Complete Ligation Of Bile Duct Research Articles

Post-cholecystectomy iatrogenic bile duct injuries: Emerging role for endoscopic management.

Post-cholecystectomy iatrogenic bile duct injuries (IBDIs), are not uncommon and although the frequency of IBDIs vary across the literature, the rates following the procedure of laparoscopic cholecystectomy are much higher than open cholecystectomy. These injuries caries a great burden on the patients, physicians and the health care systems and sometime are life-threatening. IBDIs are associated with different manifestations that are not limited to abdominal pain, bile leaks from the surgical drains, peritonitis with fever and sometimes jaundice. Such injuries if not witnessed during the surgery, can be diagnosed by combining clinical manifestations, biochemical tests and imaging techniques. Among such techniques abdominal US is usually the first choice while Magnetic Resonance Cholangio-Pancreatography seems the most appropriate. Surgical approach was the ideal approach for such cases, however the introduction of Endoscopic Retrograde Cholangio-Pancreatography (ERCP) was a paradigm shift in the management of such injuries due to accepted success rates, lower cost and lower rates of associated morbidity and mortality. However, the literature lacks consensus for the optimal timing of ERCP intervention in the management of IBDIs. ERCP management of IBDIs can be tailored according to the nature of the underlying injury. For the subgroup of patients with complete bile duct ligation and lost ductal continuity, transfer to surgery is indicated without delay. Those patients will not benefit from endoscopy and hence should not do unnecessary ERCP. For low-flow leaks e.g. gallbladder bed leaks, conservative management for 1-2 wk prior to ERCP is advised, in contrary to high-flow leaks e.g. cystic duct leaks and stricture lesions in whom early ERCP is encouraged. Sphincterotomy plus stenting is the ideal management line for cases of IBDIs. Interventional radiologic techniques are promising options especially for cases of failed endoscopic repair and also for cases with altered anatomy. Future studies will solve many unsolved issues in the management of IBDIs.

Cholangioscopy and double-balloon enteroscopy mediated "sandwich puncture" of a completely closed choledochojejunostomy.

Video 1Percutaneous cholangioscopy was performed to confirm complete closure of the choledochojejunostomy. Percutaneous cholangioscopy revealed complete closure of the anastomosis. Our attempt to pass a guidewire through the anastomosis failed accordingly.

Partial Bile Duct Ligation in the Mouse: A Controlled Model of Localized Obstructive Cholestasis.

In rodents, complete bile duct ligation (cBDL) of the common bile duct is an established surgical technique for studying obstructive cholestasis and bile duct proliferation. However, long-term experiments can lead to increased morbidity and mortality. In select mouse strains with underlying liver disease, meaningful comparisons can be made even with ligation of a single lobe of the liver, which can reduce animal losses and expenses. Here, we describe partial bile duct ligation (pBDL) in the mouse, in which only the left hepatic bile duct is ligated, causing biliary obstruction in the left lobe but not the remaining lobes. With careful microsurgical technique, pBDL experiments can be cost-effective, since the unligated lobe serves as an internal control to the ligated lobes, when subjected to the same conditions in the same animal. Unlike cBDL, a separate sham-operated control group is not necessary. pBDL is highly useful to directly compare localized versus systemic effects of cholestasis and other retained bile components. pBDL can also be repurposed as a novel method to investigate mechanisms related to medications and cell migration.

Partial Bile Duct Ligation in the Mouse: A Controlled Model of Localized Obstructive Cholestasis

In rodents, complete bile duct ligation (cBDL) of the common bile duct is an established surgical technique for studying obstructive cholestasis and bile duct proliferation. However, long-term experiments can lead to increased morbidity and mortality. In select mouse strains with underlying liver disease, meaningful comparisons can be made even with ligation of a single lobe of the liver, which can reduce animal losses and expenses. Here, we describe partial bile duct ligation (pBDL) in the mouse, in which only the left hepatic bile duct is ligated, causing biliary obstruction in the left lobe but not the remaining lobes. With careful microsurgical technique, pBDL experiments can be cost-effective, since the unligated lobe serves as an internal control to the ligated lobes, when subjected to the same conditions in the same animal. Unlike cBDL, a separate sham-operated control group is not necessary. pBDL is highly useful to directly compare localized versus systemic effects of cholestasis and other retained bile components. pBDL can also be repurposed as a novel method to investigate mechanisms related to medications and cell migration.

