Anti-tumor activity and mechanism of oligoclonal hepatocellular carcinoma tumor-infiltrating lymphocytes in vivo and in vitro.

Objective: To explore a method for culturing hepatocellular carcinoma and tumor-infiltrating lymphocytes (HCC-TIL) and investigate the mechanism of TIL in killing tumors. Methods: The distribution of regulatory T cells (Treg) in HCC was detected by immunohistochemistry. Conventional TIL and oligoclonal TIL were isolated by the traditional method of enzyme digestion combined with mechanical treatment for whole HCC and micro HCC tissue block culturing method. MTT was used to compare the killing activity of TIL. Flow cytometry was used to analyze the proportion of CD8+ T cells and Treg cells in TIL. Tumor-bearing mice were established, and TIL adoptive immunotherapy was performed. Results: Treg cells were mainly distributed in the stroma of HCC. In vitro experiments showed oligoclonal TIL had higher cytotoxicity to tumor cells which negatively correlated with the proportion of Treg cells. In vivo experiments showed oligoclonal TIL had a higher anti-tumor effect. IFN-γ in peripheral blood and the positive rate of intratumoral lymphocytic infiltration in oligoclonal TIL group were both higher. TGF-ß and IL-10 in peripheral blood and the positive rate of intratumoral FoxP3 and IL-17 were both lower than those in conventional TIL group. Conclusion: The oligoclonal TIL culture method could obtain TIL with higher purity, and cytotoxicity to tumor cells was associated with Treg cells. The oligoclonal TIL had cytotoxicity to autologous HCC cells and significant inhibitory effect on the growth of transplanted tumors. The mechanism might be associated with the inhibition of Treg cells proliferation, increase of IFN-γ secretion, and decrease of TGF-ß, IL-10, and IL-17 secretion.

Survival Mechanisms and Influence Factors of Circulating Tumor Cells.

Circulating tumor cells (CTCs) are cancer cells shed from either the primary tumor or its metastases that circulate in the peripheral blood. The CTCs are regarded as the source of tumor recurrence and metastasis and speculated as the indicators of residual tumors, thereby indicating a poor prognosis. Although CTCs play a vital role in tumor metastasis and recurrence, little is known about the underlying survival mechanisms in the blood circulation. The accumulating evidence has revealed that CTCs might survive in the peripheral blood by overcoming the mechanical damage due to shear stress, resistance to anoikis, evasion of immune destruction, and resistance to chemotherapy. The present review addresses the putative survival mechanisms underlying the formation and migration of CTCs according to their biological characteristics and blood microenvironment. In addition, the relationship between CTCs and microenvironment is illustrated, and the influencing factors related to the interactions of CTCs with various components in the peripheral blood are reviewed with respect to the platelets, immune cells, cytokines, and circulating tumor microemboli (CTM). Furthermore, the recent advances in the new treatment strategies targeting the survival mechanisms of CTCs are also discussed.

Randomized Controlled Trial of Hepatic Portal Reocclusion as a New Option for Detecting Bile Leakage during Hepatic Resection.

BACKGROUND/AIMS: To explore the possibility and feasibility of hepatic portal reocclusion for detecting bile leakage during hepatectomy. METHODS: Data were prospectively collected from 200 patients who underwent hepatectomy alone for removal of various benign or malignant tumors between March 2014 and November 2014. The surgical procedure used a conventional method for all patients, and one additional step (hepatic portal reocclusion) was included in group B. The postoperative outcomes of the patients in group A (subjected to the traditional procedure) and group B (subjected to hepatic portal reocclusion) were compared during the same period, and the incidence rates of postoperative bile leakage and other complications in the 2 groups were also analyzed. RESULTS: The incidence of postoperative bile leakage in group B was significantly lower than that in group A (1.0 vs. 9.2%, p = 0.009), although no significant differences in postoperative indicators of liver dysfunction and other complications were observed between the 2 groups (p > 0.05). CONCLUSIONS: Hepatic portal reocclusion effectively reduced the incidence of bile leakage compared to the traditional procedure, without significantly affecting liver function. Therefore, this method might be an alternative to other tests for bile leakage.

Intrahepatic splenosis mimics hepatocellular carcinoma in a patient with chronic hepatitis B: A case report and literature review.

