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Association between Helicobacter bilis in bile and biliary tract malignancies: H. bilis in bile from Japanese and Thai patients with benign and malignant diseases in the biliary tract.

Japan and Thailand have high incidences of bile duct carcinoma and gallstones. The presence of Helicobacter bilis (H. bilis) detected by polymerase chain reaction (PCR) and 16S rRNA analysis in bile samples from Chileans with chronic cholecystitis was reported. The association between H. bilis in bile and biliary tract malignancies has not been investigated, and therefore the aim of this study is to determine whether malignant diseases of the biliary tract are associated with the presence of H. bilis in bile samples obtained from two high-risk populations. Bile samples from 45 Japanese and 40 Thai patients were subjected to PCR analysis using H. bilis-specific primers, and six of the H. bilis amplicons were sequenced. Thirteen out of 15 (87%) Japanese and 11 out of 14 (79%) Thai patients with bile duct or gallbladder cancer tested positive for the presence of H. bilis in their bile. Eight out of 16 (50%) Japanese and 10 out of 26 (38%) Thai patients with gallstone and / or cholecystitis tested positive for H. bilis. Only 4 out of 14 (29%) subjects without biliary disease tested positive for H. bilis among the Japanese. Bile duct and gallbladder cancer showed significantly higher positive rates for H. bilis than did the non-biliary diseases among the Japanese (P < 0.01) and the odds ratios for bile duct or gallbladder cancer with H. bilis in comparison with gallstone and / or cholecystitis were 6.50 (95%CI 1.09 - 38.63) in the Japanese and 5.86 (1.31 - 26.33) in the Thai patients. In conclusion, H. bilis infection in bile was associated with biliary tract and gallbladder cancers in two high risk populations, Japanese and Thai.

Bile↗

Helicobacter bilis infection in biliary tract cancer.

BACKGROUND: Biliary tract cancer is a highly fatal disease with poor prognosis, but the aetiology is poorly understood. AIM: We aimed to identify Helicobacter bilis infection in the gallbladder in patients with biliary tract disease. METHODS: Archival gallbladder specimens from 34 patients (14 males and 20 females) with an average age of 61.4 +/- 12.2 years (mean +/- SE) were retrieved, consisting of 11 cases of gallbladder cancer, three of bile duct cancer, 16 of cholecystolithiasis and four of pancreatic cancer. DNA was extracted and nested PCR using primers specific for 16S rRNA of H. bilis was performed. RESULTS: Amplification was observed in 3 of 11 gallbladder cancer cases (27.2%) and one of three cases with biliary duct cancer (33.3%). In total, four of 14 cases with biliary tract cancer were positive for H. bilis (28.6%). In addition, the presence of H. bilis was shown in two of 16 cases (12.5%) with cholecystolithiasis. Notably, although the number of cases examined was small, none of the four cases with pancreatic cancer showed the presence of H. bilis infection in the gallbladder without apparent abnormalities. CONCLUSION: H. bilis infection may play a role in biliary tract disease, particularly in biliary tract cancer.

Biliary Tract Neoplasms↗

Contemporary Management of Biliary Tract Infections.

Biliary tract infections are a worldwide problem, with a large financial burden on health care. Biliary infections can result from multiple causes, but the most common culprit is cholelithiasis. In the past decade, our knowledge of the mechanism of disease, microbiology of infections, and management options has grown enormously. Although at times perplexing, it is important to understand this information to allow for efficient, quality, and cost-effective health care.

Journal Article↗

[Percutaneous intraluminal ultrasound studies of the biliary tract in the diagnosis of malignant biliary obstruction].

