Combined cholecystotomy, retrograde hydropulsion, and choledochal stenting to treat extrahepatic biliary tract obstruction in 3 cats.

Extrahepatic biliary tract obstruction (EHBO) is uncommonly encountered in cats. Surgical treatment aims to decompress the biliary tract and insure bile duct patency. In veterinary medicine, cholecystotomy is not widely used in practice. The objective was to describe the use of cholecystotomy, retrograde hydropulsion of choleliths, and choledochal stenting to remove choleliths from the extrahepatic biliary tract back in the gallbladder. Three adult domestic shorthair cats were presented with anorexia, lethargy, and vomiting. Serum biochemistry revealed hyperbilirubinemia and increased hepatic enzymes. Abdominal ultrasonography showed evidence of EHBO requiring surgical intervention. Choleliths were localized in the proximal and middle portions of the common bile duct (CBD) in the first case, in the distal portion of the CBD and within the major duodenal papilla in the second case, and in the middle and distal portions of the CBD in the third case. Cholecystotomy was followed by retrograde hydropulsion of the choleliths into the gallbladder, after which choledochal stenting was performed. Complications were defined as major when requiring additional medical or surgical treatment, or minor when not. Three major complications were reported. In 2 cases, severe anemia requiring blood transfusion occurred 24 h postoperatively; in 1 case, EHBO recurrence was encountered 41 d postoperatively. All cats were discharged within 4 d following surgery. Two cats were still alive at 12 and 14 mo after surgery, respectively. In the last case, owners refused revision surgery and the cat was euthanized. Key clinical message: Cholecystotomy combined with retrograde hydropulsion of choleliths permitted removal of choleliths and decompression of the biliary tract in 3 cats. Major complications included severe anemia and EHBO recurrence.

Cholécystotomie combinée, hydropulsion rétrograde et pose de stent cholédocien pour traiter l'obstruction des voies biliaires extra-hépatiques chez 3 chats. Les obstructions biliaires extra-hépatiques (OBEH) sont peu fréquentes chez le chat. Le traitement chirurgical vise à lever l'obstruction et s'assurer de la perméabilité des voies biliaires. En médecine vétérinaire, la cholécystotomie est une technique peu pratiquée. L'objectif de ce rapport de cas était de décrire l'utilisation de la cholécystotomie, de l'hydropulsion rétrograde des cholélithes et d'une prothèse endoluminale cholédoquale (PEC) pour repousser les cholélithes présents dans les voies biliaires extrahépatiques dans la vésicule biliaire (VB).Trois chats européens adultes ont été présentés pour anorexie, léthargie et vomissements. La biochimie sérique a révélé une hyperbilirubinémie et une augmentation des enzymes hépatiques. L'échographie abdominale a mis en évidence une OBEH nécessitant une intervention chirurgicale. Les cholélithes étaient situés dans la portion proximale et moyenne du canal cholédoque pour le premier cas; dans la portion distale et la papille duodénale majeure dans le second cas; dans la portion moyenne et distale pour le troisième cas. Une cholécystotomie a été suivie d'une rétro-hydropulsion des cholélithes dans la VB, puis une PEC a été placée. Les complications ont été définies comme majeures lorsqu'elles nécessitaient un traitement médical ou chirurgical supplémentaire, ou mineures lorsqu'elles n'en nécessitaient pas.Trois complications majeures ont été rapportées : chez 2 cas, une anémie sévère a été observée 24 h après l'intervention, nécessitant une transfusion sanguine; chez un cas, une récidive d'obstruction biliaire a eu lieu à 41 jours postopératoire. Tous les patients sont sortis de l'hôpital dans les 4 jours suivant l'opération. Deux cas étaient encore en vie 12 et 14 mois après l'intervention. Pour le dernier cas, la seconde chirurgie a été refusée par les propriétaires et le chat a été euthanasié.Message clinique clé :La cholécystotomie combinée à l'hydropulsion rétrograde des cholélithes a permis le retrait de cholélithes obstructives (dont certaines distales) et la décompression du tractus biliaire chez 3 chats. Les complications majeures incluaient une anémie sévère et une récidive d'obstruction biliaire.(Traduit par les auteurs).

Computed tomographic diagnosis of a common bile duct abscess and secondary extrahepatic biliary duct obstruction in a potbelly pig.

