Evaluation of risk factors and clinicopathologic features for intrahepatic cholangiocarcinoma in Southern China: a possible role of hepatitis B virus.

BACKGROUND: Recent efforts suggest an etiologic role of hepatitis B virus (HBV) infection in intrahepatic cholangiocarcinoma (ICC) and the involvement of hepatic progenitor cell in ICC development, without definitive conclusions. This case-control study was undertaken to investigate risk factors for ICC, and clinicopathological features of HBV-associated ICC were analyzed. METHODS: The report comprised 98 patients with pathologically confirmed ICC and 196 healthy control subjects. Logistic regression was used to determine odds ratios and 95% confidence intervals. The sex and age distributions of HBV-related and unrelated ICC patients were compared respectively with those of 882 HBV-associated hepatocellular carcinoma patients from a random selection, and the clinicopathological data of 62 ICC patients with or without HBV infection undergoing surgical resection were compared. RESULTS: There was an association between ICC and each of HBV infection, liver cirrhosis, hepatolithiasis, and liver fluke infestation with the odds ratios (95% confidence intervals) of 2.75 (1.27-5.95), 8.42 (2.50-28.37), 22.81 (7.16-72.68), and 3.55 (1.60-7.89), respectively, with a marked synergism of cirrhosis and HBV infection (20.67; 5.40-79.06). Compared with HBV-unrelated ICC patients, HBV-related ICC patients were more common in male and younger subjects, had a higher incidence of abnormal serum alfa-fetoprotein level, cirrhosis, and neutrophilic infiltration, and had a lower proportion of elevated carbohydrate antigen 19-9 (CA19-9) values. CONCLUSIONS: The independent association of HBV infection with ICC, synergy between cirrhosis and HBV infection, and some clinicopathological similarities between HBV-related ICC and hepatocellular carcinoma suggests that both may share similar or common tumorigenic process and may possibly originate from malignant transformation of hepatic progenitor cell.

[Diagnosis and treatment of primary clear cell carcinoma of the liver].

OBJECTIVE: To investigate the clinicopathological features, diagnosis, treatment and prognosis of primary clear cell carcinoma of the liver (PCCCL). METHODS: The clinicopathological data of 24 cases with pathologically proven PCCCL in the First Affiliated Hospital of Guangxi Medical University from May 1996 to December 2003 were collected and analyzed. RESULTS: There were 21 males and 3 females in this group, with an average age of 46 years (range: 30 approximately 78 years). HBV infection was detected in 83.3%, and AFP expression was found in 75.0% of them. Of the 24 cases, 28 tumors were found with an average size of (6.64 +/- 5.54) cm. Liver cirrhosis was found in 75.0% of the patients. Macroscopic and microscopic tumor thrombi were found in 20.8% and 29.2%, respectively. Lymph node metastasis was found in 4.2% of the patents. The 1-, 3-, and 5-year overall survival rates of the 24 cases were 75.0%, 41.7% and 27.8%, respectively, with a median survival time of 29 months. CONCLUSION: The clinical characteristics of primary clear cell carcinoma of the liver are similar to that of common hepatocellular carcinoma. It is difficult to be diagnosed preoperatively and final diagnosis depends on pathological examination. Surgical resection is an effective way to achieve favorable treatment outcome and even long-term survival.

[Comparative proteomic approach in differentiating multicentric occurrence and intrahepatic metastasis in multinodular hepatocellular carcinomas].

BACKGROUND AND OBJECTIVE: Multinodular hepatocellular carcinoma(HCC) might originate from multicentric occurrence (MO) or intrahepatic metastasis(IM). This study was to find out proteins which play important roles in clonal origin of multinodular hepatocellular carcinoma bt screening the differentially expressed proteins between the MO and IM tissues using comparative proteomic analysis. METHODS: Total protein extracted was separated by two-dimensional gel electrophoresis. Comparative analyses of the 2-DE protein patterns between the two groups were carried out using computerized imaging techniques. Proteins exhibiting significant alternations were subsequently isolated and identified by mass spectrometry. RESULTS: A total 1025+/-52 and 900+/-98 spots were detected in the protein profile in IM and MO, respectively. Twenty-five protein spots were statistically different at expression levels between the two groups. Twenty of them were identified by MALDI-TOF-MS and bioinformatics. CONCLUSIONS: The protein profile of MO HCC tissues is different from that in IM HCC tissues. The twenty differentially expressed proteins might play a key role in the carcinogenesis and progression of multinodular HCC. These newly identified proteins might be potential and valuable biomarkers for identifying the multinodular HCC of clonal origin.

