Risk factors of poor prognosis and portal vein tumor thrombosis after curative resection of solitary hepatocellular carcinoma

BACKGROUND:Predictors of poor prognosis of solitary hepatocellular carcinoma(SHCC),a subgroup encompassing most patients with the malignancy,are still controversial.Hence,risk factors for portal vein tumor thrombosis(PVTT) in SHCC are obscure.The present study was designed to address this issue.METHOD:Clinicopathological and follow-up data for 156 consecutive patients with SHCC following curative hepatic resection were analyzed using uni-and multi-variate analyses.RESULTS:Univariate analysis showed that PVTT,tumornode-metastasis(TNM) stage,Edmondson-Steiner grade and preoperative serum alpha-fetoprotein(AFP) level were associated with the overall and disease-free survival,whereas tumor size only influenced the overall survival.In multivariate Cox regression tests,Edmondson-Steiner grade and TNM stage were independent prognostic markers for both overall and diseasefree survival.In addition,the Chi-square test showed that AFP level and Edmondson-Steiner grade were correlated with PVTT.Among them,only Edmondson-Steiner grade was shown to be of independent significance for PVTT in multi-variate logistic regression analysis.Additionally,AFP,the sole preoperative factor for PVTT,was not adequately sensitive and specific.CONCLUSIONS:Factors relating to post-surgical prognosis and PVTT in SHCC are all tumor-related.Of these,EdmondsonSteiner grade and TNM stage might be of particular importance in survival analysis.In addition,accurate prediction of PVTT by clinicopathological parameters before surgery remains difficult.

Serial therapies oriented by surgery for large primary liver carcinoma

Objective: To discuss the methods and effects of serial therapies oriented by surgery in the treatment of pri- mary large liver cancers. Methods: From January 1993 to June 1999, 191 pa- tients with large liver carcinoma were treated surgi- cally. The size of tumors varied from 5.2 to 19.7 cm (mean 9.4 cm). Several types of liver resections were made in 121 patients and as a supplement, cry- osurgery was carried out for the remaining 70 pa- tients. Importable drug delivery system was institu- ted intraoperatively. Transcatheter arterial chemo- embolization (THP 30-60 mg, E-ADM 20-40 mg, CDDP 40-80 mg, MMC 10-20 mg, iodin oil 5-30 ml), percutaneous ethanol injection, bioimmunother- apy and traditional Chinese medicine were used pre- and post-operatively. CT angiography and CT dur- ing arterial portography were used to find satellite nodules. Early stage recurrences were predicted by AFPmRNA in peripheral blood. Child-Pugh's classi- fication plus branch chain amino acid/aromatic ami- no acid ratio (BCAA/AAA) was adopted in evalua- ting pre-operative liver functions. Results: Marked results were observed after serial treatments oriented by surgery. The 1-, 3- and 5- year survival rates in resection group were 75.8 %, 45.6% and 30.4%. respectively. The 1- and 3-year survival rates in cryosurgery group were 63.2 % and 37.0 %. The operative mortality was 1.57 %. Recur- rence rates were 69.2 % in AFPmRNA positive group and 33.3% in AFPmRNA negative group (P< 0.05). The BCAA/AAA ratio was lower than 1.5 in two patients who died of hepatic failure after resec- tion. Conclusions: Serial treatments with surgery as the chief modality gives satisfactory results in patients with large primary liver carcinoma. This regimen should be regarded as a main strategy to deal with large liver carcinoma. AFPmRNA in the peripheral blood, signifying a recurrence, may become a new clinical parameter. The BCAA/AAA ratio plus Child-Pugh's classification is able to evaluate more accurately liver function reserve before surgery.

