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Spontaneous Remission of Hepatocellular Carcinoma Without Any Treatment

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Spontaneous Remission of Hepatocellular Carcinoma Without Any Treatment Journal of Cancer Research and Practice 3 (2016) 128e131 Contents lists available at ScienceDirect Journal of Cancer Research and Practice journal homepage: http://www.journals.elsevier.com/journal-of-cancer- research-and-practice Case Report Spontaneous remission of hepatocellular carcinoma without any treatment * Shao-Ciao Luo a, , Cheng-Chung Wu a, Shao-Bin Jheng a, Zhen-Yi Huang b a Division of General Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan b Department of Radiology, Taichung Veterans General Hospital, Taichung, Taiwan article info abstract Article history: Hepatocellular carcinoma (HCC) is a major leading cause of cancer death in Taiwan. The prognosis will be Received 29 January 2016 fatal without treatment. However, about 80 cases of the rare phenomenon of spontaneous remission of Received in revised form HCC have been reported in the English literature. 8 June 2016 A 61 year old asymptomatic woman visited our outpatient clinic (OPC) with a high alpha-fetal protein Accepted 14 June 2016 (AFP) level. A computed tomogram (CT) revealed a 4.1 cm hypervascular tumor (arterial phase) at S4 of Available online 31 August 2016 the liver and washed out in venous phase. Her Hepatitis B Surface Antigen (HBsAg) was negative and Hepatitis C Antibody (anti-HCV) was positive. This patient also had esophageal varices. She refused any Keywords: Spontaneous regression treatment and returned to our OPC about 2 years later. Her AFP level was 11.8 ng/ml. The following CT Hepatocellular carcinoma scan revealed a small amount of cirrhosis, but no mass, in the liver, so that spontaneous remission of HCC was determined. She was treated by oral diuretics. Here we report the case and review of literature. Copyright © 2016, The Chinese Oncology Society. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 1. Introduction 2. Case report Hepatocellular carcinoma (HCC) is the third most common A 61 years old Taiwanese woman with Child-Pugh B liver cancer and is a leading cause of cancer death in Taiwan.1 The cirrhosis due to HCV infection visited our outpatient clinic (OPC) on prognosis is fatal without any treatment, and the 1- 2- and 3-year 15th/May/2012 for elevated liver enzymes noted by a local medical survival rate is 54%, 40%, and 28%, respectively.2,3 Even with treat- clinic. Body weight loss of 5 kg within one month was also reported. ment, the mortality of this disease is still very high, and the median She had no history of hypertension, diabetes mellitus or other survival is 17.7 months, while the 5-year survival rate is 10.7%.4 systemic diseases. She denied alcohol drinking and cigarettes Spontaneous remission of malignant tumors is a rare phenome- smoking. She took no drugs. Results of a physical examination were non, and the first case defined in 1959 by Cole and Everson.5 unremarkable, and there was no abdominal pain, jaundice, nor Spontaneous remission of HCC is an extremely rare phenomenon general edema. The abdomen was soft and flat, with neither and the underlying mechanisms of HCC with spontaneous regres- palpable masses nor ascites. sion still remain unclear. Two mechanisms have been suggested to At that time, her laboratory examinations showed hemoglobin explain the etiology of HCC with spontaneous regression, either (Hb) of 10.4 g/dl (normal: 11.3e15.3), and platelets of 36,000/mm3 through tumor ischemia, or systemic inflammation.6 However, (normal: 150,000e400,000), and WBC count of 3800/mm3 those mechanisms cannot appropriately explain all reported cases (normal: 4000e11,000). The liver function showed serum albumin of HCC with spontaneous regression. We report a case of HCC was 3.2 g/dl, total bilirubin was 1.7 mg/dl, alkaline phosphotate was without any treatment, and spontaneous partial regression was 184 U/l (normal À190), aspartate aminotransferase (AST) was 70 U/l noted. (normal: 8e38), alanine aminotransferase (ALT) was 56 U/l (normal: 10e35), alpha-fetal protein (AFP) was 624 ng/ml (normal <12), international normalized ratio (INR) was 1.52 (normal: * Corresponding author. Division of General Surgery, Department of Surgery, 0.85e1.15). Her HBsAg was negative and anti-HCV was positive. Her 7 Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, Taichung Child-Pugh score was 7 (Child-Pugh class B). Abdominal ultraso- 40705,Taiwan. nography showed one bulging tumor, 4.2 Â 3.2 cm in size. The triple E-mail address: [email protected] (S.-C. Luo). phase CT scan of the liver demonstrated an ill-defined low density Peer review under responsibility of The Chinese Oncology Society. http://dx.doi.org/10.1016/j.jcrpr.2016.06.003 2311-3006/Copyright © 2016, The Chinese Oncology Society. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). S.