Management of ERCP complications.

Managing complications of ERCP poses a significant clinical challenge to endoscopists. ERCP complications can occur even after all preventive measures, which can lead to significant morbidity and even mortality. Major complications include pancreatitis, bleeding, perforation, cholangitis, and sedation-related adverse events. Early recognition of post-ERCP pancreatitis (PEP) is feasible by monitoring clinical parameters and specific cutoffs of serum amylase and lipase at 2-6 h post-ERCP. Pancreatic stenting for PEP is not recommended and can increase the incidence of infected necrosis in addition to being technically challenging. Post-sphincterotomy bleeds can be treated by diluted epinephrine with or without thermal therapy, or mechanical therapy (clips or fully covered metallic stents) failing which angiographic embolization and rarely open surgical vessel ligation may be warranted. Post-ERCP perforations can lead to significant morbidity and are usually treated with endoscopic closure of the defect, diverting bile flow, draining collections, and reducing fluid load at the site of perforation failing which surgery may be warranted. Broad-spectrum antibiotics with endoscopic or radiologic drainage of undrained segments help treat post-ERCP cholangitis. Hypoxia and hypertension are the most common sedation-related adverse events without long-term consequences except aspiration pneumonia (<0.5%). Awareness with a high index of suspicion is crucial for timely diagnosis and management of uncommon post-ERCP complications.

Intrabiliary Rupture of a Hepatic Hydatid Cyst: A Case Report.

BACKGROUND Hydatid disease is a common parasitic infection in many areas of Asia, South America, and Africa. It can affect any organ, most commonly the liver. The hydatid is often asymptomatic and the diagnosis is made when complications arise. The most common complication of this disease is opening in the bile ducts, which is a life-threatening condition causing serious acute cholangitis. We report a case of acute cholangitis caused by hydatid cyst rupture into the right bile duct. CASE REPORT A 33-year-old woman, with no medical or surgical history, presented to our Emergency Department with abdominal pain, jaundice, and fever for 3 days prior to admission. The patient was hemodynamically stable. In the examination, we noticed right upper-quadrant tenderness with guarding, icterus sclera, and negative Murphy sign. A CT scan showed a liver hydatid cyst of the 4th and 8th of segments, with intrahepatic and extrahepatic biliary duct dilation. The cyst communicated with the right hepatic bile duct via a large fistula. A diagnosis of acute cholangitis was made and she underwent conservative treatment with external drainage of the pericystic cavity through the biliary duct. The postoperative course was uncomplicated and she was discharged 15 days later. CONCLUSIONS The surgical approach to hepatic hydatid must be customized based on the specific characteristics of the cyst and associated complications. Acute hydatid cholangitis is a rare but serious complication of a hydatid cyst, which requires early diagnosis and adequate surgical management.

Assessing the clinical utility of abdominal computed tomography in sepsis patients with unknown origin: A retrospective cohort study.

Early identification of the sources of infection in emergency department (ED) patients of sepsis remains challenging. Computed tomography (CT) has the potential to identify sources of infection. This retrospective study aimed to investigate the role of CT in identifying sources of infection in patients with sepsis without obvious infection foci in the ED. A retrospective chart review was conducted on patients with fever and sepsis visiting the ED of Linkou Chang Gung Memorial Hospital between July 1, 2020 and June 30, 2021. Data on patient demographics, vital signs, clinical symptoms, underlying medical conditions, laboratory results, administered interventions, length of hospital stay, and mortality outcomes were collected and analyzed. Of 218 patients included in the study, 139 (63.8%) had positive CT findings. The most common sources of infection detected by CT included liver abscesses, acute pyelonephritis, and cholangitis. Laboratory results showed that patients with positive CT findings had higher white blood cell and absolute neutrophil counts and lower hemoglobin levels. Positive blood culture results were more common in patients with positive CT findings. Additionally, the length of hospital stay was longer in the group with positive CT findings. Multivariate logistic regression analysis revealed that hemoglobin levels and positive blood culture results independently predicted positive CT findings in patients with fever or sepsis without an obvious source of infection. In patients with sepsis with an undetermined infection focus, those presenting with leukocytosis, anemia, and elevated absolute neutrophil counts tended to have positive findings on abdominal CT scans. These patients had high rates of bacteremia and longer lengths of stay. Abdominal CT remains a valuable diagnostic tool for identifying infection sources in carefully selected patients with sepsis of undetermined infection origins.