[Application of polymerase chain reaction with confronting two-pair primers in aldehyde dehydrogenase-2 typing].

OBJECTIVE: To study the distribution of aldehyde dehydrogenase-2 (ALDH2) polymorphisms between healthy Zhuang and Han ethnic individuals in Guangxi Autonomous Region and its influence to the behaviors of alcohol consumption. METHODS: Polymerase chain reaction with confronting two-pair primers (PCR-CTPP) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques were used to genotype ALDH2, respectively, and alcohol consumption was recorded in a constructed questionnaire. RESULTS: The frequencies of ALDH2 alleles (ALDH2(1)/ALDH2(2)) among Zhuang and Han ethnics were 0.511, 0.489 and 0.508, 0.492 respectively (chi2 = 0.001, P > 0.05). The ALDH2 genotypes were verified with PCR-RFLP method. The frequencies of ALDH2(1) genotype in alcoholics (> or = 3 times drinking per week) were 35.59% and 15.67% in Zhuang and Han groups respectively (chi2 = 5.800, P = 0.016). CONCLUSION: There was no significant different distribution of ALDH2 genotype among healthy Zhuang and Han ethnic people. The genotype of ALDH2 in different ethnicity might influence individual behavior of alcohol consumption.

Changed clinical aspects of primary liver cancer in China during the past 30 years.

BACKGROUND: Primary liver cancer (PLC) is one of the most frequently seen tumors in China. Thirty years ago, patients with PLC were often detected at relatively late stage, with a palpable mass or marked clinical symptoms and poor prognosis. In the past 30 years, the diagnosis and treatment of PLC have been greatly improved with better prognosis. METHODS: In order to study the changes of PLC during the 30 years, the clinical data of 3250 patients with PLC from 10 medical institutions of China were collected, analyzed, and compared with those of 3254 PLC patients before the 30 years. RESULTS: In the 3250 patients aged 1-80 years, with an average age of 49.1 years, the male to female ratio (2.3:1) was lower than that before the 30 years. 73.5% of the 3250 patients sought medical advice within 3 months after the onset of the disease in contrast to 63.8% before the 30 years. Compared with those patients before the 30 years the symptoms and signs were alleviated generally. The HBsAg positive rate was 81.0%, but the HCV-Ab positive rate was 13.2%. The AFP level in 75% of patients was elevated, but in the remaining 25% was normal. 1912 patients (58.8%) were confirmed pathologically. Among them 1755 patients (91.8%) had hepatocellular carcinoma. The overall resection rate was 46.3%. Those who had early, middle, late stage carcinoma accounted for 29.9%, 51.5%, and 18.6% respectively in contrast to 0.4%, 47.0%, and 52.6% reported before the 30 years. The 1-, 3-, 5-year survival rates of the patients were 66.1%, 39.7%, and 32.5% respectively, whereas 93.5%, 70.1%, and 59.1% for the early stage patients, and 65.3%, 30.5%, and 23.5% for the middle stage patients. The half and 1-year survival rates of the late stage patients were 52.5%, and 14.7%, respectively. CONCLUSION: Comparison with the clinical data before and after the 30 years show that PLC can be diagnosed early. More PLC patients tend to undergo resection while receiving a better conservative treatment, which ensures a prognosis.

[Changes of clinical aspect of primary liver cancer in China during the past 30 years--control study for 3,250 cases with primary liver cancer].