BACKGROUND: Splenosis is a benign and relatively uncommon condition caused by trauma or splenectomy or other procedures involving splenic tissue. It is usually asymptomatic, and often diagnosed accidentally, especially misdiagnosed as malignant tumor. METHODS: A 54-year-old man with prior history of chronic hepatitis B virus infection and underwent splenectomy for traumatic splenic rupture following a traffic accident 23 years previously was admitted to our hospital and found a hepatic mass in the right upper quadrant during an imaging examination. The diagnosis of his was not clear and finally he agreed to receive a surgical treatment. RESULTS: During the operation, we found a mass in the right posterior lobe of the liver and a hard nodule on the right side of the diaphragm, both were completely resected, and postoperative histopathologic examination revealed that all excised tissues were proved to have histological structure typical for the spleen. CONCLUSIONS: The occurrence of intrahepatic splenosis is rare with only few cases previously reported in the literature. It is a benign disease and sometimes difficult to distinguish from diseases of the liver. The need for positive surgical resection of splenosis is still controversial.

A novel scoring system predicts adjuvant chemolipiodolization benefit for hepatocellular carcinoma patients after hepatectomy.

Our aim in this study was to develop a prognostic scoring system with which to identify patients most likely to benefit from adjuvant chemolipiodolization (ACL) after liver resection for hepatocellular carcinoma (HCC). Data from 1150 HCC patients who underwent liver resection between 2002 and 2008 at the Eastern Hepatobiliary Surgery Hospital were used to develop the scoring system. Patients were stratified into prognostic subgroups using the new scoring system, and the outcomes of patients who received ACL and those who did not were compared in each subgroup. Using data from 379 patients operated on between 2008 and 2010 for validation, the scoring system had a concordance index (C-index) of 0.75 for predicting post-resectional overall survival (OS). It optimally stratified patients into three prognostic subgroups with scores of 0-5, 6-9 and ≥ 10, having better, medium and worse survival outcomes, respectively. A difference in OS between ACL and non-ACL patients was only detected in the subgroup with scores ≥ 10 (1-, 3-, and 5-year OS rates: 63.9%, 22.6%, and 9.0% vs. 33.8%, 5.6%, and 2.8%, p = 0.001). Our proposed scoring system provides an effective tool for selecting the patients most likely to benefit from ACL.

Loss of function of Notch1 identifies a poor prognosis group of early stage hepatocellular carcinoma following hepatectomy.

Notch1 has previously been implicated in the carcinogenesis of hepatocellular carcinoma (HCC). The present study aimed to investigate the prognostic value of Notch1 in early stage HCC patients after hepatectomy. The differential expression of Notch1 in paired tumor and non-tumorous tissue was evaluated by RT-PCR, western blotting and immunohistochemistry. The correlation between Notch1 expression and the surgical outcome of patients at BCLC stage 0/A and its ≤5 cm subgroup was retrospectively investigated in 206 patients from the Eastern Hepatobiliary Surgery Hospital (training cohort), and prospectively validated in 185 patients from the same center and retrospectively verified in 129 patients from the Fujian Medical University (validation cohort 1 and 2, respectively). Compared with paired non-tumorous tissues, loss of Notch1 was observed in tumor tissue. Patients with normal Notch1 had better prognosis than those with loss of Notch1 in the training cohort and ≤5 cm subgroup (time to recurrence: 38.5±6.1 vs. 16.0±3.2 months, P<0.001 and 53.0±6.1 vs. 21.7±3.5 months, P=0.004; 1-, 3-, 5-year survival rates: 91, 64 and 49% vs. 73, 31 and 22%, P<0.001 and 93, 71, 57% vs. 76, 39, 24%, P<0.001). Notch1 expression was an independent factor for recurrence and survival (hazard ratio: 1.901, 2.154; 2.038 and 2.337). Moreover, Notch1 status affected early tumor recurrence, as the 2-year recurrence rate was 61.2 vs. 26.9% (P<0.001) and 51.2 vs. 21.3% (P=0.002) in tumors with reduced or increased Notch1 expression in this cohort and subgroup. These results were fully confirmed by the study in our prospective and retrospective validation cohorts. The status of Notch1 is useful for predicting the prognosis of patients with early stage HCC undergoing hepatectomy.

Pancreatic fistula after central pancreatectomy: case series and review of the literature.

