Actual long-term survival in HCC patients with portal vein tumor thrombus after liver resection: a nationwide study.

BACKGROUND: Liver resection for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) offers a chance of cure, although survival is often limited. The actual 3-year survival and its associated prognostic factors have not been reported. METHODS: A nationwide database of HCC patients with PVTT who underwent liver resection with 'curative' intent was analyzed. The clinicopathologic characteristics, the perioperative, and survival outcomes for the actual long-term survivors were compared with the non-long-term survivors (patients who died within 3 years of surgery). Univariable and multivariable regression analyses were performed to identify predictive factors associated with long-term survival outcomes. RESULTS: The study included 1590 patients with an actuarial 3-year survival of 16.6%, while the actual 3-year survival rate was 11.7%. There were 171 patients who survived for at least 3 years after surgery and 1290 who died within 3 years of surgery. Multivariable regression analysis revealed that total bilirubin > 17.1 µmol/l, AFP > 400 ng/ml, types of hepatectomy, extent of PVTT, intraoperative blood loss > 400 ml, tumor diameter > 5 cm, tumor encapsulation, R0 resection, liver cirrhosis, adjuvant TACE, postoperative early recurrence (< 1 year), and recurrence treatments were independent prognostic factors associated with actual long-term survival. CONCLUSION: One in nine HCC patients with PVTT reached the long-term survival milestone of 3 years after resection. Major hepatectomy, controlling intraoperative blood loss, R0 resection, adjuvant TACE, and 'curative' treatment for initial recurrence should be considered for patients to achieve better long-term survival outcomes.

[Expression of Wnt5b in patients with HBV-related hepatocellular carcinoma and its clinical significance].

OBJECTIVE: To investigate the expression of Wnt5b in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) tissues and its correlation with the clinicopathological parameters. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining were employed to measure Wnt5b mRNA and protein expressions in two groups of HBV-related HCC patients (100 cases in each) selected from a cohort of 289 cases with HBV-related HCC using simple random sampling method. The correlation of Wnt5b expression with the clinicopathological parameters and the prognosis of HCC patients was analyzed. RESULTS: Wnt5b mRNA expression was significantly higher in HCC tissues than that of adjacent noncancerous tissues in 65.0% (65/100) of the cases, and the positivity rate of Wnt5b protein was significantly higher in HCC tissues than that of adjacent noncancerous tissues (58.0% vs 22.0%, P<0.05). Wnt5b expression was significantly correlated with the tumor size (P<0.05), tumor number (P<0.01, only at the protein level), tumor differentiation (P<0.01, only at the protein level), TNM stage (P<0.05), BCLC stage (P<0.05), metastasis (P<0.05) and recurrence (P<0.01). The patients with up-regulated Wnt5b mRNA and protein had a shorter relapse-free survival (P<0.01). CONCLUSION: s Up-regulated Wnt5b might contribute to the progression of HBV-related HCC and predicts a poor prognosis.

Loss of tumor suppressor miR-126 contributes to the development of hepatitis B virus-related hepatocellular carcinoma metastasis through the upregulation of ADAM9.