A potbelly pig was evaluated for anorexia and icterus. Clinicopathologic abnormalities suggested an active inflammatory hepatobiliary process. Ultrasound and CT of the abdomen revealed an extrahepatic biliary obstruction of the common bile duct (CBD). Surgical exploration and choledochotomy revealed a markedly dilated CBD containing a large volume of intraluminal inspissated biliary material. This case report describes the imaging findings of an extrahepatic biliary obstruction secondary to abscessation within the CBD in a pig.

Clinical use of uncovered balloon-expandable metallic biliary stents for treatment of extrahepatic biliary tract obstructions in cats and dogs: 11 cases (2012-2022).

OBJECTIVE: To describe the application of uncovered balloon-expandable metallic biliary stents for treatment of extrahepatic biliary obstructions (EHBOs) and the outcomes for dogs and cats treated for EHBO with this technique. STUDY DESIGN: Retrospective single institutional study. ANIMALS: Eight dogs and three cats treated at the Veterinary Specialty Hospital of San Diego for EHBO between January 2012 and February 2022. METHODS: Data collected from the medical records included signalment, presenting complaint, laboratory and imaging findings, surgical findings, hospitalization time, complications, and follow-up information. RESULTS: Median duration of short-term follow up was 16 days (6-45 days). Improved biochemical abnormalities and resolution of clinical signs were recorded in 10/11 cases. Two dogs died within 2 weeks of surgery. One dog developed systemic inflammatory response syndrome 5 days postoperatively and was euthanized; the cause of death in the second case was unknown. Long-term follow up was available in seven cases, with a median duration of 307.5 days (62-2268 days). Bile-duct patency was maintained for at least 356-622 days (median: 446 days) in three cats and 62-2268 days (median: 650.5 days) in four dogs with long-term follow up available. One cat had recurrent obstruction with choledocholiths 446 days postoperatively. One stent was removed 614 days postoperatively due to recurrent cholangiohepatitis. CONCLUSION: Uncovered balloon-expandable metallic biliary stents were placed successfully and relieved EHBO in all cases that survived to discharge. CLINICAL SIGNIFICANCE: Use of uncovered balloon-expandable metallic biliary stents should be considered as an alternative to temporary choledochal luminal stenting or cholecystoenterostomy to manage EHBO.

Predictive factors in the differential diagnosis of benign and malignant causes in patients undergoing endoscopic retrograde cholangiopancreatography for extrahepatic cholestasis.

OBJECTIVE: Diagnosing benign vs. malignant extrahepatic cholestasis is challenging despite the currently available advanced imaging and endoscopic techniques. This study aims to determine the predictive accuracy of initial biochemical data and bile duct dilatation findings in transabdominal ultrasound (US) to differentiate between benign and malignant disease in patients with extrahepatic cholestasis. PATIENTS AND METHODS: We reviewed the case records of 814 patients who had undergone endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (in cases of unsuccessful ERCP) for extrahepatic cholestasis. The etiology of biliary obstruction was determined based on ERCP, endoscopic ultrasonography, radiology, cytology, biopsy, and/or clinical follow-up at one year. The patients were divided into benign and malignant groups according to the underlying etiology of biliary obstruction. A complete biochemical profile, transabdominal ultrasonography at presentation, and other demographic data were recorded. RESULTS: Alkaline phosphatase (p = 0.002), aspartate aminotransferase (p = 0.038), and bilirubin levels were significantly higher in malignant patients. The mean age of patients with malignancy was 69.5 years, vs. 60.6 years in benign patients (p < 0.001). The likelihood of malignancy increased with the increased bilirubin levels (> 200 µmol/l: 30.0% sensitivity, 97.6% specificity). The total bilirubin level predicting malignancy as the best cut-off value was 111 mmol/L with optimum sensitivity and specificity (61.8% and 83.8%, respectively) and area under the curve = 0.756, (p < 0.001). Intrahepatic bile duct (IHBD) dilatation was significantly higher in malignant patients (p < 0.001). CONCLUSIONS: A serum bilirubin level of 111 µmol/L or higher and the detection of IHBD dilatation on abdominal ultrasonography are important predictors in the differential diagnosis of benign and malignant causes of extrahepatic cholestasis.

