Bleeding in portal hypertensive gastropathy evaluated in terms of gastric mucosal microcirculation and coagulation-fibrinolysis system

Gastric intramucosal bleeding in portal hypertensive gastropathy was investigated in terms of gastric mucosal microcirculation, coagulation-fibrinolysis factors, and local fibrinolysis in patients with liver cirrhosis. The gastric mucosa was examined by endoscopy, and the patients were classified into two groups with or without bleeding. Gastric mucosal blood flow was measured simultaneously with coagulation-fibrinolysis factors or local fibrinolysis in both groups. As gastric mucosal blood flow, the gastric mucosal blood volume (IHb) and the oxygenated hemoglobin concentration (ISO2) were determined by the organ reflection spectrum method. Coagulation-fibrinolysis factors were measured in the blood. For evaluation of local fibrinolysis, gastric biopsy specimens were placed on a standard fibrin plate, and the fibrinolysis area was measured. Compared with the non-bleeding group, the bleeding group showed increased IHb and decreased ISO2 (p < 0.05), suggesting marked congestion of blood flow. Gastric intramucosal bleeding was frequently observed in patients with marked congestion of blood flow and markedly abnormal values of coagulation-fibrinolysis factors. Gastric local fibrinolysis was also significantly enhanced in the bleeding group (p < 0.05). In addition, local fibrinolysis was correlated positively with the gastric mucosal blood volume (r = 0.68, p < 0.05) and negatively with the oxygenated hemoglobin concentration (r = -0.58, p < 0.05). These results suggest the following mechanism of gastric mucosal bleeding in liver cirrhosis and portal hypertension. Congestion of gastric mucosal blood flow is present in liver cirrhosis and portal hypertension. An increase in the microvascular pressure and hypoxia cause release of tissue plasminogen activators from gastric mucosal cells and vascular endothelial cells. As a result, gastric local fibrinolysis is enhanced, causing gastric mucosal bleeding.     

Effect of the dietary vitamin concentrate Ammivit on survival of irradiated BALB/c mice]

Hemorrhage from duodenal varices may be severe and life threatening. We report a patient with portal hypertension and bleeding duodenal varices caused by cirrhosis of the liver. Endoscopic sclerotherapy and intravenous vasopressin failed to control bleeding in this patient. Hemorrhage was subsequently controlled by placement of a transjugular intrahepatic portosystemic shunt. We recommend that in patients with life-threatening hemorrhage from duodenal varices caused by cirrhosis of the liver, transjugular intrahepatic portosystemic shunt be considered in the management.     

Effects on gastric circulation of treatment for portal hypertension in cirrhosis

We evaluated the gastric circulatory effects of the type of treatment administered for portal hypertension. Of 14 patients with cirrhosis, seven received a transjugular intrahepatic portosystemic shunt (TIPS; group T) and seven received percutaneous transhepatic portographic embolization (PTPE; group P). Patients were evaluated over the course of one year. After treatment, portal venous pressure was significantly reduced from 39 +/- 6 cm H2O to 32 +/- 5 (P < 0.001) in group T and was significantly elevated from 29 +/- 10 to 33 +/- 8 (P < 0.05) in group P. The portal flow velocity (Vmean) was significantly higher in group T vs group P (P < 0.0001). The congestion index was significantly lower in group T than in group P (P < 0.0001). The gastric mucosal blood flow was increased in group T but was unchanged in group P. Esophageal varices showed some improvement in both groups, but the portal hypertensive gastropathy was improved only in group T. These findings help to explain the differing effects on the gastric circulation related to the type of treatment used for portal hypertension.     

