Catharanthus roseus intoxication mimicking acute cholangitis.

BACKGROUND: Catharanthus roseus, a Madagascar native flowering plant, is known for its glossy leaves and vibrant flowers, and its medicinal significance due to its alkaloid compounds. As a source of vinblastine and vincristine used in chemotherapy, Catharanthus roseus is also employed in traditional medicine with its flower and stalks in dried form. Its toxicity can lead to various adverse effects. We report a case of Catharanthus roseus juice toxicity presenting as acute cholangitis, emphasizing the importance of healthcare providers obtaining detailed herbal supplement histories. CASE PRESENTATION: A 65-year-old woman presented with abdominal pain, fever, anorexia, and lower limb numbness. Initial diagnosis of acute cholangitis was considered, but imaging excluded common bile duct stones. Further investigation revealed a history of ingesting Catharanthus roseus juice for neck pain. Laboratory findings showed leukocytosis, elevated liver enzymes, and hyperbilirubinemia. The patient developed gastric ulcers, possibly due to alkaloids in Catharanthus roseus. No bacterial growth was noted in blood cultures. The patient recovered after discontinuing the herbal extract. CONCLUSIONS: Catharanthus roseus toxicity can manifest as fever, hepatotoxicity with cholestatic jaundice, and gastric ulcers, mimicking acute cholangitis. Awareness of herbal supplement use and potential toxicities is crucial for healthcare providers to ensure prompt diagnosis and appropriate management. This case emphasizes the need for public awareness regarding the possible toxicity of therapeutic herbs and the importance of comprehensive patient histories in healthcare settings.

Targeting pathogenic CD8+ tissue-resident T cells with chimeric antigen receptor therapy in murine autoimmune cholangitis.

Primary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by autoreactive T cell response against intrahepatic small bile ducts. Here, we use Il12b-/-Il2ra-/- mice (DKO mice) as a model of autoimmune cholangitis and demonstrate that Cd8a knockout or treatment with an anti-CD8α antibody prevents/reduces biliary immunopathology. Using single-cell RNA sequencing analysis, we identified CD8+ tissue-resident memory T (Trm) cells in the livers of DKO mice, which highly express activation- and cytotoxicity-associated markers and induce apoptosis of bile duct epithelial cells. Liver CD8+ Trm cells also upregulate the expression of several immune checkpoint molecules, including PD-1. We describe the development of a chimeric antigen receptor to target PD-1-expressing CD8+ Trm cells. Treatment of DKO mice with PD-1-targeting CAR-T cells selectively depleted liver CD8+ Trm cells and alleviated autoimmune cholangitis. Our work highlights the pathogenic role of CD8+ Trm cells and the potential therapeutic usage of PD-1-targeting CAR-T cells.

BILE DUCT INJURY REPAIR IN A PATIENT WITH SITUS INVERSUS TOTALIS.

BACKGROUND: Bile duct injury (BDI) causes significant sequelae for the patient in terms of morbidity, mortality, and long-term quality of life, and should be managed in centers with expertise. Anatomical variants may contribute to a higher risk of BDI during cholecystectomy. AIMS: To report a case of bile duct injury in a patient with situs inversus totalis. METHODS: A 42-year-old female patient with a previous history of situs inversus totalis and a BDI was initially operated on simultaneously to the lesion ten years ago by a non-specialized surgeon. She was referred to a specialized center due to recurrent episodes of cholangitis and a cholestatic laboratory pattern. Cholangioresonance revealed a severe anastomotic stricture. Due to her young age and recurrent cholangitis, she was submitted to a redo hepaticojejunostomy with the Hepp-Couinaud technique. To the best of our knowledge, this is the first report of BDI repair in a patient with situs inversus totalis. RESULTS: The previous hepaticojejunostomy was undone and remade with the Hepp-Couinaud technique high in the hilar plate with a wide opening in the hepatic confluence of the bile ducts towards the left hepatic duct. The previous Roux limb was maintained. Postoperative recovery was uneventful, the drain was removed on the seventh post-operative day, and the patient is now asymptomatic, with normal bilirubin and canalicular enzymes, and no further episodes of cholestasis or cholangitis. CONCLUSIONS: Anatomical variants may increase the difficulty of both cholecystectomy and BDI repair. BDI repair should be performed in a specialized center by formal hepato-pancreato-biliary surgeons to assure a safe perioperative management and a good long-term outcome.

Pathophysiology of severe gallstone pancreatitis: A new paradigm.

