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A case of multiple hepatocellular carcinoma experiencing complete responses to sorafenib and atezolizumab–bevacizumab and developing severe, refractory venous congestive cutaneous ulcers on either regimen

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Abstract

A man in his eighties presented with a history of bilateral leg congestive phlebitis, and multiple hepatocellular carcinoma (HCC) treated with sorafenib. When the dose was increased to 400 mg, ulcers appeared under both knees, which worsened, and the drug was discontinued 2 months after administration. However, the ulcers to 30 mm in diameter, requiring debridement and antibiotics. The HCC showed a complete response (CR) based on modified-RECIST criteria; however, after several rounds of locoregional therapy for recurrence, multiple HCCs and metastatic lesions in the Morrison’s fossa were detected. Therefore, atezolizumab 1200 mg–bevacizumab 900 mg was started. After the first course, the patient complained of pain below both knees, and when the second course was administered, leg ulcers re-appeared and rapidly worsened. The ulcers were circular and multiple and progressed to deep digging, leading to tendon exposure. Bevacizumab-induced congestive venous ulcer was diagnosed, requiring skin grafts to heal. HCC then showed a CR based on m-RECIST criteria. Initially, the cause of the ulcer was thought to be immune-related adverse effects due to atezolizumab, but experience with sorafenib led us to conclude that the cause was stagnant venous ulcers due to vascular endothelial growth factor receptor inhibitor, which inhibited angiogenesis.

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Acknowledgements

This work was supported by Research Funds to Promote Hospital Functions Provided by the Japan Organization of Occupational Health and Safety.

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Authors and Affiliations

  1. Department of Gastroenterology, Kanto Rosai Hospital, 1-1 Kizukisumiyoshi-cho, Nakahara-ku, Kawasaki, Kanagawa, 211-8510, Japan

    Yorihito Hayashi, Rena Kaneko & Takashi Ikehara

  2. Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, 6-11-1 Omorinishi, Ota-ku, Tokyo, 143-8541, Japan

    Yorihito Hayashi, Takashi Ikehara, Hidenari Nagai & Takahisa Matsuda

  3. Department of Plastic Surgery, Kanto Rosai Hospital, Kawasaki, Japan

    Hiroki Ogino

  4. Department of Pathology and Diagnostics, Kanto Rosai Hospital, Kawasaki, Japan

    Toshimasa Uekusa

  5. Department of Dermatology, Kanto Rosai Hospital, Kawasaki, Japan

    Mayako Kitajima

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  1. Yorihito Hayashi
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  2. Rena Kaneko
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  8. Takahisa Matsuda
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Contributions

YH: conceptualization, resources, writing original draft, review, and editing, RK: conceptualization, resources, writing original draft, review, editing and funding acquisition. HO, TU, MK, TI: review, and editing. HN, TM: supervision, review, and editing.

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Correspondence to Rena Kaneko.

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All procedure followed have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Hayashi, Y., Kaneko, R., Ogino, H. et al. A case of multiple hepatocellular carcinoma experiencing complete responses to sorafenib and atezolizumab–bevacizumab and developing severe, refractory venous congestive cutaneous ulcers on either regimen. Clin J Gastroenterol 16, 229–236 (2023). https://doi.org/10.1007/s12328-023-01756-3

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