Cholecystitis induced by Yttrium-90 radioembolization of advanced liver tumors: prospective evaluation of a management algorithm in 197 consecutive patients.

BACKGROUND: Cholecystitis is a rare but dolorous complication after Y90-radioembolization of liver malignancies. PURPOSE: To decide the occlusion of the cystic artery (CA) to prevent cholecystitis after Y90 radioembolization using an algorithm. MATERIAL AND METHODS: In 130 patients, the gallbladder was at risk of embolization as the right liver lobe was targeted. Precautionary measures (e.g. coil occlusion of the cystic artery) were decided by enhancement of the gallbladder in pre-treatment Tc99m-MAA SPECT/CT and performed directly before Y90 radioembolization. In non-enhancing cases, the CA was left open. The outcome was determined by clinical symptoms of acute or chronic cholecystitis as well as imaging and laboratory parameters. Findings were additionally classified according to the Tokyo Guidelines of acute cholecystitis. RESULTS: Only 16 patients demonstrated enhancement of the gallbladder in Tc99m-MAA SPECT/CT. Including additional indications from angiographic findings, prophylactic measures were scheduled in 22 patients (standard of care). Thus, 121 patients were at risk of non-target embolization to the gallbladder during Y90 microsphere administration (investigative arm). Four cases (3.0%) of cholecystitis occurred by clinical presentation: two patients with onset of acute symptoms within 48 h after Y90 radioembolization ("embolic cholecystitis") and two patients with late onset of symptoms ("radiogenic cholecystitis"). The incidence of cholecystitis was not significantly more frequent without indication of precautionary measures (investigative cohort 2.9% vs. standard of care 4.7%; P = 0.53). CONCLUSION: The overall incidence of cholecystitis after Y90 radioembolization is low. Determination of cystic artery intervention using Tc99m-MAA SPECT/CT successfully balances the incidence of symptomatic cholecystitis with unnecessary vessel occlusion.

Possible dulaglutide-associated cholecystitis with safe continuation post cholecystectomy.

PURPOSE: Possible dulaglutide-induced cholecystitis, with successful resumption of dulaglutide after cholecystectomy, is discussed. SUMMARY: A 72-year-old White man was started on dulaglutide for outpatient management of type 2 diabetes, in addition to his existing antihyperglycemic regimen of metformin, glipizide, pioglitazone, and insulin glargine. His glycated hemoglobin (HbA1c) concentration improved from 8.2% to 7.2% with the addition of dulaglutide. Furthermore, the use of dulaglutide did not lead to weight loss. After 16 months of treatment with dulaglutide, he presented to the emergency room with nausea, loss of appetite, and progressive sharp, nonradiating right upper quadrant pain. Based on symptom presentation, laboratory workup, and computed tomography scan results, acute cholecystitis was diagnosed. He underwent a cholecystectomy to remove what was found to be a gangrenous gallbladder. Per documented surgical dictation from the cholecystectomy, the gallbladder was removed, but portions of the biliary tree were left intact. The patient was continued on dulaglutide postoperatively without recurrence of bile stones, biliary tree disease, or abdominal symptoms at 8 months after initial cholecystitis incident. CONCLUSION: A male patient with possible dulaglutide-induced cholecystitis was successfully continued on dulaglutide therapy post cholecystectomy without recurrent complications within the biliary tract.

A Case of Hemorrhagic Cholecystitis and Hemobilia Under Anticoagulation Therapy.

BACKGROUND Hemorrhagic cholecystitis is a rare disease which can be fatal in some cases. Hemorrhagic cholecystitis can sometimes be confused with common biliary diagnoses, as its symptoms imitate other hepatobiliary diseases. We report a case of hemorrhagic cholecystitis with hemobilia caused by the administration of anticoagulant agents. CASE REPORT A 70-year-old man was admitted with abdominal distention and pain. Ultrasound (US) and computed tomography (CT) showed a distended and wall-thickened gallbladder with hyperdense materials. Based on these findings and the laboratory data, the patient was diagnosed with acute cholecystitis with cholangitis. Because the patient's hemodynamics were stable, endoscopic retrograde cholangiopancreatography (ERCP) was performed first to improve the bile flow. The results of ERCP showed blood from the common bile duct by cannulation, which was suspected to reflect hemorrhagic cholecystitis. As the abdominal symptom and CT findings worsened on the day after ERCP, emergency laparoscopic cholecystectomy was performed. An examination of the specimen revealed ulcer formation on the mucosal side of the gallbladder. The patient was discharged 6 days after the operation without any surgical complications. CONCLUSIONS ERCP and early laparoscopic cholecystectomy were performed for a patient with hemorrhagic cholecystitis and hemobilia. Early diagnosis and treatment can lead to good outcomes in patients with hemorrhagic cholecystitis. Since the number of patients who are taking antithrombotic agents is increasing, hemorrhagic cholecystitis should be considered when any unusual imaging findings associated with cholecystitis are observed.