Endoscopic recanalization technique for complete ligation of bile duct after cholecystectomy

Endoscopic recanalization technique for complete ligation of bile duct after cholecystectomy

Sp707 Endoscopic Recanalization Technique for Complete Ligation of Bile Duct after Cholecystectomy

Bile Duct Injury after cholecystectomy remains a major problem in current surgical practice. BDI is associated with poor survival, increased morbidity and impaired quality of life. The current standard practice for management of BDI is the following: Amsterdam Type A and B lesions (cystic and bile duct leak) should be treated with sphincterotomy and placement of stent; Type C lesions (strictures) should be treated by endoscopy (failures should be considered for surgery); Type D lesions (transection or ligation of the bile duct) should be treated by surgery. In this presentation, we will, for the first time, demonstrate an endoscopic method of biliary recanalization in three patients with complete ligation of the common bile duct. We will present three cases of patients that had undergone cholecystectomy and presented, after 2 to 4 weeks, clinical evidence of jaundice. By a three-step ERCP procedure, we accessed the common bile duct and passed a specialized needle through the complete stenosis. It was used a specialized needle catheter that presented some characteristics, such as an 18-gauge needle, internal channel that fitted a .35-inch guidewire, and a distal tip covered by a flexible metallic sheath with 10 cm length. At this first moment, we used a .35-inch guidewire to maintain proximal bile duct access and performed plastic stent (first case) or self-expandable metallic stent placement. In the first patient, it was a three step procedure that consisted in 8.5 Fr plastic stent placement, followed by balloon dilation of the stenosis with multi-stent placement, and finalized by the multi-stent removal. In the second and third cases, instead of a plastic stent, a self-expandable metallic stent was used. This alternative reduced the treatment to two steps and it was not necessary to perform a balloon dilation of the stenosis. A clinical resolution of the stenosis was observed in the three patients, with a mild narrowing of CBD in radioscopic images. It is important to know that, before performing this procedure, all patients had undergone a colangioresonance, which demonstrated that cranial and distal biliary stumps were aligned. Endoscopic recanalization of CBD was an effective technique and avoided surgery in patients with Type D bile duct injury. We hypothesize that patients whose MRCP demonstrate just CBD ligation are more likely to have a successful outcome, while those with complete transection should be referred to surgical evaluation, however we present a case series demonstrating feasibility of endoscopic recanalization by using a specialized needle catheter.

Quercetin improves bone strength in experimental biliary cirrhosis

Metabolic bone disorders and reduced bone mass are common complications in patients with biliary cirrhosis. As a result of there being no clear etiology, no specific therapy has been established yet. Previous studies have reported that quercetin, a plant-derived flavonoid, might improve bone quality. The present study was designed to investigate the effect of quercetin on bone strength of biliary cirrhotic rats. Twenty-four male Sprague-Dawley rats aged 6-7 months were randomized into three groups of eight. One group served as control (sham operated), while the other two groups underwent a complete bile duct ligation (BDL). Four weeks after the operation, serum bilirubin, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase were measured in animal blood samples to confirm the occurrence of cirrhosis in the BDL rats. Then, one of the BDL groups received placebo and the other one was injected once a day with 150 µmol/kg of quercetin for 4 weeks. At the end of the study, femora were removed and tested for bone strength and histomorphometric parameters. The serum levels of osteocalcin, C-terminal cross-linked telopeptide of type I collagen, calcium and phosphorus were determined as bone turnover markers. Femur breaking strength was dramatically lower in the BDL group compared with control. However, receiving quercetin could reverse the deteriorating effect of cirrhosis on bone strength of BDL rats. Quercetin could noticeably elevate osteocalcin as a bone formation marker. These data suggest that quercetin can significantly improve bone strength particularly due to increasing bone formation in biliary cirrhosis.

Acute effects of endothelin receptor antagonists on hepatic hemodynamics of cirrhotic and noncirrhotic ratsThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.

Hepatic and circulating endothelin-1 (ET-1) are increased in patients with cirrhosis and in cirrhotic animals. However, the distinct roles of ET receptor subtypes ETA and ETB in cirrhosis and portal hypertension (PHT) have not been clearly elucidated. Thus, we studied the effects of selective ET-1 antagonists (ETA-ant or ETB-ant) and nonselective ET-1 antagonist (ETA/B-ant) on hepatic hemodynamics in cirrhotic rats. Liver fibrosis and PHT were induced by complete bile duct ligation (BDL) in rats. Two weeks after BDL or sham surgery, hemodynamic responses were measured during intraportal infusion of incremental doses of the following ET-ants: (i) BQ-123, (ii) BQ-788, and (iii) bosentan. After equilibration with vehicle, doses of ET-ants were infused for 30 min periods, and steady-state systemic and hepatic hemodynamics, portal venous pressure (PVP), and hepatic blood flow (HBF) were measured. BDL induced significant PHT and elevated concentrations of plasma ET-1 compared with sham. ETA-ant decreased PVP of cirrhotic rats but had no effect on sham, whereas ETB-ant increased PVP in sham but had no effect in BDL. Nonselective ETA/B-ant decreased PVP of BDL similarly to ETA-ant. Both ETA-ant and ETB-ant decreased local HBF, whereas a nonselective antagonist did not change HBF in sham; however no significant changes were observed in HBF of BDL rats with any of the antagonists. These findings suggest ETA activation contributes to PHT in cirrhotic rats, whereas ETB-mediated portal depressor effects are attenuated in cirrhotic rats compared with noncirrhotic rats.