Assessment of hemodynamic changes in rat stomachs by laser Doppler velocimetry and reflectance spectrophotometry. Effects of ethanol and prostaglandin E2 under ischemic and congestive conditions

One of the ulcerogenic mechanisms by which ethanol induces mucosal lesions in the stomach is the depression of gastric mucosal blood flow (GMBF). The goal of this study was to determine whether lesion formation is the result of vascular ischemia alone or ischemia combined with congestion. The aims of this study were to answer this question by evaluating the relationship between GMBF, oxygen saturation (ISO2) and hemoglobin volume (IHb) in the gastric mucosa under the influences of ethanol and prostaglandin E2 (PGE2) in the ischemic and congestive states, using a laser Doppler flowmeter and tissue spectrum analyzer. Ligation of the gastric celiac artery or vein markedly decreased the GMBF and the ISO2 level. The former procedure also reduced but the latter increased the IHb level. Ethanol administration produced effects similar to venous ligation, i.e. vascular stasis with ischemia. There was a negative correlation between GMBF and severity of lesion formation after ethanol administration. However, at the lesion site all the hemodynamic parameters were significantly reduced, indicating that a necrotic condition had occurred. PGE2 preincubation (25 micrograms) elevated GMBF, ISO2 and IHb levels. It also alleviated the reduction of blood flow induced by ethanol and increased the recovery rate of GMBF and ISO2 after the release of arterial or venous ligation. It is concluded that the decrease in blood flow due to ethanol is probably caused by constriction of venules rather than arterioles inside the mucosa, and this effect could lead to vascular congestion. PGE2 probably dilates both arterioles and venules in the gastric mucosa and thereby increases the blood flow in the gastric mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of hemorrhages by rupture of cardio-tuberous varices with transjugular intrahepatic portasystemic shunt

Twelve consecutive patients admitted for bleeding from ruptured gastric varices were treated with transjugular intrahepatic portosystemic shunts and followed for a mean of 6 +/- 3 months (range: 8-293 days). The shunt was performed successfully in all 12 patients. The shunt occluded in 3 patients (respectively 19, 101 and 103 days after insertion) of whom one remained asymptomatic and two experienced rebleeding. Four patients presented with acute encephalopathy, spontaneously in two and after rebleeding in two. Three patients died, two after rebleeding and one of septic shock secondary to pneumonia. Overall, 9 patients survived a mean of 211 +/- 92 days with no rebleeding, 8 of whom have not yet experienced any complications. These results suggest that transjugular intrahepatic portosystemic shunts could be useful in treating hemorrhages from ruptured gastric varices and in preventing their recurrence.     

Transjugular intrahepatic portosystemic shunt. Treatment of patients with recurrent bleeding from esophageal varices

We report the results of transjugular intrahepatic portosystemic shunt (TIPS) procedure in six patients with liver cirrhosis and recurrent bleeding or acute intractable bleeding from oesophageal varices in spite of multiple sessions of sclerotherapy. Median follow-up was 15 months (range 1-24 months). The procedure was technically successful in all patients without procedure-related morbidity or mortality. Four of the procedures were performed electively and two as an emergency procedure. The portosystemic pressure gradient decreased to below 12 mmHg following TIPS implantation and the shunt bloodflow was one quarter to three-quarters of the portal bloodflow determined by Doppler ultrasound. Recurrent bleeding occurred in one patient but was amenable to endoscopic sclerotherapy. In this patient the shunt had developed a stenosis that was treated by balloondilatation and insertion of an additional stent six months following the initial procedure, and no further bleeding occurred. The remaining five patients had no rebleeding episodes. Repeated Doppler examinations in the followup period demonstrated patency of all shunts. None of the patients developed portosystemic encephalopathy. One patient died of cerebral haemorrhage, unrelated to TIPS, 16 months following implantation. Another patient died 14 months following TIPS due to acute mesenteric occlusion and septicaemia. We conclude that TIPS is feasible and effective in selected patients with liver cirrhosis and persistent or recurrent variceal bleeding following repeated endoscopic therapy.     