Hemorrhagic cholecystitis with rare imaging presentation: a case report and a lesson learned from neglected medication history of NSAIDs.

BACKGROUND: Gallbladder carcinogenesis, frequently occurredin chronic cholecystitis patients, requires radical resection. We herein describe a hemorrhagic cholecystitis case that failed to be differentiated from gallbladder cancer preoperatively owing to the neglected medication history of long term oral nonsteroidal anti-inflammatory drugs (NSIADs) intake. CASE PRESENTATION: A 57-year-old Chinese female was admitted for right upper quadrant pain with the initial diagnosis of cholecystitis. Radiological studies were unable to exclude the differential diagnosis of suspected gallbladder cancer. During the scheduled radical resection of the suspected lesions, the gross dissection showed an interesting presentation of hemorrhagic cholecystitis, without any pathological evidence of malignancies. Additional postoperative investigation revealed a neglected medication history of long-term NSAIDs use. CONCLUSIONS: This case suggests the importance of preoperative review of medication history and patient education on prescription drug abuse.

Effects of Liraglutide Compared With Placebo on Events of Acute Gallbladder or Biliary Disease in Patients With Type 2 Diabetes at High Risk for Cardiovascular Events in the LEADER Randomized Trial.

OBJECTIVE: To explore gallbladder- and biliary tract-related events reported for the liraglutide and placebo groups in the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial. RESEARCH DESIGN AND METHODS: LEADER was an international, randomized, double-blind, controlled cardiovascular (CV) outcomes trial. Participants with type 2 diabetes at high risk for CV events (n = 9,340) were randomized 1:1 to receive either liraglutide (≤1.8 mg daily; n = 4,668) or placebo (n = 4,672), with both groups also receiving standard care (treatment period: 3.5-5 years). Acute gallstone disease was a medical event of special interest. This post hoc analysis categorized captured events of acute gallbladder or biliary disease into four groups: uncomplicated gallbladder stones, complicated gallbladder stones, cholecystitis, and biliary obstruction. Time to first event by treatment group was analyzed using Cox regression. RESULTS: There was an increased risk of acute gallbladder or biliary disease with liraglutide versus placebo (n = 141 of 4,668 vs. n = 88 of 4,672 patients, respectively; hazard ratio [HR] 1.60; 95% CI 1.23, 2.09; P < 0.001). Similar trends were observed for each of the four categories of gallbladder- or biliary tract-related events. Cholecystectomy was performed more frequently in liraglutide-treated patients (HR 1.56; 95% CI 1.10, 2.20; P = 0.013) but for similar proportions of the patients who experienced gallbladder- or biliary tract-related events (57% with liraglutide vs. 59% with placebo). CONCLUSIONS: Although LEADER was not specifically designed to assess acute gallbladder or biliary disease, the trial showed an increased risk of gallbladder- or biliary tract-related events with liraglutide versus placebo, which appeared to be consistent across four categories of these events. Further studies should investigate the relevant mechanisms.

Case series of cancer patients who developed cholecystitis related to immune checkpoint inhibitor treatment.