Evaluation of renal arterial resistive index in patients with extrahepatic cholestasis.

OBJECTIVE: Biliary obstruction has been shown to cause acute renal failure. The Renal Resistive Index (RRI) has been recognized to be an important index for evaluating changes in renal plasma flow and renal damage in cholestatic patients. We aimed to investigate the effects of cholestasis on renal hemodynamics in patients with extrahepatic cholestasis by RRI. PATIENTS AND METHODS: The prospective study included patients with extrahepatic cholestasis due to benign biliary stricture, choledocholithiasis, or periampullary tumor between January 1, 2022, and December 31, 2022. Renal and liver function tests, as well as renal doppler ultrasound for RRIs, were conducted before and after cholestasis treatment. RESULTS: Patients who experienced cholestasis resolution after treatment showed lower cholestasis enzymes and bilirubin values and higher glomerular filtration rates compared to pre-treatment values. RRI values significantly decreased in patients with resolved cholestasis compared to pre-treatment levels (p=0.009). Patients with malignant cholestasis had higher RRI values than those with benign cholestasis (p=0.006). Bilirubin levels were higher (p=0.001), and glomerular filtration rates were lower (p=0.046) in patients with malignant cholestasis compared to those with benign cholestasis. CONCLUSIONS: Acute renal injury in cholestatic patients can be demonstrated non-invasively by RRI and is reversible once cholestasis has resolved. Patients with benign cholestasis had lower RRI values than those with cholestasis due to periampullary tumors.

An unusual cause of extrahepatic cholestasis associated with solid liver lesions: a case report.

IgG4-related sclerosing cholangitis is a special type of cholangiopathy often associated with autoimmune pancreatitis. In this article, we report an unusual case of IgG4-SC limited to the common hepatic duct and associated with pseudo tumoral liver lesions, but without evidence of pancreatic involvement. Corticosteroid therapy was rapidly effective and allowed normalization of liver tests.

Features, management, and long-term outcome in dogs with pancreatitis and bile duct obstruction treated medically and surgically: 41 dogs (2015-2021).

OBJECTIVE: Pancreatitis resulting in extrahepatic biliary obstruction (EHBO) can cause substantial morbidity and mortality. Endoscopic retrograde cholangiopancreatography is utilized for diagnostic and therapeutic purposes in humans; however, this is not available in veterinary medicine. Treatment options include medical management and biliary drainage procedures. The aim of this study was to describe the management of EHBO secondary to pancreatitis in dogs, treated medically and surgically and to determine whether the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) differ between the treatment groups. ANIMALS: 41 dogs treated for EHBO secondary to pancreatitis during the period of May 2015 to November 2021. METHODS: Records from 41 dogs diagnosed with EHBO secondary to pancreatitis were reviewed, and information extracted included clinical signs, ultrasound findings, NLR, PLR, histopathology, treatment, and outcomes. RESULTS: 18 of 19 (95%) surgical patients survived, while 12 of 21 (57%) medical patients survived. There was no difference in the length of hospitalization or time to return to adequate function between the groups; however, there was a significant difference in the 2- and 12-month survival between those treated surgically and medically. There was no difference in the NLR or PLR between surgically versus medically treated dogs or between survivors and nonsurvivors. CLINICAL RELEVANCE: The mortality rate of surgery for EHBO secondary to pancreatitis may be lower than previously described, and in this cohort of dogs, those treated surgically had improved survival at 2 and 12 months compared to those treated medically.

Does lithium attenuate the liver damage due to oxidative stress and liver glycogen depletion in experimental common bile duct obstruction?

