ABSTRACT
This study was planned to assess the role of pVHL, MET and TFE3 in development, morphogenesis and diagnosis of differen1 types of renal cell carcinomas [RCCs]. Also to assess of there is a link between the pathogenetic ways of these molecules. We studied 59 selected cases of different RCCs types. These were 24 clear cell RCCs [CRCC], 7 papillary RCCs type 1 [PRCC1], 5 papillary RCCs type 2 [PRCC2], 11 XpJl.2 translocation RCCs [XP11:2RCC], 9 chromophobe RCCs [ChRCC] and 3 sarcomatoid RCCs [SRCC]. Paraffin-embedded sections were immunostained using primary antibodies against pVHL, MET and TFE3; the antigen antibody reaction was detected by a streptavidin-biotin kit. We found under expression of pVHL in all CRCG, all SRCC and 6 PRCC1. MET was overe xpressed in 2 PRCC1 and 7 Xp 11:2RCC. Other tumor types showed under expression of MET except 1 SRCC. TFE3 was detected in all Xp11:2RCC as strong nuclear staining Over expression of pVHL was detected in RCCs with papillary pattern. No change in expressions of these molecules in ChRCC was detected. A small correlation between the mean expressions of these molecules was found. No correlation between expressions of these molecules and tumor behavior could be detected Moderate to strong correlation between tumor inflammatory cell infiltrate, tumor necrosis, Fuhrman grade and metastasis was noticed. RCCs have different oncogenic pathways that interact in some points. Such interaction may determine tumor phenotype and histological pattern. Diagnosis of RCCs depends largely on histology however expression of these molecules contributes to the diagnosis. Prognostic factors for RCCs include: tumor inflammation, necrosis and Fuhrman grade
ABSTRACT
The aim of this work is to evaluate the presence of factor V Leiden mutation and the activity of the natural anticoagulants in variceal bleeding in infants and children. This study included 50 infants and children with variceal bleeding who were admitted at the Gastroenterologoy, Hepatology and Malnutrition Unit, Pediatric University Hospital, Assiut University. The search was done in the period from January 2004 till July 2006. The age was between 5 months up to 14 years with mean age of 8.7 +/- 3.9 years. Twenty children of matchable age and sex were enrolled as controls. After the consent of the parents of patients and controls complete clinical examination with the following investigations for the cases and controls were done: 1. Liver function tests [total bilirubin, direct bilirubin, Alanine transaminase [ALT], Aspartate transaminase [AST], Alkaline phosphatase [ALP]] and hepatitis markers. 2. Prothrombin time [PT]. 3. Activated partial thromboplastine time [APTT]. 4. Thrombin time [TT]. 5. Prothrombin concentration [PC]. 6. Fibrinogen. 7. Natural anticoagulants; Protein S, Protein C, Antithrombin III [A TIII]. For cases the following investigations were done: 1. Evaluation of factor V Leiden mutation. 2. Abdominal ultrasound and Doppler. 3. Ultrasound guided needle biopsy to the liver and pathological examination. 4. Upper endoscopy with sclerotherapy or band ligation if needed. Follow up endoscopy after 2 months was done for each case. Out of the 50 patients 14 patients [28%] were diagnosed to have extrahepatic portal hypertension [EHPH] due to portal vein thrombosis [PVT]. 5 of them gave a history of admission in the neonatal intensive care unit and 7 suffered liver cirrhosis. The rest of cases 36[72%] were diagnosed as having intrahepatic portal hypertension [IHPH] 8/50 [16%] cryptogenic cirrhosis, 5/50 [10%] congenital hepatic fibrosis, 10/50 [20%] chronic HBV infection, 5/50 [10%] chronic HCV infection, 3/50 [6%] autoimmune hepatitis, 2/50 [4%] Wilson disease, 1/50 [2%] biliary cirrhosis and 2/50 [4%] neonatal hepatitis. Oesophageal varices was detected in 40 [80%], both oesophageal and gastric varices in 6 [12%] and isolated gastric in 4 [8%] of the cases. In cases with IHPH serum bilirubin and indirect bilirubin as well as liver transaminases and ALP were significantly higher than those of the EHPH and controls. No significant difference was found between EHPH and the controls. Natural anticoagulants were significantly decreased in cases with IHPH in comparison to EHPH and controls. Cases with EHPH show low levels of the natural anticoagulants in 4 while normal values were found in the remaining 10 patients. Leiden mutation was positive in 6 cases of portal vein thrombosis [42%] 4 of them suffered liver cirrhosis and in 3 cases with chronic HCV and in 2 cases with chronic HBV. One of the causes of portal hypertension in infants and children is portal vein thrombosis. PVT may be due to local precipitating factors as umbilical catheterization, umbilical sepsis or neonatal sepsis or due to an inherited factor like inherited thrombophilic mutation as FVL mutation that causes activated protein C resistance. Other inherited factors like inherited deficiency of Protein S, Protein C and ATIII may be the cause of PVT. Band ligation of the oesophageal varices may be beneficial in the treatment especially in cases due to PVT. Sclerotherapy may represent a trigger factor for PVT in cirrhotic patients with genetic thrombophilia. Screening for FVL mutation could be helpful in cases of hepatic cirrhosis to prevent PVT and also is diagnostic for most of the unexplained cases. The use of anticoagulant therapy maybe useful in the recently discovered cases of PVT and so decrease the risk to develop varices and their complications