Surgical approach to posthepatitic cirrhotic patient today

A posthepatitic cirrhotic patient may undergo elective or urgent abdominal operation for an extra-hepatic or hepatic disease. According to the high postoperative morbidity (61%), surgery is indicated only for symptomatic or complicated cholelithiasis. A surgical procedure for refractory ascites has been devised to create a permanent peritoneo-venous shunt by a one way pressure-sensitive valve (Leveen). The procedure is simple and brings a long lasting relief with recovery in strength and nutrition and improved kidney function. Sclerotherapy is widely used to treat acute variceal bleeding while repeated sclerotherapy is used in the long-term management to eradicate varices. When indicated, liver transplantation is the best treatment to prevent variceal bleeding recurrence. Also portosystemic shunts effectively prevent recurrent variceal bleeding. They are, however, major operations with an important morbidity and mortality, particularly in poor risk patients. The most advocated shunts today are the Warren distal splenorenal shunt and the Sarfeh portacaval shunt using a small diameter prosthetic H-graft. The transjugular intrahepatic portosystemic stent-shunt (TIPSS) is a new treatment for portal hypertension and its complications. From a haemodynamic point of view it allows balanced hepatic perfusion. Postoperative mortality is rare; further bleeding and encephalopathy are reasonably acceptable. The most relevant complications concern dislocation of the prosthesis, stenosis and thrombosis of the shunt, which can be corrected by non-invasive dilatation. Encephalopathy is the main complication of surgical portosystemic shunts. It is usually controlled by protein diet restriction, and administration of lactulose or oral antibiotics. In severe forms the patients may be treated by an oesophageal transection with oesophagogastric devascularization, and by a postoperative suppression of the portosystemic shunt using external maneuvers. Posthepatitic liver cirrhosis is frequently complicated by the onset of an hepatocellular carcinoma. Early detection (aFP, DCP, Echography) and curative resection are the best ways to improve long term prognosis. Segmentectomy achieves a good balance between liver function preservation and radical exeresis for tumours less than 5 cm in diameter. Liver transplantation may be considered for the treatment of long-staging cirrhotic patients in whom hepatocarcinoma development has been recognized at an early presymptomatic stage. Hepatic arterial chemoembolization (gelfoam, lipiodol, mitomycin C or doxorubicin) may improve the survival of patients with unresectable malignant disease of the liver. A marked reduction in liver size may occur in the weeks following an effective chemoembolization with objective (CT scan) and subjective improvement (amelioration of specific symptoms). Liver chemoembolization is absolutely contraindicated in the presence of jaundice disordered liver function (Child C) or complete portal venous obstruction. In the last years, the number of patients treated by liver transplantation has greatly increased. Surgical technique, postoperative management, and immunosuppressive therapy account for the dramatic improvement of the results. However, indications for selection of patients and the timing for liver transplantation are still not well defined.     

Paradoxical cerebral emboli after transjugular intrahepatic portosystemic shunt and coil embolization for treatment of duodenal varices

The use of the transjugular intrahepatic portosystemic shunt to treat portal hypertension has resulted in increased recognition of its associated complications. We report a patient with refractory duodenal variceal bleeding treated with transjugular intrahepatic portosystemic shunt, as well as coil embolization, who subsequently developed bilateral cerebral and cerebellar infarcts consistent with arterial emboli. This complication has not been previously described. The patient was found to have a patent foramen ovale and a right to left intracardiac shunt leading to paradoxical embolization of clots traveling from portal to systemic venous circulation, then to the left atrium. With the relative frequency of patent foramen ovale in the population, our observation has potential importance for patients with right to left cardiac shunts who are being considered for portosystemic shunt procedures, or who are undergoing embolization of bleeding varices.     

Measurement of collateral circulation blood flow in anesthetized portal hypertensive rats

