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Gyoda Y, Ichida H, Kawano F, Takeda Y, Yoshioka R, Imamura H, Mise Y, Fukumura Y, Saiura A. A patient alive without disease 32 months after conversion surgery following lenvatinib treatment for hepatocellular carcinoma with a tumor thrombus originating in the middle hepatic vein and reaching the right atrium via the suprahepatic vena cava: a case report. Clin J Gastroenterol 2024; 17:311-318. [PMID: 38277091 DOI: 10.1007/s12328-023-01909-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 12/12/2023] [Indexed: 01/27/2024]
Abstract
Conversion surgery for initially unresectable hepatocellular carcinoma appears to be increasing in incidence since the advent of new molecular target drugs and immune checkpoint inhibitors; however, reports on long-term outcomes are limited and the prognostic relevance of this treatment strategy remains unclear. Herein, we report the case of a 75-year-old man with hepatocellular carcinoma, 108 mm in diameter, accompanied by a tumor thrombus in the middle hepatic vein that extended to the right atrium via the suprahepatic vena cava. He underwent conversion surgery after preceding lenvatinib treatment and is alive without disease 51 months after the commencement of treatment and 32 months after surgery. Just before conversion surgery, after 19 months of lenvatinib treatment, the main tumor had reduced in size to 72 mm in diameter, the tip of the tumor thrombus had receded back to the suprahepatic vena cava, and the tumor thrombus vascularity was markedly reduced. The operative procedure was an extended left hepatectomy with concomitant middle hepatic vein resection. The tumor thrombus was removed under total vascular exclusion via incision of the root of the middle hepatic vein. Histopathological examination revealed that more than half of the liver tumor and the tumor thrombus were necrotic.
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Affiliation(s)
- Yu Gyoda
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Hirofumi Ichida
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Fumihiro Kawano
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Yoshinori Takeda
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Ryuji Yoshioka
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Hiroshi Imamura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Yoshihiro Mise
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Yuki Fukumura
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Akio Saiura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan.
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Ota Y, Aso K, Yokoo H, Fujiya M. Noninvasive Visualization of Tumor Blood Vessels within Hepatocellular Carcinoma by Application of Superb Microvascular Imaging to Contrast-Enhanced Ultrasonography. Diagnostics (Basel) 2024; 14:678. [PMID: 38611593 PMCID: PMC11011652 DOI: 10.3390/diagnostics14070678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 03/11/2024] [Accepted: 03/21/2024] [Indexed: 04/14/2024] Open
Abstract
The combination or sequential use of systemic therapies, such as lenvatinib and locoregional therapies, can improve the curability rate of hepatocellular carcinoma. This is based on the notion that lenvatinib remodels abnormal tumor vessels into normal vessels, potentially enhancing the efficacy of locoregional therapies. In this case report, we achieved noninvasive visualization of tumor blood vessels by applying superb microvascular imaging (SMI) to contrast-enhanced ultrasonography (CEUS). A man in his 80s with a borderline resectable hepatocellular carcinoma received preoperative therapy using lenvatinib. The patient achieved a complete response after lenvatinib therapy, underwent hepatectomy, and maintained a cancer-free status. CEUS and SMI revealed a decrease in tumor blood vessels at 1 week after lenvatinib administration and a decrease in tumor perfusion at 2 weeks. Although CEUS alone is adequate for noninvasive real-time evaluation of tumor perfusion, it is not sufficient to achieve accurate assessments of tumor blood vessels. We performed a noninvasive time-course evaluation of vascular normalization after lenvatinib administration by applying SMI. The evaluation of vascular normalization with lenvatinib therapy using CEUS and SMI can support the decision to proceed to conversion therapies.