Renal vasoactive mediator generation in portal hypertensive and bile duct ligated rats

Background/Methods: Vasoactive substances may have a role in the pathogenesis of functional renal abnormalities in patients with cirrhosis. We determined renal vasoactive mediators in rats with portal hypertension since the balance in each part of the kidney between the vasodilator activity of prostaglandin E 2 and the vasospastic activity of thromboxane A 2, leukotriene B 4, leukotriene C 4, endothelin-1 and platelet activating factor may determine renal function. Rats with partial portal vein ligation ( n=7), complete bile duct ligation ( n=6) and sham operated ( n=10) were studied. Three weeks following surgery renal function tests, including fractional excretion of sodium [Fe(Na)] were measured. Rats were anesthetized, splenic pulp pressure was measured, kidneys were removed, and cortex, medulla and papilla were separated and homogenized for determination of prostaglandin E 2, thromboxane B 2, leukotriene B 4, leukotriene C 4 and endothelin-1 by radioimmunoassay (ng/g) and platelet activating factor activity (pg/10 mg) by platelet aggregation. Results: Pulp pressure was >13 mmHg in portal vein ligated and bile duct ligated and 6 mmHg in sham operated rats. In bile duct ligated rats there was a 70% decrease in Fe(Na) and a significant decrease in cortical and papillary prostaglandin E 2, whereas cortical thromboxane B 2 and platelet activating factor activity in the cortex, medulla and papilla were double that of sham operated rats. A similar but insignificant trend of changes was found in portal vein ligated rats. Medullary leukotriene B 4 was significantly decreased in bile duct ligated rats. Papillary leukotriene B 4 was not detected in bile duct ligated and portal vein ligated rats. Renal leukotriene C 4 generation in the three groups was either unchanged (papilla) or beyond detection (cortex and medulla). Medullary and papillary endothelin-1 in portal vein ligated and bile duct ligated rats were 178%-130% higher than in sham operated rats. A significant negative correlation was found between Fe(Na) and cortical and medullary thromboxane B 2 generation and medullary platelet activating factor activity. Conclusions: 1) In bile duct ligated rats enhanced intrarenal generation of thromboxane A 2 and platelet activating factor may contribute to decreased renal sodium excretion. 2) The role of decreased intrarenal prostaglandin E 2 and increased intrarenal endothelin-1 content in bile duct ligated rats is not yet understood. 3) Renal leukotriene generation is either decreased or undetected in portal vein ligated and bile duct ligated rats.

Gastric and colonic inflammatory and vasoactive mediators in experimental portal hypertension.

Rats with portal hypertension and experimental liver disease may exhibit increased susceptibility of the gastric mucosa to damage by noxious agents, and increased bacterial translocation through the bowel wall. The aim of this study was to determine mucosal gastric and colonic generation of vasoactive substances, because they may contribute to the altered mucosal function. Rats with partial vein ligation (n = 7), complete bile duct ligation (n = 6) and sham-operated rats (n = 10) were studied. Three weeks following surgery rats were anesthetized, splenic pulp pressure was measured, stomachs and colons were removed and mucosa was extracted for determination of prostaglandin E2, thromboxane B2, leukotriene B4, leukotriene C4 and endothelin-1 by radioimmunoassay (ng/g) and platelet activating factor activity (pg/10 mg) by platelet aggregation. Pulp pressure was > 13 mmHg in partial vein ligated rats and bile duct ligated rats and 6 mmHg in sham-operated rats. No macroscopic or microscopic lesions were seen any of the removed tissues. Gastric mucosal prostaglandin E2 and thromboxane B2 generation were decreased by 35% and 7%, respectively, in bile duct ligated rats (bile duct ligated versus sham-operated, p < 0.05 for prostaglandin E2 and thromboxane B2). Gastric leukotriene B4 and C4 generation, platelet activating factor activity and endothelin-1 content did not differ significantly among the three groups. A different pattern of changes was observed in the colon. Colonic leukotriene B4 generation and endothelin-1 content were increased in bile duct ligated rats by 105% and 210%, respectively (bile duct ligated versus sham-operated, p < 0.05 for leukotriene B4 and endothelin-1). The decreased gastric mucosal prostaglandin E2 generation of bile duct ligated rats may render the gut mucosa of these animals relatively ischemic and vulnerable to damage by noxious agents. The increased colonic leukotriene B4 generation and the increased endothelin-1 content of the colonic mucosa of bile duct ligated rats may promote inflammatory and ischemic changes in the colonic mucosa and may enable bacterial translocation.