Outcome of patients with perihilar cholangiocarcinoma and previous biliary instrumentation: an observational study.

BACKGROUND: To assess the outcome of previously untreated patients with perihilar cholangiocarcinoma who present to a cancer referral center with or without pre-existing trans-papillary biliary drainage. METHODS: Consecutive patients with a diagnosis of perihilar cholangiocarcinoma presenting between January 1, 2013, and December 31, 2017, were identified from a prospective surgical database and by a query of the institutional database. Of 237 patients identified, 106 met inclusion criteria and were reviewed. Clinical information was obtained from the Electronic Medical Record and imaging studies were reviewed in the Picture Archiving and Communication System. RESULTS: 73 of 106 patients (69%) presenting with a new diagnosis of perihilar cholangiocarcinoma underwent trans-papillary biliary drainage (65 endoscopic and 8 percutaneous) prior to presentation at our institution. 8 of the 73 patients with trans-papillary biliary drainage (11%) presented with and 5 developed cholangitis; all 13 (18%) required subsequent intervention; none of the patients without trans-papillary biliary drainage presented with or required drainage for cholangitis (p = 0.008). Requiring drainage for cholangitis was more likely to delay treatment (p = 0.012) and portended a poorer median overall survival (13.6 months, 95%CI [4.08, not reached)] vs. 20.6 months, 95%CI [18.34, 37.51] p = 0.043). CONCLUSION: Trans-papillary biliary drainage for perihilar cholangiocarcinoma carries a risk of cholangitis and should be avoided when possible. Clinical and imaging findings of perihilar cholangiocarcinoma should prompt evaluation at a cancer referral center before any intervention. This would mitigate development of cholangitis necessitating additional drainage procedures, delaying treatment and potentially compromising survival.

Urgent one-stage endoscopic treatment for choledocholithiasis related moderate to severe acute cholangitis: A propensity score-matched analysis.

BACKGROUND: During emergency endoscopic retrograde cholangiopancreatography (ERCP), the safety and feasibility of performing one-stage endoscopic treatment for patients with acute cholangitis (AC) due to choledocholithiasis are unclear. AIM: To investigate the safety and feasibility of one-stage endoscopic treatment for moderate to severe AC. METHODS: We enrolled all patients diagnosed with moderate to severe cholangitis due to common bile duct stones from January 2019 to July 2023. The outcomes were compared in this study between patients who underwent ERCP within 24 h and those who underwent ERCP 24 h later, employing a propensity score (PS) framework. Our primary outcomes were intensive care unit (ICU) admission rates, ICU length of stay, and duration of antibiotic use. RESULTS: In total, we included 254 patients and categorized them into two groups based on the time elapsed between admission and intervention: The urgent group (≤ 24 h, n = 102) and the elective group (> 24 h, n = 152). Ninety-three pairs of patients with similar characteristics were selected by PS matching. The urgent ERCP group had more ICU admissions (34.4% vs 21.5%, P = 0.05), shorter ICU stays (3 d vs 9 d, P < 0.001), fewer antibiotic use (6 d vs 9 d, P < 0.001), and shorter hospital stays (9 d vs 18.5 d, P < 0.001). There were no significant differences observed in adverse events, in-hospital mortality, recurrent cholangitis occurrence, 30-d readmission rate or 30-d mortality. CONCLUSION: Urgent one-stage ERCP provides the advantages of a shorter ICU stay, a shorter duration of antibiotic use, and a shorter hospital stay.