BACKGROUND: Postoperative pancreatic fistula is one of the most common complications after pancreatectomy. This study aimed to assess the occurrence and severity of pancreatic fistula after central pancreatectomy. METHODS: The medical records of 13 patients who had undergone central pancreatectomy were retrospectively studied, together with a literature review of studies including at least five cases of central pancreatectomy. Pancreatic fistula was defined and graded according to the recommendations of the International Study Group on Pancreatic Fistula (ISGPF). RESULTS: No death was observed in the 13 patients. Pancreatic fistula developed in 7 patients and was successfully treated non-operatively. None of these patients required re-operation. A total of 40 studies involving 867 patients who underwent central pancreatectomy were reviewed. The overall pancreatic fistula rate of the patients was 33.4% (0-100%). Of 279 patients, 250 (89.6%) had grade A or B fistulae of ISGPF and were treated non-operatively, and the remaining 29 (10.4%) had grade C fistulae of ISGPF. In 194 patients, 15 (7.7%) were re-operated upon. Only one patient with grade C fistula of ISGPF died from multiple organ failure after re-operation. CONCLUSION: Despite the relatively high occurrence, most pancreatic fistulae after central pancreatectomy are recognized a grade A or B fistula of ISGPF, which can be treated conservatively or by mini-invasive approaches.

Changes of serum alpha-fetoprotein and alpha-fetoprotein-L3 after hepatectomy for hepatocellular carcinoma: prognostic significance.

BACKGROUND: Alpha-fetoprotein (AFP) is the most established tumor marker of hepatocellular carcinoma (HCC), but one of its limitations is non-specificity. Many studies have demonstrated that alpha-fetoprotein-L3 (AFP-L3) is more specific than AFP in the early diagnosis and prognosis of HCC. However, there is a lack of knowledge about the post-hepatectomy profiles of serum AFP and AFP-L3 values in HCC patients. To identify the profiles after surgical resection of HCC, we analyzed the correlation between the profiles and postoperative HCC recurrence or survival, and evaluated their utility in predicting postoperative therapeutic efficacy and prognosis. METHODS: From August 2003 to December 2004, 318 patients with positive serum AFP who had received surgical resections were enrolled in this study. Preoperative and postoperative serum AFP and AFP-L3 levels were measured simultaneously and regularly, and their postoperative profiles during a long-term follow-up were recorded and summarized. RESULTS: A high ratio of AFP-L3 to total AFP was shown to correlate with pathologic features of aggressiveness. The overall 1-, 3-, and 5-year recurrence rates of the whole series were 28%, 57%, and 84%, and the overall survival rates were 86%, 61%, and 33%, respectively. The changes of serum AFP and AFP-L3 after hepatectomy for HCC were classified into 3 groups (group A: AFP-L3 undetectable; group B: AFP-L3 <10%; and group C: AFP-L3 >10%). Patients with positive postoperative AFP-L3 had significantly earlier recurrence than those with negative results. The overall survival was significantly shorter in the positive groups than in the groups negative for postoperative AFP-L3. CONCLUSION: Post-hepatectomy changes in serum AFP and AFP-L3 levels occurred in three distinct patterns, which were closely correlated with HCC recurrence and patient survival with different prognostic values.

Adjuvant transarterial chemoembolization after curative resection of hepatocellular carcinoma: a non-randomized comparative study.

BACKGROUND/AIMS: Prevention of recurrence is the most important strategy to improve long-term survival after resection of hepatocellular carcinoma (HCC). This comparative study aimed to evaluate the outcome of adjuvant transarterial chemoembolization (TACE) after hepatectomy. METHODOLOGY: From February 1996 and September 2001, 721 consecutive patients (adjuvant TACE treatment vs. control group; 145 vs. 576) with R0 resection for HCC were analyzed. The prospective data was analyzed retrospectively. RESULTS: After a median follow-up of 75 months, 89 patients (61.4%) in the adjuvant TACE group and 355 patients (61.6%) in the control group had recurrent disease. There was no significant difference in the tumor recurrence rate between the 2 groups. There was significant difference in the tumor recurrence time between the 2 groups. The 1-, 3- and 5-year overall survival rates were 96.5%, 70.0% and 55.9%, respectively, for the adjuvant TACE group and 80.8%, 49.7% and 38.8%, respectively, for the control group. The 1-, 3- and 5-year disease-free survival rates were 79.9%, 54.9% and 48.4%, respectively, for the adjuvant TACE group and 60.2%, 39.8% and 31.5%, respectively, for the control group. The differences in the disease-free survival rates and the overall survival rates between the 2 groups were significant. In subgroup analysis, there was significant survival benefit in the adjuvant TACE group in the subgroup of patients with risk factors of recurrence - large tumor size, presence of satellite tumor nodules and narrow resection margin. CONCLUSIONS: Adjuvant TACE improved surgical outcome in those patients with risk factors of HCC recurrence.