Hepatocellular carcinoma is the most common histological type of primary liver cancer, which represents the second leading cause of cancer-related mortality. MiR-126 was reported to be downregulated in hepatocellular carcinoma tissues, compared with its levels in noncancerous tissues. However, baseline miR-126 expression levels in hepatitis B virus-related hepatocellular carcinoma patients who did not undergo pre-operational treatment remains unknown since hepatitis B virus infection and pre-operational transcatheter arterial chemoembolization were shown to upregulate miR-126 expression. Here, we demonstrated that miR-126 is generally downregulated in a homogeneous population of pre-operational treatment-naïve hepatitis B virus-related hepatocellular carcinoma patients (84.0%, 84/100), and its expression is significantly associated with pre-operational alpha-fetoprotein levels ( p < 0.05), microvascular invasion ( p < 0.05), tumor metastasis ( p < 0.05), as well as early recurrence (12 months after surgery; p < 0.01). Furthermore, the results of our study revealed that miR-126 is negatively correlated with ADAM9 expression in hepatitis B virus-related hepatocellular carcinoma patients. Overexpression of miR-126 was shown to attenuate ADAM9 expression in hepatocellular carcinoma cells, which subsequently inhibits cell migration and invasion in vitro. In addition, Cox proportional hazards regression model analysis showed that ADAM9 levels, tumor number, microvascular invasion, and tumor metastasis rate represent independent prognostic factors for shorter recurrence-free survival. In conclusion, we demonstrated that the loss of tumor suppressor miR-126 in hepatitis B virus-related hepatocellular carcinoma cells contributes to the development of metastases through the upregulated expression of its target gene, ADAM9. MiR-126-ADAM9 pathway-based therapeutic targeting may represent a novel approach for the inhibition of hepatitis B virus-related hepatocellular carcinoma metastases.

[Positive circulating tumor cells in the peripheral blood may indicate a poor prognosis in patients with hepatocellular carcinoma].

OBJECTIVE: To assess the value of detecting peripheral blood circulating tumor cells (CTCs) in the diagnosis and treatment of hepatocellular carcinoma (HCC). METHODS: A total of 296 patients diagnosed with HCC admitted in our department from July 2013 to January 2015 were analyzed, with 39 patients with benign liver disease serving as the control group. The distribution of CTCs in the peripheral blood of HCC patients were detected by CanPatrol(TM) CTCs, and its relationship with the clinical features and prognosis of the patients were analyzed. RESULTS: s CTCs were detected in 64.5% (191/296) of the HCC patients but in none of the control group (P<0.05). Positive CTCs in peripheral blood of HCC patients were significantly correlated with serum AFP level, tumor number, TNM stage, BCLC stage, portal vein tumor thrombus and metastasis (P<0.05). In 127 HCC patients receiving radical surgery, the patients positive for CTCs showed significantly shorter relapse-free survival time (P<0.05). CONCLUSION: Positive CTCs in the peripheral blood may indicate a poor prognosis in HCC patients. CTCs may serve as a indicator for monitoring the prognosis of HCC.

Bifidobacterium infantis attenuates colitis by regulating T cell subset responses.

AIM: to investigate the effect of Bifidobacterium infantis (B. infantis) on the T cell subsets and in attenuating the severity of experimental colitis in mice. METHODS: Normal BALB/c mice were fed different doses of B. infantis for 3 wk, and T cell subsets and related cytokine profiles in mesenteric lymph nodes (MLNs) were detected by flow cytometry and real-time RT-PCR. Colitis was induced by administration of trinitrobenzene sulfonic acid (TNBS) in mice. Before colitis induction, mice were fed high dose B. infantis for 3 wk. Cytokine profiles in MLNs and histological changes of colonic tissue were examined 6 d after colitis induction. RESULTS: No significant change in cytokine profiles was observed in normal mice fed low dose B. infantis. However, Th1-related cytokines (IL-2, IFN-γ, IL-12p40), Th17-related transcription factor and cytokines (RORγt, IL-21, IL-23), regulatory T cell (Treg)-related transcription factor and cytokines (Foxp3, IL-10) were increased in normal mice fed high dose B. infantis. Furthermore, flow cytometry assay showed B. infantis increased the numbers of CD4(+)Foxp3(+) Tregs and Th17 cells in MLNs. Colitis was successfully induced by TNBS in mice, characterized by colonic inflammation and aberrant Th1 and Th17 responses. Feeding high dose B. infantis for 3 wk before colitis induction decreased the inflammatory cell infiltration and goblet cell depletion and restored the intestinal epithelium. In addition, B. infantis feeding reduced Th1-related cytokines (T-bet, IL-2 and IFN-γ) and Th17-related cytokines (IL-12p40, RORγt, IL-17A, IL-21 and IL-23), and increased Treg-related molecules (Foxp3, IL-10 and TGF-ß) in colitis mice. CONCLUSION: B. infantis effectively attenuates TNBS-induced colitis by decreasing Th1 and Th17 responses and increasing Foxp3(+) Treg response in the colonic mucosa.