AIMS: The aim of this study was to develop a technique to measure collateral blood flow in portal hypertensive rats. METHODS: Morphological techniques included inspection, casts and angiographies of portosystemic shunts. The main hemodynamic measurements were splenorenal shunt blood flow (transit time ultrasound method), percentage of portosystemic shunts and regional blood flows (microsphere method). In study 1, a model of esophageal varices was developed by ligating the splenorenal shunt. In study 2, morphological studies of the splenorenal shunt were performed in rats with portal vein ligation. In study 3, the relationship between splenorenal shunt blood flow with percentage of portosystemic shunts was evaluated in dimethylnitrosamine cirrhosis. In study 4, secondary biliary, CCl4 and dimethylnitrosamine cirrhosis were compared. In study 5, rats with portal vein ligation received acute administration of octreotide. In study 6, rats with dimethylnitrosamine cirrhosis received acute administration of vapreotide. RESULTS: Blood flow of para-esophageal varices could not be measured. SRS blood flow was correlated with the mesenteric percentage of portosystemic shunts (r = 0.74, P < 0.05), splenic percentage of portosystemic shunts (r = 0.54, P < 0.05) and estimated portosystemic blood flow (r = 0.91, P < 0.01). Splenorenal shunt blood flow was 6 to 12 times higher in portal hypertensive rats, e.g., in portal vein ligated rats: 2.8 +/- 2.7 vs 0.3 +/- 0.1 mL.min-1 in sham rats (P < 0.01), and was similar in the different cirrhosis models but was higher in portal vein ligated rats than in cirrhotic rats (1.2 +/- 0.7 vs 0.6 +/- 0.6 mL.min-1.100 g-1, P = 0.05). Octreotide significantly decreased splenorenal shunt blood flow: -23 +/- 20% (P < 0.01) vs -6 +/- 8% (not significant) in placebo rats. The variation of splenorenal shunt blood flow after vapreotide was significant but not that of the splenic percentage of portosystemic shunts compared to placebo. CONCLUSIONS: The splenorenal shunt is the main portosystemic shunt in rats. The measurement of splenorenal shunt blood flow is easy, accurate and reproducible and should replace the traditional measurement of the percentage of portosystemic shunts in pharmacological studies.     

Membranoproliferative glomerulonephritis induced by portosystemic shunt surgery for non-cirrhotic portal hypertension

The liver and spleen both have important phagocytic functions and contain monocytes/macrophages which clear immune complexes. We describe here three patients who presented proteinuria and hematuria 7 to 13 years after portosystemic shunt surgery, which diverted portal venous blood to the systemic circulation. They had hematemesis and/or melena and underwent mesocaval shunt surgery and splenectomy in childhood because of non-cirrhotic portal hypertension with esophageal varices. Renal biopsy specimens revealed findings characteristic of membranoproliferative glomerulonephritis (MPGN) type I. Immunohistologically, these three cases were accompanied by a distinct IgA deposition along with a marked C3 deposition. The IgA observed in these three cases contained not only IgA1 but also IgA2, which is the predominant form of mucosal IgA. On the other hand, of 20 patients with idiopathic MPGN type I with IgA deposition (n = 20), only two were positive for IgA2, and the distribution was focal and segmental. Our study shows that MPGN type I may have developed secondary to portosystemic shunt. This secondary form of MPGN type I may be caused by a reduced clearance of immune complexes in the liver and their deposition in the glomerulus, since a portosystemic shunt routes portal venous blood from the intestinal tract directly to the systemic circulation.     

Transjugular intrahepatic portasystemic stent shunt (TIPSS). Technique of implantation

Implantation of a transjugular intrahepatic portosystemic stent shunt (TIPSS) is guided by ultrasound and fluoroscopy. Today this stent is clinically established as a concept of "minimal invasive therapy" to treat recurrent variceal bleeding in patients with portal hypertension. We describe its technical steps in detail, giving the materials used. "Intraoperative" and "postoperative" monitoring and the typical features of an ideal shunt are described.     

Longterm outcome after injection sclerotherapy for oesophageal varices in children with extrahepatic portal hypertension

A consecutive series of 36 children with bleeding from oesophageal varices secondary to extrahepatic portal hypertension was successfully treated by endoscopic injection sclerotherapy and followed up over a mean period of 8.7 years after variceal obliteration. There were no deaths from portal hypertension or its treatment and morbidity related to oesophageal sclerotherapy was minimal. Endoscopic injection sclerotherapy alone proved safe and effective in controlling variceal bleeding from portal hypertension in over 80% of the children. Recurrent variceal bleeding developed in 10 (31%) patients but half of these were effectively treated by further sclerotherapy. Gastric variceal bleeding unresponsive to sclerotherapy necessitated successful portosystemic shunt surgery in four (13%) patients. Two children required splenectomy for painful splenomegaly. In most children injection sclerotherapy is the best treatment for the primary management of bleeding oesophageal varices, reserving portosystemic shunting or other surgical procedures for those with bleeding from gastrointestinal varices.     

