Elevated Serum Alpha-fetoprotein Research Articles

Molecular Defects in Moroccan Patients with Ataxia-Telangiectasia

Ataxia-telangiectasia (AT) is a rare autosomal recessive disease, affecting neurologic and immune system. Numerous mutations are described in the ATM gene in several populations. However, in Morocco, few data are available concerning this condition. Our main goal is to determine clinical, immunological, and molecular presentation of Moroccan patients with AT. We screened 27 patients, out of 22 unrelated families, for ATM gene mutations. All our patients showed ataxia, ocular telangiectasia, and immunodeficiency, as well as elevated serum alphafetoprotein levels. Mean age at diagnosis was 5.51years, and consanguinity rate was 81.8%. Mean age at onset was 2.02years, and mean time to diagnosis was 3.68years. We found 14 different mutations in 19 unrelated families, of which 7 were not reported. Our results showed that c.5644C>T mutation was the most common in our series. However, further studies are required to demonstrate a founder effects on ATM gene in Moroccan patients, who showed mutational heterogeneity otherwise. Our data indicate that direct sequencing of coding exons is sufficient for a high detection rate in ATM in Moroccan population.

Management strategy in pregnancies with elevated second-trimester maternal serum alpha-fetoprotein based on a second assay

To assess maternal-fetal outcomes in pregnancies associated with persistently elevated second-trimester maternal serum alpha-fetoprotein. A retrospective cohort study in 658 patients with maternal serum alpha-fetoprotein ≥2.5 multiple of median, performed at routine Down syndrome screening. Maternal serum alpha-fetoprotein was assayed a second time in 341 of them. Outcomes were recorded in all cases. The group with unexplained maternal serum alpha-fetoprotein persistently ≥2.5 multiple of median was associated with more pregnancy complications 37 of 92 (40.2%) as fetal death, preeclampsia, intrauterine growth restriction, and congenital nephrotic syndrome, compared with the group with maternal serum alpha-fetoprotein that returned to a normal level 37 of 226 (16.4%) (P < .001). When maternal serum alpha-fetoprotein returns to a normal level on a second assay, the risk of adverse outcome significantly decreases, but these pregnancies are still at risk of complications and therefore need close surveillance. Repeat maternal serum alpha-fetoprotein assay allows identification of patients who should be offered amniocentesis to evaluate the risk of nephrotic syndrome and epidermolysis bullosa. Alpha-fetoprotein should be monitored in pregnancies associated with unexplained high maternal serum alpha-fetoprotein. A management strategy based on ultrasound examination, second maternal serum alpha-fetoprotein assay and amniocentesis is proposed to improve prenatal counseling and management of such pregnancies. However, a prospective study remains necessary to evaluate it.

Clinicopathological Characteristics and Prognosis of Alpha-fetoprotein Producing Gastric Cancer

Several studies reported a subgroup of gastric cancer patients showing elevated serum alpha-fetoprotein (AFP) at the time of diagnosis. We investigated the clinicopathological characteristics and prognostic factors of AFP producing gastric cancer (AFPPGC) by comparing with AFP non-producing gastric cancer (AFPNPGC). A total of 909 patients were diagnosed with gastric cancer from January 2005 to March 2013 at Gyeongsang National University Hospital and their AFP levels were measured at the time of diagnosis. After excluding 138 patients with underlying liver diseases, 34 patients with elevated serum AFP level over 10 mg/mL were assigned to AFPPGC group and the remaining 737 patients with serum level of AFP below 10 ng/mL were assigned to AFPNPGC group. The median survival length was shorter in AFPPGC group than AFPNPGC group (18.3 ± 25.5 months vs. 30.0 ± 22.0 months, p=0.004). The incidence of liver metastasis (47.1% vs. 3.3%, p<0.001) and lymph node metastasis (91.2% vs. 31.6%, p<0.001) was significantly higher in AFPPGC group. The probability of encountering metachronous liver metastasis after the operation was higher in AFPPGC group (44.4% vs. 2.0%, p<0.001). Multivariate analysis revealed that patients in the AFPPGC group who received chemotherapy (p=0.037) or underwent operation (p=0.001) had a better survival rate. AFPPGC behaves more aggressively and shows a worse prognosis. Therefore, serum AFP level should be routinely checked in all patients diagnosed with gastric cancer.