OBJECTIVE: To study the changes of the clinical aspects of primary liver cancer (PLC) during the past 30 years. METHODS: The clinical data of 3,250 patients with PLC, from 10 regions of China were collected, analyzed, and compared with the clinical data of 3254 PLC cases 30 years before. RESULTS: The 3,250 patients were aged 1- 80, with an average age of 49.1 years, younger than those 30 years before (43.7 years). The male to female ratio was 2.3:1, lower than that 30 years before (7.7:1). 73.5% of them sought medical advice within 3 months after the onset in comparison of 63.8% 30 years before. Compared with those 30 years before the symptoms and signs were alleviated in general. The HBsAg positive rate was 81.0%, the HCV-Ag positive rate was 13.2%, and the alpha-fetoprotein positive rate was 75%. 1912 cases underwent pathological examination of which 91.8% were diagnosed as with hepatocellular carcinoma. The overall resection rate was 46,3%. Those of early, median, and late stages accounted for 29.9%, 51.5%, and 18.6% respectively in comparison with the rates of 0.4%, 47.0%, and 52.6% 30 years before. The one-year survival rate, three-year survival rate, and five-year survival rate were 66.1%, 39.7%, and 32.5% respectively for the whole group, 93.5%, 70.1%, and 59.1% for the early stage patients, and 65.3%, 30.5%, and 23.5% respectively for the median stage patients. The half-year survival rate and one-year survival rate of the late stage patients were 52.5% and 14.7% respectively. Compared with the data 30 years before a lower percentages of the patients died of hepatic coma, hemorrhage of upper digestive tract and hemorrhage due to rupture of tumor, and a higher percentage of then died of asthenia universalis and other causes. CONCLUSION: In comparison with the situation 30 years ago, PLC can be diagnosed earlier. More patients undergo resection. The prognosis of PLC has been improved greatly.

Clinicopathologic characteristics and prognoses for multicentric occurrence and intrahepatic metastasis in synchronous multinodular hepatocellular carcinoma patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the outcomes for patients are still poor. It is important to determine the original type of synchronous multinodular HCC for preoperative assessment and the choice of treatment therapy as well as for the prediction of prognosis after treatment. AIMS: To analyze clinicopathologic characteristics and prognoses in patients with multicentric occurrence (MO) and intrahepatic metastasis (IM) of synchronous multinodular hepatocellular carcinoma (HCC). METHODS: The study group comprised 42 multinodular HCC patients with a total of 112 nodules. The control group comprised 20 HCC patients with 16 single nodular HCC cases and 4 HCC cases with a portal vein tumor emboli. The mitochondrial DNA (mtDNA) D-loop region was sequenced, and the patients of the study group were categorized as MO or IM based on the sequence variations. Univariate and multivariate analyses were used to determine the important clinicopathologic characteristics in the two groups. RESULTS: In the study group, 20 cases were categorized as MO, and 22 as IM, whereas all 20 cases in the control group were characterized as IM. Several factors significantly differed between the IM and MO patients, including hepatitis B e antigen (HBeAg), cumulative tumor size, tumor nodule location, cirrhosis, portal vein and/or microvascular tumor embolus and the histological grade of the primary nodule. Multivariate analysis further demonstrated that cirrhosis and portal vein and/or microvascular tumor thrombus were independent factors differentiating between IM and MO patients. The tumor-free survival time of the MO subjects was significantly longer than that of the IM subjects (25.7 ∓ 4.8 months vs. 8.9 ∓ 3.1 months, p=0.017). Similarly, the overall survival time of the MO subjects was longer (31.6 ∓ 5.3 months vs. 15.4 ∓ 3.4 months, p=0.024). The multivariate analysis further demonstrated that the original type (p=0.035) and Child-Pugh grade (p<0.001) were independent predictors of tumor-free survival time. Cirrhosis (p=0.011), original type (p=0.034) and Child-Pugh grade (p<0.001) were independent predictors of overall survival time. CONCLUSIONS: HBeAg, cumulative tumor size, tumor nodule location, cirrhosis, portal vein and/or microvascular tumor embolus and histological grade of the primary nodule are important factors for differentiating IM and MO. MO HCC patients might have a favorable outcome compared with IM patients.