Effect of Helicobacter pylori infection on esophagogastric variceal bleeding in patients with liver cirrhosis and portal hypertension.

BACKGROUND AND AIMS: Bleeding from esophageal and gastric varices is a fatal event in patients with liver cirrhosis and portal hypertension. However, the effects of Helicobacter pylori (H. pylori) infection on esophagogastric variceal bleeding are not known. The present study was aimed to elucidate the role of H. pylori infection in esophagogastric variceal bleeding. METHODS: The subjects were 196 cirrhotic patients who were admitted to the Kurume University Hospital to treat their esophagogastric varices consisted of 95 with acute bleeding and 101 with nonbleeding but high risk of bleeding. For the diagnosis of H. pylori infection, a (13) C-urea breath test was used, and serum pepsinogen (PG) I and II levels and the PG I/II ratio were also measured. RESULTS: Esophagogastric variceal bleeding was seen in 34.9% (n = 30) of the H. pylori-infected patients (n = 86) and in 59.1% (n = 65) of the noninfected patients (n = 110) (P < 0.0007). There was no significant difference in the infection rate between the bleeding sites of the esophagus and the stomach. The serum PG I and II levels and the PG I/II ratio were 65.6 ng/dL, 14.7 ng/dL, and 4.4, respectively, for the bleeding patients (n = 95), and 43.7 ng/dL, 17.7 ng/dL, and 3.1 for the nonbleeding patients (n = 101). Thus, the nonbleeding patients had significantly higher rate of H. pylori infection and lower acid secretion than bleeding patients (0.001). In addition, multivariate logistic regression analysis showed a significant negative association between H. pylori infection and esophagogastric variceal bleeding. CONCLUSIONS: These results suggest that H. pylori infection has a protective effect against esophagogastric variceal bleeding through the induction of gastric mucosal atrophy and concomitant hypoacidity.

Long-term results of balloon-occluded retrograde transvenous obliteration for gastric fundal varices: hepatic deterioration links to portosystemic shunt syndrome.

BACKGROUND AND AIMS: It is well known that a large portosystemic shunt develops during portal hypertension. In this study, we studied the long-term effects of a large splenorenal shunt (SRS) on liver function and survival. METHODS: The subjects were divided into three groups: an SRS (-) group consisting of cirrhotic patients without SRS; an SRS (+) group consisting of patients with gastric fundal varices and SRS; and a balloon-occluded retrograde transvenous obliteration (B-RTO) group with a completely obliterated SRS by B-RTO. We compared the following among these groups: the total bilirubin levels, serum albumin levels, prothrombin times, changes in Child-Pugh scores, and survival rates. RESULTS: After a 3-year follow-up period the Child-Pugh scores showed significant differences among the SRS (+), SRS (-), and B-RTO groups. The score worsened for the SRS (+) group. The cumulative survival rates were significantly different between the SRS (+) and SRS (-) groups and between the SRS (+) and B-RTO groups. The vital prognosis worsened for the SRS (+) group. CONCLUSIONS: The presence of a large splenorenal shunt (portosystemic shunt) was indicated to lower liver function and vital prognosis. B-RTO, which completely obliterates large splenorenal shunts, inhibited the lowering of hepatic functional reserve and the worsening of vital prognosis, indicating a protective role. Liver pathology and the presence of a large portosystemic shunt each separately result in progressive liver dysfunction and worsen the survival rate. We found that such a pathological condition had occurred due to a large portosystemic shunt, and it should be called 'portosystemic shunt syndrome.'

Direct cholangioscopy using a double-balloon enteroscope: choledochojejunostomy with intraductal biliary carcinoma.

A 75-year-old man who underwent choledochojejunostomy for gallstones 30 years ago was hospitalized for general malaise. Abdominal computed tomography revealed marked dilation of the intrahepatic bile duct in the right lobe and an image of a hypervascular tumor. Endoscopic retrograde cholangiography using double-balloon enteroscopy (DBE) showed a filling defect that was localized to the right hepatic bile duct. Furthermore, the scope was able to readily pass through the anastomosed site of the choledochojejunostomy and, therefore, we observed the interior of the bile duct using the same scope. We obtained an image showing a whitish, papillary-like tumor, and a biopsy of the tumor rendered the pathology of intraductal papillary mucinous carcinoma. Direct cholangioscopy using DBE is a useful diagnostic tool, particularly in patients with a past history of choledochojejunostomy.

Endoscopic retrieval of migrated plastic stent into bile duct or pancreatic pseudocyst.

