Japanese Journal of Clinical Oncology 31:454-458 (2001)
© 2001 Foundation for Promotion of Cancer Research
Spontaneous Regression of Hepatocellular Carcinoma with Multiple Lung Metastases: a Case Report
Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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Spontaneous regression of hepatocellular carcinoma is an extraordinarily unusual phenomenon. We present here a case of a 75-year-old man in whom multiple lung metastases of hepatocellular carcinoma regressed spontaneously. He underwent systemic chemotherapy for hepatocellular carcinoma with multiple lung metastases. However, the chemotherapy was not effective and he was therefore followed up without any anticancer treatments in an outpatient clinic. Four months later, multiple lung nodules regressed dramatically and the serum
-fetoprotein level decreased markedly. After an 8-month period of the regression, however, intrahepatic lesions gradually enlarged, although multiple lung metastatic lesions remained regressed. The mechanisms underlying this intriguing phenomenon remain unknown. |
INTRODUCTION |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in the world, especially in Asia and Africa. Although early detection of tumors and development of therapies for HCC are likely to improve prognosis, the prognosis of advanced HCC remains poor. Numerous reports have described cases of spontaneous regression of HCC (1–33), although the mechanisms leading to it remain unknown. Therefore, such cases, although extremely rare, should be accumulated, since this may contribute to a further understanding of this phenomenon and lead to a new strategy for HCC treatment. We report here a patient in whom multiple lung metastases from HCC spontaneously regressed 4 months after ineffective anticancer treatment.
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CASE REPORT |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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This report describes a 75-year-old Japanese man with diagnosis of HCC accompanying multiple lung metastases (Fig. 1). He had a past history of left pulmonary upper lobectomy for pulmonary tuberculosis at the age of 45 years, during which he had received a blood transfusion. He had no history of heavy alcohol intake or habitual drug use. He had no serological markers of hepatitis B virus, but antibody to hepatitis C virus was detected. In February 1995, when he was 70 years old, he was referred to our hospital with a tentative diagnosis of HCC; liver tumors located in segment 7 of the liver were detected on ultrasound examination as a routine check-up for chronic hepatitis at the previous hospital. These tumors were diagnosed as HCC by typical computed tomographic (CT) and angiographic findings and elevated serum
-fetoprotein (AFP) level. He underwent hepatic arterial infusion using lipiodol combined with zinostatin stimalamer 4 mg for HCC in February 1995. Because local relapses were observed on follow-up CT, transcatheter arterial embolization using gelatin-sponge and lipiodol combined with zinostatin stimalamer was carried out in August 1995. Thereafter, the follow-up examinations including CT and AFP every 3–4 months did not show any relapse of HCC. In November 1999, he complained of consistent dry cough. His chest X-ray revealed multiple nodular shadows in the bilateral lungs, ranging up to 2 cm in diameter and serum AFP was markedly elevated (6750 ng/ml). These lung nodules were diagnosed as multiple lung metastases of HCC, although the diagnosis was not confirmed pathologically. However, abdominal CT did not demonstrate definitive relapse of HCC in the liver. He received systemic multi-agent chemotherapy using mitoxantrone, cisplatin and 5-fluorouracil in December 1999 (34). However, chemotherapy was not effective; chest X-ray and CT in January 2000 demonstrated enlarged metastatic nodules compared with those before chemotherapy and the serum AFP level had approximately doubled (14 734 ng/ml) (Fig. 2). Therefore, systemic chemotherapy was abandoned and he was discharged for follow-up at the outpatient clinic.
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Four months after systemic chemotherapy had been abandoned, the multiple lung metastases dramatically decreased in number and sizes (Fig. 3). Moreover, serum AFP also decreased markedly (99.3 ng/dl). During this period, he had not received any anticancer treatment or medication including herbal medicine and denied any further change in habits. Moreover, he had not sustained trauma or infection and there were no remarkable changes in nutrients during the period of spontaneous regression (data not shown). This phenomenon, therefore, was regarded as spontaneous regression of HCC with multiple lung metastases.
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After an 8-month period of spontaneous regression, the intrahepatic lesions, which had been treated by hepatic arterial infusion and transcatheter arterial embolization, gradually enlarged and serum AFP began to increase again (166 ng/ml), although multiple lung metastatic lesions remained regressed. He underwent hepatic arterial infusion using lipiodol combined with zinostatin stimalamer for intrahepatic lesions in September 2000 and is currently being followed up at the outpatient clinic.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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Spontaneous regression of a malignant tumor, which was defined by Everson and Cole (1) as a partial or complete involution of a malignant tumor without specific therapy being applied, is an extraordinary and unusual phenomenon. The incidence of spontaneous regression was estimated to be one per 60 000–100 000 cases of malignancy, almost half involving renal cell carcinoma, neuroblastoma and malignant melanoma (2,3). With regard to HCC, 34 patients demonstrating this phenomenon have been reported to date as case reports in the English literature (4–33) (Table 1). The clinical course of our patient also indicated that this case was a spontaneous regression of multiple lung metastases, which was confirmed by both the marked decrease in serum AFP level and dramatic tumor regression shown on CT, although histological evidence of spontaneous regression was not available.
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What are the characteristics of patients demonstrating spontaneous regression of HCC? In previous reports, and this case, the characteristics of the patients showing spontaneous regression did not differ from those of other patients (Table 1): most of the patients showing spontaneous regression were men older than 60 years with some underlying chronic liver disease, demonstrating a wide range of tumor sizes, serum AFP levels and histopathological features.
What are the causative factors leading to spontaneous regression of HCC? The mechanism leading to spontaneous regression, which may differ individually, is still puzzling, although various causative factors have been proposed (Table 1). Because of the rarity of this phenomenon, possible mechanisms discussed in the literature originate primarily from the analysis of individual case histories. Biological factors have suggested in an attempt to explain spontaneous regression: hormonal influences, reduction of nutrients necessary for tumor growth and immunological variations. Spontaneous regression of HCC has also been reported to develop after abstinence from alcohol (6,19), persistent fever (7,12,21,28), withdrawal of androgen (5,9), blood transfusion (12), massive bleeding (8,13), rapid tumor growth (11,22), angiography (10,17), surgical trauma (8) and use of herbal medicine (7,16,33).
However, cases in which no evident event was observed during the period of spontaneous regression have also been reported (14,18,20,23–25,27,29–30,32). In our case, the mechanisms leading to spontaneous regression remain unknown, because this patient had not received any medication, including herbal medicine, and there were no evident events or changes in his habits during this period. However, some systemic factors may be strongly suggested to be causative, because the regression occurred in multiple metastatic lesions of the bilateral lungs.
In conclusion, it is difficult at present to elucidate the characteristics of patients who experience spontaneous regression and the mechanisms leading to spontaneous regression. Therefore, cases of spontaneous regression of HCC should be accumulated in the literature. Even though an individual history cannot provide a complete explanation of the underlying mechanisms, accumulation of such cases of spontaneous regression will contribute to a further understanding of this intriguing phenomenon and may also lead to a new treatment strategy for HCC.
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FOOTNOTES |
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+ For reprints and all correspondence: Shuichi Okada, Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, 1–1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. E-mail: sokada@ncc.go.jp
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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Received February 22, 2001; accepted May 18, 2001.
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