Selective periesophagogastric devascularization in portal hypertension: results of 56 patients.

BACKGROUND/AIMS: Surgery remains the most reliable treatment for bleeding esophageal varices. We propose a new modified procedure as selective periesophogastric devascularization (SPD), in which paracardial spontenous collaterals were preserved and only pericardial collaterals and perforating branches were disconnected. This study aimed to evaluate the results of SPD in variceal bleeding. METHODOLOGY: The results of 56 patients subjected to SPD for bleeding esophageal varices, were retrospectively reviewed. Etiology of portal hypertension was chronic HBV cirrhosis in 80.4% (45/56), alcoholic in 12.5% (7/56) and others 7.1% (4/56). Child-Pugh grading on admission was A: 78.6% (44/56), B: 14.3% (8/56), and C: 7.1% (4/56). Evaluation was made in terms of effectiveness in controlling the acute bleeding, postoperative morbidity and mortality, recurrent bleeding, encephalopathy and 3-year survival rate. RESULTS: Hemorrhage was controlled in all cases with no death rate. Portal vein thrombosis in 3.6% (2/56), and pleurorrhea in 8.9% (5/56) of cases. In-hospital morbidity was 12.5% (7/56). Complete eradication of varices was observed in 87.5% (49/56) patients. Recurrent variceal bleeding was noticed in 8.9% (5/56) of cases. No patient developed encephalopathy until one month postoperatively. 42 patients were followed up postoperatively for three years. The 3-year survival for patients with Child-Pugh A was 100% (32/32), B was 71.4% (5/7), and 33%(1/3) for C. CONCLUSIONS: SPD was safe and effective in control of bleeding varices in portal hypertension.

Vascular endothelial growth factor attenuates hepatic sinusoidal capillarization in thioacetamide-induced cirrhotic rats.

AIM: To investigate the effect of vascular endothelial growth factor (VEGF) transfection on hepatic sinusoidal capillarization. METHODS: Enhanced green fluorescent protein (EGFP)/VEGF transfection was confirmed by immunofluorescence microscopy and immunohistochemistry both in primary hepatocytes and in normal liver. Cirrhotic rats were generated by thioacetamide (TAA) administration and then divided into a treatment group, which received injections of 400 microg of plasmid DNA encoding an EGFP-VEGF fusion protein, and a blank group, which received an equal amount of normal saline through the portal vein. The portal vein pressure was measured in the normal and cirrhotic state, in treated and blank groups. The average number of fenestrae per hepatic sinusoid was determined using transmission electron microscopy (TEM), while the relative abundance of VEGF transcripts was examined by Gene array. RESULTS: Green fluorescent protein was observed in the cytoplasms of liver cells under immunofluorescence microscopy 24 h after transfection with EGFP/VEGF plasmid in vitro. Staining with polyclonal antibodies against VEGF illustrated that hepatocytes expressed immunodetectable VEGF both in vitro and in vitro. There were significant differences in the number of fenestrae and portal vein pressures between normal and cirrhotic rats (7.40 +/- 1.71 vs 2.30 +/- 1.16 and 9.32 +/- 0.85 cmH2O vs 17.92 +/- 0.90 cmH2O, P < 0.01), between cirrhotic and treated rats (2.30 +/- 1.16 cmH2O vs 4.60 +/- 1.65 and 17.92 +/- 0.90 cmH2O vs 15.52 +/- 0.93 cmH2O, P < 0.05) and between the treatment group and the blank group (4.60 +/- 1.65 cmH2O vs 2.10 +/- 1.10 cmH2O and 15.52 +/- 0.93 cmH2O vs 17.26 +/- 1.80 cmH2O, P < 0.05). Gene-array analysis revealed that the relative abundance of transcripts of VEGF family members decreased in the cirrhotic state and increased after transfection. CONCLUSION: Injection of a plasmid encoding VEGF through the portal vein is an effective method to induce the formation of fenestrae and decrease portal vein pressure in cirrhotic rats. Therefore, it may be a good choice for treating hepatic cirrhosis and portal hypertension.

[Flow cytometry-pathology combined study of breast cancer].

OBJECTIVE: To study the relation between histopathologic grading and some of the cytogenetic and molecular biology characteristics of breast cancer. METHODS: On the basis of estrogen receptor (ER) expression, DNA content, S-phase fraction (SPF), bcl-2 and mutant p53 protein (mtp53) expression were examined by FCM in 121 breast cancer patients. In 66 patients with invasive ductal breast cancer, histopathologic grading was also examined. RESULTS: The aneuploidy rate and DNA index (DI) were significantly different in grade I, II and III breast cancer. SPF and mtp53 expression significantly increased with increase in histopathologic grading (P < 0.05), but bcl-2 did not show this trend. SPF and mtp53 expression were significantly more in breast cancer with negative ER than in those with positive ER (P < 0.05). Again, no such differences in bcl-2 regardless of ER expression. Correlations existed between DI vs SPF, DI vs mtp53, and SPF vs mtp53 expressions (P < 0.01) but bcl-2 did not correlate with any one of them. CONCLUSION: Cytogenetic and molecular biology studies on the basis of histopathologic grading may provide more information in prognostic prediction of breast cancer.