Transforming growth factor beta1 gene variation Leu10Pro affects secretion and function in hepatic cells.

BACKGROUND: Our previous work revealed transforming growth factor beta1 (TGFß1) gene polymorphisms are associated with susceptibility to hepatocellular carcinoma and liver cirrhosis. However, no further study of functional substitution in hepatic cells has yet been reported. AIMS: This study was designed to uncover the functional mechanisms of TGFß1 gene polymorphisms in the pathogenesis of liver diseases. METHODS: Two recombinant TGFß1 expression plasmids containing TGFß1 codon 10 Leu/Pro variation were constructed with CMV promoter and transfected into human hepatoma cell lines (HepG2 and SMMU 7721), hepatic stellate cells (LX-2), and immortalized hepatocytes (L02). The secretion capacities of TGFß1 protein in the transfected cells were determined by ELISA. Apoptosis, proliferative activity, and expression of CD 105, CD83, and CD80 were also measured by use of flow cytometry. RESULTS: The ELISA results showed that cells transfected with CMV-Pro10 were more capable of TGFß1 secretion than those transfected with CMV-Leu10. Functionally, CMV-Pro10 was more apoptosis-protective and induced more proliferation than CMV-Leu10 in transfected hepatic cells. Pro10 up-regulated expression of CD105 and down-regulated expression of CD83. CONCLUSIONS: TGFß1 gene Leu10Pro variation in signal peptide has significant effects on TGFß1 secretion and functions in hepatic cells.

A case-control study of correlation between preoperative serum AFP and recurrence of hepatocellular carcinoma after curative hepatectomy.

BACKGROUND/AIMS: The prognostic impact of serum alpha-fetoprotein (AFP) on patients with hepatocellular carcinoma (HCC) undergoing curative resection remains unclear. We conducted a case-control study to investigate it. METHODOLOGY: A total of 196 HCC patients with negative preoperative AFP were admitted and treated by curative liver resection. During the same period, 196 patients with positive preoperative AFP were enrolled to match the TN M stages, Child-Pugh score and HBs-Ag status of the AFP-negative patients. Time to recurrence (TTR) and overall survival (OS) were prospectively studied. RESULTS: Through a median follow-up duration of 5.25 years, we found that the median TTR of patients with negative preoperative AFP was significantly longer than those with positive AFP (17.3 vs. 12.8 months, p=0.001). The median TTRs of AFP-negative and positive patients were 22.1 and 21.0 months (p=0.266), 145 and 7.4 months (p=0.005) and 3.7 and 2.9 months (p=0.197) in TNM stages I, II and IIIa, respectively. The median TTRs of TNM stage II patients with :≤20, 20-400, 400-1000 and >1000 ng/mL preoperative AFP concentration were 14.5, 13.7, 10.7 and 9.6 months (p=0.092), respectively. CONCLUSIONS: Preoperative AFP level is an independent prognostic factor affecting postoperative recurrence in HCC patients and correlated with the TTR of TNM II.

Sorafenib down-regulates c-IAP expression post-transcriptionally in hepatic carcinoma cells to suppress apoptosis.

Hepatocellular carcinoma (HCC) is one of leading causes of cancer-related death with a heterogeneous patient demographic and divergent pathogenic pathways. Sorafenib is the first effective drug approved for the treatment of HCC. Although it is known that sorafenib promotes apoptosis of HCC cells, the underlying mechanism remains largely obscure. Here we report that sorafenib down-regulates protein expression of the anti-apoptotic protein c-IAP1 in a time- and dose-dependent manner in HCC cells in vitro and in vivo. Furthermore, we demonstrate that sorafenib represses c-IAP1 levels without altering its transcription or protein stability. Instead, sorafenib attenuates c-IAP1 translation by targeting the internal ribosome entry site (IRES) within the c-IAP1 mRNA. Finally, ectopic expression of c-IAP1 alleviates sorafenib induced cancer cell apoptosis. In conclusion, our data highlight a previously unidentified pathway that contributes to sorafenib mediated HCC cell apoptosis and as such provide novel mechanistic insight into the rational use of sorafenib in treating HCC.