[Relationship between the expressions of indoleamine 2, 3-dioxygenase in hepatocellular carcinoma and clinicopathological parameters].

OBJECTIVE: To explore the expressions of indoleamine 2, 3-dioxygenase (IDO) in hepatocellular carcinoma and analyze its relationship with clinicopathological parameters. METHODS: Quantitative real-time polymerase chain reaction (PCR), fluorogenic quantitative PCR, immunohistochemical and immunofluorescence were used to detect the expression of indoleamine 2, 3-dioxygenase in hepatocellular carcinoma. RESULTS: The IDO mRNA expression in cancerous tissues increased markedly than that in the corresponding non-cancerous tissues (2(-ΔΔCT) = 1.71, P = 0.001) . The immunohistochemical and immunofluorescence results showed that IDO protein was expressed in cytoplasm of hepatocellular carcinoma and tumor-surrounding tissues. But there was no expression in normal liver tissues from benign hepatic lesions and corresponding non-cancerous tissues. An over-expression of IDO protein was detected in 43 patients (48.3%) , a low expression in 25 (28.1%) and no expression in 21 (23.6%). Relationship between IDO expression and clinicopathological parameters: an over-expression of IDO in HCC was associated with recurrence, survival time, metastasis and TNM stage (P < 0.05), but not associated with patient's cirrhosis, AFP level, histological differentiation type, Barcelona clinic liver cancer stage, gender, age, HbsAg positivity, number of tumors and tumor size (P > 0.05). CONCLUSION: An over-expression of IDO in HCC patients may affect patient prognosis.

[Adult-to-adult living-related donor liver transplantation: report of 2 cases].

OBJECTIVE: To investigate the feasibility and safety of adult-to-adult living-related donor liver transplantation using a right lobe graft. METHODS: The clinical data of 2 cases of living-related donor liver transplantation performed between July, 2010 and November, 2010 were analyzed. RESULTS: Liver transplantation was performed using a right lobe graft including the middle hepatic vein in one case and a right lobe graft without the middle hepatic vein in the other. The ratio of graft volume to standard liver volume was 46.2% and 47.3% in the two cases, with GR/WR of 0.83 and 0.80, and donor residue liver of 42.1% and 39.5%, respectively. The donor operation lasted for 6.5 h and 5 h in the two cases with blood loss of about 200-250 ml without blood transfusion. The donors recovered uneventfully without any surgical complications, whose liver function was normal 7 days after the operation, and were discharged 14 days and 16 days after the surgery, respectively. The recipient operation lasted for 8 h and 7 h with blood loss of about 800-1000 ml. The right hepatic vein, hepatic artery, portal vein and bile duct reconstruction were performed by end-to-end anastomoses in the 2 recipients. Bile duct anastomosis stricture occurred in the first recipient 2 months after transplantation and was treated with percutaneous transhepatic cholangiography and drainage. The second recipient recovered smoothly without any complications. The recipients have so far survived 9 months and 5 months, respectively. CONCLUSION: Adult-to-adult living-related donor liver transplantation is a safe and effective option for treatment of end-stage liver diseases in the context of cadaveric liver graft shortage.

[Safety and efficacy of Sorafenib in treatment of tumor recurrence in liver transplantation recipients].

OBJECTIVE: To investigate the therapeutic effect and safety of Sorafenib in the treatment of tumor recurrence after orthotopic liver transplantation (OLT). METHODS: Between January, 2009 and June, 2011, 10 patients with tumor recurrence after OLT were treated with Sorafenib (group A) and another 8 recipients received no Sorafenib treatment (group B); 25 patients with hepatocellular carcinoma (HCC) also received Sorafenib treatment (group C). The tumor-bearing survival time, adverse effect and toxicity associated with sorafenib were compared between the 3 groups. RESULTS: In group A, the median tumor-bearing survival time was 10 months (5-22 months), as compared to 4 months (1-8 months) in group B and 4 months (2-21 months) in group C, showing a significant difference in the survival time among the 3 groups (Kaplan-Meier, log-rank test, P=0.045). No recipient experienced acute graft rejection, but one recipient in group A died due to gastrointestinal bleeding. No significant difference was found in adverse effects associated with Sorafenib between groups A and C (P<0.05). CONCLUSION: Sorafenib can prolong the survival time of patients with tumor recurrence after OLT without increasing the risk of acute graft rejection.