The diagnostic value of percutaneous intraluminal ultrasound examination of the biliary tract (PIBUS) for the staging of malignancies that had obstructed the biliary tract was assessed in a prospective study. Intrabiliary sonography was performed 25 times in 22 patients (seven women, 15 men; mean age 66.4 +/- 16 years) with obstructive jaundice in whom percutaneous transhepatic drainage of the biliary tract had been undertaken. The obstruction involved the hepatic duct bifurcation in 15 patients, the distal portion of the choledochal duct in five and its central portion as well as hepaticojejunostomy in one patient each. Ultrasound examination made it possible to assess tumour infiltration into the lumen of the biliary tract, its wall or its surrounding structures. Correct T-staging was successful in all 12 patients with carcinoma of the biliary tract (T1: n = 4; T2: n = 2; T3: n = 6), judged against the "gold standard" of exploratory laparotomy in nine. Infiltration of the portal vein was demonstrated in three patients, lymph node metastases in the region of the hepatoduodenal ligament in seven. This experience indicates that PIBUS makes it possible correctly to T-stage carcinoma of the biliary tract, but because of its limited depth penetration it has to be combined with conventional imaging procedures for precise definition of the N and M stages.

Aged↗

Pathology of anomalous junction of the pancreaticobiliary ductal system: mutagenicity of the contents of the biliary tract and nuclear atypia of the biliary epithelium.

Congenital biliary dilatation is frequently complicated by biliary tract cancer, and anomalous junction of the pancreaticobiliary ductal system, a major factor constituting the pathology of this disease, is considered to be important as a background for carcinogenesis in the biliary tract. To clarify the mechanism of carcinogenesis in the biliary tract under the circumstance of anomalous junction, we evaluated the mutagenicity of the contents of the biliary tract in patients with congenital biliary dilatation and analyzed the nuclear atypia of the biliary epithelium by fluorocytometry. A mutagenicity test using Bacillus subtilis showed positive results in 6 of 12 patients. Since mutagenicity correlates well with carcinogenicity, these results suggest the necessity of separation surgery between the bile and pancreatic ducts in patients with anomalous junction regardless of the presence or absence of biliary dilatation. On the other hand, DNA histograms of the nuclei of gallbladder epithelial cells produced by fluorocytometry in 4 patients revealed a high incidence of polyploid DNA in 2 patients with marked hypertrophic changes. These patients were also positive for mutagenicity of the contents of the biliary tract, suggesting that mutagens are involved in the atypia at the cellular and nuclear levels.

Adolescent↗

Three-dimensional fine structure of the biliary tract: scanning electron microscopy of biliary casts.

The three-dimensional structure of the biliary tract was studied by scanning electron microscopy (SEM) of biliary casts. The replica of the biliary tract was successfully prepared by retrograde injection of low viscosity resin into the common bile duct. Bile canaliculi are intricate networks in which hexagonal and pentagonal meshworks are interconnected. Each hexagonal or pentagonal meshwork is on a plane, but adjoining meshworks are on different planes. Bile canalicular networks connect with bile ductules at the periphery of the portal tract. The intrahepatic bile duct showed considerable interspecies variation. The human bile duct has plexiform side branches and periductal sacculi, which are most numerous near the liver hilum and fewest in the smaller portal tracts. The hilar plexus and sacculi are present on opposite sides of the bile duct. The plexus formed at the bifurcation of the bile ducts exhibits a plane. Periductal sacculi were also observed in the monkey and pig bile ducts, particularly the latter, while rat bile ducts possess a peculiar portal bile ductular plexus situated between the portal tract and the surrounding liver parenchyma. No such structures were observed in either the dog or rabbit bile ducts. SEM of the biliary casts showed that the biliary tract was not a simple draining tube but had additional structures, such as periductal sacculi and plexiform side branches. These structures, together with the peribiliary vascular plexus, may be implicated in the modification of bile.

Biliary Tract↗

Ascending infection of the biliary tract after surgical sphincterotomy and biliary stenting.