Risk factors of intrahepatic cholangiocarcinoma in patients with hepatolithiasis: a case-control study.

BACKGROUND: Why 3.3% to 10% of all patients with hepatolithiasis develop intrahepatic cholangiocarcinoma (ICC) remains unknown. We carried out a hospital-based case-control study to identify risk factors for the development of ICC in patients with hepatolithiasis in China. METHODS: Eighty-seven patients with pathologically diagnosed hepatolithiasis associated with ICC and 228 with hepatolithiasis alone matched by sex, age (+/-2 years), hospital admittance and place of residence were interviewed during the period of 2000-2008. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for each risk factor. RESULTS: Among the patients with hepatolithiasis associated with ICC, the mean age was 57.7 years and 61.0% were female. Univariate analysis showed that the significant risk factors for ICC development in hepatolithiasis were smoking, family history of cancer, appendectomy during childhood (under age 20), and duration of symptoms >10 years. In multivariate stepwise logistic regression analysis, smoking (OR=1.931, 95% CI: 1.000-3.731), family history of cancer (OR=5.175, 95% CI: 1.216-22.022), and duration of symptoms >10 years (OR=2.348, 95% CI: 1.394-3.952) were independent factors. CONCLUSION: Smoking, family history of cancer and duration of symptoms >10 years may be risk factors for ICC in patients with hepatolithiasis.

Isolation of circulating tumor cells in patients with hepatocellular carcinoma using a novel cell separation strategy.

PURPOSE: To establish a sensitive and specific isolation and enumeration system for circulating tumor cells (CTC) in patients with hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: HCC cells were bound by biotinylated asialofetuin, a ligand of asialoglycoprotein receptor, and subsequently magnetically labeled by antibiotin antibody-coated magnetic beads, followed by magnetic separation. Isolated HCC cells were identified by immunofluorescence staining using Hep Par 1 antibody. The system was used to detect CTCs in 5 mL blood. Blood samples spiked with Hep3B cells (ranging from 10 to 810 cells) were used to determine recovery and sensitivity. Prevalence of CTCs was examined in samples from HCC patients, healthy volunteers, and patients with benign liver diseases or non-HCC cancers. CTC samples were also analyzed by FISH. RESULTS: The average recovery was 61% or more at each spiking level. No healthy, benign liver disease or non-HCC cancer subjects had CTCs detected. CTCs were identified in 69 of 85 (81%) HCC patients, with an average of 19 ± 24 CTCs per 5 mL. Both the positivity rate and the number of CTCs were significantly correlated with tumor size, portal vein tumor thrombus, differentiation status, and the disease extent as classified by the TNM (tumor-node-metastasis) classification and the Milan criteria. HER-2 gene amplification and TP53 gene deletion were detected in CTCs. CONCLUSION: Our system provides a new tool allowing for highly sensitive and specific detection and genetic analysis of CTCs in HCC patients. It is likely clinically useful in diagnosis and monitoring of HCC and may have a role in clinical decision making.

Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein as a marker of prognosis and a monitor of recurrence of hepatocellular carcinoma after curative liver resection.

BACKGROUND: The aim of this study was to determine the role of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) as a prognostic marker and a monitor marker of recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: From December 2002 to May 2004, 395 consecutive patients with HCC who underwent curative partial hepatectomy were included in the study. The tumor characteristics and clinical outcomes of patients with positive preoperative and postoperative AFP-L3 were compared with those with negative results. RESULTS: A high ratio of AFP-L3 to total AFP was an indicator of pathologic aggressiveness. Patients with positive preoperative AFP-L3 had significantly earlier recurrence (median time to recurrence 22.0 ± 2.4 months vs 45.0 ± 6.9 months, P < .001) when compared with those with negative preoperative results. Significantly more patients with continuously positive or negative-turn-positive AFP-L3 results after surgery developed recurrence, particularly distant metastases, when compared with patients with continuously negative AFP-L3 results. The overall and disease-free survivals were significantly shorter in the positive than the negative preoperative AFP-L3 group. The overall and disease-free survivals were significantly shorter in the continuously positive and the negative-turn-positive than the continuously negative postoperative AFP-L3 group. CONCLUSION: Positive preoperative AFP-L3 and continuously positive or negative-turn-positive AFP-L3 results after surgery predicted a more aggressive tumor behavior, higher tumor recurrence, and poorer clinical outcomes. HCC patients with an increased proportion of AFP-L3 to total AFP should be more aggressively treated and closely followed-up.