[Expression of special AT-rich sequence-binding protein 1 mRNA in hepatocellular carcinoma and its clinical significance].

OBJECTIVE: To investigate the expression of special AT-rich sequence binding protein 1 (SATB1) mRNA in hepatocellular carcinoma (HCC) and explore its correlation to the clinicopathological features, surgical outcomes and metastasis of HCC. METHODS: The total RNA was extracted from 102 HCC tissues and the adjacent tissues, and the expression of SATB1 mRNA was detected using quantitative real-time PCR. The correlations of SATB1 mRNA expression to the clinicopathological features, postoperative recurrence and metastasis of the tumor were analyzed. RESULTS: The expression of SATB1 mRNA in HCC tissues was 3.27 folds higher than that in the adjacent tissues (P<0.001). The expression of SATB1 mRNA in HCC was associated with liver cirrhosis, AFP level, tumor size, tumor thrombi, histological differentiation, TNM classification, postoperative recurrence and metastasis (P<0.05), but not to the patients' gender, age, HbsAg positivity, HCV-Ab positivity, tumor number, or the presence of tumor encapsulation (P>0.05). In patients with significant high expression, high expression, and low expression of SATB1 mRNA, the postoperative recurrence rates were 82.68%, 0, and 0, with the 3-year survival rate of 0, 52.63%, and 100%, respectively. CONCLUSION: SATB1 mRNA expression is associated with the postoperative recurrence and metastasis of HCC, and can be used as an indicator for predicting the recurrence and metastasis of HCC.

[Expression and mutations of PIK3CA gene in hepatocellular carcinomas].

OBJECTIVE: To investigate the expression and mutation of PIK3CA gene in hepatocellular carcinomas (HCC). METHODS: HCC samples and the corresponding adjacent tissues were collected from the surgical patients with pathologically verified diagnosis. The exons 1, 9 and 20 of PIK3CA gene were detected by PCR-SSCP and DNA sequencing. Immnohistochemistry was employed to test the expression of PIK3CA gene in these samples. RESULTS: No mutation was found in exons 1, 9 or 20 of PIK3CA gene in the HCC tissue and the adjacent tissues by PCR-SSCP and DNA sequencing, while abnormal superimposed peaks were found on the sequence map of exon 9 in 25 cases of HCC tissue. Immunohistochemistry showed that expression of PIK3CA was higher in the HCC tissue than in the corresponding adjacent tissue (50.81% vs 14.75%). CONCLUSION: PIK3CA gene mutation may exist in HCC in Guangxi, which can be associated with the development of HCC, but the ratio of hotspot mutations is low.

[Effect of methylene chloride upon hepatic ischemic reperfusion injury].