Proximally migrated biliary plastic stent and migrated stent in the pancreatic pseudocyst are relatively rare complications. A migrated stent causes poor drainage conditions, which leads to secondary complications such as infection, abscess, perforation and, moreover, becomes a foreign object in the body, and retrieval or re-stenting is therefore necessary. The retrieval of a migrated stent includes surgical, percutaneous and endoscopic approaches, and the most non-invasive method is endoscopic retrieval. However, because very few devices are exclusively designed for retrieval, the current situation is that the available devices are used while taking advantage of various ideas and techniques. From previously reported cases and our experiences of such cases, we herein describe the methods of endoscopic retrieval for stents that have migrated into a bile duct or pancreatic pseudocysts.

[A case of hepatic eosinophilic granuloma, which needs distinction with metastatic liver cancer].

A 68-year-old man was referred to our hospital because of eosinophilia in peripheral blood and pancreatic tumor on abdominal US. He was accustomed to eating the raw flesh of wild boar and keeping wild boar, and under medical treatment for Diabetes. Pancreatic tumor was diagnosed to the pancreatic ductal cancer by the imaging examination and endoscopic transpapillary brushing cytology for pancreatic duct. The diagnosis of hepatic eosinophilic granuloma was done by aspiration biopsy for hepatic multiple small nodules. Because of the strong positive finding for nematose in the assay of multi dot-ELISA for parasite, hepatic eosinophilic granuloma caused by visceral larva migrans was accidentally complicated by pancreatic cancer, and operation for the pancreatic cancer was done. To bear this disease in mind and to research his life history, is important to diagnose hepatic multiple nodules with eosinophilia.

Lamivudine treatment-related morphological changes of esophageal varices in patients with liver cirrhosis.

AIM: Many studies have reported the therapeutic effects of lamivudine on cirrhotic patients with hepatitis B; however, no study has investigated the morphological changes of esophageal varices after lamivudine treatment. METHOD: The morphological changes of esophageal varices in patients with cirrhosis were retrospectively compared between 12 patients treated with lamivudine and six historical untreated patients. RESULTS: In the treated group, the HBV DNA and hyaluronic acid (HA) levels in the serum were significantly lower than those in the untreated group (P = 0.013 and P = 0.009, respectively) at the end of follow-up, with a significant improvement in the Child-Pugh-Turcotte score (P = 0.022). In the treated group, the disappearance or reduction of esophageal varices was observed in six (50%) of the 12 patients. In three (25%) of the 12 patients, esophageal varices worsened. In the remaining three patients (25%), there were no changes in esophageal varices. In the untreated group, all patients showed the worsening of esophageal varices during the follow-up period, with a significant difference between this group and the treated group (P = 0.009). The serum HA level decreased in the nine treated patients without worsening of esophageal varices. However, in the three patients with worsening, the HA level significantly increased. CONCLUSION: Lamivudine treatment for patients with cirrhosis improves not only liver function but also esophageal varices.

Pro-inflammatory signaling by Jun-N-terminal kinase in inflammatory bowel disease.

Since Jun-N-terminal kinase participates in intracellular signaling cascades resulting in inflammatory responses, inhibiting this pathway may represent a new treatment for inflammatory bowel disease including ulcerative colitis and Crohn's disease. However, the functional significance of the activation of this kinase in inflammatory bowel disease remains unclear. We investigated whether Jun-N-terminal kinase activation is increased in inflammatory bowel disease and analyzed the effects of SP600125, which decreases inflammatory cytokine synthesis by inhibiting the phosphorylation of this kinase. Phosphorylation of the kinase was examined in affected human colon using an enzyme-linked immunosorbent assay and immunohistochemistry. The effect of SP600125 on cytokine production was examined in cultures of patients' leukocytes and colonic tissue. Finally, rats received injection of SP600125 (30 mg/kg, s.c.) or vehicle twice daily 2 h before the induction of colitis with dextran sulfate sodium. SP600125 effects were determined observationally and histologically. Colonic tissue contained increased phosphorylated kinase in patients with inflammatory bowel disease with expression localized to the nucleus of epithelial and lamina propria mononuclear cells in lesions. Culturing mononuclear cells or colonic tissue with SP600125 down-regulated inflammatory cytokine production. Prophylactic treatment with SP600125 significantly reduced clinical and pathological scores in dextran sulfate sodium-treated rats. This first demonstration of the pathogenetic role of Jun-N-terminal kinase in the development of intestinal inflammation suggests that inhibiting its phosphorylation could benefit patients with inflammatory bowel disease.