In extrahepatic cholestasis, the molecular mechanisms of liver damage due to bile acid accumulation remain elusive. In this study, the activation of glutamatergic receptors was hypothesized to be responsible for bile acid-induced oxidative stress and liver damage. Recent evidence showed that lithium, as an N-methyl-d-aspartate receptor (NMDAR) GluN2B subunit inhibitor, may act on the glutamate/NMDAR signaling axis. Guinea pigs were assigned to four groups, as sham laparotomy (SL), bile duct ligated (BDL), lithium-treated SL (SL + Li) and lithium-treated BDL (BDL + Li) groups. Cholestasis-induced liver injury was evaluated by aspartate aminotransferase (AST), alanine transaminase (ALT), interleukin-6 (IL-6), tissue malondialdehyde (MDA), copper­zinc superoxide dismutase and reduced glutathione levels. The liability of glutamate/NMDAR signaling axis was clarified by glutamate levels in both plasma and liver samples, with the production of nitric oxide (NO), as well as with the serum calcium concentrations. Blood glucose, glucagon, insulin levels and glucose consumption rates, in addition to tissue glycogen were measured to evaluate the liver glucose-glycogen metabolism. A high liver damage index (AST/ALT) was calculated in BDL animals in comparison to SL group. In the BDL animals, lithium reduced plasma NO and glutamate in addition to tissue glutamate concentrations, while serum calcium increased. The antioxidant capacities and liver glycogen contents significantly increased, whereas blood glucose levels unchanged and tissue MDA levels decreased 3-fold in lithium-treated cholestatic animals. It was concluded that lithium largely protects the cholestatic hepatocyte from bile acid-mediated damage by blocking the NMDAR-GluN2B subunit.

Covered versus uncovered double bare self-expandable metal stent for palliation of unresectable extrahepatic malignant biliary obstruction: a randomized controlled multicenter trial.

BACKGROUND AND AIMS: In a recent randomized controlled trial, a double bare metal stent (DBS) showed better stent patency than single-layer metal stents. However, clear evidence comparing the efficacy of uncovered (UCDBS) and partially covered (PCDBS) DBSs for distal malignant biliary obstruction (MBO) is lacking. Therefore, we compared the clinical outcomes including stent patency of UCDBSs versus PCDBSs. METHODS: A multicenter, randomized study was performed in patients with distal MBO. The primary endpoint was stent patency. Secondary endpoints were the proportion of patients with patent stents at 6 months, risk factors for stent dysfunction, overall survival, technical and clinical success rates of stent placement, and other adverse events (AEs). RESULTS: Among 258 included patients, 130 were randomly assigned to the PCDBS group and 128 to the UCDBS group. The mean duration of stent patency of the PCDBS (421.2 days; 95% confidence interval [CI], 346.7-495.7) was longer than that of the UCDBS (377.4 days; 95% CI, 299.7-455.0), although total stent dysfunction and stent dysfunction within 6 months were not different between groups. Multivariate analysis indicated that chemotherapy after stent placement was a significant factor for overall survival (hazard ratio, .570; 95% CI, .408-.796) and had a marginal impact on stent patency (hazard ratio, 1.569; 95% CI, .923-2.667). There were no remarkable differences in AEs, including pancreatitis, cholecystitis, and stent migration, between the 2 groups. CONCLUSIONS: The use of PCDBSs compared with UCDBSs in patients with distal MBO has unclear benefits regarding stent patency and overall survival, although PCDBSs have a lower rate of tumor ingrowth. (Clinical trial registration number: NCT02937246.).

An infrequent cause of cholestasis: morphine-induced cholestasis / [Una causa infrecuente de colestasis extrahepática: colestasis inducida por morfina.]

Introduction: Extrahepatic cholestasis by opiates is a very rare entity of which only case reports are recorded in the literature. Methods: We present the case of a patient who developed abdominal pain and cholestasis after consumption of high doses of morphine for pain management of her underlying disease, treated by laparoscopic surgery. Results: The patient evolved favorably in the postoperative period without bilirrhage and was discharged on the fifth day with bilirubin values ​​within normal parameters. Conclusion: Sphincter of Oddi dysfunction syndrome secondary to long-term use of opioids is a very rare entity. However, it should be suspected in cases of extrahepatic cholestasis in which no stones or tumors are observed and in patients with long-term use of high-dose opiates either due to addiction or chronic pain treatment.

Introducción: La colestasis extrahepática producida por opiáceos es una entidad sumamente infrecuente de la cual solo se registran reportes de casos en la literatura. Métodos: Se presenta el caso clínico de una paciente que desarrolló dolor abdominal y colestasis luego del consumo prolongado de morfina a altas dosis, tratada por cirugía laparoscópica. Resultados: La paciente evoluciona favorablemente en el postoperatorio sin bilirragia y es dada de alta al quinto día con valores de bilirrubina dentro de los parámetros normales. Conclusión: El síndrome de disfunción del esfínter de Oddi secundario a consumo por tiempo prolongado de opioides es una entidad muy infrecuente. Sin embargo, debe sospecharse ante cuadros de colestasis extrahepáticas en los que no se observe litiasis ni tumores y en pacientes con consumo de opiáceos a altas dosis por tiempo prolongado ya sea por adicción o por tratamiento del dolor crónico.