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Affiliation(s)
- Yu Ota
- Division of Gastroenterology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa 078-8510, Japan
| | - Kazunobu Aso
- Division of Gastroenterology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa 078-8510, Japan
| | - Hideki Yokoo
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Asahikawa Medical University, Asahikawa 078-8510, Japan
| | - Mikihiro Fujiya
- Division of Gastroenterology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa 078-8510, Japan
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Okubo Y, Toda S, Sato S, Yoshioka E, Ono K, Hasegawa C, Washimi K, Yokose T, Miyagi Y, Iwasaki H, Hayashi H. Histological findings of thyroid cancer after lenvatinib therapy. Histopathology 2023; 83:657-663. [PMID: 37501641 DOI: 10.1111/his.15013] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Revised: 07/05/2023] [Accepted: 07/07/2023] [Indexed: 07/29/2023]
Abstract
AIMS Lenvatinib is a multikinase inhibitor used for treating unresectable or metastatic cancers, including thyroid cancer. As total thyroidectomy followed by radioactive iodine therapy is a commonly recommended initial treatment for thyroid cancer, histological findings of the thyroid after lenvatinib therapy remain unclear. Therefore, the aim of this study was to analyse in-vivo changes in patients who underwent thyroidectomy after lenvatinib therapy. METHODS AND RESULTS We screened 167 patients with thyroid cancer [papillary thyroid cancer (PTC), n = 102; follicular thyroid cancer (FTC), n = 26; anaplastic thyroid cancer (ATC), n = 39] who underwent lenvatinib therapy. Among these patients, six underwent thyroidectomy (lenvatinib-treated group: PTC, n = 3; FTC, n = 1; ATC, n = 2), and the specimens were examined. Five patients with PTC who did not receive lenvatinib therapy were included for comparison (untreated group). Microvessel density (MVD) was evaluated in both groups. The PTC and FTC specimens showed relatively more ischaemic changes than ATC specimens. Coagulative necrosis and ischaemic changes in cancer cells were frequently observed. ATC specimens showed fibrosis and mild cell damage. As hypothyroidism is a common side effect of lenvatinib therapy, non-cancerous thyroid tissues were also examined. Histological findings included mild lymphocytic infiltration, lymphoid follicular formation, histiocytic reaction and follicular epithelial destruction. The MVD in lenvatinib-treated tissues was significantly lower than that in untreated tissues. CONCLUSIONS Lenvatinib therapy probably induces relatively specific ischaemic changes in thyroid cancer cells. Moreover, inflammatory cell infiltration and decreased MVD occur to varying degrees in non-cancerous thyroid tissue and may be related to hypothyroidism, a side effect of lenvatinib.
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Affiliation(s)
- Yoichiro Okubo
- Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan
| | - Soji Toda
- Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Shinya Sato
- Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan
- Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan
| | - Emi Yoshioka
- Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan
| | - Kyoko Ono
- Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan
| | - Chie Hasegawa
- Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan
| | - Kota Washimi
- Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan
| | - Tomoyuki Yokose
- Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan
| | - Yohei Miyagi
- Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan
- Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan
| | - Hiroyuki Iwasaki
- Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Hiroyuki Hayashi
- Department of Pathology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan
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Tai Y, Morita Y, Makino M, Ida S, Muraki R, Kitajima R, Takeda M, Kikuchi H, Hiramatsu Y, Takeuchi H. A Case of Giant Hepatocellular Carcinoma Successfully Treated with Lenvatinib Followed by Parenchymal-Sparing Hepatectomy. THE JAPANESE JOURNAL OF GASTROENTEROLOGICAL SURGERY 2023; 56:547-559. [DOI: 10.5833/jjgs.2022.0104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Affiliation(s)
- Yuta Tai
- Department of Surgery, Shizuoka City Shimizu Hospital
| | | | | | - Shinya Ida
- Department of Surgery, Hamamatsu University School of Medicine
| | - Ryuta Muraki
- Department of Surgery, Hamamatsu University School of Medicine
| | - Ryo Kitajima
- Department of Surgery, Hamamatsu University School of Medicine
| | - Makoto Takeda
- Department of Surgery, Hamamatsu University School of Medicine
| | | | - Yoshihiro Hiramatsu
- Department of Surgery, Hamamatsu University School of Medicine
- Department of Perioperative Functioning Care and Support, Hamamatsu University School of Medicine
| | - Hiroya Takeuchi
- Department of Surgery, Hamamatsu University School of Medicine
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Sano S, Asahi Y, Kamiyama T, Kakisaka T, Orimo T, Nagatsu A, Aiyama T, Kazui K, Shomura H, Ueki S, Sakamoto Y, Shirakawa C, Kamachi H, Sugino H, Mitsuhashi T, Taketomi A. Conversion surgery after lenvatinib treatment for multiple lung metastases from hepatocellular carcinoma. Int Cancer Conf J 2023; 12:7-13. [PMID: 36605836 PMCID: PMC9807693 DOI: 10.1007/s13691-022-00567-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 07/13/2022] [Indexed: 01/09/2023] Open