Overexpression of aspartyl-(asparaginyl)-beta-hydroxylase in hepatocellular carcinoma is associated with worse surgical outcome.

UNLABELLED: The association between the overexpression of aspartyl-(asparaginyl)-beta-hydroxylase (AAH) and the invasiveness of hepatocellular carcinoma (HCC) in vitro has been reported. However, the prognostic value of AAH expression in HCC remains unclear. The purpose of this study was to investigate the relationship between AAH expression, tumor recurrence, and patient survival. We identified AAH as the most overexpressed gene in HCC by way of complementary DNA microarray hybridization. A prospective study of 233 patients undergoing curative resection indicated that AAH expression was an independent factor affecting recurrence (hazard ratio [HR] 3.161, 95% confidence interval [CI] 2.115-4.724, P < 0.001) and survival (HR 2.712, 95% CI 1.734-4.241, P < 0.001). Patients with AAH overexpression had a poorer prognosis than those with AAH underexpression (P < 0.001 for both recurrence and survival). In Barcelona Clinic Liver Cancer stage A patients with AAH overexpression or underexpression, the tumor recurrence and survival rates were also statistically different (45% and 85% versus16% and 33% in 1- and 3-year cumulative recurrence rates, respectively; 73% and 37% versus 90% and 80% in 1- and 3-year survival rates, respectively; P < 0.001 for both). Furthermore, in stage A patients with tumors measuring < or =5 cm in diameter, the time to recurrence was 26.7 +/- 1.6 versus 51.9 +/- 2.8 months, and the 1- and 3- year survival rates were 97% and 52% versus 100% and 90% in AAH overexpression and underexpression patients, respectively (P < 0.001 for both). CONCLUSION: AAH overexpression in HCC is strongly correlated with worse surgical outcome, and this molecule likely provides a more precise prognostic predictor in early stage HCCs.

[Clinical study of 169 patients with hepatic angiomyolipoma].

OBJECTIVE: To review and investigate the optimal preoperative diagnostic means and treatment principles of hepatic angiomyolipoma (HAML). METHODS: The clinical features, treatment, prognostic and follow-up data of 169 HAML patients treated between January 1992 and May 2010 were retrospectively analyzed. The median age of the patients, including 46 male and 123 female (male/female, 1/2.7), was 45 years (range, 17 - 73 years). The mean case history was 0.54 year with a range of 2 d to 16 years. RESULTS: Among the 169 patients, 149 patients (88.2%) had a solitary tumor and 96 patients (56.8%) were detected in the right lobe. The overall preoperative diagnostic rate was 13.6% and 119 patients (70.4%) were misdiagnosed as hepatocellular carcinoma or hepatic cavernous hemangioma. The diagnostic accuracy of MRI is higher than CT in distinguishing the nature of the tumor (χ² = 5.508, P = 0.019). One hundred and sixty-eight patients received surgical resection and one received percutaneous microwave coagulation therapy. One patient occurred postoperative hemorrhage and 3 patients developed hydrothorax. The postoperative mortality and recurrence for all the patients were 0. Postoperative pathology confirmed the diagnosis of hepatic angiomyolipoma. Follow-up study showed a benign course and no signs of recurrence. CONCLUSIONS: MRI is the main diagnostic means of HAML. Treatment strategies of HAML depends largely on tumor size, location and growth rate. Surgical management is suggested to patients with the following criteria: (1) tumor size greater than 5 cm; (2) with clinical symptoms; (3) faster tumor growth; (4) the tumor located at 1, 4, 5, 8 segments of liver.

Treatment of portal vein tumor thrombus of hepatocellular carcinoma with percutaneous laser ablation.