Gastroschisis and Omphalocele: A Case report

Fetal gastroschisis and omphalocele are congenital defects of abdominal wall that are often diagnosed by prenatal ultrasound done for routine screening or for obstetric indications such as evaluating an elevated maternal serum alpha fetoprotein (AFP). Prenatal ultrasound could potentially identify the overwhelming majority of abdominal wall defects and accurately distinguish omphalocele from gastroschisis. Here we report two cases of gastroschisis and omphalocele diagnosed at routine prenatal ultrasound. NJR I VOL 2 I ISSUE 1 42-45 Jan-June, 2012 DOI: http://dx.doi.org/10.3126/njr.v2i1.6980

High expression of AP-4 predicts poor prognosis for hepatocellular carcinoma after curative hepatectomy

The aim of this study was to evaluate the association between activating enhancer binding protein 4 (AP-4) tissue expression and patient prognosis in hepatocellular carcinoma (HCC). The levels of AP-4 mRNA and protein in tumor and para-tumor tissue were evaluated in 30 HCC cases by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Additionally, AP-4 protein expression in 112 HCC was analyzed by immunohistochemistry. The correlation of AP-4 expression and patients' clinicopathological parameters was evaluated. Survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. By RT-PCR and Western blot, the levels of AP-4 mRNA and protein were significantly higher in HCC, compared to that in para-tumor tissue (p < 0.001). Immunohistochemical staining revealed that AP-4 was highly expressed in 53.6% of the HCC patients. The AP-4 expression level was closely associated with serum alpha fetoprotein elevation, tumor size, histological differentiation, tumor recurrence, tumor metastasis, and tumor stage. Kaplan-Meier survival analysis showed that a high expression level of AP-4 resulted in a significantly poor prognosis of HCC patients. Multivariate analysis revealed that AP-4 expression level was an independent prognostic parameter for the overall survival rate of HCC patients. These findings provide evidence that a high expression level of AP-4 serves as a biomarker for poor prognosis for HCC. Thus, we speculate that AP-4 may be a potential target of antiangiogenic therapy for HCC.

Expression of HBx protein in hepatitis B virus-infected intrahepatic cholangiocarcinoma

Hepatitis B virus (HBV) is an etiological factor of intrahepatic cholangiocarcinoma (ICC), but the pathogenic mechanisms remain unclear. This study aimed to investigate the expression and possible role of HBx, an HBV-encoded potentially oncogenic protein, in HBV-infected ICC. Tissue samples were obtained from 54 specimens of HBV-infected ICC. Forty-four specimens were of peripheral type and 10 hilar type. Formalin-fixed, paraffin-embedded sections of the specimens were immunohistochemically stained for HBx and p53. HBx expression was found in 70.4% (38/54) of the specimens, and it was more frequently seen in the peripheral type than in the hilar type (79.5% vs 30.0%, P=0.002). All three well-differentiated ICCs expressed HBx, whereas 76.9% (30/39) moderately-differentiated and 41.7% (5/12) poorly-differentiated ICCs had HBx expression (P=0.033). Patients with HBx expression had a significantly higher prevalence of elevated serum alpha-fetoprotein (P=0.033). p53 protein expression was found in 18 of 54 cases (33.3%), and was not correlated with that of HBx. HBx may contribute to the pathogenesis of ICC, particularly the peripheral type. p53 abnormality may not play a significant role in HBx-mediated oncogenicity during ICC carcinogenesis.