Hepatic trisegmentectomy for 29 patients with huge liver neoplasms

Objective: To evaluate retrospectively the feasibility and effect of hepatic trisegmentectomy in therapy of huge neoplasms of the liver. Methods: From July 1993 to October 1999, 29 pa- tients with huge hepatic neoplasms underwent hepatic trisegmentectomy. Of these, 23 patients suffered from primary liver cancer, 1 hepatic infiltration of gallbladder cancer, 1 metastasis of colon cancer, 1 hepatic angiosarcoma, 1 hepatic neurofibroma, and 2 huge liver cysts. Twenty-six patients were subjected to right trisegmentectomy and the rest 3 left triseg- mentectomy. All trisegmentectomies were performed under normothermic interruption of the porta hepatis at single time and these interruptions lasted 15 to 40 minutes. Results: The relatively good effect was seen in our se- ries. The 1-, 3-, 5-year survival rates for primary liver cancer patients were 63.6%, 36.4% and 27.3 %, respectively. The survival period for the pa- tients with hepatic infiltration of gallbladder cancer and liver metastasis of colon cancer was 6 months. Those with hepatic angiosarcoma, hepatic neurofi- broma and huge liver cysts have been surviving 35, 26, 25 and 40 months, respectively. Major complica- tions were noted in 5 patients, and one (3.4%, 1/29) died. Conclusion: Hepatic trisegmentectomy is safe and ef- fective in treatment of huge hepatic neoplasms if its indications and operative techniques are properly mastered.

Both the 5th and 6th Editions of TNM Staging System Fail to Independently Predict Long-term Prognosis after Radical Hepatectomy in Hepatocellular Carcinoma Sized > or = 5cm

Objective To validate the predictive power of the 5th and 6th editions of TNM staging system(TNM-5,TNM-6) in a Chinese patient cohort with hepatocellular carcinoma(HCC) sized > or = 5 cm after radical hepatectomy.Methods Consecutive 121 patients with HCC sized > or = 5 cm undergoing radical hepatectomy between January 1995 and December 2002 were included.The impact of clinicopathological variables on prognosis was determined by univariate and multivariate analyses,after excluding 2 perioperative deaths.Results In univariate analysis,TNM-5 stage did not show prognostic significance for overall or disease-free survival,as opposed to TNM-6 stage,Edmondson-Steiner grade,portal vein tumor thrombosis(PVTT),vascular invasion,satellite nodule,Child-Pugh grade,and hepatitis B surface antigen(HBsAg) positivity.When these significant variables were entered in multivariate analysis,Edmondson-Steiner grade was the sole independent prognosticator for both overall and disease-free survival,whereas Child-Pugh grade independently influenced disease-free survival.However,TNM-6 stage lost its predictive potential in multivariate analysis.Conclusions Neither TNM-5 nor TNM-6 staging system is revealed to be independently prognostic in patients with HCC sized > or = 5 cm after radical hepatectomy.Therefore,TNM-6 calls for more support in many subsets of HCC patients.

Targeting the m6A mRNA demethylase FTO suppresses vascular endothelial growth factor release and choroidal neovascularization

Dear Editor,Vascular endothelial growth factor-A(VEGFA,also known as VEGF)is a critical angiogenic factor that regulates the physiological and pathological blood vessel growth.1 Increased abundance of VEGF in the eye underlies many forms of aberrant ocular angiogenesis and resultant vision loss,including in neovascular age-related macular degeneration(nvAMD),proliferative diabetic retinopathy(PDR).

Nucleoside reverse transcriptase inhibitors and Kamuvudines inhibit amyloid-βinduced retinal pigmented epithelium degeneration

Nonfibrillar amyloid-βoligomers(AβOs)are a major component of drusen,the sub-retinal pigmented epithelium(RPE)extracellular deposits characteristic of age-related macular degeneration(AMD),a common cause of global blindness.We report that AβOs induce RPE degeneration,a clinical hallmark of geographic atrophy(GA),a vision-threatening late stage of AMD that is currently untreatable.We demonstrate that AβOs induce activation of the NLRP3 inflammasome in the mouse RPE in vivo and that RPE expression of the purinergic ATP receptor P2RX7,an upstream mediator of NLRP3 inflammasome activation,is required for AβO-induced RPE degeneration.Two classes of small molecule inflammasome inhibitors—nucleoside reverse transcriptase inhibitors(NRTIs)and their antiretrovirally inert modified analog Kamuvudines—both inhibit AβOs-induced RPE degeneration.These findings crystallize the importance of P2RX7 and NLRP3 in a disease-relevant model of AMD and identify inflammasome inhibitors as potential treatments for GA.