BACKGROUND: Portal vein tumor thrombus (PVTT) is a common complication of hepatocellular carcinoma (HCC), and is associated with extremely poor prognosis. PATIENTS AND METHODS: In this retrospective study, we first evaluate the application of percutaneous laser ablation as a treatment for PVTT due to advanced hepatocellular carcinoma. 108 patients (2002.7-2005.12) that have adequate liver function and be in reasonably good general condition were enrolled at Eastern hepatobiliary surgery hospital. The thrombus was ablated via an optic fiber placed in the guide needle with the guiding of ultrasound. In the follow-ups, the serial imaging and laboratory routines were examined and the overall clinical progress was measured at regular intervals until time of death. In the clinical assessment, survival time and factors affecting survival time were analyzed. The changes of laboratory test (alanine transaminase and alpha fetoprotein) and clinical manifestation (ascites and diarrhea) of the PVTT patients before and after laser ablation were observed. RESULTS: Patency of the tumor-occluded portal vein branch is the only factor that affect the survival time, the longer the patency time, the longer the survival time. The long-term survivals of patients in our study are 55.56, 33.58 and 22.38% at 1, 2 and 3 years, respectively. Both laboratory test and clinical presentations were improved. Alphalpha fetoprotein in the positive patients decreased and alanine transaminase in the abnormal patients normalized at 1 month after the treatment. Ascites disappeared in 44.00% patients (11/25), and diarrhea ameliorated in 57.14% (12/21). CONCLUSION: Laser ablation might be a novel and effective treatment for PVTT associated with advanced HCC.

Protective effect of prednisolone on ischemia-induced liver injury in rats.

AIM: To investigate the effects of prednisolone on cell membrane bleb formation, calpain mu activation and talin degradation during hepatic ischemia-reperfusion injury in rats. METHODS: The hilar area of the left lateral and median lobes of rat liver (68%) was clamped for 60 min and followed by 120 min reperfusion. Prednisolone was administered at 1.0, 3.0, or 10 mg/kg at 30 min before ischemia. In addition to biochemical and microscopic analyses, activation of calpain micro was determined using specific antibodies against the intermediate (activated) form of calpain mu. Degradation of talin was also studied by Western blotting. RESULTS: In the control and prednisolone (1.0 mg/kg) groups, serum aspartate transaminase (AST) and alanine transaminase (ALT) level were elevated, and cell membrane bleb formation was observed after 120 min of reperfusion. Moreover, calpain mu activation and talin degradation were detected. Infusion of prednisolone at 3.0 or 10 mg/kg significantly suppressed serum AST and ALT, and prevented cell membrane bleb formation. At 10 mg/kg, prednisolone markedly suppressed calpain mu activation and talin degradation. CONCLUSION: Prednisolone can suppress ischemia-reperfusion injury of the rat liver. Its cytoprotective effect is closely associated with the suppression of calpain mu activation and talin degradation.

[Percutaneous laser ablation in the treatment of portal vein tumor thrombus in 93 hepatocellular carcinoma patients].

OBJECTIVE: To evaluate the efficacy of percutaneous laser ablation (LA) in the treatment for portal vein tumor thrombus (PVTT) of hepatocellular carcinoma (HCC). METHODS: The PVTT of HCC patients were treated through percutaneous transhepatic laser ablation (PTLA). The survival rate, thrombus size, blood flow of embolized portal vein by thrombus, liver function, ascites and clinical presentation were observed. RESULTS: The 6-month, 1-year and 2-year survival rate of these 93 patients were 82.8%, 53.0% and 34.1%, respectively. In 11 patients with partially occluded portal vein by PVTT, the cut-surface of the PVTT diminished significantly 6 months after LA. The color blood stream signal was seen again one day after LA in all of the other 82 patients with totally occluded portal vein by thrombus, and it could still be seen in 67 of those one month later, 57 (of 71) 3 months later, 40 (of 57) 6 months later, 27 (of 32) 1 year and 4 (of 6) 2 years later after LA. In the 38 patients who survived over 1 year, PVTT was gradually atrophied and disappeared eventually in 14, PVTT was atrophied and the portal vein changed into honeycomb-like appearance in 14. In the remaining 10 patients, PVTT continued to grow and made the portal vein enlarged. It was also observed that liver function, clinical symptom and ascites were improved in various degree after LA. CONCLUSION: Percutaneous laser ablation might be an effective and safe treatment method for controlling portal vein tumor thrombus of hepatocellular carcinoma.