Hepatolithiasis: Epidemiology, presentation, classification and management of a complex disease.

The term hepatolithiasis describes the presence of biliary stones within the intrahepatic bile ducts, above the hilar confluence of the hepatic ducts. The disease is more prevalent in Asia, mainly owing to socioeconomic and dietary factors, as well as the prevalence of biliary parasites. In the last century, owing to migration, its global incidence has increased. The main pathophysiological mechanisms involve cholangitis, bile infection and biliary strictures, creating a self-sustaining cycle that perpetuates the disease, frequently characterised by recurrent episodes of bacterial infection referred to as syndrome of "recurrent pyogenic cholangitis". Furthermore, long-standing hepatolithiasis is a known risk factor for development of intrahepatic cholangiocarcinoma. Various classifications have aimed at providing useful insight of clinically relevant aspects and guidance for treatment. The management of symptomatic patients and those with complications can be complex, and relies upon a multidisciplinary team of hepatologists, endoscopists, interventional radiologists and hepatobiliary surgeons, with the main goal being to offer relief from the clinical presentations and prevent the development of more serious complications. This comprehensive review provides insight on various aspects of hepatolithiasis, with a focus on epidemiology, new evidence on pathophysiology, most important clinical aspects, different classification systems and contemporary management.

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.

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.

Bile Culture May Guide Antibiotic Stewardship in Acute Bacterial Cholangitis.

BACKGROUND: Bile cultures are often sent with blood cultures in patients with acute bacterial cholangitis. AIMS: To assess the yield of blood and bile cultures in patients with cholangitis and the clinical utility of bile cultures in guiding therapy. METHODS: All patients diagnosed with cholangitis, based on the Tokyo 2013/2018 guidelines were recruited retrospectively over ten years. The clinical and investigation details were recorded. The results of bile and blood cultures including antibiotic sensitivity patterns were noted. The concordance of microorganisms grown in blood and bile cultures and their sensitivity pattern were assessed. RESULTS: A total of 1063 patients with cholangitis were included. Their mean age was 52.7 ± 14 years and 65.4% were males. Blood cultures were positive in 372 (35%) patients. Bile culture was performed in 384 patients with 84.4% being positive, which was significantly higher than the yield of blood culture (p < 0.001). Polymicrobial growth was more in bile (59.3%) than in blood cultures (13.5%, p < 0.001). E.coli, Klebsiella, Enterococcus and Pseudomonas were the four most common organisms isolated from both blood and bile. Extended spectrum betalactamase producing organisms were isolated in 57.7% and 58.8% of positive blood and bile cultures, respectively. Among 127 patients with both blood and bile cultures positive, complete or partial concordance of organisms was noted in about 90%. CONCLUSION: Bile and blood cultures have a similar microbial profile in most patients with cholangitis. As bile cultures have a significantly higher yield than blood cultures, they could effectively guide antimicrobial therapy, especially in those with negative blood cultures.

Biliary Taeniasis: Case Series and Literature Review.

Biliary taeniasis is uncommon in clinical practice. We report two cases in our hospital. The first patient was diagnosed with acute biliary pancreatitis. Endoscopic retrograde cholangiopancreatography (ERCP) showed a white, flat, segmented 1-cm-wide tapeworm drilling into the duodenal papilla that was identified as Taenia saginata. After tapeworm removal, bile duct sweeping, and anthelmintic therapy, the patient recovered uneventfully. The second patient was diagnosed with acute cholangitis and multiple stones in the common bile duct and gallbladder. Emergency ERCP showed no tapeworm in the duodenum. During a subsequent ERCP 6 days later, a flat tapeworm, also T. saginata, was identified drilling into the duodenal papilla. We review five patients cases with acute acalculous cholecystitis or cholangitis caused by T. saginata or Taenia solium, and 1 patient with T. saginata drilling into the T-tube. Taeniasis should be taken into consideration when dealing with biliary and pancreatic disease.