Abstract
Although systemic treatment for hepatocellular carcinoma has advanced after the development of tyrosine kinase inhibitors such as sorafenib and lenvatinib, the effectiveness of a single tyrosine kinase inhibitor in survival extension of unresectable hepatocellular carcinoma is limited to a few months. Therefore, novel treatment options are required for unresectable hepatocellular carcinomas, including those with multiple lung metastases. This case report describes a hepatocellular carcinoma patient with a recurrence of multiple lung metastases, which was successfully treated with conversion pneumonectomy after treatment with tyrosine kinase inhibitors. A 79-year-old man underwent right hepatectomy for hepatocellular carcinoma, along with removal of the tumor thrombus in the inferior vena cava. Multiple lung metastases were detected 4 months after hepatectomy. Treatment with tyrosine kinase inhibitors, mainly lenvatinib, resulted in complete remission of the lung metastases, except for one lesion in segment 3 of the right lung which gradually enlarged. Twenty-three months after hepatectomy, partial resection of the right lung was performed using video-assisted thoracic surgery for this residual lesion in the right lung. The patient remained disease-free for 11 months after conversion pneumonectomy, without any adjuvant therapies. This is the first case report of multiple lung metastases originating from hepatocellular carcinoma which were successfully treated with conversion pneumonectomy after treatment with tyrosine kinase inhibitors. Conversion pneumonectomy after systemic therapy with tyrosine kinase inhibitors should be considered as a treatment strategy for patients with unresectable multiple lung metastases from hepatocellular carcinomas.
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Affiliation(s)
- Shunji Sano
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Yoh Asahi
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Toshiya Kamiyama
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Tatsuhiko Kakisaka
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Tatsuya Orimo
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Akihisa Nagatsu
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Takeshi Aiyama
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Keizo Kazui
- Department of Surgery, JCHO Hokkaido Hospital, 8-3-18, Nakanoshima, Toyohiraku, Sapporo, Hokkaido 062-8618 Japan
| | - Hiroki Shomura
- Department of Surgery, JCHO Hokkaido Hospital, 8-3-18, Nakanoshima, Toyohiraku, Sapporo, Hokkaido 062-8618 Japan
| | - Shinya Ueki
- Department of Surgery, JCHO Hokkaido Hospital, 8-3-18, Nakanoshima, Toyohiraku, Sapporo, Hokkaido 062-8618 Japan
| | - Yuzuru Sakamoto
- Department of Surgery, JCHO Hokkaido Hospital, 8-3-18, Nakanoshima, Toyohiraku, Sapporo, Hokkaido 062-8618 Japan
| | - Chisato Shirakawa
- Department of Surgery, JCHO Hokkaido Hospital, 8-3-18, Nakanoshima, Toyohiraku, Sapporo, Hokkaido 062-8618 Japan
| | - Hirofumi Kamachi
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Hirokazu Sugino
- Department of Surgical Pathology, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-8638 Japan
| | - Tomoko Mitsuhashi
- Department of Surgical Pathology, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-8638 Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
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Clinical effectiveness of surgical treatment after lenvatinib administration for hepatocellular carcinoma. Int J Clin Oncol 2022; 27:1725-1732. [PMID: 35962255 DOI: 10.1007/s10147-022-02229-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 07/31/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND There is little evidence concerning survival after surgery in patients with hepatocellular carcinoma who have received lenvatinib treatment. The aim of this study was to evaluate whether post-lenvatinib surgical treatment in patients with hepatocellular carcinoma improves overall survival. METHODS The cohort of this retrospective study comprised 55 patients with hepatocellular carcinoma who had undergone lenvatinib treatment. We classified them into two groups according to post-lenvatinib surgical treatment status and compared clinicopathologic factors and prognosis between the two groups with the aim of identifying predictors of overall survival. RESULTS The median duration of lenvatinib administration was 5.8 months (range, 0.4-24.0 months). Twelve of the 55 patients underwent surgery after receiving lenvatinib. There was no significant difference in assessed clinicopathological factors between patients who did and did not undergo surgery after being treated with lenvatinib. Multivariate analysis revealed that older age was associated with a significantly worse overall survival (hazard ratio: 2.332; 95% confidence interval 1.062-5.168; P = 0.0369) and that surgery after treatment with lenvatinib achieved better overall survival than other forms of treatment (hazard ratio: 0.121; 95% confidence interval 0.016-0.901; P = 0.0393). CONCLUSIONS Surgical treatment after lenvatinib administration may be a useful therapeutic option for select patients with hepatocellular carcinoma.