Development and validation of a risk score for predicting clinical success after endobiliary stenting for malignant biliary obstruction.

BACKGROUND: Endoscopic drainage is the primary treatment for unresectable malignant biliary obstruction (MBO). This study developed and validated a pre-endoscopic predictive score for clinical success after stent placement. METHODS: Patients with unresectable MBO undergoing ERCP-guided endobiliary stent placement between 2007 and 2017 were randomly divided into derivation (n = 383) and validation (n = 128) cohorts. To develop the risk score, clinical parameters were built by logistic regression to predict (1) ≥ 50% total bilirubin (TB) resolution within 2 weeks and (2) bilirubin normalization (TB level <1.2 mg/dL) within 6 weeks following stenting. The scoring scheme was applied to the validation cohort to test its performance. RESULTS: A ≥ 50% TB resolution within 2 weeks was shown in 70.5% of cases. The risk scoring scheme had areas under the receiver operating characteristic curve (AUROC) of 0.70 (95% CI, 0.64-0.76) and 0.67 (95% CI, 0.57-0.77) in the derivation and validation cohorts, respectively. Thirty-one percent had TB normalization within 6 weeks after stenting. Significant predictors for TB normalization were extrahepatic biliary obstruction (odds ratio [OR] = 2.35), pre-endoscopic TB level (OR = 0.88), and stent type (OR = 0.42). The AUROC of a risk score for predicting TB normalization within 6 weeks was 0.78 (95% CI, 0.72-0.83) and 0.76 (95% CI, 0.67-0.86) in the derivation and validation cohorts, respectively. A score > 1.30 yielded a specificity of 98% and a positive predictive value of 84% for predicting TB normalization. A score of < -4.18 provided a sensitivity of 80%-90% and a negative predictive value of 90%-93% for predicting the absence of TB normalization. CONCLUSIONS: The pre-endoscopic scoring system comprising biliary obstruction level, liver biochemistry, and type of stent provides prediction indices for TB normalization within 6 weeks after stenting. This scheme may help endoscopists identify patients with unresectable MBO suited for palliative stenting.

Nrf2 deficiency causes hepatocyte dedifferentiation and reduced albumin production in an experimental extrahepatic cholestasis model.

The transcription factor Nrf2 modulates the initiation and progression of a number of diseases including liver disorders. We evaluated whether Nrf2 mediates hepatic adaptive responses to cholestasis. Wild-type and Nrf2-null mice were subjected to bile duct ligation (BDL) or a sham operation. As cholestasis progressed to day 15 post-BDL, hepatocytes in the wild-type mice exhibited a tendency to dedifferentiate, indicated by the very weak expression of hepatic progenitor markers: CD133 and tumor necrosis factor-like weak induced apoptosis receptor (Fn14). During the same period, Nrf2 deficiency augmented this tendency, manifested by higher CD133 expression, earlier, stronger, and continuous induction of Fn14 expression, and markedly reduced albumin production. Remarkably, as cholestasis advanced to the late stage (40 days after BDL), hepatocytes in the wild-type mice exhibited a Fn14+ phenotype and strikingly upregulated the expression of deleted in malignant brain tumor 1 (DMBT1), a protein essential for epithelial differentiation during development. In contrast, at this stage, hepatocytes in the Nrf2-null mice entirely inhibited the upregulation of DMBT1 expression, displayed a strong CD133+/Fn14+ phenotype indicative of severe dedifferentiation, and persistently reduced albumin production. We revealed that Nrf2 maintains hepatocytes in the differentiated state potentially via the increased activity of the Nrf2/DMBT1 pathway during cholestasis.

Enteral extended biliary stents versus conventional plastic biliary stents for the treatment of extrahepatic malignant biliary obstruction: a single-center prospective randomized controlled study.