Bifidogenic growth stimulator for the treatment of active ulcerative colitis: a pilot study.

OBJECTIVES: Experimental studies have shown that luminal antigens are involved in chronic intestinal inflammatory disorders. Bifidogenic growth stimulator (BGS) is a prebiotic preparation produced by Propionibacterium freudenreichii isolated from Swiss cheese. Previously BGS was shown to act in the colon as a growth stimulator of Bifidobacteria. This study investigated the efficacy and safety of BGS in the treatment of ulcerative colitis. METHODS: Twelve patients with mildly to moderately active ulcerative colitis received orally 4.5 g of BGS daily for 4 wk in an open-label treatment protocol while the baseline anti-inflammatory therapy was continued. The response to treatment was evaluated clinically and endoscopically. Concentrations of short-chain fatty acids and the composition of commensal bacteria, including Bifidobacteria, Enterobacteria and Bacteroides species, were studied in stool samples. RESULTS: Patients showed improvement in their clinical activity index scores, with a significant decrease in the score from 7.4 +/- 2.8 to 4.7 +/- 1.5 (mean +/- standard error of the mean, P < 0.01). The endoscopic index score decreased from 4.4 +/- 1.7 to 2.8 +/- 1.8 (P < 0.05) with treatment. Patients showed an increase in stool butyrate concentrations after BGS treatment (P < 0.05). There were no significant changes in stool levels of bacteria as a result of BGS treatment. No side effects related to BGS were observed. CONCLUSIONS: Oral BGS therapy may represent a non-toxic way to treat ulcerative colitis. However, controlled studies are needed to demonstrate its efficacy in the treatment of this disorder.

Endoscopic ultrasonography-guided cystogastrostomy for large pancreatic pseudocyst with obstructive jaundice--a case report.

The patient was a 45-year-old man with a history of heavy drinking. A pseudocyst about 30 mm in diameter was found in the head of his pancreas. About four weeks later an upper abdominal mass, abdominal pain and obstructive jaundice were confirmed. Abdominal CT revealed that the cyst had increased in size to about 60 mm, compressing the lower common bile duct and the surrounding digestive tract. Therefore endoscopic ultrasonography-guided cystogastrostomy following percutaneous transhepatic biliary drainage (PTBD) was performed. Postoperatively, the cyst quickly decreased in size and jaundice improved. Because of persistent common bile duct stenosis, an endoscopic retrograde biliary stent was implanted. There has been no recurrence at ten months after the endoscopic therapy. While invasive surgery is generally employed in the treatment of pancreatic pseudocyst complicated by obstructive jaundice, EUS-guided cystogastrostomy appears to be a useful procedure, particularly when considering the relatively minor degree of surgical invasion.

[Arterial infusion chemotherapy for patients with advanced pancreatic cancer].

Although various therapies have been tried to improve advanced nonresectable pancreatic cancer, a sufficient consensus has not yet been obtained about the treatment. We have performed arterial infusion chemotherapy for pancreatic cancer in order to maintain QOL. The response rate was 17.3%, the mean survival time 282.1+/-204.7 days, median survival time 243.0+/-84.7 days, and many patients were continuously treated on an outpatient basis. It is thus expected that survival time and maintenance of QOL can be extended by self-sustaining arterial infusion chemotherapy.

A case of mediastinal pancreatic pseudocyst successfully treated with somatostatin analogue.

A 57-year-old man with a 3-year history of chronic pancreatitis was admitted to our hospital with upper abdominal pain. Based on examination findings, the patient was diagnosed as having pseudocysts in the pancreatic body and the mediastinum that were associated with acute aggravation of chronic pancreatitis. Because of the patient refused an operation, he was submitted to conservative management including intramuscular injection with somatostatin analogue of 100 microg/day. On the 14th day of the treatment, pleural effusion and pseudocyst in the pancreatic head were additionally diagnosed based on the findings of computed tomography, magnetic resonance imaging and other examinations, and the dose of somatostatin analogue was increased to 200 microg/day. As a result, on the 28th day of the treatment, pancreatitis was inactivated, and the pseudocysts in the mediastinum and the pancreas disappeared. The patient has been followed up for 15 months, and there has been no recurrence.

Clinicopathologic study of neovascularization and VEGF expression in superficial esophageal carcinoma.

