Clinical Study For Risk Prediction And Treatment Of Esophageal Variceal Bleeding In Patients With Liver Cirrhosis

Background:Variceal pressure has been identified as the key factor leading to variceal rupture.Measuring variceal pressure is important in predicting esophageal variceal bleeding andtreatment efficacy. Noninvasive balloon techniques assume that varices behave as anelastic structure because of their thin walls and lack of external tissue support; thus, thepressure needed to compress a varix (which can be sensed under direct vision usingclear balloons) equals the pressure inside the varix. Manometry uses an endoscopicballoon to measure variceal pressure. Up until now, this method relied on the visualappearance of the varices and, therefore, was subjected to observer bias. Endoscopicballoon methods of measuring variceal pressure have not gained wide popularity. Wehave recently developed a computerized endoscopic balloon manometry (CEBM), withcomputer visualization to determine the moment of variceal wall collapse duringballoon manometry instead of the visual evaluation of variceal compression used in thetraditional balloon method. In this paper, we report the preliminary results of in-vitroand in-vivo testing of CEBM. Whether CEBM can predict efficiently risk of esophagealvariceal bleeding in patients with liver cirrhosis or not haven't reported until now.Portal hypertension can damage living severely and esophageal varices withsubsequent variceal hemorrhage leads to significant mortality in patients with livercirrhosis. Surgery used for the treatment of esophageal varices with subsequent varicealhemorrhage has important clinical significance; however, the ideal surgical modalityhas not yet been identified. The pericardial devascularization appears to be effective forthe control of variceal hemorrhage due to portal hypertension, but also lack of thereaserch of the portal vein pressure and the rate of portal hypertensive gastropathy occurred. With the in-depth study of the pathophysiology and anatomy ofperipheral vascularesophageal, selective periesophagogastric devascularizationcombines advantages of traditional devascularization and shunt, has become a hotpoint, it is a reasonable surgical approach, but lack of more clinical effectliterature. Now, there is still a lot of controversy about carrying out preventive surgeryor not for the portal hypertension patients but without gastrointestinal bleeding. Butthere were more risk of death when the upper gastrointestinal bleeding happened. So,we need take more research about preventive surgery for the patients who have highervariceal pressure and high risk of bleeding.To search and explore drugs which can decrease portal hypertension and preventvariceal hemorrhage effectively is very important. Somatostatin (SST) is used for thetreatment of acute variceal bleeding based on its ability to decrease portal pressure andcollateral blood flow in past two decades. The usual schedule for SST administration isan initial bolus of250g, followed by an infusion of250g/h which is maintained untila48to72-hour bleed-free period is achieved. However, the dose of SST infusedclinically (250g/h) is largely empirical. Hemodynamic studies have shown that toeffectively decrease portal pressure and azygos blood flow, a larger dose may berequired (500g/h). A higher infusion dose of SST (500g/h) resulted in morepronounced effects on the hepatic venous pressure gradient than the classic dose of250g/h. Moreover, bolus administration of SST can cause transient, but dramaticdecreases in portal pressure, porto-collateral blood flow and variceal pressure, however,the effects of SST have not been adequately evaluated.To produce effective tamponadeof actively bleeding varices, the ideal drug therapy should quickly reduce portal venousflow (PVF) and pressure, preferably within seconds to minutes. In view of this, it issomewhat surprising that virtually all previous hemodynamic studies have examineddrug effects at30–240min after the start of bolus administration. To date, there are nostudies which have focused on the immediate-early effects (between1–30min) of SST. ObjectiveThe aims of the present study were:1To evaluate the value of computerized endoscopic balloon manometry (CEBM)on prediction of endoscopic variceal bleeding firstly,and to explore the riskfactors of endoscopic variceal bleeding;2To understand effectiveness for the control of variceal hemorrhage due toportal hypertension of selective pericardial devascularization by comparedwith classical pericardial devascularization, and to explore the clinicalfeasibility of preventive pericardial devascularization;3To validate the clinical effectiveness and reliability of Somatostatin ondecreasing portal hypertension, to validate the clinical effectiveness ofSomatostatin on decreasing portal hypertension by increasing impact dosesand maintenance doses of Somatostatin.Materials and Methods1To assess the applicability of computerized endoscopic balloon manometry(CEBM) for predict a first variceal hemorrhage in cirrhotic patients during theprospective study, and to detect clinical factors in the evaluation of the risk ofbleeding. Fifty-seven patients with liver cirrhosis and esophageal varices whohad never experienced variceal bleeding were followed for12months. Thepatients