Value of portal hemodynamics and hypersplenism in cirrhosis staging.

AIM: To determine the correlation between portal hemodynamics and spleen function among different grades of cirrhosis and verify its significance in cirrhosis staging. METHODS: The portal and splenic vein hemodynamics and spleen size were investigated by ultrasonography in consecutive 38 cirrhotic patients with cirrhosis (Child's grades A to C) and 20 normal controls. The differences were compared in portal vein diameter and flow velocity between patients with and without ascites and between patients with mild and severe esophageal varices. The correlation between peripheral blood cell counts and Child's grades was also determined. RESULTS: The portal flow velocity and volume were significantly lower in patients with Child's C (12.25+/-1.67 cm/s vs 788.59+/-234 mm/min, respectively) cirrhosis compared to controls (19.55+/-3.28 cm/s vs 1254.03+/-410 mm/min, respectively) and those with Child's A (18.5+/-3.02 cm/s vs 1358.48+/-384 mm/min, respectively) and Child's B (16.0+/-3.89 cm/s vs 1142.23+/-390 mm/min, respectively) cirrhosis. Patients with ascites had much lower portal flow velocity and volume (13.0+/-1.72 cm/s vs 1078+/-533 mm/min) than those without ascites (18.6+/-2.60 cm/s vs 1394+/-354 mm/min). There was no statistical difference between patients with mild and severe esophageal varices. The portal vein diameter was not significantly different among the above groups. There were significant differences in splenic vein diameter, flow velocity and white blood cell count, but not in spleen size, red blood cell and platelet counts among the various grades of cirrhosis. The spleen size was negatively correlated with red blood cell and platelet counts (r = -0.620 and r = -0.8.34, respectively). CONCLUSION: An optimal system that includes parameters representing the portal hemodynamics and spleen function should be proposed for cirrhosis staging.

Angiogenesis effect on rat liver after administration of expression vector encoding vascular endothelial growth factor D.

AIM: To verify the expressing efficiency and angiogenesis effect after administration of expression vector encoding for vascular endothelial growth factor D in normal and ischemic rat liver. METHODS: Ten female S-D rats were administrated with liver tissue dot injection of naked PCHO/hVEGF-D, 50 microg/dot, three dots for each. The same amount of physiological saline was used as control in the neighboring lobe. Fourteen S-D rats, using inflow occlusion of left lateral lobe, were divided into two groups, seven rats in each group. One was ischemic plasmid group, which received naked plasmid PCHO/hVEGF-D injection of 150 microg. The other received the equal amount of natural saline injection and designed as control. The expressions of hVEGF-D in mRNA and protein levels were identified by in situ hybridization and immunohistochemistry, respectively. Endothelial cells were labeled by the factor VIII immunohistochemistrically. The average number of peri-sinusoidal capillaries of each group was calculated and compared statistically 8 days after injection. RESULTS: A large amount of hVEGF-D in mRNA level was found in both normal and ischemic plasmid groups and but none in their corresponding control groups. The protein of hVEGF was also highly expressed in both normal and ischemic plasmid groups than in the controls. The mean number of capillaries under microscopy (X200) of the plasmid group and control was 10.2+/-2.78 vs 7.1+/-2.02 (P<0.05), and those of ischemic plasmid group and ischemic control were 7.43+/-1.72 vs 4.71+/-1.11 with statistical difference (P<0.05). CONCLUSION: The naked PCHO/hVEGF-D dot injection to normal, ischemic rat liver can produce comparatively high expression of hVEGF in both protein and mRNA levels, and prominently increase the number of new capillaries around hepatic sinuses. Therefore, it could be another ideal choice for the treatment of ischemic liver diseases.

Expressions of vascular endothelial growth factor in cirrhotic tissues and their relations to proto-oncogene c-fos, c-myc.

OBJECTIVE: To investigate the significance of vascular endothelial growth factor (VEGF) in the pathogenesis of liver cirrhosis and the correlation between VEGF and proto-oncogene c-fos and c-myc in cirrhotic liver. METHODS: The proteins of VEGF, c-fos, and c-myc were identified immunohistochemically in each tissue section of 53 cases of liver cirrhosis. The correlations between VEGF, c-fos and c-myc were analyzed. The levels of VEGF protein in different Child gradings were also compared. RESULTS: The proteins of VEGF were more highly expressed in Child A and B patients than in Child C patients and controls. The expressions of both c-fos and c-myc were not statistically significant between VEGF positive and negative patients. CONCLUSIONS: The protein level of VEGF can reflect the compensation status of cirrhosis patients and may act as an anti-cirrhotic factor. The proto-oncogene c-fos, c-myc and VEGF may have different mechanisms in the course of cirrhosis or hepatic tumorigenesis.