Among superficial esophageal carcinomas (SECs), mucosal carcinoma (m) and submucosal carcinoma (sm) markedly differ regarding the presence or absence of lymph node metastases and long-term survival. To clarify differences in the growth pattern of these two superficial carcinomas, we investigated neovascularization around the site of tumor growth and expression of vascular endothelial growth factor (VEGF) in tumor cells, in patients undergoing radical esophagectomy or endoscopic mucosal resection (EMR). Moreover, we investigated whether these factors were related to the prognosis in patients undergoing treatment of SEC. This study included 90 SEC patients undergoing radical esophagectomy (surgery group) and 35 patients undergoing EMR (EMR group). For immunohistochemical staining antibodies against factor VIII-related antigen and against VEGF were used. The microvessels around the tumor were counted to calculate the vascular index (VI). VI and VEGF expression in the tumor were compared in relation to clinicopathologic findings. In the surgery group, the VI and the percent of VEGF-positive cells were significantly higher in the case of sm carcinomas. Furthermore, tumors with a high VI showed a significantly worse prognosis. In the EMR group, the VI and percent of VEGF-positive cells increased with the depth of the tumor. The VI and VEGF expression were significantly higher in sm carcinomas. This may in part explain the difference in cancer progression between m and sm carcinomas. In patients undergoing resection or EMR, examination of neovascularization using VI may be potentially useful in evaluating the prognosis of SEC.

Intestinal microflora as a therapeutic target in inflammatory bowel disease.

Although the causes of inflammatory bowel disease (IBD) remain incompletely understood, increasing evidence implicates intestinal microflora in the pathogenesis of these disorders. Alteration of intestinal flora therefore may offer a plausible therapeutic approach. Although recent data support a potential therapeutic role for probiotics and prebiotics in patients with IBD, such treatments need to be further assessed by large, double-blind controlled trials. A better understanding of the intestinal microflora and the mechanisms of their action may help us to develop more effective treatment for IBD.

Propranolol ameliorates thrombocytopenia in patients with cirrhosis.

BACKGROUND: Propranolol causes splanchnic arterial vasoconstriction owing to the unopposed alpha vasoconstriction resulting from the blockade of beta-2 adrenoceptors. It is therefore hypothesized that this drug may cause vasoconstriction in the splenic arterial circulation and, thus, modify the manifestations of hypersplenism, such as thrombocytopenia. The aim of the present study was to test this hypothesis. METHODS: Nineteen patients with cirrhosis and thrombocytopenia (fewer than thrombocytes 7 x 10(4)/mm3) were include. The subjects of the study. All of them were studied in the morning after an overnight fast. To evaluate splenic arterial hemodynamics, the pulsatility index was measured by Doppler ultrasonography. Platelet counts and platelet-associated immunoglobulin G levels were also recorded. The subjects were then randomized to receive propranolol (n = 10) or placebo (n = 9). The measurements were repeated after 1 week of propranolol or placebo administration. The dose of propranolol was determined so that a 20% to 25% reduction in heart rate was achieved. RESULTS: Placebo administration caused no significant changes in splenic artery hemodynamics. In contrast, propranolol administration significantly increased the intra splenic artery pulsatility index (from 1.10+/-0.06 to 1.24+/-0.08; P < 0.01). Placebo administration caused no significant changes in the platelet count. In contrast, propranolol administration significantly increased the platelet count (from 4.5+/-0.3 to 6.1+/-0.73 x 10(4)/mm3; P < 0.05). Furthermore, the change in platelet count was significantly correlated with either the change in extrasplenic artery pulsatility index (r = 0.78, P < 0.05) or the change in intrasplenic artery pulsatility index (r = 0.78, P < 0.01). Platelet-associated immunoglobulin G levels were not modified in either of the two groups. CONCLUSIONS: Propranolol ameliorates thrombocytopenia in patients with cirrhosis. This effect may be caused mainly by hemodynamic changes in the spleen, rather than being caused by immunological mechanisms.

Germinated barley foodstuff, a prebiotic product, ameliorates inflammation of colitis through modulation of the enteric environment.