underwent variceal pressure measurement by CEBM technique. Theendpoint of the study was the presence or absence of a variceal hemorrhage.The relation between variceal hemorrhage with age, sex, etiology of cirrhosis,endoscopic findings of varices (size of varices, red color signs), varicealpressure, Child-Pugh's class, and ascites were studied.2Fourty-five patients with liver cirrhosis and esophageal varices were followed for3years. Twenty-three of that underwent selective pericardialdevascularization, as for treatment group, and twenty-two of that underwentclassical pericardial devascularization, as for control group. FPP was measuredrespectively with venous cannula before and after cutting spleen and the end ofoperation. Splenic fossa effusion and fever were observed after operation. Therelationship between operation with re-hemorrhage, hepatic encephalopathy,portal hypertensive gastropathy and survival were studied.3The aim of this study was to compare the efficacy of different schedules ofSST therapy with placebo on portal pressure in patients with portalhypertension treated with portal-azygous disconnection, and to test whether anincrease in bolus or infusion dose can improve the clinical efficacy of SSTtherapy through double-blind clinical trial.Results1In all57cirrhotic patients, thirty-four patients (34/57,59.6%) developed avariceal hemorrhage. In univariate analysis, the level of variceal pressure(bleeder28.87±2.61mmHg; nonbleeder20.43±2.98mmHg; P <0.001), thediameter of varices (bleeder8.91±2.04mm; nonbleeder7.09±2.75mm; P=0.006), and the endoscopic red color sign on the variceal wall (bleeding rate,bleeder81%vs nonbleeder47.2%, P=0.012) predicted a higher risk ofvariceal hemorrhage. With the results obtained from univariate analysis, amultiple logistic regression model was created which revealed that varicealpressure was major predictor of the risk for a first variceal bleeding (OR=2.817, P=0.003,95.0%C.I. were1.437to5.521). The area under the receiveroperating characteristic (ROC) of variceal pressure for predicting varicealbleeding was0.98and at variceal pressure cutoff value of25.3mmHg,specificity and sensitivity were91%. Higher variceal pressures have been documented in patients with large varices (grade Ⅲ26.56±4.46mmHg vsgrade Ⅱ21.74±4.49mmHg, P=0.02), and in those with red color signs(bleeder,28.40±2.41mmHg vs23.25±3.69mmHg, P <0.001; nonbleeder,26.74±4.95mmHg vs19.97±2.18mmHg, P <0.001), which are those moreprone to bleed.2There was no difference in FFP before and after cutting spleen between twogroups. FFP in different group was (28.19±2.3) mmHg (in control group)andwas (23.25±2.17) mmHg (in treatment group) respectively the end ofoperation. The incidence of spleen nest effusion and postoperative fever inobservation group was significantly lower than control group (P <0.05). For along-term following-up in observation group, the results of survival rate, portalhypertensive gastropathy, hepatic encephalopathy was more good than controlgroup (P <0.05). The esophageal varicose vein pressure inpreventivesurgery patients with preoperative were higher than the treatmentgroup (P <0.05), the treatment group have an advantage than that of controlgroup with3years after surgery (P <0.05).3Patients in the three SST treatment groups demonstrated marked, rapid andhighly significant decreases in portal pressure. The decline in portal pressurewas moderate at1min, achieved a peak effect at5min and remaineddecreased at30min. Infusion of SST at a constant rate of250g/h resulted ina moderate, but significant reduction in portal pressure. The500g/h dosecaused a more pronounced decrease in portal pressure than the250g/h dose;however, there was no statistically significant difference between these2groups. A double bolus injection of SST rapidly induced a more pronounceddecrease in portal pressure than a single bolus injection at1min. However,there was no statistically significant difference between these2groups. Asingle bolus or double bolus injection of SST did not decrease HR, systemic blood pressure or CVP. A continuous infusion of either250g/h or500g/hof SST given after a single bolus injection did not induce significant changesin HR, systemic blood pressure or CVP.ConclusionOur preliminary results indicate that CEBM of esophageal varices is feasible andaccurate. This technique may become a more reliable method for noninvasivemeasurement of variceal pressure and warrants further investigation. The level ofvariceal pressure is a major predictor for variceal bleeding in cirrhotic patients.Selectiveperiesophagogastric devascularization have more advantages, such as simple operationmethods, reliable, practical, and also have a wide range of indications.The postoperative effects are better than the classic devascularization. It combines theadvantages of traditional devascularization and shunt, becomes a new techniquefor our clinical treatment. We found that carrying out preventive devascularization for apatient who had a high degree of risk of bleeding and esophageal varicose vein pressureincreased significantly is safe and feasible. This study shows that SST is effective indecreasing portal pressure within30minutes of administration in patients with livercirrhosis. The clinical schedule used in this study was reasonable and safe.