BACKGROUND: Immune checkpoint inhibitors (ICIs) represent a promising novel class of cancer therapy, but immune-mediated adverse events can complicate ICI treatment. Acute cholecystitis in patients receiving ICI therapy has not been characterized. We aimed to describe the clinical features of patients who developed ICI-related cholecystitis. METHODS: We evaluated a case series of patients at a tertiary cancer center who received ICI therapy and developed cholecystitis, diagnosed by clinical presentation and diagnostic imaging, during 2010-2018. Patients with a history of chronic cholecystitis or other etiologies of acute cholecystitis, such as cholelithiasis, were excluded. A chi-square test was used to compare the frequency of cholecystitis between ICI regimens. Kaplan-Meier and log rank analyses were used to compare survival between subgroups. RESULTS: Of the 4253 patients who received ICIs in the study period, 25 (0.6%) patients developed suspected ICI-related cholecystitis. Alternatively, of the 31,426 cancer-matched patients who received non-ICI therapy, 72 (0.2%) developed acalculous cholecystitis (P < 0.001). Among the 25 included patients, the median time from ICI initiation to cholecystitis was 6 months (range, 0.1-31 months). Fifteen (60%) patients received an inhibitor of programmed death protein 1 (anti-PD-1) or of its ligand (anti-PD-L1) as a single agent, and 10 (40%) patients received an inhibitor of cytotoxic T-lymphocyte associated protein 4 (anti-CTLA-4) therapy alone or combined with anti-PD-1/L1. Anti-CTLA-4 monotherapy was associated with a higher risk of cholecystitis (P = 0.006). ICI therapy was discontinued in 20 patients, in three (12%) as a result of acute cholecystitis. Two (8%) patients developed sepsis, and four (16%) had perforation of the gallbladder wall. Five (20%) patients underwent surgical cholecystectomy, and eight (32%) underwent percutaneous drainage. Five (20%) patients were treated with steroids; two of them required surgery. Ten (40%) patients were able to restart ICI therapy. Patients who received a combination of anti-CTLA-4 and anti-PD-1/L1 had more complications of cholecystitis than did patients who received either agent alone (P = 0.03). CONCLUSIONS: ICI treatment can result in a clinical condition similar to typical acute cholecystitis in a minority of patients. ICI-related cholecystitis should be managed in a similar fashion to typical cholecystitis. The efficacy of steroids for the treatment of ICI-related cholecystitis is unclear.

New Avenues in the Regulation of Gallbladder Motility-Implications for the Use of Glucagon-Like Peptide-Derived Drugs.

CONTEXT: Several cases of cholelithiasis and cholecystitis have been reported in patients treated with glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) and GLP-2 receptor agonists (GLP-2RAs), respectively. Thus, the effects of GLP-1 and GLP-2 on gallbladder motility have been investigated. We have provided an overview of the mechanisms regulating gallbladder motility and highlight novel findings on the effects of bile acids and glucagon-like peptides on gallbladder motility. EVIDENCE ACQUISITION: The articles included in the present review were identified using electronic literature searches. The search results were narrowed to data reporting the effects of bile acids and GLPs on gallbladder motility. EVIDENCE SYNTHESIS: Bile acids negate the effect of postprandial cholecystokinin-mediated gallbladder contraction. Two bile acid receptors seem to be involved in this feedback mechanism, the transmembrane Takeda G protein-coupled receptor 5 (TGR5) and the nuclear farnesoid X receptor. Furthermore, activation of TGR5 in enteroendocrine L cells leads to release of GLP-1 and, possibly, GLP-2. Recent findings have pointed to the existence of a bile acid-TGR5-L cell-GLP-2 axis that serves to terminate meal-induced gallbladder contraction and thereby initiate gallbladder refilling. GLP-2 might play a dominant role in this axis by directly relaxing the gallbladder. Moreover, recent findings have suggested GLP-1RA treatment prolongs the refilling phase of the gallbladder. CONCLUSIONS: GLP-2 receptor activation in rodents acutely increases the volume of the gallbladder, which might explain the risk of gallbladder diseases associated with GLP-2RA treatment observed in humans. GLP-1RA-induced prolongation of human gallbladder refilling may explain the gallbladder events observed in GLP-1RA clinical trials.

Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial of BMS-986020, a Lysophosphatidic Acid Receptor Antagonist for the Treatment of Idiopathic Pulmonary Fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) causes irreversible loss of lung function. The lysophosphatidic acid receptor 1 (LPA1) pathway is implicated in IPF etiology. Safety and efficacy of BMS-986020, a high-affinity LPA1 antagonist, was assessed vs placebo in a phase 2 study in patients with IPF. METHODS: IM136003 was a phase 2, parallel-arm, multicenter, randomized, double-blind, placebo-controlled trial. Adults with IPF (FVC, 45%-90%; diffusing capacity for carbon monoxide, 30%-80%) were randomized to receive placebo or 600 mg BMS-986020 (once daily [qd] or bid) for 26 weeks. The primary end point was rate of change in FVC from baseline to week 26. RESULTS: Of 143 randomized patients, 108 completed the 26-week dosing phase. Thirty-five patients discontinued prematurely. Patient baseline characteristics were similar between treatment groups (placebo: n = 47; 600 mg qd: n = 48; 600 mg bid: n = 48). Patients treated with BMS-986020 bid experienced a significantly slower rate of decline in FVC vs placebo (-0.042 L; 95% CI, -0.106 to -0.022 vs -0.134 L; 95% CI, -0.201 to -0.068, respectively; P = .049). Dose-related elevations in hepatic enzymes were observed in both BMS-986020 treatment groups. The study was terminated early because of three cases of cholecystitis that were determined to be related to BMS-986020 after unblinding. CONCLUSIONS: BMS-986020 600 mg bid treatment for 26 weeks vs placebo significantly slowed the rate of FVC decline. Both regimens of BMS-986020 were associated with elevations in hepatic enzymes. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01766817; URL: www.clinicaltrials.gov.

Haemorrhagic cholecystitis in a newly anticoagulated patient.

A 74-year-old man undergoing rehabilitation after pneumonia developed right upper quadrant abdominal pain. Five days earlier he had been commenced on apixaban for a new diagnosis of atrial fibrillation. Ultrasound and CT scans revealed an acalculous grossly thickened gallbladder, with high attenuation non-echogenic material both within and surrounding the structure. Active contrast extravasation was seen at the neck. On laparotomy, a perforated internally bleeding gallbladder containing a single calculus was found, with significant free blood within the abdomen. After cholecystectomy, the patient recovered slowly in hospital before nursing home placement.

Daclatasvir and Asunaprevir Combination Therapy-induced Hepatitis and Cholecystitis with Coagulation Disorder due to Hypersensitivity Reactions.

A 70-year-old woman with chronic hepatitis C was admitted to our hospital due to liver injury, cholecystitis, and disseminated intravascular coagulation with a fever and skin rash. She had been on a combination regimen of daclatasvir and asunaprevir for 2 weeks of a 24-week regimen. Because of the symptoms, laboratory findings, results of a drug-induced lymphocyte stimulation test, and pathological findings of liver biopsy, we diagnosed her with drug-induced liver injury. Although daclatasvir and asunaprevir combination therapy is generally well-tolerated, some serious adverse effects have been reported. Our findings indicate that immunoallergic mechanisms were associated with daclatasvir and asunaprevir-induced liver injury.

[A case of hemorrhagic cholecystitis associated with Churg-Strauss syndrome].

A woman in her 70s with Churg-Strauss syndrome presented with epigastric pain. She was being treated with steroids at the time of admission. Computed tomography showed swelling of the gallbladder, and percutaneous transhepatic cholangiography revealed bloody secretion. On duodenoscopy, bleeding was observed from the orifice of the major duodenal papilla. Emergency cholecystectomy was performed under a diagnosis of hemorrhagic cholecystitis;intraoperatively, extensive hematoma was detected in the thickened wall of the gallbladder. Subsequent histopathological examination revealed mucosal ulceration with infiltration of inflammatory cells, torn small vessels, and extensive transmural bleeding and abscess formation in the thickened wall of the gallbladder. We considered that the hemorrhagic cholecystitis was induced by either vasculitis or corticosteroid therapy. To the best of our knowledge, this is the first report of hemorrhagic cholecystitis associated with Churg-Strauss syndrome.

Review of the impact of antineoplastic therapies on the risk for cholelithiasis and acute cholecystitis.

BACKGROUND: Development of cholecystitis in patients with malignancies can potentially disrupt their treatment and alter prognosis. This review aims to identify antineoplastic interventions associated with increased risk of cholecystitis in cancer patients. METHODS: A comprehensive search strategy was developed to identify articles pertaining to risk factors and complications of cholecystitis in cancer patients. FDA-issued labels of novel antineoplastic drugs released after 2010 were hand-searched to identify more therapies associated with cholecystitis in nonpublished studies. RESULTS: Of an initial 2,932 articles, 124 were reviewed in the study. Postgastrectomy patients have a high (5-30 %) incidence of gallstone disease, and 1-7 % develop symptomatic disease. One randomized trial addressing the role of cholecystectomy concurrent with gastrectomy is currently underway. Among other risk groups, patients with neuroendocrine tumors treated with somatostatin analogs have a 15 % risk of cholelithiasis, and most are symptomatic. Hepatic artery based therapies carry a risk of cholecystitis (0.02-24 %), although the risk is reduced with selective catheterization. Myelosuppression related to chemotherapeutic agents (0.4 %), bone marrow transplantation, and treatment with novel multikinase inhibitors are associated with high risk of cholecystitis. CONCLUSIONS: There are several risk factors for gallbladder-related surgical emergencies in patients with advanced malignancies. Incidental cholecystectomy at index operation should be considered in patients planned for gastrectomy, and candidates for regional therapies to the liver or somatostatin analogs. While prophylactic cholecystectomy is currently recommended for patients with cholelithiasis receiving myeloablative therapy, this strategy may have value in patients treated with multikinase inhibitors, immunotherapy, and oncolytic viral therapy based on evolving evidence.

