Acute acalculous cholecystitis following extended administration of nirmatrelvir/ritonavir for persistent SARS-CoV-2 infection.

Immunocompromised patients with hematologic malignancies, particularly those treated with anti-CD20 antibodies such as rituximab and obinutuzumab, are known to be at risk of prolonged infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Prolonged administration or combination therapy with antiviral medications reportedly yields favorable outcomes in these patients. However, knowledge regarding the adverse events associated with such therapeutic approaches is limited. Herein, we report a case of acute acalculous cholecystitis (AAC) following extended administration of nirmatrelvir/ritonavir (NMV/r) in a 68-year-old Japanese man with persistent SARS-CoV-2 infection. The patient had received obinutuzumab and bendamustine for follicular lymphoma and was diagnosed with coronavirus disease 2019 (COVID-19) approximately one year after treatment initiation with these drugs. Subsequently, he was admitted to a different hospital, where he received antiviral drugs, monoclonal antibodies, and steroids. Despite these interventions, the patient relapsed and was subsequently transferred to our hospital due to persistent SARS-CoV-2 infection. Remdesivir administration was ineffective, leading to the initiation of extended NMV/r therapy. One week later, he exhibited elevated gamma-glutamyl transpeptidase (GGT) levels, and one month later, he developed AAC. Cholecystitis was successfully resolved via percutaneous transhepatic gallbladder drainage and administration of antibiotics. We speculate that extended NMV/r administration, in addition to COVID-19, may have contributed to the elevated GGT and AAC. During treatment of persistent SARS-CoV-2 infection with extended NMV/r therapy, patients should be carefully monitored for the appearance of findings suggestive of biliary stasis and the development of AAC.

Neutropenic acute acalculous cholecystitis (AAC) in a 12-year-old boy with T-acute lymphoblastic leukemia successfully managed with conservative treatment.

Acute acalculous cholecystitis (AAC) is an inflammation of the gallbladder without the presence of gallstones. In children with malignancies or chemotherapy-induced neutropenia, AAC is very rare. Clinical diagnosis of AAC remains difficult in this patient population but an early recognition followed by an appropriate intervention may confer a benefit. Only three pediatric patients with underlying hematological malignancies whose clinical treatment course was complicated by the development of AAC have been described. We describe a neutropenic pediatric patient who developed AAC following chemotherapy for acute T-cell acute lymphoblastic leukemia (T-ALL), which was successfully managed with conservative treatment. ABBREVIATIONS: AAC: Acute acalculous cholecystitis; T-ALL: T-cell acute lymphoblastic leukemia; TPN: Total parenteral nutrition.

Can cannabinoids contribute to cholecystitis - a case of gangrenous acalculous cholecystitis.

SUMMARY: Cannabis legalisation continues to grow globally and its effects on the vascular system have been scrutinized.1 Cannabis has become recognised as a contributor to cardiovascular, cerebrovascular and peripheral vascular disease.2,3 This case report highlights the case of a young male patient presenting with atypical symptoms following cannabis use who developed gangrenous cholecystitis (GC) following vasospasm of his cystic artery. We believe that this is the first-ever case, shared with the anticipation of stimulating more research and prompting recognition of vascular events in this group of patients as our knowledge on the effects of cannabis continues to grow.

Acute Acalculous Cholecystitis in a Multiple Sclerosis Patient Treated with Natalizumab.

Natalizumab is a disease-modifying drug that has proved greatly effective and well-tolerated in highly-active Multiple Sclerosis (MS). However, it may increase the risk for opportunistic infections, such as viral ones. We describe a 37-year-old woman treated with Natalizumab for Relapsing-Remitting Multiple Sclerosis (RR-MS) who presented to our clinic with malaise, arthromyalgias, rash, and fever. She later developed diarrhea and severe abdominal pain. A diagnosis of parvovirus B19 (B19V) infection and acute acalculous cholecystitis (AAC) was eventually made. To our knowledge, this is the first reported case of AAC possibly related to Natalizumab therapy and B19V infection.

Lenvatinib-induced acute acalculous cholecystitis in a patient with hepatocellular carcinoma.

The patient was a 67-year-old man with advanced hepatocellular carcinoma (HCC) due to chronic hepatitis B. Due to refractoriness to radiofrequency ablation and transcatheter arterial chemoembolization, lenvatinib, a new oral mutikinase inhibitor, was started with a daily dose of 12 mg. However, on day 6 the patient developed acute-onset, right upper quadrant pain associated with fever; laboratory tests revealed leukocytosis and liver dysfunction. CT scan showed the swollen gallbladder with wall thickening with no evidence of gallstones, and the diagnosis of acute acalculous cholecystitis was made. After the resolution of cholecystitis by antibiotics and endoscopic nasogallbladder drainage placement, lenvatinib was resumed at a reduced daily dose of 4 mg. However, acute acalculous cholecystitis recurred, supporting lenvatinib as a cause of acute acalculous cholecystitis. Using the Naranjo adverse drug reaction probability scale, a score of 6 was derived, which indicates that this adverse event was probably caused by lenvatinib. In summary, we present a patient with advanced HCC who underwent repeated episodes of acute acalculous cholecystitis as a rare adverse event associated with lenvatinib.

