Successful Treatment of Hepatocellular Carcinoma with Lung Metastasis Using Hepatic and Bronchial Artery Infusion Chemotherapy

Yoshida, Tsukasa; Kamada, Kei; Miura, Kouichi; Goto, Takashi; Ohshima, Shigetoshi; Sato, Wataru; Shibuya, Tomomi; Dohmen, Takahiro; Kanata, Ryo; Sakai, Toshitaka; Chiba, Mitsuru; Fujiwara, Junichi; Sugimoto, Yoshimi; Ishioka, Mitsuaki; Hasegawa, Itsuki; Takahashi, Ken­ichi; Minami, Shinichiro; Fujita, Akashi; Hashimoto, Manabu; Ohnishi, Hirohide

doi:10.2169/internalmedicine.53.2957

Cited by 5 publications

(4 citation statements)

References 24 publications

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“…So only tumors in the liver with its two circulations would be very relevant to our present model in the lung. Indeed, it is known that the systemic hepatic circulation provides the primary blood flow to liver tumors (28), much like the bronchial circulation being essential for large tumors in the lung parenchyma as shown here.…”

Section: Discussionmentioning

confidence: 86%

“…As early as 1969, bronchial artery infusion therapy was used as a route for more direct delivery of chemotherapy to lung tumors in patients with lung cancer (27), and such approaches to treat NSCLC and hepatocellular carcinoma lung metastases are still being used (28, 29). It is also common for patients with NSCLC to experience life-threatening hemoptysis, and for decades it has been routine practice to embolize small branches of the bronchial artery as an effective treatment (30, 31).…”

Section: Discussionmentioning

confidence: 99%

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Bronchial Artery Angiogenesis Drives Lung Tumor Growth

et al. 2016

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Angiogenesis is vital for tumor growth but in well-vascularized organs such as the lung its importance is unclear. This situation is complicated by the fact that the lung has two separate circulations, the pulmonary and the systemic bronchial circulation. There are few relevant animal models of non-small cell lung cancer, which can be used to study the lung’s complex circulations, and mice, lacking a systemic bronchial circulation cannot be used. We report here a novel orthotopic model of non-small cell lung cancer in rats, where we have studied the separate contributions of each of the two circulations for lung tumor growth. Results show that bronchial artery perfusion, quantified by fluorescent microspheres (206% increase in large tumors) or HRCT scans (276% increase in large tumors), parallels the growth in tumor volume, while pulmonary artery perfusion remained unchanged. Ablation of the bronchial artery after the initiation of tumor growth resulted in a decrease in tumor volume over a subsequent course of 4 weeks. These results demonstrate that while the existing pulmonary circulation can supply the metabolic needs for tumor initiation, further growth of the tumor requires angiogenesis from the highly proliferative bronchial circulation. This model may be useful to investigate new therapeutic approaches that target specifically the bronchial circulation.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Bronchial Artery Angiogenesis Drives Lung Tumor Growth

et al. 2016

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“…BAI chemotherapy even showed efficacy in the treatment of metastatic lung tumors. 16 However, as is the case with other types of chemotherapy, BAI chemotherapy also resulted in worsening symptoms in some patients (2.8%), although symptom worsening associated with BAI occurred less often than symptom worsening associated with conventional intravenous chemotherapy.…”

Section: Discussionmentioning

confidence: 86%

Neoadjuvant chemotherapy by bronchial arterial infusion in patients with unresectable stage III squamous cell lung cancer

Zhu

Zhang

Jiang

et al. 2017

Ther Adv Respir Dis

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Background:We investigated the effects of neoadjuvant chemotherapy administered via bronchial arterial infusion (BAI) on unresectable stage III lung squamous cell carcinoma (SCC).Methods:This was a single-arm retrospective study of chemotherapy with gemcitabine plus cisplatin (GP) administered via BAI to patients with unresectable lung SCC. Data regarding the post-treatment response rate, downstage rate, and surgery rate, as well as progression-free survival (PFS), overall survival (OS), quality of life, and post-BAI side effects were collected.Results:A total of 36 patients were enrolled in this study between August 2010 and May 2014. The response rate was 72.2%, and the downstage rate was 22.2%. Among the patients who were downstaged, 16 (44.4%) patients were because of their T stage, and 5 (13.9%) patients were downstaged due to to their N stage. The surgery rate was 52.8%, the 1-year survival rate was 75.4%, and the 2-year survival rate was 52.1%. The median PFS was 14.0 months [95% confidence interval (CI): 8.6–19.4], and the median OS was 25.0 months (95% CI: 19.1–30.9). The quality of life was significantly improved, and the chemotherapy was well tolerated.Conclusions:Compared with intravenous neoadjuvant chemotherapy, BAI chemotherapy significantly improved the surgery rate, prolonged PFS and OS, and improved the quality of life in patients with unresectable stage III lung SCC.

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“…The main cause of treatment failure and death is the formation of metastases [ 5 ]. Circulatory dissemination of CRC cells to the liver occurs via the portal vein system [ 6 ]. Cancer cells get arrested in capillaries of a similar diameter to that of the cells, and extravasation typically occurs in small capillaries [ 7 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

MIF, secreted by human hepatic sinusoidal endothelial cells, promotes chemotaxis and outgrowth of colorectal cancer in liver prometastasis

Guo

Feng

et al. 2015

Oncotarget

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Growth and invasion of metastatic colorectal cancer (CRC) cells in the liver depend on microenvironment. Here, we showed that human hepatic sinusoidal endothelial cells (HHSECs) induce chemotaxis and outgrowth of CRC cells. Macrophage migration inhibitory factor (MIF), released by HHSECs, stimulated chemotaxis of CRC cells. MIF secreted by HHSECs, but not by CRC cells themselves, promoted migration and epithelial-mesenchymal transition (EMT) and facilitated proliferation and apoptotic resistance of CRC cells. In orthotopic implantation models in nude mice, exogenous MIF stimulated growth of CRC cells and metastasis. Furthermore, MIF accelerated mobility of CRC cells by suppressing F-actin depolymerization and phosphorylating cofilin. Noteworthy, MIF levels were correlated with the size of hepatic metastases. We suggest that HHSECs and paracrine MIF promote initial migration and proliferation of CRC cells in the hepatic sinusoids to generate liver metastases.

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Successful Treatment of Hepatocellular Carcinoma with Lung Metastasis Using Hepatic and Bronchial Artery Infusion Chemotherapy

Cited by 5 publications

References 24 publications

Bronchial Artery Angiogenesis Drives Lung Tumor Growth

Bronchial Artery Angiogenesis Drives Lung Tumor Growth

Neoadjuvant chemotherapy by bronchial arterial infusion in patients with unresectable stage III squamous cell lung cancer

MIF, secreted by human hepatic sinusoidal endothelial cells, promotes chemotaxis and outgrowth of colorectal cancer in liver prometastasis

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