The CT findings of pancreatic acinar cell carcinoma in five cases

ObjectivesThe aim of this study is to analyze the computed tomographic (CT) findings of pancreatic acinar cell carcinoma (ACC). Materials and methodsThe CT features and clinical presentations of five patients (four men, one woman; mean age, 52 years) with pathology-proven pancreatic ACC were reviewed. The image characteristics included the lesion location and size, the exophytic nature of the tumor, intratumoral hemorrhage, calcification, the presence of cystic or necrotic components, bile or pancreatic duct dilation, attenuation on the noncontrast image, attenuation on the arterial- and venous-phase images, peripancreatic invasion, peripancreatic lymphadenopathy, and distant metastases. ResultsThe tumors were located at the pancreatic tail in three cases and at the pancreatic head in two cases. The average lesion size was 5.3 cm. Exophytic features and cystic/necrotic components were found in 80% (4/5) and 60% (3/5) of cases, respectively. The ACC showed a mild hypodense appearance on noncontrast CT in 100% (3/3) of cases and a hypodense appearance on arterial-/venous-phase CT in 80% (4/5) of cases. The exception was one lesion that showed a significantly hyperdense appearance and a mildly hyperdense appearance on the arterial- and venous-phase images. None of the CT images showed enhancement of a capsule, calcification, intratumoral hemorrhage, bile or pancreatic duct dilation, vascular encasement, or distant metastatic disease, but three cases showed peripancreatic invasion and lymphadenopathy. ConclusionsWith persistent mild enhancement, the typical ACC appears as an exophytic tumor with a focal cystic/necrotic component and the lack of ductal dilatation. The predilection for older male patients and elevated serum alpha fetoprotein are useful clinical features for confirming an ACC diagnosis.

Clinicopathological Characteristics of Hepatocellular Carcinoma in Turkey

Hepatocellular carcinoma (HCC), the main malignant tumor of the liver, is very common and highly lethal. The aim of this study was to determine its clinicopathologic characteristics and risk factors in Turkey. In this study, patients who were diagnosed as suffering from HCC in the period between August 2004 and December 2011 were evaluated retrospectively. A total of 98 patients were included, with a median age 61 (range: 16 to 82). Seventy nine (80.6%) were male 59 (60.2%) were infected with hepatitis B virus (HBV) and 15 (15.3%) with HCV, another 15 (15.3%) being alcohol abusers. Seventy two (73.5%) were at advanced stage and 54 (55.1%) had elevated serum alpha-fetoprotein (AFP). Surgery, chemoembolization, systemic chemotherapy and application of the tyrosine kinase inhibitor sorafenib were the major treatment options. According to our findings HCC is mostly diagnosed in advanced stage and age, being five times more common in males than females. Main risk factors of HCC are HBV infection, HCV infection and alcohol abuse. Elevation in AFP may facilitate early diagnosis of HCC in high risk groups.

Up‐regulated aldo‐keto reductase family 1 member B10 in chronic hepatitis C: association with serum alpha‐fetoprotein and hepatocellular carcinoma

BackgroundElevated serum alpha-fetoprotein (AFP) is not only a diagnostic marker for hepatocellular carcinoma (HCC), but is also a risk factor for HCC in chronic hepatitis C patients who do not have HCC.AimThe aim was to analyse the hepatic gene expression signature in chronic hepatitis C patients with elevated AFP, who were at high risk for HCC.MethodsLiver tissue samples from 48 chronic hepatitis C patients were stratified by their serum AFP levels and analysed for gene expression profiles. The association between aldo-keto reductase family 1 member B10 (AKR1B10) expression and serum AFP was confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemical analyses. A matched case-control study was performed to evaluate the risk of AKR1B10 expression for HCC development.ResultsDistinct hepatic gene expression patterns were demonstrated in patients with elevated AFP (≥10 ng/mL) and normal AFP (<10 ng/mL). Of the 627 differently expressed genes, the most abundantly expressed gene in patients with elevated AFP was AKR1B10 (fold change, 26.2; P < 0.001), which was originally isolated as an overexpressed gene in human HCC. The qRT-PCR and immunohistochemical studies confirmed a proportional correlation between AKR1B10 expression and serum AFP. A matched case-control study identified that AKR1B10 up-regulation (>6%) was an independent risk factor for HCC development (hazard ratio, 21.4; P = 0.001).ConclusionAKR1B10 was up-regulated in association with serum AFP, and was an independent risk factor for HCC in chronic hepatitis C patients, suggesting its possible involvement at a very early stage of hepatocarcinogenesis.

