Long term results of balloon-occluded retrograde transvenous obliteration for portosystemic shunt encephalopathy in patients with liver cirrhosis and portal hypertension.

This study examined 19 patients with portosystemic shunt encephalopathy caused by a splenorenal shunt (SRS), which was treated with balloon-occluded retrograde transvenous obliteration (B-RTO). Long-term treatment outcomes were evaluated based on hepatic functional reserve and vital prognosis. Encephalopathy improved in all patients after shunt embolization and closure. Albumin, serum ammonia, and the Child-Pugh score, a measure of liver function, were significantly improved 3 years after B-RTO, and exacerbation of damage to liver function was avoided (p<0.01). During the follow-up period, three patients died from liver failure and two patients from hepatocellular carcinoma. Patients had a poor prognosis if their albumin levels were less than 2.8 mg / dL before B-RTO (p<0.05). Encephalopathy patients had complete response to B-RTO, but long-term prognosis was affected by hepatic functional reserve before B-RTO and by concurrent hepatocellular carcinoma. The results of this study suggest that in patients with SRS, it is important to perform B-RTO at an early stage when the hepatic functional reserve is still satisfactory.

Balloon-occluded retrograde transvenous obliteration versus endoscopic injection sclerotherapy for isolated gastric varices: a comparative study.

Isolated gastric varices (IGV) have a lower risk of bleeding than esophageal varices, however IGV bleeding is associated with a higher mortality than bleeding of esophageal varices. In recent years, two widely used treatments for IGV have been balloon-occluded retrograde transvenous obliteration (B-RTO) and endoscopic injection sclerotherapy (EIS) using cyanoacrylate or ethanolamine oleate (EO). This study compared these two treatment methods for IGV. The subjects were 112 patients who were treated at our hospital for IGV bleeding between October 1990 and December 2003. Forty-nine (49) patients were treated with B-RTO and 63 patients with EIS. These two patient groups were compared as regards content of treatment, post-treatment incidence of variceal bleeding, incidence of IGV rebleeding, survival rate, cause of death, and complications. Multivariate analysis was performed on post-treatment variceal bleeding and survival. Although EO was used in higher amounts in the B-RTO group than in the EIS group, the B-RTO group had a significantly lower number of treatment sessions and a significantly shorter treatment period (p<0.05). The EIS group had significantly more patients with IGV rebleeding after treatment than the B-RTO group. Treatment method was the only independent prognostic factor of IGV bleeding after treatment (p=0.024). The two groups did not differ significantly in the percentage of patients with aggravated esophageal varices after treatment. Bleeding from ectopic varices was not observed in any patient. There was no significant difference in survival by treatment method. The presence of hepatocellular carcinoma was the only independent prognostic factor for survival (p=0.003). It is concluded that B-RTO was more effective than EIS in the eradication of IGV and prevention of IGV recurrence and rebleeding.

Contrast-enhanced ultrasonograpic studies on pancreatic carcinoma with special reference to staining and muscular arterial vessels.

Comparative study of contrast-enhanced ultrasonography (CE-US) and histopathology of surgically resected specimens in 13 patients with pancreatic carcinoma. A time intensity curve was used to determine the percentage brightness increase in cancerous and normal regions and the patients were divided into two groups, hyperperfusion, with a percentage brightness increase over 80% (n=6) and hypoperfusion, with an increase of less than 80% (n=7) on CE-US. The hyperperfusion group included well-differentiated tubular adenocarcinoma, adenosquamous cell carcinoma and acinar cell carcinoma, while all 7 patients in the hypoperfusion group had moderately differentiated tubular adenocarcinoma. Immunological staining (α-SMA and anti-CD34) of the resected specimens showed significantly higher microartery count (MAC) in the hyperperfusion group (p<0.005) than in the hypoperfusion group or normal pancreas. In the normal pancreas, the mean vessel diameter was significantly higher (over 100 µm) than in the hyperperfusion group (30 µm; p<0.005). It was concluded that a muscular arterial vessel density of less than 30 µm is an important factor in determining staining degree and carcinoma progression by CE-US in pancreatic carcinoma.

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.

Endoscopic ultrasonographic study of autoimmune pancreatitis and the effect of steroid therapy.