Severe gallstone pancreatitis (GSP) refractory to maximum conservative therapy has wide clinical variations, and its pathophysiology remains controversial. This Editorial aimed to investigate the pathophysiology of severe disease based on Opie's theories of obstruction, the common channel, and duodenal reflux and describe its types. Severe GSP might be a hybrid disease with pathology polarized between acute cholangitis with mild pancreatitis (biliary type) and necrotizing pancreatitis uncomplicated with biliary tract disease (pancreatic type), in which hepatobiliary and pancreatic lesion severity is inversely related to the presence or absence of impacted ampullary stones. Severe GSP is caused by stones that are persistently impacted at the ampulla with biliopancreatic obstruction (biliary type), and probably, stones that are either temporarily lodged at the duodenal orifice or passed into the duodenum, thereby permitting reflux of bile or possible duodenal contents into the pancreas (pancreas type). When the status of the stones and the presence or absence of impacted ampullary stones with biliopancreatic obstruction are determined, the clinical course and outcome can be predicted. Gallstones represent the main cause of acute pancreatitis globally, and clinicians are expected to encounter GSP more often. Awareness of the etiology and pathogenesis of severe disease is mandatory.

Perioperative outcomes after open biliary bypass for malignant biliary obstruction (MBO) in resource-limited setups; a multicenter prospective cohort study, 2023.

INTRODUCTION: Obstructive jaundice is the most common symptom of malignant diseases of the extrahepatic biliary system and necessitates either non-operative or operative biliary bypass. Because of percutaneous and endoscopic approaches, the use of palliative surgical procedures has decreased in recent years. However, in resource-limited situations, open biliary bypasses remain a viable option. This study aimed to identify factors associated with adverse perioperative outcomes following open biliary bypass. METHODS: From June 2022 to May 2023, 69 patients underwent open biliary bypass for malignant biliary obstruction. Postoperative morbidity and mortality within 30 days of surgery were assessed. A Kaplan-Meier was used for categorical variables, and a log-rank test was used to determine the statistically significant difference between variables. A Cox regression analysis was conducted to identify factors associated to time to develop complications. RESULTS: The hazard of developing complications among those with preoperative cholangitis was 2.49 times higher than those without preoperative cholangitis (HR 2.49, 95% CI [1.06, 5.84]). For every hour increment in the length of surgery, the hazard of getting complications increased by 2.47 times (HR 2.47, 95% CI [1.28, 4.77]). As serum bilirubin increased by 1 mg/dl, the hazard of developing complications increased by 14% (HR 1.14, 95% CI [1.03, 1.17]). CONCLUSION: Patients who had long operation times, preoperative cholangitis, and elevated total bilirubin levels are at increased risk for poor perioperative outcomes. Clinicians may use these results to optimize these patients to decrease their elevated risk of serious morbidity and mortality.

[Air embolism after biliary stent removal during endoscopic retrograde cholangiopancreatography for cholangitis after biliary reconstruction: a case report].

A 62-year-old male patient underwent pancreaticoduodenectomy with modified Child reconstruction for distal cholangiocarcinoma. After eight years, a contrast-enhanced computed tomography (CT) revealed a recurrent lesion at the biliojejunal anastomosis, and a biliary stent was placed for obstructive cholangitis in the right posterior segment of the liver. A right hepatectomy was planned for a local recurrent lesion;thus, percutaneous transhepatic portal embolization was performed on the portal vein's right branch to enlarge the left liver. However, he was referred to our department for endoscopic retrograde biliary drainage for the subsequent cholangitis and liver abscess appearance. A double-balloon enteroscope under CO2 insufflation was used to reach the bile duct-jejunal anastomosis. After removing the bile duct stent with grasping forceps, his general condition suddenly deteriorated, causing cardiopulmonary arrest. He was diagnosed with air embolism based on the findings of air in the heart, aorta, and brain on CT after the return of spontaneous circulation. Treatment for the air embolism and subsequent complications continued in the intensive care unit, but he eventually died 114 days after the onset of the air embolism due to his deteriorating general condition. Pathological autopsy revealed cholangiocarcinoma that extends from the porta hepatis to the posterior segment. Additionally, the proximity between the bile duct and vein extended by the adenocarcinoma and the fibrous obstruction of the vein were revealed, indicating the possibility of a bile duct-vein shunt.

Bacterial Infections After Liver Transplantation and the Role of Oral Selective Digestive Decontamination: A Retrospective Cohort Study.