Transjugular intrahepatic portosystemic shunts (TIPS)

Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure recently introduced for the management of complications of portal hypertension. TIPS can be placed in the liver with relative ease by a skilled radiologist with a low risk of mortality. The major complications following the procedure are infection, especially in patients undergoing emergency TIPS, intra-abdominal haemorrhage from capsular punctures, and long-term problems related to encephalopathy and stenosis of the shunt. Encephalopathy is more of a problem in older patients with wide diameter shunts. Stenosis of the shunt is related to pseudo-intimal hyperplasia, probably related to transection of bile ductules during placement of the shunt. In view of the high rate of encephalopathy and stenosis following the shunt, a careful follow-up of all patients, including ultrasonographic and angiographic examination of the shunt, is mandatory. TIPS is used predominantly for the control of acute variceal haemorrhage, prevention of recurrent variceal bleeding, and refractory ascites when conventional treatment has failed. However, the role of TIPS in the management of complications of portal hypertension still awaits the outcome of clinical trials.     

Current status and future possibilities of transjugular intrahepatic portosystemic shunts in the management of portal hypertension

Transjugular intrahepatic portosystemic shunt (TIPS) is an exciting new method for treating complications of cirrhosis. Technical advances have allowed TIPS to be widely applied in the treatment of variceal bleeding. This article presents and discusses the results of recent experiences in TIPS placement. TIPS can be successfully placed in almost all patients. The complication rate of the procedure is low. TIPS is an effective means of controlling variceal bleeding and is especially useful for controlling bleeding in patients awaiting liver transplantation. It may also have a role in the treatment of ascites and other conditions related to portal hypertension. The most important issue facing TIPS is the long-term patency of the shunt. Potential solutions to the problem of long-term shunt patency are discussed.     

Decompression sickness presenting as forearm swelling and peripheral neuropathy: a case report

Bleeding stomal varices is a rare complication of portal hypertension. We report the case of a cirrhotic patient, with a history of colonic adenocarcinoma, who had recurrent bleeding stomal varices. Treatment with transjugular intrahepatic portosystemic shunt and stomal varice embolization was performed because failure of medical treatment of portal hypertension and sclerotherapy. Twenty six months later only one stomal hemorrhage was noted. This suggests that transjugular intrahepatic portosystemic shunt and stomal varice embolization is effective in case of recurrent bleeding of stomal varices.     

Hypergastrinaemia in cirrhosis of liver

The basal acid output (BAO), post-pentagastrin acid output (MAO), fasting and post-prandial gastrin levels in 40 patients with proven cirrhosis of the liver were compared with those in 20 normal controls. The mean BAO and MAO were significantly lower than normal, the mean fasting gastrin level was significantly higher than normal, and the postprandial gastrin response was significantly increased and prolonged. These differences were still significant even when the patients were divided into cryptogenic and alcoholic subgroups. A significant inverse relationship between MAO and the integrated gastrin response to meal was observed both in the normal controls and in the cirrhotic patients. The MAO and integrated gastrin response of the cirrhotic patients did not correlate with the degree of liver function impairment. In five cirrhotic patients fasting and postprandial gastrin levels were unchanged after splenorenal shunt operation. A more consistent abnormality of the gastric mucosa as assessed by endoscopy and biopsies appeared to be mucosal congestion with occasional atrophic gastritis. the severity of mucosal abnormality, however, was unrelated to the degree of hypoacidity. these results indicate, firstly, that the hypergastrinaemia in cirrhotic patients is a reflection of gastric hypoacidity and bears no direct relationship to hepatic dysfunction. Secondly, the gastric hypoacidity does not accrue solely from mucosal abnormality. It is suggested that this hypoacidity may result from the presence of excessive amounts of circulating acid-inhibiting intestinal peptides, which the diseased liver fails to metabolise.     

