Comparative effects of 5% ethanolamine oleate versus 5% ethanolamine oleate plus 1% polidocanol for sclerosing esophageal varices.

Sixty-six patients with portal hypertension and esophageal varices due to liver cirrhosis were randomized to receive either 5% ethanolamine oleate (EO) or 5% EO plus 1% polidocanol (EOP) as a sclerosant for endoscopic injection sclerotherapy (EIS). The two groups were well matched with regard to age, sex and the severity of liver disease. In no patient in the two groups was there any major complication, such as esophageal perforation or esophageal bleeding. Eradication of esophageal varices was attained with an average of 4.7 and 4.3 sessions of endoscopic injection sclerotherapy in the ethanolamine oleate and polidocanol groups, respectively. Data on one patient in the ethanolamine oleate group had to be excluded because he left the hospital after 2 sessions of endoscopic injection sclerotherapy. Esophageal ulcers occurred earlier in the polidocanol group (after an average of 2.8 weeks) than in the ethanolamine oleate group (3.8 weeks), the difference being statistically significant (P < 0.01). The rate of occurrence of esophageal stricture requiring more than 2 sessions of bougienage was significantly (P < 0.01) higher in the polidocanol group (16/33, 48%) than in the ethanolamine oleate group (4/32, 12%). This study suggests that the two sclerosants have equal efficacy for treating patients with esophageal varices. With polidocanol there was ulceration and stricture in the distal esophagus.     

Differences in hemostasis among sclerosing agents in endoscopic injection sclerotherapy

Endoscopic injection sclerotherapy is useful in stopping bleeding from esophageal varices. We compared thein vivo effects of sclerosants on thrombogenesis, hemostasis, and endothelial injury. We injected aethoxysclerol (AS) or ethanolamine oleate (EO) into the small veins of the rat intestine. The maximum thrombogenic index with AS was 30.7 and with EO was 9.2. The venous flow stopped sooner with EO than with AS. The thrombi caused by EO were mixed with red blood cells. Heparin pretreatment decreased the thrombogenic index with AS by 96.7%, but not that with EO. The area of the fluorescein-albumin conjugate that permeated from veins with AS was larger than that with EO. The fluorescent intensity with AS was lower than that with EO. We thus concluded that: (1) the size of thrombi is not necessarily proportional to the hemostatic efficacy; (2) changes in a patient's coagulation may affect the potential of sclerosants; (3) the excellent hemostatic efficacy of EO is based on localized injury to the endothelium and the involvement of red blood cells aggregation; and (4)in vivo microscopy is useful in determining the rational selection of sclerosants.     

Ethanolamine oleate is superior to polidocanol (aethoxysklerol) for endoscopic injection sclerotherapy of esophageal varices: a prospective randomized trial

Thirty-four consecutive patients with liver cirrhosis and esophageal varices were included in a prospective randomized trial done to investigate the efficacy and safety of two sclerosants 5% ethanolamine oleate (EO) and polidocanol (1% Aethoxysklerol [AS]) for use in endoscopic injection sclerotherapy (EIS). Eighteen patients were randomly allocated to the group given EO and 16 to the AS group. These two groups were comparable with regard to age, sex, etiology and severity of the liver disease. The bleeding rate from esophageal ulcers which developed during the course of repeated EIS was significantly (P less than 0.05) higher in the AS group (31.3%, 5/16) than in the EO group (0%, 0/18). In 4 occasions bleeding from the esophageal ulcer could not be controlled with AS. In 3 of these 4 bleeding episodes, EO successfully halted bleeding from esophageal ulcer. In the other patient, a Sengstaken-Blakemore tube was inserted to stop the hemorrhage. The period and number of sessions of EIS for eradication of esophageal varices were significantly (P less than 0.05) shorter in the EO group than the AS group (EO: 4.0 +/- 0.8 [means +/- SD] sessions during 4.7 +/- 1.5 weeks versus AS: 4.8 +/- 1.2 sessions during 5.4 +/- 1.6 weeks). The rate of early mortality did not differ between the two groups. We conclude that 5% ethanolamine oleate seems to be superior to 1% Aethoxysklerol when used for sclerosing esophageal varices.     