Intrahepatic recurrence of hepatocellular carcinoma 13 years after orthotopic liver transplantation for hepatitis C-related cirrhosis with occult hepatocellular carcinoma: A case report

Intrahepatic recurrence of hepatocellular carcinoma 13 years after orthotopic liver transplantation for hepatitis C-related cirrhosis with occult hepatocellular carcinoma: A case report

Abstract 2381: ApoStreamtm, an antibody independent platform, captures circulating tumor cells in patients with hepatocellular carcinoma

Abstract Biopsies of HCC can be technically difficult, given the vascular nature of the liver and underlying liver disease. Many HCC patients do not get biopsies, and molecular characterization of these tumors is not possible. Capture of CTCs from blood allows for analysis of cancer cells in metastatic dissemination. The use of EpCAM-based enrichment platforms limits the type of tumor cells that can be recovered, as it selects only for cells which express the antigen of interest. Nonselective methods of CTC analysis are needed. An ongoing study is evaluating the recovery of CTCs in HCC patients with elevated serum alpha-fetoprotein (AFP) using the novel antibody-independent ApoStream™ platform, which utilizes the principle of dielectrophoretic field-flow fractionation to position cells in a hydrodynamic flow profile for sorting. Paired blood samples from HCC patients were analyzed by CellSearch and ApoStream™. Collected cells were immunophenotyped using antibodies against Cytokeratin (CK), CD45, DAPI, and AFP, and analyzed by quantitative laser scanning cytometry. In comparison with the CellSearch platform, ApoStream™ isolated higher number of CK+/CD45-/DAPI+ CTCs in HCC cancer patients. A majority of the CK+/CD45-/DAPI+ CTCs enriched by the ApoStream™ platform (62-98%) were AFP+. ApoStreamTM also isolated AFP+, putative CTCs with the CK-/CD45-/DAPI+ phenotype (9-85 cells), and cells with CK+/CD45+/DAPI+ phenotype (1-978 cells). Conclusion: The ApoStreamTM CTC enrichment platform successfully isolated a greater number of CTCs from HCC patients. ApoStream™ CTC analysis is also being used for pharmacodynamic analysis in an ongoing phase I study of the combination of sorafenib and vorinostat in patients with advanced HCC. In preclinical models, the combination synergistically induces tumor cell death through activation of CD95. In this study, CTC analysis will compare the expression of CD95 and other markers prior to and after drug combination exposure. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2381. doi:1538-7445.AM2012-2381

Adult hepatoblastoma: Learning from children

Hepatoblastoma is the most common malignant liver tumour in infants and young children. Its occurrence in the adult population is debated and has been questioned. The aim of this paper is to review the histological and clinical features of adult hepatoblastoma as described in the adult literature, and to compare the findings with those of paediatric hepatoblastoma. The developmental and molecular aspects of hepatoblastoma are reviewed and their potential contribution to diagnosis of adult hepatoblastoma discussed. Case reports of adult hepatoblastoma identified by a PubMed search of the English, French, German, Italian, and Spanish literature through March 2011 were reviewed. Forty-five cases of hepatoblastoma were collected. Age at presentation was variable. Survival was uniformly poor, except for the rare patients who presented with the relatively differentiated, foetal type. The common denominator between adult and paediatric cases is the occurrence of embryonal or immature aspect of the tumours. Whether the adult cases of hepatoblastoma represent blastemal tumours, stem cell tumours, or unusual differentiation patterns in otherwise more frequent adult liver tumours remains to be established. Adult tumours labelled as hepatoblastoma are characterised by malignant appearing mesenchymal components. Surgical management is the cornerstone of therapy in children and also appears to confer an improved prognosis in adults. Whether adult hepatoblastoma exists, remains controversial. Indeed, several features described in adult cases are markedly different from hepatoblastoma as it is understood in children, and other differential diagnoses should also be entertained. Nonetheless, hepatoblastoma should be considered in adults presenting with primary liver tumours in the absence of pre-existing liver disease. Adult and paediatric patients with immature hepatoblastoma appear to have worse outcomes, and adults presenting with presumed hepatoblastoma have an overall poorer prognosis than children with hepatoblastoma. In all patients, surgery should be the treatment of choice, neoadjuvant chemotherapy is advisable.