BACKGROUND: Germinated barley foodstuff (GBF), which contains glutamine-rich protein and hemicellulose-rich fiber, exhibits therapeutic effects in ulcerative colitis; however, its mechanism is still under investigation. The aim of this study was to evaluate the anti-inflammatory effects of GBF on colitis in terms of the epithelial inflammatory response. METHODS: Mice with dextran sulfate sodium-induced colitis were used. The effects of GBF on the colitis were evaluated by measuring the body weight; disease activity; mucosal damage (histology, mucosal inflammatory parameters, nuclear factor kappa B [NFkB] activation, and signal transducer and activator of transcription 3 [STAT3]); serum interleukin 6 (IL-6) level; cecal short-chain fatty acids (SCFAs); and bile acid contents. RESULTS: GBF significantly prevented disease activity and body weight loss after induction of colitis. Serum IL-6 level and mucosal STAT3 expression were also significantly attenuated, with a conspicuous reduction of mucosal damage; NFkB activity showed the same tendency. Cecal butyrate content was significantly higher and, interestingly, GBF mice had lower bile acid concentrations than the control group. CONCLUSIONS: GBF has the potential to reduce the epithelial inflammatory response by depressing STAT-3 expression and inhibiting NFkB binding activity. These effects may be brought about by an increase of butyrate production and adsorption of bile acids.

Prebiotic treatment of experimental colitis with germinated barley foodstuff: a comparison with probiotic or antibiotic treatment.

There is increasing evidence that intestinal microflora play an important role in the pathogenesis of ulcerative colitis. Therefore, modification of the microflora by prebiotics, probiotics, and antibiotics may be a rational approach for controlling intestinal inflammation. Germinated barley food-stuff (GBF) is an insoluble mixture of glutamine-rich protein and hemicellulose-rich dietary fiber. GBF is utilized efficiently by Bifidobacterium, Lactobacillus, and Eubacterium and converted by them into lactate, acetate, and butyrate. These bacterial organic acids preserve a favorable intestinal condition. We have previously shown that GBF has attenuated intestinal inflammation in patients with ulcerative colitis and experimental colitis models through prebiotic actions. The aim of this study was to compare the effect of GBF with that of probiotics and antibiotics in an experimental colitis model. Colitis was induced by feeding male SD rats with a diet containing 3.0-3.5% dextran sodium sulfate (DSS). The therapeutic effect of oral administration of a prebiotic (GBF), probiotics (mixture of Lactobacillus and Clostridium butyricum), antibiotics (vancomycin, metronidazole), and the vehicle was determined by assessing clinical and pathological scores on day 6 after initiation of colitis. Butyrate concentrations in the cecal content were also determined. GBF treatment significantly reduced colonic inflammation as assessed by clinical scores with an increase in cecal butyrate levels. Probiotic treatment with a mixture of Lactobacillus and Clostridium butyricum did not show such an effect. Both antibiotic treatments significantly attenuated clinical and pathological scores. However, in contrast to GBF, this treatment led to a significant decrease in cecal butyrate levels. These data suggest that modification of the intestinal microflora by prebiotics, including GBF, may serve as a useful adjunct in the treatment of ulcerative colitis as well as antibiotic treatment.

Germinated barley foodstuff prolongs remission in patients with ulcerative colitis.

Germinated barley foodstuff (GBF) is a prebiotic which increases luminal butyrate production by modulating the microfloral distribution. GBF has been shown to reduce both clinical activity and mucosal damage in active ulcerative colitis (UC) with mild to moderate activity. However, the efficacy of GBF in patients with UC during the remission stage is unknown. The aim of this study was to investigate the efficacy of GBF as a maintenance therapy in patients with UC while in remission. Fifty-nine patients with UC in remission according to Rachmilewitz's clinical activity index (CAI) score of

Treatment of ulcerative colitis patients by long-term administration of germinated barley foodstuff: multi-center open trial.

Germinated barley foodstuff (GBF), which mainly consists of dietary fiber and glutamine-rich protein, is a prebiotic for ulcerative colitis (UC). In our previous study, we carried out a clinical trial of GBF with mildly to moderately active UC patients and showed that GBF treatment was able to attenuate the symptoms of UC in a relatively short-term. The aim of this study was to investigate the efficacy of long-term administration of GBF in the treatment of UC in a multi-center open trial. Twenty-one patients with mildly to moderately active UC received 20-30 g of GBF for 24 weeks in an open-label protocol while baseline treatments (5-amino-salicyrate compounds and/or steroids) were continued. The response to the GBF treatment was evaluated using a clinical scoring and after 24 weeks of observation, the GBF group showed a significant decrease in clinical activity index (especially, the degree of visible blood in stools and the presence of nocturnal diarrhea) compared with the control group (p<0.05). No side effects related to GBF were observed. In conclusion, GBF can reduce the clinical activity of UC over long-term as well as short-term administration. Nutraceutical GBF therapy may have a place in long-term management of UC, but controlled studies are needed to demonstrate its efficacy in the treatment of this disorder.