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Shindoh J, Kawamura Y, Kobayashi M, Akuta N, Okubo S, Matsumura M, Suzuki Y, Hashimoto M. Prognostic Advantages of Individual Additional Interventions After Lenvatinib Therapy in Patients with Advanced Hepatocellular Carcinoma. J Gastrointest Surg 2022; 26:1637-1646. [PMID: 35715641 DOI: 10.1007/s11605-022-05388-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 05/14/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND Increasing number of patients with advanced hepatocellular carcinoma (HCC) has recently achieved salvage interventions after introduction of new biologic agents, while there are insufficient data to determine if such additional intervention(s) after treatment with newer biologic agents are truly advantageous for patients with advanced HCC. METHODS The clinical records of 107 consecutive patients who underwent lenvatinib treatment for advanced HCC were extensively reviewed and the prognostic advantages of individual additional treatments after lenvatinib treatment were investigated through a regression analysis considering time-dependent covariates. RESULTS Multivariate analysis revealed that R0 resection or curative-intent radiofrequency ablation (RFA) (hazard ratio [HR], 0.07; 95% CI, 0.01-0.32), transarterial chemoembolization or transarterial infusion therapy (HR, 0.39; 95% CI, 0.19-0.81), and subsequent line of systemic therapy (HR, 0.25; 95% CI, 0.10-0.63) were associated with improved disease-specific survival (DSS), while R2 resection or palliative-intent RFA showed no correlation with DSS. The best response during lenvatinib therapy, nutritional status, plasma des-gamma-carboxyprothrombin level, a baseline CT enhancement pattern, and BCLC stage were also selected as independent predictors for DSS. Among the various treatments performed after lenvatinib therapy, R0 resection also showed clear prognostic advantage in both progression-free survival (HR, 0.30; 95% CI, 0.16-0.58) and time-to-treatment failure (HR, 0.08; 95% CI, 0.02-0.39), suggesting that successful conversion to surgery may prolong survival outcomes through prolonged cancer-free interval in advanced HCC. CONCLUSIONS Additional intervention(s)/treatment(s) after lenvatinib therapy for advanced HCC may have prognostic advantage in strictly selected populations. Successful conversion to curative resection may offer survival benefit with acceptable clinical outcomes.
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Affiliation(s)
- Junichi Shindoh
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
- Okinaka Memorial Institute for Medical Disease, Tokyo, Japan.
| | | | | | - Norio Akuta
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Satoshi Okubo
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Masaru Matsumura
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | | | - Masaji Hashimoto
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
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Hidaka Y, Tomita M, Desaki R, Hamanoue M, Takao S, Kirishima M, Ohtsuka T. Conversion surgery for hepatocellular carcinoma with portal vein tumor thrombus after successful atezolizumab plus bevacizumab therapy: a case report. World J Surg Oncol 2022; 20:228. [PMID: 35831894 PMCID: PMC9277871 DOI: 10.1186/s12957-022-02691-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 06/30/2022] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND The treatment of hepatocellular carcinoma (HCC) requires diverse and multidisciplinary approaches. In recent years, new agents with good antitumor effects have emerged for systemic chemotherapy, and conversion surgery (CS) after systemic chemotherapy is expected to be an effective treatment strategy for unresectable HCC. We herein report a case of unresectable HCC with portal vein tumor thrombus (PVTT) in which atezolizumab plus bevacizumab therapy induced PVTT regression, followed by CS with R0 resection. CASE PRESENTATION The patient was a 79-year-old man with S2/S3 HCC who was referred to our department due to tumor re-growth and PVTT after two rounds of transcatheter arterial chemoembolization. The PVTT extended from the left portal vein to the main trunk, and it was determined that the resection of the left portal vein would be difficult to perform with R0 status. Based on the diagnosis of unresectable HCC, treatment with atezolizumab plus bevacizumab was initiated. After two courses of treatment, contrast-enhanced computed tomography showed that the PVTT had regressed to the peripheral side of the left portal vein, and R0 resection became possible. The patient developed grade 3 skin lesions as an immune-related adverse event, and it was determined that the continuation of chemotherapy would be difficult. Four weeks after the second course of atezolizumab plus bevacizumab administration, left lobectomy was performed. Intraoperative ultrasonography was used to confirm the location of the tumor thrombus in the left portal vein during the resection, and a sufficient surgical margin was obtained. The histopathological findings showed that primary tumor and PVTT were mostly necrotic with residues of viable tumor cells observed in some areas. The liver background was determined as A1/F4 (new Inuyama classification). The resection margins were negative, and R0 resection was confirmed. There were no postoperative complications. No recurrence was observed as of five months after surgery. CONCLUSIONS CS with atezolizumab plus bevacizumab therapy has potential utility for the treatment of unresectable HCC with PVTT.