New approach for the investigation of liver diseases

We hypothesised that liver-derived mRNA, such as albumin (ALB) mRNA, would be released into human plasma as a result of liver cell death. We genotyped the ALB mRNA molecules in plasma and whole blood of liver or bone marrow transplantation recipients by RNA-single nucleotide polymorphism analysis. The plasma and whole blood ALB mRNA genotypes were compared with the DNA genotypes in the recipients and donors. Our data revealed that ALB mRNA in plasma was liver-derived, while tissue compartments other than the liver also contributed to the ALB mRNA detected in whole blood. We then used a reverse transcription quantitative real-time PCR assay to show that the plasma ALB mRNA concentrations were elevated in patients with hepatocellular carcinoma, cirrhosis or chronic hepatitis B than healthy controls. Only 21.5% of patients with liver pathologies had elevated alanine transaminase (ALT) when 73.8% of them had elevated plasma ALB mRNA concentrations. Only 49% of the hepatocellular carcinoma patients had elevated serum alpha-fetoprotein, while 91.4% had elevated plasma ALB mRNA concentrations. Liver-derived plasma mRNA may become a new class of biomarkers for the sensitive detection of liver diseases. Acknowledgement Supported by the Hong Kong Research Grants Council Earmarked Research Grant (CUHK463207).

Cognitive Functions in Ataxia with Oculomotor Apraxia Type 2

Background: Ataxia with oculomotor apraxia type 2 (AOA2) is characterized by cerebellar atrophy, peripheral neuropathy, oculomotor apraxia, and elevated serum alpha-fetoprotein (AFP) levels. The disease is caused by a recessive mutation in the senataxin gene. Since it is a very rare cerebellar disorder, no detailed examination of cognitive functions in AOA2 has been published to date. The aim of the present study was to investigate the neuropsychological profile of a 54-year-old patient with AOA2. Methods: A broad range of neuropsychological examination protocol was administered including the following domains: short-term, working- and episodic-memories, executive functions, implicit sequence learning, and the temporal parameters of speech. Results: The performance on the Listening Span, Letter Fluency, Serial Reaction Time Task, and pause ratio in speech was 2 or more standard deviations (SD) lower compared to controls, and 1 SD lower on Backward Digit Span, Semantic Fluency, articulation rate, and speech tempo. Conclusion: These findings indicate that the pathogenesis of the cerebrocerebellar circuit in AOA2 is responsible for the weaker coordination of complex cognitive functions such as working memory, executive functions, speech, and sequence learning.

Clinicopathological analysis of 14 patients with combined hepatocellular carcinoma and cholangiocarcinoma

Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an uncommon subtype of primary hepatic carcinoma, and its prognosis is poor. This study was undertaken to investigate the prognosis and the clinicopathological characteristics of cHCC-CC, including their possible cellular origin. Among 852 patients with a primary hepatic carcinoma who underwent hepatectomy from January 1998 to April 2008 at our hospital, cHCC-CC was identified in 14 patients. The clinicopathological characteristics of the 14 patients were analyzed retrospectively. The expression of the liver stem cell markers (c-kit, CD90, CD133 and CK19) in the tumor tissue was detected by immunohistochemistry, and the Kaplan-Meier method was used to evaluate survival. Among the 14 patients, 9 presented with abdominal pain, 3 with anorexia and debilitation, and the remaining two patients were asymptomatic. The mean age was 53.6+/-3.0 (range 38-74) years. Among the included patients, 11 had an elevated serum alpha-fetoprotein level, 13 were infected with hepatitis B virus, 9 had vascular invasion and 1 had lymph node metastasis. The average diameter of the tumors was 9.9+/-1.1 (range 5.0-16.0) cm. The median overall survival time was 7.9+/-1.0 months. In addition, the presence of the liver stem cell markers, c-kit, CD90, CD133 and CK19 was 71.4%, 85.7%, 92.9% and 78.6%, respectively. All four markers were simultaneously expressed in eight cases. cHCC-CC has aggressive characteristics and the prognosis is extremely dismal. The high expression of liver stem cell markers in the tumor tissue suggests that these tumors may derive from liver stem cells.