Acalculous cholecystitis in a patient with metastatic renal cell carcinoma treated with sunitinib.

A 62-year-old woman was treated with sunitinib as a second-line therapy for metastatic clear-cell renal carcinoma. She was given oral sunitinib 50 mg once daily, 4 weeks on followed by 2 week off. During the fourth week of her first cycle, the patient was admitted to our hospital because of an acute-onset, right upper quadrant pain associated with nausea and vomiting. She was diagnosed with acute acalculous cholecystitis, which was treated with broad-spectrum antibiotics, and sunitinib therapy was discontinued. A follow-up computed tomography scan of the abdomen revealed a complete resolution of gallbladder changes. Our patient did not have major risk factors for developing an acalculous cholecystitis except for a relative immunosuppressed state secondary to her advanced renal cancer. The Naranjo Adverse Drug Reaction Probability Scale score for this event was 5, indicating a probable association of the event with sunitinib. Because the use of sunitinib is expanding in clinical practice, we want to alert the oncology community about this uncommon and life-threatening complication in patients receiving sunitinib or another agent with antiangiogenic activity.

A mechanical model for CCK-induced acalculous gallbladder pain.

This study investigates the potential correlation between acalculous biliary pain and mechanical stress during the bile-emptying phase. This study is built on the previously developed mathematical model used to estimate stress in the gallbladder wall during emptying [Li, W. G., X. Y. Luo, et al. Comput. Math. Methods Med. 9(1):27-45, 2008]. Although the total stress was correctly predicted using the previous model, the contribution from patient-specific active stress induced by the cholecystokinin (CCK) test was overlooked. In this article, we evaluate both the active and passive components of pressure in a gallbladder, which undergoes isotonic refilling, isometric contraction and emptying during the infusion of CCK. The pressure is estimated from in vivo ultrasonographical scan measurements of gallbladder emptying during CCK tests, assuming that the gallbladder is a thin ellipsoidal membrane. The passive stress is caused by the volume and shape changes during refilling at the gallbladder basal pressure, whereas the active stress arises from the pressure rise during the isometric gallbladder contraction after the CCK infusion. The effect on the stress estimates of the gallbladder to the liver is evaluated to be small by comparing numerical simulations of a gallbladder model with and without a rigid 'flat top' boundary. The model was applied to 51 subjects, and the peak total stress was found to have a strong correlation with the pain stimulated by CCK, as measured by the patient pain score questionnaires. Consistent with our previous study for a smaller sample, it is found that the success rate in predicting of CCK-induced pain is over 75%.

Diagnostic value of gallbladder emptying variables in chronic acalculous cholecystitis as assessed by fatty meal cholescintigraphy.

OBJECTIVE: The main purpose of this study was to determine the diagnostic value of gallbladder emptying variables in chronic acalculous cholecystitis (CAC). The variables investigated were latent period, gallbladder ejection fraction (GBEF) and patterns of gallbladder emptying. In addition, two other biliary system motility variables were investigated including the onset of gallbladder filling and biliary-to-bowel transit time. METHODS: Thirty-nine healthy volunteers underwent fatty meal cholescintigraphy (CS) prospectively to determine the normal values of these variables. Retrospectively, fatty meal CS studies of 88 patients suspected of having CAC were retrieved and reprocessed to obtain corresponding values of these variables, which then compared with normal values. RESULTS: The mean onset of gallbladder filling for patient groups was not significantly different from volunteer group mean. The mean+/-SD GBEF value for CAC group (29+/-20%) was significantly lower than volunteer group value (54+/-23%), whereas for non-CAC group (60+/-21%) it was not significantly different. The latent period was found invariable and not significant in CAC diagnosis. Two patterns of gallbladder emptying were noted: ended and continuous. The pattern of gallbladder emptying did not affect the mean GBEF and was found insignificant in the diagnosis of CAC. There was no significant difference in the number of cases with late biliary-to-bowel transit time between the groups. CONCLUSION: The single most important gallbladder emptying variable in diagnosing CAC is the GBEF. The latent period and the pattern of gallbladder emptying as well as the onset of gallbladder filling and biliary-to-bowel transit time are of no significant diagnostic value in CAC.