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Affiliation(s)
- Yoshifumi Hidaka
- Department of Surgery, Tanegashima Medical Center, 7463 Nishinoomote, Nishinoomote, Kagoshima, 891-3198, Japan.
| | - Miyo Tomita
- Department of Surgery, Tanegashima Medical Center, 7463 Nishinoomote, Nishinoomote, Kagoshima, 891-3198, Japan
| | - Ryosuke Desaki
- Department of Surgery, Tanegashima Medical Center, 7463 Nishinoomote, Nishinoomote, Kagoshima, 891-3198, Japan
| | - Masahiro Hamanoue
- Department of Surgery, Tanegashima Medical Center, 7463 Nishinoomote, Nishinoomote, Kagoshima, 891-3198, Japan
| | - Sonshin Takao
- Department of Surgery, Tanegashima Medical Center, 7463 Nishinoomote, Nishinoomote, Kagoshima, 891-3198, Japan
| | - Mari Kirishima
- Department of Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Takao Ohtsuka
- Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical and Dental Science, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
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Arita J, Ichida A, Nagata R, Mihara Y, Kawaguchi Y, Ishizawa T, Akamatsu N, Kaneko J, Hasegawa K. Conversion surgery after preoperative therapy for advanced hepatocellular carcinoma in the era of molecular targeted therapy and immune checkpoint inhibitors. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2022; 29:732-740. [PMID: 35306748 DOI: 10.1002/jhbp.1135] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 01/06/2022] [Accepted: 01/24/2022] [Indexed: 11/12/2022]
Abstract
BACKGROUND Optimal strategies for advanced hepatocellular carcinoma (HCC) tumors, such as those with vascular tumor thrombus and those with extrahepatic metastases are unclear. METHODS A literature review was conducted focusing on conversion surgery for HCC after molecular targeted therapy and therapy using immune checkpoint inhibitors. RESULTS Upfront surgical resection of advanced HCC tumors has been challenged at some institutions because of lack of promising therapeutic options. Preoperative transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy, and radiotherapy in patients with unresectable HCC were developed to improve long-term outcome, but the results were not promising. Nonetheless, the recent advent of molecular targeted therapies and immune check-point inhibitors, enabling frequent tumor responses, has accelerated the use of conversion surgery after these therapies in patients with initially unresectable HCC. Increasing numbers of conversion surgeries after lenvatinib therapy has been reported, and the first prospective clinical trial assessing conversion surgery after lenvatinib therapy in initially unresectable HCC has been commenced. Furthermore, the superiority of combination therapy using atezolizumab and bevacizumab over sorafenib, a conventional first-line drug for unresectable HCC, in terms of overall survival and tumor response has been demonstrated, and the use of this regimen alongside conversion surgery is expected in addition to lenvatinib. CONCLUSION The literature demonstrated the feasibility of conversion surgery after systemic therapy. Further clinical investigation of surgery after systemic therapy for advanced HCC may be undertaken by clearly distinguishing the tumor status as technically unresectable or oncologically unresectable but technically resectable.