Alpha-foetoprotein producing endometrial serous carcinoma

Elevated serum levels of alpha-fetoprotein, a fetal serum protein, occurs on development of hepatoma or germ cell tumors, mainly yolk sac tumor. Very few cases of endometrial carcinoma associated with elevated serum alpha-fetoprotein have been reported. It is important to be aware of such entities to ensure correct diagnosis and hence patient management. We report a case of a 71 years old lady presenting with postmenopausal bleeding and elevated serum alpha-fetoprotein. Investigations confirmed the patient had an alpha-fetoprotein producing endometrial serous carcinoma. This is the third case of alpha-foetoprotein producing serous carcinoma. We discuss the clinicopathological features of the case and review the literature for previously reported alpha-fetoprotein producing endometrial carcinomas. These cases show aggressive behavior and very poor prognosis.

Retroperitoneal Histologic Findings of Patients With Elevated Serum Alpha-fetoprotein and Pure Seminoma at Orchiectomy

To report the retroperitoneal histologic findings from a contemporary series of patients with pure seminoma at orchiectomy with an elevated serum α-fetoprotein (AFP) level. These patients underwent treatment on the assumption that the lesion was nonseminomatous germ cell tumor (NSGCT). We identified 22 patients from 1989 to 2009 with pure seminoma diagnosed at orchiectomy with an elevated serum AFP level (>15 ng/mL) either before or after orchiectomy. The retroperitoneal histologic and relapse data are reported. The median preorchiectomy and prechemotherapy serum AFP level was 248 ng/mL (interquartile range 48-4693) and 279 ng/mL (interquartile range 66-5311), respectively. The percentage of patients with clinical Stage I, II, and III disease was 5%, 50%, and 45%, respectively. The percentage of patients with a good, intermediate, and poor risk status according to the International Germ Cell Cancer Collaborative Group was 32%, 32%, and 36%, respectively. Of the 22 patients, 21 underwent induction chemotherapy followed by retroperitoneal lymph node dissection. Overall, 67% of patients had NSGCT elements in the retroperitoneum. The histologic findings were pure teratoma in 38%, malignant transformation in 14%, and viable NSGCT in 14%. Also, 59% had some component of teratoma in the retroperitoneum. Only 1 patient (5%) had any seminoma in the retroperitoneum, but this patient also had retroperitoneal teratoma. Of the 22 patients, 7 developed a relapse and received salvage chemotherapy. The actuarial relapse-free survival rate at 5 and 10 years was 76% and 61%, respectively, reflecting the high percentage of patients with Stage II-III disease. Pure seminoma at orchiectomy with an elevated serum AFP level portends a high likelihood of NSGCT elements in the retroperitoneum.

