gsk-3 Over years later she returned to our OPC

Over 2 years later, she gsk-3 returned to our OPC on 27th/July/2014 after developing abdominal distension and leg edema over the previous three weeks. The physical examination showed abdomen distension with ascites and pitting edema. Her AFP level was 11.8 ng/ml, serum albumin was 2.4 g/dl, total bilirubin was 1.7 mg/dl, AST was 61 U/l, ALT of was 38 U/l, alkaline phosphotate was 132 U/l. The following triple phase CT scan of the liver revealed no obvious mass in the liver, with a poor enhancing lesion over the previous HCC site (Fig. 2). Her liver cirrhosis status with progression was noted with clinic symptoms attacked. She denied any treatment (including invasive procedures, radiation, medications, and herb drugs) and was only treated with oral diuretics for controlling symptoms during these two years. She also reported no gastrointestine bleeding, shock, trauma, blood transfusion, or other special episodes. In addition, she did not attend regular follow-up appointments due to personal reasons. Approximately thirty months after initial diagnosis, the last triple phase CT scan of the liver still revealed no obvious tumor recurrence (Fig. 3). Taken together, a patient with spontaneous remission of HCC was determined in this case.
Discussion Spontaneous remission of cancer is a rare phenomenon, and defined by Cole and Everson as partial or complete disappearance of a malignant tumor in the absence of any treatment, or in the presence of the therapy which is considered to be inadequate to exert a significant influence on neoplastic disease. Most malignant tumor with spontaneous regression occurs on renal cell carcinoma, neuroblastoma, melanoma, and choriocarcinoma; these constituted more than half of all cases. Incidence rate of spontaneous regression of cancer is estimated to be 1 in 60,000–100,000 cancer patients. Unfortunately, spontaneous regression of HCC is a more rare event, and the reported incidence rate is 1 in 140,000 cases of HCC. The first case of HCC with spontaneous regression is described by Johnson and colleagues in 1972. Until now, about 80 cases have been reported in English literature. The first biopsy-proven Taiwanese patient had been documented in 1992. After review the literatures and several clinical events were documented, including abstinence from alcohol, androgen withdrawal, persistent fever, pain, gastrointestinal bleed requiring transfusion, herbal therapies, use of vitamin K, anti-estrogen therapy, sepsis, blood transfusion, portal vein tumor thrombosis, angiography related angiospasm or arterial thrombosis. However, the most appropriate etiology to explain possible mechanisms for the above clinical events are still unclear. Besides, the possibility of a tumor with spontaneous regression seem not to be associated with tumor size, tumor number, the level of serum alpha-fetal protein presence or not of distance metastasis distance metastasis. Two common mechanisms of HCC with spontaneous regression were suggested: tumor hypoxia and systemic inflammatory activation. Tumor hypoxia mechanism contributes about 28.0% of all recorded case in English literatures. The clinical events include portal vein tumor thrombosis, angiography related angiospasm or arterial thrombosis, rapid growth of the tumor, massive gastrointestinal bleed, and so on. This hypothesis can easily be accepted just like using transhepatic arterial chemoembolization (TACE) or the anti-angiogenesis effect of sorafenib to treat HCC. Another possible mechanism is systemic inflammatory activation, which contributes more (about 33.3%) than tumor hypoxia in all recorded cases in English literature. We trust that some clinical events activate an inflammatory mechanism that leads to tumor regression, due to elevation of several cytokine and biomarkers (ex: IL-2, IL-6, IL-12, IL-18, interferon (IFN) – gamma, tumor necrosis factor (TNF) – alpha) were documented. Besides, tumor hypoxia mechanism cannot fully explain spontaneous regression of HCC with distance metastasis. Some pathological evidences of an active inflammation mechanism were described as the presence of overactivated macrophages (CD163+) or lymphocytic infiltration. The most appropriate etiology of spontaneous tumor regression still remains uncertain, but activated inflammation mechanism must play an important role. We described herein a case of HCC with spontaneous regression without any obvious clinical markers of tumor hypoxia or systemic inflammatory activation. Unfortunately, this case was not proven histologically due to the patient refusing any invasive treatment. The diagnosis of HCC was determined based on a single positive imaging technique showing hypervascularization and associated with more than 400 ng/ml of AFP level, according to the Barcelona Clinic Liver Cancer (BCLC) staging classification. This case demonstrates to us there are still some unknown mechanisms affecting tumor regression. Severe cirrhosis related tumor hypoxia might be a possible mechanism causing this particular case of tumor regression, but it can not be proven. The severity of cirrhosis seemed unrelated to the possibility of tumor with spontaneous regression after reviewing literature. The interesting phenomenon of tumor regression is undoubtedly a hint to help us to find the new treatment therapies for HCC. The collection and accumulation of those special cases is the first step towards advancing understanding of the phenomenon.