OBJECTIVE: To investigate the effects and mechanisms of methylene chloride (MC) in hepatic ischemic reperfusion injury. METHODS: Eighty SD-rats were divided equally into 4 groups: control group (n = 20), donors without any treatment; CoPP group (n = 20), donors injected with CoPP (5 mg/kg, ip) at 24 h; ZnPP group (n = 20), donors injected with ZnPP (20 mg/kg, ip) at 24 h; MC group (n = 20), donors fed with MC (500 mg/kg) per day for 7 days before graft procurement. Syngeneic orthotopic liver transplantation was performed in rats with modified Kamada's two-cuff technique. And SD rats were used as donors (n = 10)and recipients respectively. 5 recipients in each group were sacrificed and the grafts were procured at day 3 after transplantation, the post-operative survival time was observed in the remnant. The tests were determined as following: the level of serum ALT, AST in recipients; heme oxygenase-1 (HO-1) expression of graft was tested by immunohistochemistry and Western blot; the index of graft apoptosis examined by TUNEL method; the pathology of graft assessed by Suzuki's criteria. RESULTS: The level of serum ALT [(65 +/- 28) U/L], AST [(187 +/- 43) U/L] in CoPP and ALT [(75 +/- 16) U/L], AST [(185 +/- 42) U/L] in MC group was significantly lower than that ALT [(346 +/- 45) U/L], AST [(474 +/- 90) U/L] in control group and ALT [(578 +/- 75) U/L], AST [(1084 +/- 128) U/L] in ZnPP group (P < 0.01). The median expression of HO-1 in MC group was no significantly different with that in control group (P > 0.05). While the median expression of HO-1 in CoPP group was higher than that in control group (P < 0.05). The index of graft apoptosis in MC group and CoPP group, 4.1% +/- 0.6% and 3.2% +/- 0.8% respectively, was significantly lower than that (12.5% +/- 2.4%) in control group and (25.8% +/- 3.1%) in ZnPP group (P < 0.05). Compared with the other two groups, MC and CoPP groups had lesser neutrophil infiltration and a lower grade of hepatocytic injury in grafts. Suzuki's scores in grafts of MC and CoPP groups were lower than that in control and ZnPP groups (P < 0.05). The median post-transplantation survival time of the recipients in MC and CoPP groups was 100 and 93 days respectively while that in control and ZnPP groups was 85 and 12 days (P < 0.05). CONCLUSION: Over-expression of HO-1 and MC both have protective effects in hepatic ischemic reperfusion injury.

Effect of perioperative fluid therapy on early phase prognosis after liver transplantation.

BACKGROUND: Although liver transplantation (LT) has made rapid progress, early pulmonary complications still occur. More attention should be paid to fluid therapy that may be an important factor leading to these complications. It is necessary to investigate the correlation between intraoperative and postoperative fluid therapy and early pulmonary complications after LT, then attempt to provide a reasonable fluid therapy in the perioperative period. METHODS: Sixty-two patients who had undergone LT were enrolled and analyzed retrospectively. Based on early phase prognosis after LT, the 62 patients were divided into a non-pulmonary complication group and a pulmonary complication group. Twenty perioperative variables were analyzed in both groups to screen out several factors causing early pulmonary complications, then the parameters reflecting postoperative recovery were analyzed. RESULTS: The pulmonary complication group had 29 patients (46.77%), 3 (4.84%) of whom died during the perioperative period. Using monofactorial analysis for each variable, the two groups differed in the following variables: preoperative lung function, volume of intraoperative transfusion, volume of intraoperative bleeding, and volume of intraoperative net fluid retention and fluid balance (< or =-500 ml) in > or =2 of the first 3 days after operation. Analysis of the relationship between multivariate factors and pulmonary complications after LT by logistic multivariate regression analysis showed that preoperative lung function, volume of intraoperative bleeding, and fluid balance (< or =-500 ml) in > or =2 of the first 3 days after operation were influential factors. CONCLUSIONS: It is important to maintain fluid balance during the perioperative period of LT. If the hemodynamics are stable, appropriate negative fluid balance in the first 3 days after operation apparently decreases the incidence of early pulmonary complications after LT. These measures are associated with better postoperative recovery.

[Transfection with virus interleukin-10 to prolong murine heart allograft].

