positions -511 and -31 in IL-1B were analyzed. RESULTS: The IL-1beta level in the antrum was significantly higher in genotype IL-1B-511C/C than in H. pylori-negative patients (P < 0.05). The IL-1B polymorphism did not influence the degree of gastric neutrophil and mononuclear cell infiltration, or gastric atrophy. IL-1beta levels in the corpus, but not those in the antrum, correlated to the severity of gastric atrophy. CONCLUSIONS: These findings indicate that IL-1B polymorphisms enhance IL-1beta production in the antrum; however, other factors might regulate the production of IL-1beta in the corpus of the stomach, regardless of IL-1B polymorphisms, and high IL-1beta production may be associated with the grade of gastric atrophy in the corpus mucosa in patients with H. pylori infection.

Relationship between gastric mucosal IL-8 levels and histological gastritis in patients with Helicobacter pylori infection.

To determine the role of host immune responses in H. pylori infection, we examined the relationship between gastric mucosal IL-8 levels and histological gastritis in patients with H. pylori infection. Biopsy tissue obtained from 99 patients were homogenizedand mucosal IL-8 levels measured by ELISA. The gastric mucosal IL-8 levels in both the antrum and corpus were higher in patients with H. pylori than in H. pyloi negativepatients. IL-8 levels in the corpus but not the antrum correlated with the severity of the atrophy. The IL-1B polymorphism had no influence on the degree of IL-8 production. These findings indicate that IL-8 production is independent of IL-1B polymorphisms and IL-8 may play an important role in the development of atrophic gastritis.

Successful Endoscopic Resection in a Case of Ectopic and Metachronous Quintuple Gastric Cancers.

A 71-year-old man was referred to us from another hospital for endoscopic treatment of a IIc lesion at the anterior wall of the lower body of the stomach. In November 2008, he underwent resection of this lesion with endoscopic submucosal dissection (ESD). Follow-up endoscopy revealed a IIc lesion in the posterior wall of the lower body of the stomach, and ESD was again performed in February 2009. At the same time, Helicobacter pylori was detected, and successful first-line eradication therapy was verified in May 2009. Subsequent follow-up endoscopy detected multiple ectopic and metachronous gastric cancers at three sites, all of which were endoscopically resected (quintuple gastric cancer). Although ectopic and metachronous recurrence of gastric cancer was detected immediately after H. pylori eradication, recurrence of gastric cancer has not been detected in the 5 years since eradication. Future directions include determining the time point at which the preventative effects of H. pylori eradication therapy appear against gastric cancer recurrence. We report our findings herein, along with a review of the related literature.

Cytokine expressions and H. pylori-associated gastric mucosal lesion.

To determine the role of host genetic factors in Helicobacter pylori infection, we examined the relation between gastroduodenal diseases and IL-1B polymorphisms in patients with H. pylori infection. In addition, we also compared gastric mucosal cytokine levels in those patients. We confirmed the findings that the IL-1B-31 C-to-T base transition was inverted in association with the -511 T-to-C base transition. There was no relation regarding to IL-1B polymorphisms and clinical outcomes. The gastric mucosal IL-1B level of the body of the stomach but not the antrum was significantly different among IL-1B genotypes. Furthermore, the IL-8 levels in the body were also higher in IL-1B-511C/C/ IL-1B-31TT than H. pylori negative patients. These findings suggested that IL-1B polymorphisms enhance not only IL-1-B production but also IL-8 production in the gastric body and may play an important role in the development of atrophic gastritis.

[cag PAI and gastric carcinogenesis-association with p53 gene mutation].

It is widely accepted that carcinogenesis is a multistep process in which regulation of both cell proliferation and apoptosis is disturbed. p53, which is considered the cellular gatekeeper for growth and division, induces apoptosis. Helicobacter pylori(Hp) infection is an accepted risk factor for the development of gastric cancer, but not all infected individuals develop gastric cancer. Because CagA+ Hp induces increased cell proliferation, the CagA+ strain is believed to play an important role in the pathogenesis of gastric cancer. We have reported that p53 alteration were more frequently found in the CagA+ Hp infection in gastric cancer patients. In this chapter, we summarized recent findings of the relation among p53, CagA and cag PAI.

A case of small bowel ulcer caused by NSAIDs and detected after capsule endoscope retention.

We recently detected an annular ulcer thought to have been caused by non-steroidal anti-inflammatory drugs (NSAIDs) when we performed small bowel capsule endoscopy on a patient with suspected small-bowel bleeding and a history of frequent use of oral NSAIDs. The patient was a 64-year-old woman who complained of bloody stools and abdominal pain. The annular ulcer showed concentric stenosis, which caused retention of the capsule endoscope. NSAIDs are some of the most frequently used anti-inflammatory analgesics, and even more frequent use can be expected with the aging of society. No reports to date appear to have described retention of a capsule endoscope due to annular ulceration caused by NSAIDs. We report herein our experience with a patient showing small-bowel ulcer caused by NSAIDs.