Hepatic total 3α-hydroxy bile acids concentration and enzyme activities in prednisone-treated dogs

Summary High serum alkaline phosphatase (alp) activity is considered a sensitive marker of cholestasis in most mammalian species, including dogs. Induction of high serum alp activity in association with cholestasis is dependent on high hepatic bile acids concentrations. Treatment of dogs with glucocorticoids also results in high serum alp activity. The possible causal relation between serum alp activity and bile acids concentration was investigated in dogs treated with glucocorticoids. The relation of glucocorticoid treatment to changes in the activity of individual alp isoenzymes, alanine transaminase (alt) and γ-glutamyltransferase (ggt) also was investigated. Eight conditioned dogs were given 4 mg of prednisone/kg of body weight, im, daily for 10 days. Blood samples were taken prior to treatment and on treatment days 3, 5, 7, and 10. Liver tissue was then taken from each dog. Serum total alp activity was significantly (P &lt; 0.05) high at day 3 in prednisone-treated dogs. Isoenzyme analysis indicated that this increase was attributable to an increase in the liver alp isoenzyme (LALP). Significant increases in serum corticosteroid-induced alp (calp) and bone alp were first observed on days 7 and 10, respectively. Serum alt and ggt activities were significantly increased by day 5. Increased serum or hepatic tissue bile acids concentrations were not observed in prednisonetreated dogs, compared with values in 8 clinically normal (control) dogs, but were high in 3 dogs with complete bile duct ligation. Hepatic activities of LALP, calp, and ggt were higher in prednisone-treated dogs than values in controls, indicating probable increased hepatic synthesis of these enzymes. Hepatic alt activity was not increased. The ratio of serum to tissue lalp activity was increased in prednisone-treated dogs, compared with values in controls, indicating that lalp may have been preferentially released into serum. There was no difference in the ratio of serum to liver ggt activity between prednisone-treated dogs and controls. The lalp and ggt ratios were increased in bile duct-obstruction dogs. It was concluded that, although lalp is the principal alp isoenzyme in serum during the first 10 days of prednisone treatment, hepatic bile acid concentrations are not increased and, therefore, are not likely to be responsible for induction and release of alp into serum. Prednisone may, therefore, be directly responsible for induction of alp activity in dogs treated thusly.

Promotion of cholangiocarcinogenesis in the hamster liver by bile duct ligation after dimethylnitrosamine initiation.

Administration of hepatocarcinogenic nitrosamines before or after infection with the liver fluke, Opisthorchis viverrini (OV), results in marked development of cholangiocellular and hepatocellular precancerous and cancerous lesions in the hamster liver. The promoting effects of OV are believed to be exerted either mechanically, chemically or immunologically. To test the influence of possible mechanical effects, Syrian hamsters were initiated with a single i.p. injection of dimethylnitrosamine (DMN) 20 mg/kg and subjected 2 weeks later either to a sham operation or to complete ligation of the extrahepatic bile duct to the left lateral lobe. At the end of week 40, the animals receiving DMN-initiation and ligation had a 60.9% incidence of cholangiofibrosis, 21.7% of mucous cystadenomas and 39.1% of cholangiocarcinomas, whereas the group given DMN alone only developed cholangiofibrosis, limited to 5% of the animals. In the latter case neither cystadenomas nor cholangiocarcinomas were observed. The incidence of hepatocellular nodules did not differ between the two groups and no tumorous lesions developed in either the ligated or the untreated groups without DMN pretreatment. Complete ligation of the bile duct itself led to a series of events; obstruction of bile flow being followed by dilatation, cyst formation, and necrosis of the bile duct epithelium and surrounding affected areas leading to regenerative proliferation. The results are in line with the conclusion that parasite-associated proliferation in target cell populations is, at least in part, responsible for the influence of OV on liver tumor development.