Endoscopic features of low-phospholipid-associated cholelithiasis syndrome: A retrospective cohort study.

BACKGROUND AND OBJECTIVE: LPAC (low phospholipid-associated cholelithiasis) syndrome is a rare genetic form of cholelithiasis. ERCP (endoscopic retrograde cholangiopancreatography) is often used to remove gallstones in the bile duct. No published data is available on the role of ERCP in LPAC syndrome. PATIENTS AND METHODS: In this retrospective cohort study, we included patients diagnosed with LPAC syndrome in a single tertiary referral center between 2009 and 2021. Our aim was to assess the frequency, indications, modalities, results, and complications of ERCP, as well as predictive factors for ERCP, in LPAC syndrome. Independent factors associated with ERCP occurrence were identified using a multivariable Cox regression analysis. RESULTS: ERCP was required in 31.2 % of the 269 patients included for analysis. Among patients who required ERCPs, 78.6 % had the procedure before diagnosis (i.e., starting UDCA). Most common indications were choledocholithiasis (53.6 %) and acute cholangitis (29.5 %). Post ERCP pancreatitis, perforation and bleeding rates were 7.2 %, 2.6 %, and 1.3 %, respectively. Age and history of cholelithiasis in first-degree relatives were associated with a higher risk of ERCP (Hazard-ratio [HR]=1.30 [95 %confidence-interval [CI] 1.04-1.62] and HR=1.88 [95 %CI 1.15-3.07] respectively). Female gender and UDCA intake ≥ 1 year were associated with a lower risk of ERCP (HR=0.49 [95 %CI 0.29-0.82] and HR=0.44 [95 %CI 0.22-0.90] respectively). Median follow-up was 10.8 years. CONCLUSION: One-third of patients with LPAC syndrome undergo sphincterotomy. However, most procedures are performed before diagnosis and UDCA is associated with a lower risk of endoscopic procedure. Earlier diagnosis and treatment with UDCA may further reduce the need for ERCP in patients with LPAC syndrome.

Comparative Risks of Post-ERCP Adverse Events in Patients with Asymptomatic and Symptomatic Choledocholithiasis: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is the standard of care for the management of choledocholithiasis but carries risk of complications which may result in significant morbidity and mortality. While currently available guidelines endorse the use of ERCP for the management of symptomatic common bile duct stones, the need for ERCP in incidentally found asymptomatic choledocholithiasis is more controversial, and practice varies on a geographic and institutional level. This systematic review and meta-analysis is conducted to compare post-ERCP adverse events between asymptomatic and symptomatic choledocholithiasis patients. METHODS: We searched PubMed/Embase/Web of Science databases to include all studies comparing post-ERCP outcomes between asymptomatic and symptomatic choledocholithiasis patients. The primary outcome was post-ERCP pancreatitis (PEP), while secondary outcomes included post-ERCP cholangitis, bleeding, and perforation. We calculated pooled risk ratios (RR) and 95% confidence intervals (CIs) using the Mantel-Haenszel method within a random-effect model. RESULTS: Our analysis included six observational studies, totaling 2,178 choledocholithiasis patients (392 asymptomatic and 1786 symptomatic); 53% were female. Asymptomatic patients exhibited a higher risk of PEP compared with symptomatic patients (11.7% versus 4.8%; RR 2.59, 95% CI 1.56-4.31, p ≤ 0.001). No significant difference was observed in post-ERCP cholangitis, bleeding, or perforation rates between the two groups. CONCLUSIONS: Asymptomatic patients with choledocholithiasis appear to have a higher risk of PEP than symptomatic patients, while the risk of other post-ERCP adverse events is similar between the two groups. Interventional endoscopists should thoroughly discuss potential adverse events (particularly PEP) with asymptomatic patients before performing ERCP and utilize PEP-prevention measures more liberally in this subgroup of patients.

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.

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.