Immunohistochemical localization of vascular endothelial growth factor in the rat portal hypertensive gastropathy.

BACKGROUND AND AIMS: Portal hypertensive gastropathy (PHG) is now recognized to be a distinct entity. Recently, angiogenesis has been noticed as a key factor in clarifying the pathophysiology of various diseases. Angiogenesis in the PHT of explored gastric mucosa has yet to be explored. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. The aim of the present study was thus to investigate whether the hypoxic state exists in PHG, and whether VEGF appears more strongly in PHG than in normal gastric mucosa and, if so, what exactly is the role of the hypoxic state and VEGF in PHG. METHODS: At 1, 3, 7 and 14 days after either a portal ligation or sham operation, the portal venous pressure, the gastric mucosal blood flow volume and the blood gas were measured and, the expression of VEGF and antiproliferating cell nuclear antigen (PCNA) in gastric mucosal specimens was immunohistochemically assessed. RESULTS: The portal pressure (PP) and the gastric mucosal blood flow (GMBF) in the PHT rats were significantly greater than in the control (CTR). Both the SaO2 and PaO2 of the arterial blood gas were lower in the PHT rats than in the control rats. The percentage of VEGF expression in the PHG was found to be higher than that in the control gastric mucosa. The percentage of PCNA expression in the PHG was higher than that in the control gastric mucosa. CONCLUSION: The levels of SaO2 and PaO2 were lower in the PHT rats. There is a possibility that a kind of portal hypertensive gastric change may trigger an enhanced histochemical expression of VEGF. The increased activity of VEGF may have a possibility of the hypoxic gastric mucosal state caused by the presence of active congestion. This damaged mucosal state 'PHG' may thus facilitate the fragility in PHG and such lesions may be slow and insidious, which may therefore lead to sudden and severe anemia, thus causing massive and sometimes fatal hemorrhaging.

Role of nitric oxide and endothelin-1 in a portal hypertensive rat model.

BACKGROUND: Portal hypertension is often accompanied by a hyperdynamic circulation state. Some reports have suggested that nitric oxide (NO) plays an important role in this hyperdynamic state. On the other hand, although endothelin (ET)-1, a powerful vasoconstrictor, was recently identified, little is known about its role in portal hypertension or about the interaction between NO and ET-1. The aim of this study was therefore to investigate whether or not the inhibitor of NO synthase (NOS) might improve portal hypertension, and also to clarify the relationship between NO and ET-1. METHODS: Portal hypertensive (PHT) rats, in which hypertension was induced by a two-step ligation of the portal vein (PVL), were used. The mean arterial pressure (MAP), portal pressure (PP), visceral blood flow volume (BFV), and serum levels of NO and ET-1 were determined in PVL rats treated with two NOS inhibitors with different functions: N(G)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AG). Control (CTR) rats. treated by a sham operation (SO), were also studied. RESULTS: Two-step PVL treatment induced a significant increase in the serum level of NO3-and ET-1 in the portal vein. L-NAME and AG administration significantly decreased PP at doses of 50 mg/kg in PHT rats after 60 min administration, while no inhibitor effected any modification in the CTBR rats. Both NOS inhibitors increased MAP and decreased PP and BFV in the portal vein, gastric mucosa, and spleen, in addition to decreasing the serum levels of NO3- and ET-1 in the PHT rats, while neither blockade modified any parameters in the CTR rats. In PHT rats, L-arginine, a NO substance, reversed the effect of L-NAME, while it did not induce any recovery from the AG effect. CONCLUSIONS: In PHT rats, NO seems to contribute to portal hypertension. PVL increases not only the serum level of NO3-, but also that of ET-1 in the portal vein. Both L-NAME and AG reduce PP and BFV of the portal vein, spleen, gastric mucosa. and liver. In addition, the inhibition of NOS diminishes the serum level not only of NO, but also of ET-1. Use of an appropriate NOS inhibitor may therefore positively affect the hyperdynamic state in portal hypertension.

Endoscopic ligation of oesophageal varices compared with injection sclerotherapy in primary biliary cirrhosis.