It has been widely accepted that there is an ascending route of bacterial infection of the biliary tract but there is a lack of direct evidence. This hypothesis was tested in an animal experiment using the cat as an animal model. The implantation of biliary stents and surgical sphincterotomy were performed in these animals, with sham controls. Stents bypassing the sphincter of Oddi with the tip in the duodenal micro-organisms and the biliary tract was heavily contaminated. Blockage of these stents resulted in biliary obstruction. Stents implanted within the common bile duct, proximal to the sphincter were largely unaffected by biofilm formation. After surgical sphincterotomy the biliary tract was also contaminated but, in the absence of obstruction, the animals did not develop any symptoms. It was concluded that ascending infection by duodenal biliary reflux, via the sphincter of Oddi, is an important route of infection in the biliary system.

Animals↗

[Biliary tract infection].

Biliary tract infection is a frequently encountered clinical problem and requires prompt diagnosis, proper understanding of the pathologic manifestations, and adequate treatment. If not managed properly, it can be the cause of disseminated intravascular coagulation and multiple organ failure and its prognosis can be fatal. This paper focuses on two of its representative diseases: acute cholecystitis and acute cholangitis.

Acute Disease↗

Phase II study of capecitabine and cisplatin in previously untreated advanced biliary tract cancer.

BACKGROUND: Biliary tract cancer is one of the most aggressive and chemotherapy-refractory tumors. Although only curative treatment modality is surgery, most patients are not suitable for surgery due to advanced stage of the disease at diagnosis. Thus most patients with biliary tract cancer are possible candidates for palliative chemotherapy. The standard chemotherapeutic regimen is still to be defined, however. We performed a phase II study of combination chemotherapy with capecitabine and cisplatin in these patients to evaluate efficacy and toxicity of the regimen. METHODS: Patients with previously untreated metastatic, recurrent, or inoperable biliary tract cancer were enrolled. Eligible patients were screened as following: (1) histologically confirmed, (2) age between 18 and 75 years, (3) at least one measurable lesion according to RECIST criteria, (4) ECOG performance status <or=2, (5) a life expectancy of at least 3 months, and (6) adequate laboratory values. Patients received capecitabine (2,500 mg/m2/day, days 1 to 14) and cisplatin (60 mg/m2, day 1) every 3 weeks. Response was assessed for every two cycles of chemotherapy and treatment was stopped when tumor had progressed or stable with no further response. RESULTS: Thirty-two patients were enrolled, 20 (62.5%) were male and 12 (37.5%) were female and the median age was 54 years (33-71 years). Fifteen patients (46.9%) had gallbladder cancer, 13 (40.6%) had intrahepatic cholangiocarcinoma, and 4 (12.5%) had extrahepatic biliary cancer. The most frequent metastatic sites were lymph nodes (20/32, 62.5%) and liver (28/32, 56.3%). No complete response was observed and partial response was observed in 13/32 patients. By the intent-to-treat analysis, the overall response rate was 40.6% (95% CI, 23.7-59.4) with 0 CR and 13 PRs. Stable disease was observed in 3 patients (9.4%), and 11 patients (34.4%) had progressive disease. The median time to progression was 3.5 months (95% CI, 1.3-5.8), and the median overall survival was 12.4 months (95% CI, 6.3-18.5) after the median follow-up duration of 9.5 months (4.8-26.1 months). A total of 108 cycles of chemotherapy was delivered. Grade 3 hematologic toxicities included neutropenia (5, 15.6%), anemia (1, 3.1%), and thrombocytopenia (1, 3.1%) per patient, and no grade 4 hematologic toxicities were observed. Grade 3 non-hematologic toxicities included hyperbilirubinemia (2, 6.3%), increase of alkaline phosphatase (2, 6.3%), hand-foot syndrome (2, 6.3%), anorexia, and diarrhea (1, 3.1%) per patient, respectively. There was no treatment-related death. CONCLUSION: The combination chemotherapy of capecitabine and cisplatin demonstrated a promising antitumor activity with mild toxicity profile in patients with advanced biliary tract cancer.

Adult↗