OBJECTIVE: To prolong murine heart allograft by modifying hematopoietic stem cells with virus interleukin-10 (vIL-10). METHODS: The recombinant of murine stem cell virus (MSCVneo) vIL-10 was composed of MSCVneo and vIL-10 cDNA and transduced hematopoietic stem cells from CBA (H-2(K)) mice's bone marrow in vitro. The transduced hematopoietic stem cells were transplanted into a syngenic CBA (H-2(K)) mouse with lethal irradiation (900 rad) in the same day through penis vein. The mouse's heterotopic heart transplantation was conducted using CBA (H-2(K)) mice as recipients, which vIL-10 in serum were positive by enzyme-linked immunosorbent assay, and donors hearts from C57BL/6 (H-2b) mice. Five animals in each group were sacrificed to test histopathology changes, the expression of interleukin (IL)-2, IL-4, IL-6, mIL-10, interferon (IFN)-gamma, inducible nitric oxide synthase (iNOS), B7-1, B7-2 and CD(4)(+) and CD(8)(+) T cells subset infiltration in heart transplants with reverse transcriptase polymerase chain reaction, immunohistochemistry and regular pathology. RESULTS: Survival time of mice's allografts experimental group was (80.0 +/- 33.3) days. And survival time of control groups were (10.4 +/- 1.0) days, (11.6 +/- 1.1) days and (11.2 +/- 1.7) days, respectively (P < 0.01). Heart transplants from experimental group were characterized by sparse lymphocytes infiltration, mild endocarditis and vasculitis and preserved myocardial architecture, which had acute rejection of grade I. Cardiac allografts from other control groups developed severe cellular rejection with severe infiltrating lymphocytes, myocyte injury and necrosis, interstitial edema and hemorrhage, which had acute rejection of grade III. The expression of IL-2, INF-gamma, B7-1, B7-2 and iNOS mRNA in allografts in experimental group markedly down-regulated, whereas that in allografts in control groups markedly upregulated (P < 0.05). CD(4)(+) and CD(8)(+) T cell subsets infiltration in heart transplants from experimental group decreased, and that in control groups increased (P < 0.05). CONCLUSION: Engineering Hematopoietic stem cells with vIL-10 can protect cardiac allografts from acute rejection and prolong cardiac allografts survival.

Intestinal perforation after combined liver-kidney transplantation for a case of congenital polycystic disease.

AIM: To highlight the intestinal perforation (IP), an uncommon and catastrophic complication after combined liver-kidney transplantation. METHODS: Combined liver-kidney transplantation (LKTx) with left kidney excision and a cyst fenestration procedure on the right kidney were performed on a case of 46-year-old female with congenital polycystic disease (CPCD). RESULTS: Two sites of IP were noted 40-50 cm proximal to ileocecal area during emergent laparotomy 10 d postoperatively. Despite aggressive surgical and medical management, disease progressed toward a fatal outcome due to sepsis and multiple organ failure 11 d later. CONCLUSION: Long duration of operation without venovenous bypass, overdose of steroid together with postoperative volume excess may all contribute to the risk of idiopathic multiple IPs. Microbiology and pathology inspections suggested that the infected cyst of the fenestrated kidney might be one reason for the fatal intra-peritoneal infection. Thus for the CPCD patients who seem to be very susceptible to infectious complications, any sign of suspected renal-infection found before or during LKTx is indication for the excision of original kidney. And the intensity of immunosuppression therapy should be controlled cautiously.

Clinical epidemiological study on intrahepatic cholelithiasis: analysis of 8585 cases.

OBJECTIVE: To investigate the clinical epidemiology of intrahepatic cholelithiasis in Guangxi area, China. METHODS: 8585 cases of cholelithiasis proved by surgery in a period of 19 years were analyzed retrospectively. Data were collected and analyzed by computer software package PEMS. RESULTS: Cases of intrahepatic cholelithiasis accounted for more than one third of cases of cholelithiasis treated in the same period. The prevalence of intrahepatic cholelithiasis in farmers increased from 23.4% out of all cases with gallstone in 1981-1985 to 55.8% in 1991-1999. The constituent ratio of intrahepatic cholelithiasis in males was nearly the same in females. The peak prevalence age of patients with intrahepatic cholelithiasis ranged from 31 to 40 years, and the mortality was the highest among all bile stone cases. CONCLUSION: Intrahepatic cholelithiasis is by no means a vanishing disease, especially in rural area.