Listeria monocytogenes cholecystitis: a possible new syndrome.

The U.S. Food and Drug Administration recently added potentially fatal Listeria monocytogenes infection to the list of opportunistic infections that can occur in patients who receive tumor necrosis factor inhibitor therapy. In this study, the first reported case of L monocytogenes cholecystitis associated with etanercept use is described. It also appears that tumor necrosis factor inhibitor therapy likely increases the risk for Listeria cholecystitis. Clinicians need to be aware of this association when selecting antimicrobial therapy for these patients.

Decade of molecular targeted therapy: abdominal manifestations of drug toxicities--what radiologists should know.

OBJECTIVE: Novel drugs targeting molecular pathways involved in tumor development have revolutionized cancer treatment. Radiologists often focus on therapeutic response when evaluating cancer patients and may miss important signs of drug toxicity. This article familiarizes radiologists with the complications of molecular targeted agents in abdominal solid organs, enabling early identification and appropriate intervention and thus reducing patient morbidity and mortality. CONCLUSION: Knowledge of the common abdominal toxicities--including hepatitis, cholecystitis, pancreatitis, fluid retention, and infection--is crucial for early diagnosis, which may spare patients devastating complications or the need for surgery.

Evaluation of Lysimachia christinae Hance extracts as anticholecystitis and cholagogic agents in animals.

ETHNOPHARMACOLOGICAL RELEVANCE: Lysimachia christinae Hance is one of the herbs commonly used in traditional Chinese medicine for the treatment of cholecystitis and cholagogic efficiency. AIMS OF THE STUDY: The water extract of Lysimachia christinae Hance was investigated to see if it possesses cholecystitis and cholagogic effects through traditional pathways. MATERIALS AND METHODS: Lithocholic acid (LCA) and Escherichia coli were used to induce cholecystitis in adult guinea pigs. The present study evaluated the cholagogic effects of LCHE treatment on bile secretion and bile emptying in Sprague-Dawley rats and male Kunming mice. RESULTS: The results showed that LCHE not only produced excellent anticholecystitis effects but also improved lesion severity in gallbladders induced by LCA. Similarly, LCHE administered to animals in the high-dose group exhibited an antibacterial effect in acute cholecystitis, and treatment with a mid-range or a high dose of LCHE resulted in an antipyretic effect, however, three doses of LCHE treatment groups had no effect on pathological change induced by Escherichia coli in gallbladder. Treatment with a high dose of LCHE significantly promoted bile secretion (0-90min, P<0.01), and treatment with a mid-range dose also significantly promoted bile secretion (30-60min P<0.05). Furthermore, treatment with a high dose of LCHE significantly promoted bile emptying (P<0.01). CONCLUSIONS: Our results demonstrate that LCHE exhibits a marked anticholecystitis and cholagogic activity in animals, which supports previous claims of its use in traditional Chinese medicine.

[Acute pancreatitis associated with the administration of ceftriaxone in an adult patient].

We report a case of a 35-year-old patient with acute pancreatitis after administration of ceftriaxone. She was given ceftriaxone (2g/day) for 9 days because of diverticulitis of the colon. She was admitted to our hospital again because of epigastralgia 12 days after the first administration of ceftriaxone. Laboratory examination showed markedly elevated serum amylase, and CT scan demonstrated findings consistent with acute pancreatitis, in addition to sludge in the common bile duct and gall bladder, which was not identified before the administration of ceftriaxone. We should be aware of the fact that administration of ceftriaxone sometimes results in the formation of biliary sludge and can cause severe adverse events such as cholecystitis and pancreatitis, not only in children, but also in adult patients.