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Affiliation(s)
- Junichi Arita
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Akihiko Ichida
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Rihito Nagata
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Yuichiro Mihara
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Yoshikuni Kawaguchi
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Takeaki Ishizawa
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Nobuhisa Akamatsu
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Junichi Kaneko
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
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Endo Y, Shimazu M, Sakuragawa T, Uchi Y, Edanami M, Sunamura K, Ozawa S, Chiba N, Kawachi S. Successful treatment with laparoscopic surgery and sequential multikinase inhibitor therapy for hepatocellular carcinoma: A case report. World J Gastrointest Surg 2022; 14:260-267. [PMID: 35432767 PMCID: PMC8984515 DOI: 10.4240/wjgs.v14.i3.260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 01/08/2022] [Accepted: 03/17/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) with massive portal vein tumor thrombosis (PVTT) and distant metastasis is considered unresectable. However, due to recent developments in systemic chemotherapy, successful cases of conversion therapy for unresectable diseases have been reported. Herein, we report a successful multidisciplinary approach for treatment of multi-visceral recurrence with sequential multikinase inhibitor and laparoscopic surgery.
CASE SUMMARY A 63-year-old woman with chronic hepatitis B virus infection was diagnosed with HCC. Subsequently, she underwent two rounds of laparoscopic partial hepatectomy, laparoscopic left adrenalectomy, and transcatheter arterial chemoembolization plus sorafenib for recurrence. Four years after initial hepatectomy, she presented with a 43-mm mass in the spleen and tumor thrombus involving the main portal vein trunk with ascites. Her liver function was Child-Pugh B (8), and protein induced by vitamin K absence or antagonist II (PIVKA II) levels were elevated up to 46.291 mAU/mL. Since initial treatment with regorafenib for three months was unsuccessful, the patient was administered lenvatinib. Ten months post-treatment, there was no contrast enhancement of PVTT or splenic metastasis. Chemotherapy was discontinued due to severe diarrhea. Afterward, splenic metastasis became viable, and PIVKA II increased. Therefore, hand-assisted laparoscopic splenectomy was performed. She experienced no clinical recurrence 14 mo after resection.
CONCLUSION Conversion surgery after successful multikinase inhibitor treatment might be considered an effective treatment option for advanced HCC.
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Affiliation(s)
- Yutaka Endo
- Department of Surgery, Tama Kyuryo Hospital, Tokyo 1940297, Japan
| | - Motohide Shimazu
- Department of Surgery, Tama Kyuryo Hospital, Tokyo 1940297, Japan
| | | | - Yusuke Uchi
- Department of Surgery, Tama Kyuryo Hospital, Tokyo 1940297, Japan
| | - Motonori Edanami
- Department of Surgery, Tama Kyuryo Hospital, Tokyo 1940297, Japan
| | - Ken Sunamura
- Department of Surgery, Tama Kyuryo Hospital, Tokyo 1940297, Japan
| | - Soji Ozawa
- Department of Surgery, Tama Kyuryo Hospital, Tokyo 1940297, Japan
| | - Naokazu Chiba
- Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Tokyo 1930998, Japan
| | - Shigeyuki Kawachi
- Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Tokyo 1930998, Japan
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Naganuma A, Suzuki Y, Hoshino T, Yasuoka H, Tamura Y, Naruse H, Tanaka H, Hirai K, Sakamoto I, Ogawa T, Hatanaka T, Kakizaki S. A case of conversion hepatectomy for huge ruptured hepatocellular carcinoma after transarterial embolization and lenvatinib therapy. Clin J Gastroenterol 2022; 15:177-184. [PMID: 34811701 DOI: 10.1007/s12328-021-01558-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 11/10/2021] [Indexed: 12/09/2022]
Abstract
We herein report a successfully treated case of huge ruptured hepatocellular carcinoma (HCC) by conversion hepatectomy after transarterial embolization (TAE) and lenvatinib therapy. A 33-year-old male patient with right hypochondralgia and liver tumor was referred to our hospital. He had a history of surgery for heart malformation. The tumor at the right lobe was 15 cm in diameter with bloody ascites. Right atrial thrombus 4.5 cm in diameter and marked cardiac dilatation were observed. TAE with ethanol suspended in lipiodol and gelatin sponge achieved hemostasis of the ruptured HCC. Although viable HCC remained after TAE, surgical treatment was abandoned because of abdominal wall invasion and his heart function. Lenvatinib and rivaroxaban were then initiated for HCC and atrial thrombus, respectively. Lenvatinib treatment resulted in a reduction in tumor marker levels and the tumor size. First, we planned conversion hepatectomy after 5 months of lenvatinib. However, recurrence of atrial thrombus prompted us to put off the surgery, and lenvatinib was re-administered. After improvement of atrial thrombus, we finally performed conversion hepatectomy 10 months after starting lenvatinib administration. The tumor was completely removed by combined resection of the diaphragm, and the patient has been doing well without any signs of recurrence.