Surveillance for Hepatocellular Carcinoma in Patients With Cirrhosis

Clinical Scenario A man was referred to liver transplantation clinic for the evaluation of enlarging abdominal girth and welling of feet during the preceding 2 months. The patient was Cambodian native who immigrated to the United States 5 ears ago. The patient was first diagnosed with chronic hepatitis virus (HBV) infection shortly after his entry into the United tates. However, he was not further evaluated, treated, or folowed. He had no personal or family history of liver disease or iver cancer. Physical examination of the abdomen showed mild epatosplenomegaly with positive shifting dullness from a oderate amount of ascites. There was no abdominal tenderess. Laboratory results included platelet count, 95,000/ L; spartate aminotransferase, 100 U/L; alanine aminotransferase, 5 U/L; and Model for End-Stage Liver Disease score, 13. Viral erology showed hepatitis B surface antigen–positive and entigen–positive and HBV DNA of 5 million IU/mL. Serum lpha-fetoprotein (AFP) was normal at 4 ng/mL. An abdominal ltrasound (US) showed cirrhotic liver contour and evidence of ortal hypertension. An esophagogastroduodenoscopy showed arge esophageal varices. The patient was started on the followng medications: spironolactone and furosemide for the ascites, ropranolol for the varices, and entecavir for HBV. Patient was urther assessed and then listed for liver transplantation. During the ensuing 12 months, the patient had substantial linical improvement including resolution of ascites as well as epatitis B e seroconversion. He also underwent abdominal US nd serum AFP measurement on a 6-month interval. An abominal US performed 18 months after his presentation howed a new 2.1-cm hyperechoic nodule in the right lobe of he liver along with mild elevation of serum AFP at 22 ng/mL. subsequent triphasic abdominal computed tomography (CT) can showed a 2.2-cm well-circumscribed vascular mass that ad arterial enhancement and venous washout, thus meeting he radiographic diagnosis criteria for hepatocellular carcinoma HCC) of the American Association for the Study of Liver isease (AASLD). The patient underwent transarterial chemombolization and subsequently received a liver transplant. Four ears later, the patient is doing well with satisfactory liver unction with no evidence of recurrent HBV or HCC.

Spontaneous regression of a large hepatocellular carcinoma: case report.

The prognosis of untreated advanced hepatocellular carcinoma (HCC) is grim with a median survival of less than 6 months. Spontaneous regression of HCC has been defined as the disappearance of the hepatic lesions in the absence of any specific therapy. The spontaneous regression of a very large HCC is very rare and limited data is available in the English literature. We describe spontaneous regression of hepatocellular carcinoma in a 65-year-old male who presented to our clinic with vague abdominal pain and weight loss of two months duration. He was found to have multiple hepatic lesions with elevation of serum alpha-fetoprotein (AFP) level to 6,500 µg/L (normal <20 µg/L). Computed tomography revealed advanced HCC replacing almost 80% of the right hepatic lobe. Without any intervention the patient showed gradual improvement over a period of few months. Follow-up CT scan revealed disappearance of hepatic lesions with progressive decline of AFP levels to normal. Various mechanisms have been postulated to explain this rare phenomenon, but the exact mechanism remains a mystery.

Elevated serum alpha fetoprotein levels promote pathological progression of hepatocellular carcinoma

To investigate the biological role of alpha fetoprotein (AFP) and its clinical significance in carcinogenesis of hepatocellular carcinoma (HCC). Clinical analysis of HCC patients and immunohistochemical examination were conducted to evaluate the relationship between serum AFP level and patient mortality. Confocal microscopy, Western blotting, dimethylthiahzolyl-2,5-diphenyl-tetrazolium bromide, Cell Counting Kit-8 assays and flow cytometry were performed to explore the possible mechanism. Among the 160 HCC patients enrolled in this study, 130 patients survived 2 years (81.25%), with a survival rate of 86.8% in AFP < 2 0 μg/L group, 88.9% in AFP 20-250 μg/L group, and 69.6% in AFP > 250 μg/L group, demonstrating a higher mortality rate in HCC patients with higher AFP levels. Surgical treatment was beneficial only in patients with low AFP levels. The mortality rate of HCC patients with high AFP levels who were treated surgically was apparently higher than those treated with conservative management. The results of immunohistochemistry showed that AFP and AFP receptor were merely expressed in tissues of HCC patients with positive serum AFP. Consistently, in vitro analysis showed that AFP and AFPS were expressed in HepG2 but not in HLE cells. AFP showed a capability to promote cell growth, and this was more apparent in HepG2 cells, in which the proliferation was increased by 3.5 folds. Cell cycle analysis showed that the percentage of HepG2 cells in S phase after exposure to AFP was modestly increased. HCC patients with higher AFP levels show a higher mortality rate, which appears to be attributable to the growth promoting properties of AFP.