BACKGROUND AND AIMS: Oesophageal varices are an important complication in primary biliary cirrhosis (PBC). However, there have yet to be any studies made on treatment of oesophageal varices in PBC. We therefore studied the efficacy and related complications of endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS) as an initial treatment in primary biliary cirrhotic patients. METHODS: From December 1985 to March 1999, 29 biliary cirrhotic Japanese patients with portal hypertension and oesophageal varices were treated in our clinics. Eleven patients were treated with EVL and EIS, and 18 patients underwent EIS only. The liver function, renal function and respiratory function were studied before and after endoscopic treatment and any complications were also examined. RESULTS: In stages III and IV, significant differences were observed in the serum levels for total bilirubin and gamma-glutamic pyruvic transaminase only in the EIS group. Significant differences were observed in the rate of appearance of pyrexia, retrosternal pain and pleural effusion between the EIS and EVL groups. CONCLUSION: EVL significantly reduced the adverse effects associated with EIS at the initial session in primary biliary cirrhotic patients.

Role of vascular endothelial growth factor in portal hypertensive gastropathy.

BACKGROUND AND AIMS: Portal hypertensive gastropathy (PHG) is now recognized as a distinct entity; however, the angiogenesis in the portal hypertensive gastric mucosa has yet to be elucidated. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor involved in both physiological and pathological angiogenesis. The aim of this study was thus to examine the function of VEGF in the portal hypertensive and non-portal hypertensive gastric mucosa. METHOD: Forty-five cirrhotic patients were divided into 3 groups as follows. Group I included 15 patients without PHG who were treated with 1.5 g teprenone/day for 8 weeks: PHG(-)-t. Group II included 15 patients with PHG who were not treated with teprenone: PHG(+)-n. Group III included 15 patients with PHG who were treated with teprenone for 8 weeks: PGH(+)-t. The gastric mucosal blood flow (GMBF), the concentration of gastric mucosal VEGF and hexosamine and the endoscopic findings were studied both before and after medication. RESULTS: Before teprenone treatment, the GMBF in the antrum, fundus, fornix were significantly higher in PHG(+)-n than PHG(-)-t. After treatment, the GMBF in the fundus and fornix significantly decreased more than before treatment in the PHG(+)-t. After treatment, the GMBF in the antrum increased significantly more than before treatment in PHG(-)-t. The gastric VEGF and hexoxamine concentration in the antrum were significantly higher in PHG(+)-n than in PHG(-)-t. After treatment, the gastric VEGF and hexosamine concentration in the antrum significantly decreased in PHG(+)-t while no change in concentration was recognized in PHG(+)-n. In the endoscopic findings, a decrease in the PHG score was recognized in 2 patients in PHG(+)-t. CONCLUSION: Portal hypertensive gastric mucosal change was thus found to trigger a high concentration of VEGF and hexosamine. Such increased activity of VEGF and hexosamine may thus account for the presence of active congestion in PHG.

Laparoscopic splenectomy for splenic artery aneurysm.

Two cases undergoing a laparoscopic splenectomy for the treatment of a splenic artery aneurysm are herein reported. This lesion is relatively rare. Surgical treatment is indicated for such cases since approximately 10% of these aneurysms tend to rupture which thus results in fatal hemorrhaging. Both cases demonstrated aneurysms measuring more than 2 cm in diameter based on the ultrasonography, computed tomography and celiac angiography findings and, as a result, a laparoscopic splenectomy was thus prophylactically performed. This procedure is the preferred technique for high risk patients, such as those with chronic renal failure, as observed in case 1, since patients can be spared the disadvantages of undergoing a laparotomy.

A selective cyclo-oxygenase-2 inhibitor, NS-398, may improve portal hypertension without inducing gastric mucosal injury.