BACKGROUND AND AIMS: The main limitation of plastic stents is the relatively short stent patency due to occlusion. We designed enteral extended biliary stents with lengths of 26 cm (EEBS-26 cm) and 30 cm (EEBS-30 cm) to prolong stent patency. This study aimed to compare patency among EEBS-26 cm, EEBS-30 cm, and conventional plastic biliary stent (CPBS). METHODS: A single-center prospective randomized controlled study was conducted. Eligible patients were randomized into the EEBS-26 cm, EEBS-30 cm, and CPBS groups, respectively. All patients were followed up every 3 months until stent occlusion, patient death, or at 12-month follow-up. The primary outcome was stent patency. The secondary outcomes included stent occlusion rate, patient survival, mortality, the rate of technical success, and adverse events. RESULTS: Totally 117 patients were randomized into the three groups. There were no significant differences among the three groups in technical success rate, hospital stay, mortality, patient survival, and adverse events (P = 1.000, 0.553, 0.965, 0.302, and 0.427, respectively). Median stent patency durations in the EEBS-26 cm, EEBS-30 cm, and CPBS groups were 156.0 (95% CI 81.6-230.4) days, 81.0 (95% CI 67.9-94.1) days, and 68.0 (95% CI 20.0-116.0) days, respectively (P = 0.002). The EEBS-26 cm group had longer stent patency compared with the CPBS (P = 0.007) and EEBS-30 cm (P < 0.001) groups. The EEBS-26 cm group had lower stent occlusion rates compared with the other groups at 6 months (48.1% vs. 90.5% vs. 82.8%, P = 0.001) and 9 months (75.0% vs. 100.0% vs. 92.9%, P = 0.022). CONCLUSION: EEBS-26 cm has prolonged stent patency and is safe and effective for the alleviation of unresectable extrahepatic malignant biliary obstruction.

Features of Ductular Reaction in Rats with Extrahepatic Cholestasis.

Ductular reaction develops during liver regeneration, fibrosis, and carcinogenesis. However, the types, stages of formation, and topography of ductular profiles in various pathologies remain insufficiently studied. Using the model of common bile duct occlusion, we showed that the number and topography of ductular profiles are closely related to the duration of biliary obstruction. The ductular profiles can be located inside the portal tract, along the existing bile ducts, and/or intramurally, around the portal vein, periportally, inside the lobules, in the portocaval fibrous connections, in the adventitia of the hepatic veins, in the septs connecting the portal tracts, and also in the "portal plate" of the liver. The ductular profiles can be formed as a result of expansion of existing bile ducts, cholangiocyte proliferation, as well as transdifferentiation of hepatocytes and activation of mesenchymal stem cells.

Cholecystectomy in 23 cats (2005-2021).

OBJECTIVE: To describe the clinical presentation, treatments, and long-term outcomes following cholecystectomy in cats. STUDY DESIGN: Clinical retrospective study. ANIMALS: Twenty-three client-owned cats. METHODS: Medical records of all cats undergoing cholecystectomy between 2005 and 2021 at a single referral hospital were retrospectively reviewed. No cats were excluded. An owner questionnaire assessed long-term outcomes. RESULTS: Vomiting, jaundice, and abdominal pain were the most common clinical signs; median duration of signs was 4 days (range 1-21). Cholelithiasis was the major indication for cholecystectomy followed by cholecystitis. Intraoperative hypotension and postoperative anemia were commonly encountered. Nine cats required a postoperative blood product transfusion. Cardiopulmonary arrest and death occurred in five cats. Eighteen cats (78.3%) survived to discharge. Long-term follow up (>60 days) was available for 16 cats at a median of 1003 days (range 81-4995). Fifteen cats survived over 6 months with eight cats (44.4%) surviving over 3 years. The most common short-term and long-term postoperative complication was vomiting. Owners assessed postoperative outcome as excellent in all cats and quality of life as excellent or good. CONCLUSION: The most common indication for cholecystectomy was cholelithiasis. Perioperative complications were commonly encountered. Perioperative mortality rate was 21.7%. Long-term owner evaluation of clinical outcome was considered excellent. CLINICAL SIGNIFICANCE: Cats undergoing cholecystectomy for non-neoplastic causes can have a favorable prognosis for recovery and quality of life. Concurrent extrahepatic biliary duct obstruction is not a contraindication for cholecystectomy provided that patency of the common bile duct is restored.