BACKGROUND: Bacterial infections are common after liver transplantation (LT) and cause serious morbidity and mortality. In our center, prolonged selective digestive decontamination (SDD) is the standard of care, which may lead to a reduced number and severity of bacterial infections. The aim of the current study was to investigate bacterial infection rates, the causative pathogens, localization, and the possible influence of SDD within the first year after LT. METHODS: A retrospective single-center cohort study was performed. Patients within their first year after LT between 2012 and 2017 were included. Patients received SDD for 3 weeks immediately after LT. The type of infection, bacterial subtype, CSI classification, severity, and potential interventions were recorded. RESULTS: One hundred eighty-six patients were included in the study. Seventy-eight patients (41.9%) had a bacterial infection within the first year after LT. The most common types of infection were cholangitis (25.8%) and secondary infected abdominal fluid collections (25.3%). The most common bacteria were Gram-positive enterococcal- (36.5%) and Gram-negative enterobacterial species (34.2%). 35.5% of the infections occurred within the first month after LT, mainly caused by Gram-positive bacteria (76.7%). CONCLUSIONS: Cholangitis and infected abdominal fluid are the most common types of infection within one year after LT, mainly caused by enterococcal- and enterobacterial species. Within the first month after LT, infections were mostly caused by Gram-positive bacteria, which could be a consequence of protocol use of SDD. The results can be used for the choice of empirical antibiotic therapy based on the most common types of bacteria and the time frame after LT.

A rare incidence of a hepatic artery pseudoaneurysm following plastic biliary stent insertion.

Hepatic artery pseudoaneurysms have been reported to occur in approximately 1% of cases after metal stenting for malignant biliary obstruction. In contrast, only a few cases have been reported as complications after plastic stenting for benign biliary disease. We report a 61-year-old man with cholangitis who presented with a rare complication of hemobilia after implantation of 7 Fr double pigtail plastic biliary stents. No bleeding was observed approximately one month after biliary stent tube removal. Contrast-enhanced CT scan revealed a circularly enhanced lesion (5 mm in diameter) in the arterial phase at the tip of the previously inserted plastic bile duct stent. Color Doppler ultrasonography enhanced the lesion and detected arterial blood flow inside. He was diagnosed with a hepatic artery pseudoaneurysm. However, he had no risk factors such as prolonged catheterization, severe cholangitis, liver abscess, or long-term steroid use. Superselective transarterial embolization using two metal microcoils was successfully completed without damage to the surrounding liver parenchyma. If hemobilia is suspected after insertion of a plastic bile duct stent, immediate monitoring using contrast-enhanced computed tomography or Doppler ultrasonography is recommended.

Cholangitis with bacteremia due to Pseudomonas nitroreducens in a patient with pancreatic neuroendocrine tumors: a case report.

BACKGROUND: Pseudomonas nitroreducens is a non-fermenting, gram-negative, rod-shaped bacterium commonly inhabiting soil, particularly soil contaminated with oil brine. To our knowledge, no cases of human infection with P. nitroreducens have been previously reported. Here, we present the first documented case of cholangitis caused by P. nitroreducens in a patient with bacteremia. CASE PRESENTATION: A 46-year-old Japanese man with an advanced pancreatic neuroendocrine tumor was hospitalized with fever and chills. Four days before admission, the patient developed right upper abdominal pain. Two days later, he also experienced fever and chills. Endoscopic retrograde cholangiopancreatography was performed on the day of admission, and the patient was diagnosed as having cholangitis associated with stent dysfunction. Gram-negative rods were isolated from blood cultures, but attempts to identify the bacteria using VITEK2 and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with VITEK MS ver. 4.7.1 (bioMérieux Japan Co. Ltd., Tokyo, Japan) were unsuccessful. Finally, the organism was identified as P. nitroreducens using MALDI-TOF MS with a MALDI Biotyper (Bruker Daltonics Co., Ltd., Billerica, MA, USA) and 16 S ribosomal RNA sequencing. Despite thorough interviews with the patient, he denied any exposure to contaminated soil. The patient was treated with intravenous cefepime and oral ciprofloxacin for 16 days based on susceptibility results, achieving a good therapeutic outcome. At the outpatient follow-up on day 28, the patient was in good general condition. CONCLUSIONS: This is the first reported human case of cholangitis with bloodstream infection caused by P. nitroreducens. This report provides clinicians with novel insights into the clinical manifestations and diagnostic methods necessary for the accurate diagnosis of P. nitroreducens, along with guidance on treatment.

Differences in the perceptions of patients with primary biliary cholangitis and physicians from various hospital departments: An online survey.