-C. Luo et al. / Journal of Cancer Research and Practice 3 (2016) 128e131 129 and hypervascular soft tissue mass in the left lobe of liver (Coui- HCC.11 The first case of HCC with spontaneous regression is naud's segement 4b, S4b),8 approximately 41 mm in diameter, with described by Johnson and colleagues in 1972.12 Until now, about 80 early enhancing in the arterial phase and washout in the delayed cases have been reported in English literature. The first biopsy- phase on the after contrast medium CT, that showed compatibility proven Taiwanese patient had been documented in 1992.13 After with HCC (Fig. 1). Para-esophageal varices, multiple collateral ves- review the literatures and several clinical events were documented, sels in the abdomen, mild ascites and splenomegaly were also including abstinence from alcohol, androgen withdrawal, persis- noted. The diagnosis of HCC was determined based on a single tent fever, pain, gastrointestinal bleed requiring transfusion, herbal positive imaging technique showing hypervascularization associ- therapies, use of vitamin K, anti-estrogen therapy, sepsis, blood ated with more than 400 ng/ml of AFP level. In addition, the patient transfusion, portal vein tumor thrombosis, angiography related e did not take any medications and surgical treatment in our clinic, angiospasm or arterial thrombosis.6,9,14 20 However, the most and also did not return to our OPC to follow up her HCC appropriate etiology to explain possible mechanisms for the above progression. clinical events are still unclear. Over 2 years later, she returned to our OPC on 27th/July/2014 Besides, the possibility of a tumor with spontaneous regression after developing abdominal distension and leg edema over the seem not to be associated with tumor size, tumor number, the level previous three weeks. The physical examination showed abdomen of serum alpha-fetal protein presence or not of distance metastasis distension with ascites and pitting edema. Her AFP level was distance metastasis.21 Two common mechanisms of HCC with 11.8 ng/ml, serum albumin was 2.4 g/dl, total bilirubin was 1.7 mg/ spontaneous regression were suggested: tumor hypoxia and sys- dl, AST was 61 U/l, ALT of was 38 U/l, alkaline phosphotate was temic inflammatory activation. Tumor hypoxia mechanism con- 132 U/l. The following triple phase CT scan of the liver revealed no tributes about 28.0% of all recorded case in English literatures.6 The obvious mass in the liver, with a poor enhancing lesion over the clinical events include portal vein tumor thrombosis, angiography previous HCC site (Fig. 2). Her liver cirrhosis status with progression related angiospasm or arterial thrombosis, rapid growth of the was noted with clinic symptoms attacked. She denied any treat- tumor, massive gastrointestinal bleed, and so on. This hypothesis ment (including invasive procedures, radiation, medications, and can easily be accepted just like using transhepatic arterial chemo- herb drugs) and was only treated with oral diuretics for controlling embolization (TACE) or the anti-angiogenesis effect of sorafenib to e symptoms during these two years. She also reported no gastro- treat HCC.22 24 intestine bleeding, shock, trauma, blood transfusion, or other spe- Another possible mechanism is systemic inflammatory activa- cial episodes. In addition, she did not attend regular follow-up tion, which contributes more (about 33.3%) than tumor hypoxia in appointments due to personal reasons. Approximately thirty all recorded cases in English literature.6 We trust that some clinical months after initial diagnosis, the last triple phase CT scan of the events activate an inflammatory mechanism that leads to tumor liver still revealed no obvious tumor recurrence (Fig. 3). Taken regression, due to elevation of several cytokine and biomarkers (ex: together, a patient with spontaneous remission of HCC was deter- IL-2, IL-6, IL-12, IL-18, interferon (IFN) e gamma, tumor necrosis e mined in this case. factor (TNF) e alpha) were documented.25 31 Besides, tumor hyp- oxia mechanism cannot fully explain spontaneous regression of 32 3. Discussion HCC with distance metastasis. Some pathological evidences of an active inflammation mechanism were described as the presence of Here we report a rare case of HCC with spontaneous regression, overactivated macrophages (CD163þ) or lymphocytic infiltra- 33,34 where the evidence of tumor remission was confirmed by a series tion. The most appropriate etiology of spontaneous tumor of CT scans and associated with the decrease of serum AFP levels regression still remains uncertain, but activated inflammation without any treatment. mechanism must play an important role. Spontaneous remission of cancer is a rare phenomenon, and We described herein a case of HCC with spontaneous regression defined by Cole and Everson as partial or complete disappearance without any obvious clinical markers of tumor hypoxia or systemic of a malignant tumor in the absence of any treatment, or in the inflammatory activation.
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