Acalculous Cholecystitis in a Patient with Hepatocellular Carcinoma on Sorafenib

Sanda, Mariko; Tamai, Hideyuki; Deguchi, Hisanobu; Mori, Yoshiyuki; Moribata, Kosaku; Shingaki, Naoki; Inoue, Izumi; Maekita, Takao; Iguchi, Mikitaka; Yanaoka, Kimihiko; Oka, Masashi; Ichinose, Masakazu

doi:10.5402/2011/201529

Cited by 12 publications

(8 citation statements)

References 13 publications

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“…Of note, the patient had received treatment with multiple TKIs for a long time, so long-term treatment with TKIs might have induced the gallbladder perforation. However, previous reports (8)(9)(10)(11)(12) showed that cholecystitis developed about four weeks after initiating TKIs. These findings suggest that TKI-related cholecystitis developed after a relatively short treatment duration.…”

Section: Discussionmentioning

confidence: 93%

“…In patients with thyroid cancer treated with lenvatinib, five cases of acalculous cholecystitis were reported in post-marketing surveillance from 2015 to 2017 in Japan. In contrast, five cases of acute acalculous cholecystitis in patients treated with other tyrosine kinase inhibitors (TKIs) were reported, including two patients with sorafenib and three with sunitinib (8)(9)(10)(11)(12).…”

Section: Discussionmentioning

confidence: 99%

“…The homeostasis between the vascular endothelium and platelets may be disturbed by lenvatinib-mediated damage to vascular endothelial cells, allowing platelets to aggregate more readily on the surface of the vascular endothelium and inducing ischemic damage (21). Although the relationship between TKIs and cholecystitis is unclear, previous reports suggest that this TKI-related ischemic damage is likely the pathologic mechanism of sorafenib and sunitinib-related cholecystitis (8)(9)(10)(11). In fact, in the present case, AMI developed during sorafenib treatment; thus, the vascular endothelial cells may be susceptible to damage by TKIs.…”

Section: Discussionmentioning

confidence: 99%

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Repeated Perforation of the Gallbladder in a Patient with Hepatocellular Carcinoma Receiving Lenvatinib

et al. 2020

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A 59-year-old man who was receiving lenvatinib as a third-line tyrosine kinase inhibitor to treat hepatocellular carcinoma and multiple bone metastases complained of general fatigue four months after starting lenvatinib. A blood examination showed unexpectedly elevated serum C-reactive protein (CRP) levels. Computed tomography (CT) revealed rupture of the gallbladder wall, indicating gallbladder perforation. After conservative treatment, the patient received lenvatinib again under informed consent; however, one month later, CT revealed repeated rupture of the gallbladder wall. Gallbladder perforation had again been induced by lenvatinib. For this reason, lenvatinib is strongly considered a causative drug for gallbladder perforation.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Repeated Perforation of the Gallbladder in a Patient with Hepatocellular Carcinoma Receiving Lenvatinib

et al. 2020

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“…First, the blockage exerted on the VEGF signaling pathway can ultimately result in an increased platelet activation and arterial thromboembolism via the reduction of prostaglandin I-2 and nitric oxide [17]. The arteriolar thrombosis in gallbladder could lead to ischemia and acalculous AC, as documented in a patient with HCC treated with sorafenib [18]. Furthermore, since cholangiocytes express VEGFR-2 and VEGFR-3 and secrete VEGF which has an important role in inducing their proliferation in response to cholestasis [19], drugs inhibiting VEGF-R are predicted to cause biliary diseases.…”

Section: Discussionmentioning

confidence: 99%

High Prevalence and Conservative Management of Acute Cholecystitis during Lenvatinib for Advanced Thyroid Cancer

et al. 2020

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Introduction: Lenvatinib (LEN) is a multitarget tyrosine kinase inhibitor currently used for advanced, radioiodine refractory differentiated thyroid cancer (RAI-R DTC). Among adverse events (AEs), nausea, vomiting, and decreased appetite have been frequently described. We aimed to evaluate the prevalence, the clinical presentation, and the effectiveness of conservative treatment of gallbladder disorders in a consecutive series of patient treated with LEN. Methods: Patients with RAI-R DTC experiencing clinical symptoms suggestive for gallbladder disorders during LEN treatment were evaluated with laboratory investigations and contrast-enhanced abdominal computed tomography (CT) and ultrasound scan (US). Results: After a median time of 2 months from the start of treatment, 5/13 patients (38.4%) complained of gastrointestinal symptoms, with increased biliary enzymes levels, especially γGT, and CT/US suggestive of acute cholecystitis (AC). The onset of symptoms and the peak of γGT levels frequently corresponded to the highest reduction in body weight during the first months of treatment. All patients were treated with supportive care and, when appropriate, with ursodeoxycholic acid; in 4 patients, LEN dose reduction or short interruption was needed, too. Conclusions: In patients with RAI-R DTC treated with LEN, a high prevalence of AC in the first months of treatment was documented. Mainly due to the low specificity of symptoms such as anorexia, nausea, and vomiting, this AE is likely to be frequently misdiagnosed. The onset of the disease was associated to the weight loss observed during the first months of treatment and contributes to further decrease in body weight. Therefore, particularly during the first months of treatment, or at any time of huge reduction of body weight, monitoring of γGT and US is crucial for prompt diagnosis and treatment. Conservative medical treatment and LEN dosage titration, together with dietary and rehabilitative supports, can limit or avoid the need for drug withdrawal and cholecystectomy.

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“…The etiology of gallbladder toxicity is uncertain, although such toxicity has also been reported for others TKIs. 8-10 There is clear evidence that VEGF plays a role in modulating cholangiocyte proliferation in response to cholestasis and that cholangiocytes express VEGFR. 11 Inhibition of VEGFR in biliary tract cells can represent an imbalance of stress adaption, causing biliary diseases.…”

Section: Discussionmentioning

confidence: 99%

Acute Acalculous Cholecystitis in a Patient with Metastatic Renal Cell Carcinoma Treated with Sunitinib

Fonseca

Barroso‐Sousa

Sabbaga

et al. 2014

Clinics and Practice

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A 55-year old man was treated with sunitinib 50 mg/day for 4 weeks on and 2 weeks off, as a first-line therapy for metastatic renal cell carcinoma. During the fourth week of the first cycle, he was admitted to the Emergency Department with abdominal pain and vomiting. Acute acalculous cholecystitis was diagnosed. Sunitnib-associated cholecystitis is a rare adverse event previously reported in few cases. The mechanism behind this complication is not fully understood, although vascular endothelial dysfunction may play a role. The use of this drug is expanding in clinical oncology, and physicians should be aware of this life-threating adverse event.

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Acalculous Cholecystitis in a Patient with Hepatocellular Carcinoma on Sorafenib

Cited by 12 publications

References 13 publications

Repeated Perforation of the Gallbladder in a Patient with Hepatocellular Carcinoma Receiving Lenvatinib

Repeated Perforation of the Gallbladder in a Patient with Hepatocellular Carcinoma Receiving Lenvatinib

High Prevalence and Conservative Management of Acute Cholecystitis during Lenvatinib for Advanced Thyroid Cancer

Acute Acalculous Cholecystitis in a Patient with Metastatic Renal Cell Carcinoma Treated with Sunitinib

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