Acute gastroduodenal mucosal lesion

AGML (acute gastric mucosal lesion) is now recognized as one of the important causal disease for gastrointestinal bleeding. If patients have sudden onsets of epigastralgia, epigastric discomfort, vomiting, hematemesis and melena following probable causes, it seems quite reasonable to make diagnosis of AGML by endoscopy with findings of gastric erosion, hemorrhagic gastritis and gastric ulcer. There are a variety of causes for AGML such as psychological and physical stress, drugs (NSAIDs, antibiotics, adrenal corticoid steroid, anti cancer drug), alcohol, serious organ failure of liver, kidney, heart, anisakiasis and etc. There are aslso a variety of endoscopic findings of AGML such as redness, edema, erosion, ulcer, bleeding which vary quickly in a short time. In this article we describe the definition, the cause, the clinical course, the location, the diagnosis, the endoscopic findings, our cases, the treatment of AGML.     

Transjugular intrahepatic portosystemic stent-shunt

The transjugular intrahepatic portosystemic stent-shunt is a non-surgical method for creating a portosystemic shunt. Early reports suggest that it is effective for treating portal hypertension and variceal bleeding. This review describes the technique and discusses the indications and complications.     

Sucralfate attenuates gastric mucosal lesions and increased vascular permeability induced by ischaemia and reperfusion in rats

Recent evidence suggests that oxygen-derived free radicals are involved in mediating gastric microvascular and parenchymal cell injuries induced by ischaemia and reperfusion. Therefore, the effect of the locally acting anti-ulcer drug, sucralfate, was studied on ischaemia and reperfusion (e.g. induced gastric lesions, intraluminal bleeding, changes in vascular permeability and non-protein sulfhydryl levels in the rat stomach). Allopurinol was used as a known standard antioxidant drug. Rats were subjected to 30 min of gastric ischaemia in the presence of 100 mmol/L hydrochloric acid and reperfusion periods of 15, 30 or 60 min duration. The gastric lesions were assessed microscopically under an inverted microscope. The vascular permeability was quantified by measuring the extravasated Evans blue in the stomach. There were significantly greater numbers of gastric lesions, intraluminal bleeding and leakage of Evans blue during all reperfusion periods as compared with those of ischaemia, with maximum effects occurring at 60 min following reperfusion. Pretreatment with sucralfate (31.25-250 mg/kg, p.o.) or allopurinol (12.5-50 mg/kg, i.p.) 30 min before the procedure, dose-dependently reduced the gastric lesions, intraluminal bleeding, and decreased the vascular permeability induced by ischaemia and reperfusion. Furthermore, sucralfate dose-dependently reverses the ischaemia and reperfusion-induced depletion of mucosal non-protein sulfhydryl levels and inhibited the superoxide radical production in both cell-free xanthine-xanthine oxidase and in the stimulated polymorphonuclear cellular systems. These results suggest that the protection produced by sucralfate against gastric injury may be due to its antioxidant effects.     

Creation of transjugular intrahepatic portosystemic shunts with the wallstent endoprosthesis: results in 100 patients

One hundred patients underwent transjugular intrahepatic portosystemic shunt (TIPS) creation for variceal bleeding (n = 94), intractable ascites (n = 3), hepatorenal syndrome (n = 2), and preoperative portal decompression (n = 1). Shunts were completed in 96 patients. Portal vein pressure was reduced from 34.5 mm Hg +/- 7.6 (standard deviation) to 24.5 mm Hg +/- 6.2; the residual portal vein-hepatic vein gradient was 10.4 mm Hg +/- 0.9. Acute variceal bleeding was controlled in 29 of 30 patients. Of the 96 patients who underwent successful TIPS creation, 26 have died and 22 have undergone liver transplantation; the remaining 48 patients have survived an average of 7.6 months. Variceal bleeding recurred in 10 patients. Fifteen patients developed shunt stenosis (n = 6) or occlusion (n = 9). Patency was reestablished in eight of the nine occluded shunts. Seventeen patients developed new or worsened encephalopathy. The authors conclude that TIPS creation is an effective and reliable means of lowering portal pressure and controlling variceal bleeding, particularly in patients with acute variceal bleeding unresponsive to sclerotherapy and patients with chronic variceal bleeding before liver transplantation.