OBJECTIVES: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that affects the quality of life (QoL) of patients. This study aimed to evaluate the differences in perceptions of PBC among physicians from different hospital departments and patients with PBC. METHODS: An online survey regarding the general knowledge, diagnosis, and management of PBC was completed by physicians and patients. RESULTS: A total of 239 patients with PBC and 239 physicians from eight hospital departments (gastroenterology, infectious diseases, rheumatology, hepatobiliary surgery, pathology, clinical laboratory, ultrasound, and radiology) completed the survey. The results showed that physicians from departments other than gastroenterologists and rheumatologists lacked knowledge of PBC, and that junior gastroenterologists were uncertain about the diagnostic and treatment pathways of PBC. Importantly, the lack of knowledge significantly impacted the QoL of patients, especially the emotional scores of PBC-40 (odds ratio -2.556, 95% confidence interval -3.852 to -1.260, P < 0.001). In addition, there was a perceived knowledge gap between patients and gastroenterologists. CONCLUSIONS: Physicians must improve their awareness of PBC. Patient education and patient-physician communication are important for improving the patient's QoL.

Revisiting the Malignant Masquerade at the Liver Hilum: Have We Made Progress?

BACKGROUND: Distinguishing malignant from benign causes of obstruction at the liver hilum can pose a diagnostic dilemma. This study aimed to determine factors that predict benign causes of hilar obstruction and long-term outcomes after resection. METHODS: Consecutive patients who underwent surgery for hilar obstruction at a single institution between 1997 and 2022 were retrospectively analyzed. Median follow-up was 26 months (range 0-281 months). RESULTS: Among 182 patients who underwent surgery for hilar obstruction, 25 (14%) patients were found to have benign disease. Median CA19-9 level after normalization of serum bilirubin was 80 U/mL (range 1-5779) and 21 U/mL (range 1-681) among patients with malignant and benign strictures, respectively (p = 0.001). Cross-sectional imaging features associated with malignancy were lobar atrophy, soft tissue mass/infiltration, and vascular involvement (all p < 0.05). Factors not correlated with malignancy were jaundice upon presentation, peak serum bilirubin, sex, and race. Preoperative bile duct brushing or biopsy had sensitivity and specificity rates of 82% and 55%, respectively. Among patients who underwent resection with curative intent, grade 3-4 complications occurred in 55% and 29% of patients with malignant and benign strictures, respectively (p = 0.028). Postoperative long-term complications of chronic portal hypertension and recurrent cholangitis occurred in ≥ 10% of patients with both benign and malignant disease (p = non-significant). CONCLUSIONS: Strictures at the liver hilum continue to present diagnostic and management challenges. Postoperative complications and long-term sequelae of portal hypertension and recurrent cholangitis develop in a significant number of patients after resection of both benign and malignant strictures.

[Acute cholangitis due to Candida glabrata and Klebsiella pneumoniae]. / Colangitis aguda por Candida glabrata y Klebsiella pneumoniae.

Acute cholangitis is a bile duct infection associated with bile duct obstruction. Bile culture is positive in most cases, and the most frequent etiological agent is Escherichia coli. Candida sp acute cholangitis is a rare finding, which is more common in patients with immunosuppression, use of corticosteroids, prolonged antibiotic treatment or surgical procedures of the bile duct. We present the case of a 67-year-old woman with none of the above-mentioned history who consulted for fever, abdominal pain and jaundice. MRI of the abdomen revealed a lithiasic image in the common bile duct with dilation. It required endoscopic drainage of the biliary tract. Direct microscopic examination of the bile fluid revealed gram-negative bacilli and yeast, and in the culture of bile fluid Klebsiella pneumoniae producing extended spectrum beta-lactamase (ESBL) and Candida glabrata were isolated. The patient completed the antibiotic treatment with piperacillin tazobactam and anidulafungin with good evolution. Bile duct infection by association of Gram-negative bacilli and Candida sp is a rare entity, more in patients without underlying diseases.

La colangitis aguda es una infección de la vía biliar, asociada a la obstrucción de esta. El cultivo de la bilis es positivo en la mayoría de los casos y el agente etiológico más frecuente es Escherichia coli. La colangitis aguda por Candida sp es un hallazgo poco común, que es más frecuente en pacientes con inmunocompromiso, uso de corticoides, tratamiento antibiótico prolongado o procedimientos quirúrgicos de la vía biliar. Presentamos el caso de una mujer de 67 años, que no presentaba ninguno de los antecedentes mencionados, y que consultó por fiebre, dolor abdominal e ictericia. En la resonancia magnética nuclear de abdomen se constató imagen litiásica en el colédoco con dilatación de la vía biliar. Requirió drenaje endoscópico del tracto biliar. En el examen microscópico directo del líquido biliar se evidenciaron levaduras y bacilos Gram negativos, y en el cultivo se aisló Klebsiella pneumoniae productora de betalactamasa de espectro extendido (BLEE) y Candida glabrata. La paciente completó el tratamiento antibiótico con piperacilina tazobactam y anidulafungina con buena evolución. La infección de la vía biliar por la asociación de bacilos Gram negativos y Candida sp es una entidad poco frecuente, más en pacientes sin enfermedades subyacentes.