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Affiliation(s)
- Atsushi Naganuma
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Yuhei Suzuki
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Takashi Hoshino
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Hidetoshi Yasuoka
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Yuki Tamura
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Hiroaki Naruse
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Hiroshi Tanaka
- Department of Surgery, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Keitaro Hirai
- Department of Surgery, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Ichiro Sakamoto
- Department of Surgery, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Tetsushi Ogawa
- Department of Surgery, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Takeshi Hatanaka
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, 564-1 Kamishindenmachi, Maebashi, Gunma, 371-0821, Japan
| | - Satoru Kakizaki
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan.
- Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan.
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Asahi Y, Kamiyama T, Kakisaka T, Orimo T, Shimada S, Nagatsu A, Aiyama T, Sakamoto Y, Kamachi H, Taketomi A. Outcomes of reduction hepatectomy combined with postoperative multidisciplinary therapy for advanced hepatocellular carcinoma. World J Gastrointest Surg 2021; 13:1245-1257. [PMID: 34754392 PMCID: PMC8554724 DOI: 10.4240/wjgs.v13.i10.1245] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 08/21/2021] [Accepted: 09/17/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The prognosis of advanced hepatocellular carcinoma (HCC) that is not indicated for curative hepatectomy remains poor, despite advances in the treatment of HCC, including the development of tyrosine kinase inhibitors (TKIs). The outcomes of reduction hepatectomy and multidisciplinary postoperative treatment for advanced HCC that is not indicated for curative hepatectomy, including those of recently treated cases, should be investigated.
AIM To examine the outcomes of combination treatment with reduction hepatectomy and multidisciplinary postoperative treatment for advanced HCC that is not indicated for curative hepatectomy.
METHODS Thirty cases of advanced HCC that were not indicated for curative hepatectomy, in which reduction hepatectomy was performed between 2000 and 2018 at the Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, were divided into postoperative complete remission (POCR) (+) and POCR (-) groups, depending on whether POCR of all evaluable lesions was achieved through postoperative treatment. The cases in the POCR (-) group were subdivided into POCR (-) TKI (+) and POCR (-) TKI (-) groups, depending on whether TKIs were administered postoperatively.
RESULTS The 5-year overall survival rate and mean survival time (MST) after reduction hepatectomy were 15.7% and 28.40 mo, respectively, for all cases; 37.5% and 56.55 mo, respectively, in the POCR (+) group; and 6.3% and 14.84 mo, respectively, in the POCR (-) group (P = 0.0041). Tumor size, major vascular invasion, and the number of tumors in the remnant liver after the reduction hepatectomy were also found to be related to survival outcomes. The number of tumors in the remnant liver was the only factor that differed significantly between the POCR (+) and POCR (-) groups, and POCR was achieved significantly more frequently when ≤ 3 tumors remained in the remnant liver (P = 0.0025). The MST was 33.52 mo in the POCR (-) TKI (+) group, which was superior to the MST of 10.74 mo seen in the POCR (-) TKI (-) group (P = 0.0473).
CONCLUSION Reduction hepatectomy combined with multidisciplinary postoperative treatment for unresectable advanced HCC that was not indicated for curative hepatectomy was effective when POCR was achieved via multidisciplinary postoperative therapy. To achieve POCR, reduction hepatectomy should aim to ensure that ≤ 3 tumors remain in the remnant liver. Even in cases in which POCR is not achieved, combined treatment with reduction hepatectomy and multidisciplinary therapy can improve survival outcomes when TKIs are administered.
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Affiliation(s)
- Yoh Asahi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan
| | - Toshiya Kamiyama
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan
| | - Tatsuhiko Kakisaka
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan
| | - Tatsuya Orimo
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan
| | - Shingo Shimada
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan
| | - Akihisa Nagatsu
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan
| | - Takeshi Aiyama
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan
| | - Yuzuru Sakamoto
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan
| | - Hirofumi Kamachi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan
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13
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Yamamura K, Beppu T. Conversion surgery for hepatocellular carcinoma after multidisciplinary treatment including lenvatinib. Hepatol Res 2021; 51:1029-1030. [PMID: 34596312 DOI: 10.1111/hepr.13691] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Kensuke Yamamura
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan
| | - Toru Beppu
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan
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