BACKGROUND AND AIMS: Prostacyclin has been shown to play a role in hyperdynamic circulation in portal hypertension. Recently, a new subtype of cyclo-oxygenase (COX), COX-2, which acts as an inducible synthase in response to various stimuli. The aim of this study was to investigate whether COX-2 contributes to portal hypertension and whether a COX-2 blockade induces the same sort of gastric mucosal injury as a COX-1 blockade. METHODS: Portal hypertension (PHT) in rats was induced by a two-step ligation of the portal vein. The mean arterial pressure (MAP), portal pressure (PP), visceral blood flow volume (BFV), serum levels of 6-keto-prostaglandin F1alpha (PGF1alpha), thromboxane B2 (TXB2) and gastric mucosal injury induced by pure ethanol were all measured in PHT rats receiving different inhibitors (indomethacin, a highly selective COX-1 inhibitor; NS-398, a highly selective COX-2 inhibitor). Control rats treated by a sham operation were also studied. RESULTS: The NS-398 administration significantly decreased PP to the same extent as indomethacin at doses of 5 and 10 mg/kg in PHT rats after a 60 min administration, while neither inhibitor affected the control rats. Both inhibitors significantly increased PP after a 30 min administration in the PHT and control rats at a dose of 5 mg/kg while both inhibitors significantly decreased PP after 60 min administration only in the PHT rats. Portal vein ligation treatment induced a significant increase in PP and BFV of the portal vein, gastric mucosa, oesophageal mucosa and the serum levels of 6-keto-PGF1alpha and TXB2, while portal vein ligation treatment induced a significant decrease in BFV of the liver. Both blockades increased MAP and decreased PP and BFV in the splanchnic area and decreased the serum level of 6-keto-PGF1alpha and TXB2 in the PHT rats, while neither blockade modified any parameters in the control rats, except that indomethacin administration significantly decreased the BFV of the gastric mucosa. Indomethacin administration significantly increased the ulcer index (UI). The NS-398 had no effect on UI in either the PHT or control rats. Only indomethacin significantly increased the number of rats demonstrating gastric mucosal long lesions (> 2 cm) in the PHT rats. CONCLUSION: In the PHT rats, prostaglandin seemed to contribute to portal hypertension. Both COX blockades reduced PP and BFV of the portal vein and gastric mucosa. NS-398, a selective COX-2 inhibitor, may, therefore, improve portal hypertension without inducing gastric mucosal injury.

The effect of carbon dioxide pneumoperitoneum on the portal hemodynamics in a portal-hypertensive rat model.

As use of laparoscopic surgery grows, various complications with pneumoperitoneum have been reported. However, there are no reports on the relation between the carbon dioxide (Co2) pneumoperitoneum and portal hemodynamics. The purpose of this study was to determine how the pneumoperitoneum affects the portal hypertensive state. Portal-hypertensive rats, control rats, and sham operation rats were studied. The mean arterial pressure, portal venous pressure, central venous pressure, red blood flow volume of the viscera, and liver and renal function were investigated. The findings of this study suggest that Co2 pneumoperitoneum at less than 10 mm Hg does not present any undue risk to the portal hemodynamics in portal-hypertensive rats; however, more attention should be paid to the IAP in PHT patients undergoing surgery.

Laparoscopic splenectomy for an inflammatory pseudotumor of the spleen: operative technique and case report.

The case of a primary inflammatory pseudotumor of the spleen in a 44 year-old female is herein reported. This lesion is extremely rare, with only 33 cases previously reported. The splenic tumor was preoperatively diagnosed as a hemangioma by the combined modalities of ultrasonography, computed tomography and magnetic resonance imaging. A laparoscopic splenectomy was, thus, performed in order to make a final diagnosis. Pathological examination of the mass revealed an inflammatory process. Based on the above findings, a laparoscopic splenectomy is recommended when the tumor is suspected to be benign.

Jejunal variceal bleeding after esophageal transection in a patient with idiopathic portal hypertension.

This report describes a 38-year-old man with massive gastrointestinal bleeding from jejunal varices. He had been previously diagnosed to have idiopathic portal hypertension and esophageal varices, and had undergone an esophageal transection 8 years earlier. The pre-operative diagnosis was a suspected hemorrhage from the small intestine as visualized by 99mTc-HSAD scintigraphy (technetium 99m-labeled human serum albumin D-type) and was not considered to be repeated massive lower GI tract bleeding. An exploratory laparotomy was performed, and intra-operative endoscopy revealed active bleeding from the jejunal varices. A partial resection of the small intestine resulted in a complete resolution of the bleeding. A review of the literature thereafter disclosed twelve previously reported cases of jejunal variceal bleeding.