A Unique Case of Caroli Disease in Kenya's Medical Landscape.

BACKGROUND If a young patient presents with fever, abdominal pain, jaundice and significant imaging abnormalities, especially dilation of the biliary system, it is usually due to obstruction from stones or strictures. However, on very rare occasions, it can be due to complications of congenital cystic dilatation of the biliary system, known as Caroli disease. We present such a patient and discuss the differential diagnosis and implications for long-term management. CASE REPORT A 14-year-old boy presented to the Emergency Department with a sudden onset of high-grade fever and abdominal pain for 2 weeks, accompanied by vomiting of blood. The patient had no relevant medical history. He was malnourished and had moderate pallor, jaundice, and right upper quadrant pain. Imaging revealed cystic dilatation of intrahepatic ducts and a central dot sign. There were no features suggesting advanced liver disease otherwise, and no tumors or cysts in the kidneys. A diagnosis of Caroli disease was made. The symptoms were ascribed to acute cholangitis and improved with antibiotics. He was discharged home 1 week later. No further blood loss was observed. CONCLUSIONS This case study describes a patient with ascending cholangitis, a complication of Caroli disease. This diagnosis should be considered in the differential diagnosis when a child or young adult presents with features of cholangitis, abnormal biliary imaging, and/or upper gastrointestinal bleeding, or portal hypertension. No prior cases of this disease have been encountered, documented, or published in Kenya. This case can increase awareness among primary care clinicians, including pediatricians.

Epcam regulates intrahepatic bile duct reconstruction in zebrafish, providing a potential model for primary cholangitis model.

Epithelial cell adhesion molecules (EpCAMs) have been identified as surface markers of proliferating ductal cells, which are referred to as liver progenitor cells (LPCs), during liver regeneration and correspond to malignancies. These cells can differentiate into hepatocytes and biliary epithelial cells (BECs) in vitro. EpCAM-positive LPCs are involved in liver regeneration following severe liver injury; however, the in vivo function of EpCAMs in the regenerating liver remains unclear. In the present study, we used a zebrafish model of LPC-driven liver regeneration to elucidate the function of EpCAMs in the regenerating liver in vivo. Proliferating ductal cells were observed after severe hepatocyte loss in the zebrafish model. Analyses of the liver size as well as hepatocyte and BEC markers revealed successful conversion of LPCs to hepatocytes and BECs in epcam mutants. Notably, epcam mutants exhibited severe defects in intrahepatic duct maturation and bile acid secretion in regenerating hepatocytes, suggesting that epcam plays a critical role in intrahepatic duct reconstruction during LPC-driven liver regeneration. Our findings provide insights into human diseases involving non-parenchymal cells, such as primary biliary cholangitis, by highlighting the regulatory effect of epcam on intrahepatic duct reconstruction.

Recurrent cholangitis in patients with a non-stenotic hepaticojejunostomy: incidence and risk factors.

BACKGROUND: Cholangitis is a well-known complication after hepaticojejunostomy (HJ), which is mainly caused by a stenotic anastomosis. However, the rate of cholangitis in patients with a non-stenotic (i.e. patent) HJ is unknown. We aimed to evaluate the incidence and risk factors of recurrent cholangitis in patients with a non-stenotic HJ. METHODS: This single-center retrospective cohort study included all consecutive patients who had undergone hepatobiliary or pancreatic (HPB) surgery requiring HJ (2015-2022). Primary outcome was recurrent non-stenotic cholangitis, risk factors for recurrent non-stenotic cholangitis were identified using logistic regression. RESULTS: Overall, 835 patients with a HJ were included of whom 31/698 (4.4%) patients developed recurrent cholangitis with a non-stenotic HJ during a median follow-up of 34 months (IQR 22-50) and 98/796 (12.3%) patients developed a symptomatic HJ stenosis. These 31 patients experienced 205 cholangitis episodes, median 7.0 (IQR 3.8-8.8) per patient, and 71/205 (34.6%) cholangitis episodes required hospitalization. Male sex (aOR 3.17 (95% CI: 1.34-7.49)) and benign disease (aOR 2.97, 95% CI 1.40-6.33) were identified as risk factors for recurrent cholangitis in non-stenotic HJ in both univariate and multivariable analysis. CONCLUSION: This study shows that 4% of patients developed recurrent cholangitis without an underlying HJ stenosis.