BACKGROUND: Recently, endoscopic ultrasonography (EUS) has been used for the diagnosis of chronic pancreatitis (CP); however, EUS diagnosis of autoimmune pancreatitis (AIP) varies among different researchers. We investigated EUS findings in AIP and retrospectively analyzed them before and after steroid therapy. PATIENTS AND METHODS: The subjects were 32 patients with AIP and the EUS images of the pancreatic parenchyma were evaluated with reference to the Sahai criteria. Patients' background factors detected by EUS were analyzed statistically. Peroral steroid was given to 23 of the 32 patients. EUS was also performed 2 weeks after the initiation of therapy in 14 of the 23 patients, and the changes in EUS were investigated. Microscope images were compared with EUS images in one patient who underwent surgical resection. RESULTS: EUS results included hyperechoic strands in 26 (81.3%) and lobularity in 17 (53.1%) patients. The patients' background factors included the presence of splenic and/or portal vein occlusion or narrowing around the pancreas in patients who had neither hyperechoic strands nor lobularity (p = 0.002, p = 0.004). The numbers of EUS findings before versus after steroid therapy were 11 versus 5 for hyperechoic strands and 7 versus 2 for lobularity. Microscope images showed the coexistence of relatively well-maintained lobular structures of pancreatic acini and almost complete loss of such structures. CONCLUSION: EUS findings in AIP were similar to those in early-stage CP, and hyperechoic strands and lobularity seem to suggest a condition under which the histology of lobular structures of the pancreatic acini is relatively well-maintained. EUS results had improved within about 2 weeks of steroid therapy.

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.

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.'

Current status of ectopic varices in Japan: Results of a survey by the Japan Society for Portal Hypertension.

AIM: The Clinical Research Committee of the Japan Society for Portal Hypertension has conducted a nationwide questionnaire survey to clarify the current status of ectopic varices in Japan. METHODS: A total of 173 cases of ectopic varices were collected. RESULTS: Duodenal varices were found in 57 cases, and most of them were located in the descending to transverse parts. There were 11 cases of small intestinal varices and 6 cases of colonic varices, whereas 77 patients had rectal varices, accounting for the greatest proportion (44.5%). Other sites of varices were the biliary tract, anastomotic sites, the stoma, and the diaphragm. Liver cirrhosis was the most frequent diseases (80.3%) underlying ectopic varices. It was noted that patients with rectal varices frequently had a history of esophageal varices (94.8%) and received endoscopic treatment (87.0%). The treatments for ectopic varices were as an emergency in 46.5%, elective in 35.4% and prophylactic in 18.2%. In emergency cases, endoscopic therapy was most frequent (67.4%), followed by interventional radiology (IVR; 15.2%), and endoscopy-IVR combination (6.5%). Elective treatment was performed by endoscopy in 34.3%, IVR in 28.6%, combined endoscopy-IVR in 5.7%, and surgical operation in 25.7%. The prophylactic treatment was endoscopic in 50.0%, IVR in 33.3%, combined treatments in 11.1%, and prophylactic surgery in none. The change of ectopic varices after treatment was disappearance in 54.9%, remnant in 35.4% and recurrence in 9.7%. The rate of disappearance was significantly lower in rectal varices (40.8%) than in duodenal varices (73.4%). The patient outcome did not differ among the various sites of the lesion. Conslusions: Current status of ectopic varices in Japan has been clarified by a nationwide questionnaire survey. The authors expect that the pathophysiology of ectopic varices will be further elucidated, and that improved diagnostic modalities and treatment methods are established in the future.

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.

[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.

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.

Increased circulating concentrations of growth-related oncogene (GRO)-alpha in patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory state associated with increased risk of intestinal cancers. The aim of this study is to examine serum concentrations of growth-related oncogene (GRO)-alpha, a cytokine with inflammatory and growth-regulatory properties, in patients with IBD. We measured serum concentrations of GRO-alpha in 60 patients with ulcerative colitis, 42 patients with Crohn's disease, 16 patients with other colitides, 12 patients with colorectal cancer, and 40 normal subjects using an enzyme-linked immunosorbent assay. We then analyzed how the cytokine was related to clinical and laboratory variables. Serum GRO-alpha concentrations in patients with active IBD were significantly higher than those in patients with quiescent disease, which in turn were higher than those in normal controls. Concentrations in patients with active ulcerative colitis were higher than in patients with active Crohn's disease. Analysis of paired serum samples showed a decrease in GRO-alpha after initiation of therapy. Furthermore, serum GRO-alpha correlated well with laboratory markers of IBD activity. We conclude that GRO-alpha may have an important role in development of IBD, and might itself be used as a marker of activity. Manipulation of GRO-alpha function might prove therapeutically useful.

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.