Evaluation of endoscopic variceal ligation in prophylactic therapy for bleeding of oesophageal varices: a prospective, controlled trial compared with endoscopic injection sclerotherapy

BACKGROUND: To evaluate the efficacy of endoscopic variceal ligation (EVL) in prophylactic therapy for oesophageal varices, we performed a randomized prospective trial to compare the recurrence of oesophageal varices treated by EVL with those treated by endoscopic injection sclerotherapy. METHODS: Fifty patients with liver cirrhosis were divided into two groups at random, after informed consents were obtained, to receive prophylactic therapy for bleeding of oesophageal varices. Group 1 patients underwent sessions of sclerotherapy with 5% ethanolamine oleate used as the sclerosant. Group 2 patients underwent EVL followed by one or two sessions of sclerotherapy. RESULTS: During the 18 month follow-up period, both the recurrence rate in group 2 (56%) and the incidence of bleeding (20%) were significantly higher compared with group 1 (recurrence rate 16%, bleeding 0%). CONCLUSIONS: This result indicates that EVL is not effective for prophylactic therapy for oesophageal varices in liver cirrhosis.     

Endoscopic variceal sclerotherapy in patients with Symmers periportal fibroses

This is a prospective study, carried out in patients with portal hypertension and bleeding oesophageal varices secondary to Symmers (Schistosomal) periportal fibroses, to determine the efficacy of sclerotherapy, the number of sessions needed to achieve full sclerosis, the complications associated with sclerotherapy and the incidence and risk factors for rebleeding. In total, 85 patients were studied with a mean age of 38 years, 76.5% were males. All underwent upper gastrointestinal endoscopy, had different grades of oesophageal varices and underwent intravariceal injection with 5% ethanolamine oleate until they achieved full sclerosis or were referred to surgery. Complications of sclerotherapy included oesophageal strictures, deep oesophageal ulcers, pleural effusion and ascites. Following obliteration of oesophageal varices, 3.5% and 20% developed new gastric varices and portal gastropathy, respectively. Rebleeding occurred in 32% - the only significant predictive risk factor for which was patients with GIII varices following the first sclerotherapy session. Varices recurred in 6% of patients after a mean follow-up period of one year. In total, 93% of our patients achieved full sclerosis after an average of four sessions, and 3.5% were referred for surgery. Three patients (3.5%) died, all from massive rebleeding. In conclusion, sclerotherapy is a safe effective method for treating patients with oesophageal varices due to periportal fibroses.     

Changes in blood coagulation and fibrinolysis following endoscopic injection sclerotherapy

Changes in blood coagulation and fibrinolysis were investigated in twenty seven patients with esophageal varices, who underwent endoscopic injection sclerotherapy (EIS) with 5% ethanolamine oleate with meglumine amidotrioate (EOMA), 1% Aethoxyskererol (AS) and pure ethanol. Changes in platelet aggregation between before and just after EIS were also investigated. Results obtained were as follows. 1) Remarkable changes in blood coagulation and fibrinolysis were observed in twenty patients, who underwent EIS by intravariceal injection combined with paravariceal injection. The patients showed significant change in factor XIa-alpha 1 antitrypsin complex as a result of destruction of the endothelium of varices, caused by the sclerosants. On the other hand, no significant changes were observed in seven patients, treated by paravariceal injection alone. 2) These changes were different from those observed in DIC because they were transient without bleeding tendency or multiple organ failures. 3) Paravariceal injection was suitable for EIS in the patients with very poor liver function. 4) Platelet aggregation was not elevated by EIS.     

Prediction of the recurrence of esophageal varices based on portal vein pressure and oxygen tension in portal and peripheral blood.

In 27 variceal patients completely treated by ethanolamine oleate and polidocanol and followed for more than one year, the recurrence of varices was studied by measuring portal vein pressure and oxygen tension in the portal vein and peripheral arteries and veins before and after EIS. Frequent recurrence was observed in patients with increased PVP after EIS and lower or inverse PVO2-VO2 tension after EIS. The recurrence of varices after EIS may thus possibly be predicted based on portal vein pressure and PVO2-VO2 tension differences.     

Ethanolamine Oleate versus Absolute Alcohol as a Variceal Sclerosant: A Prospective, Randomized, Controlled Trial

Forty-seven patients with esophageal variceal bleeding were randomly allocated to undergo sclerotherapy on a 3 weekly schedule with either 5% ethanolamine oleate (23 patients) or absolute alcohol (24 patients), in an attempt to compare the efficacy and safety of the two sclerosants. Sclerotherapy with absolute alcohol eradicated esophageal varices significantly earlier compared with ethanolamine oleate (12.9 +/- 5.2 vs 22.3 +/- 8.2 wk, respectively, p less than 0.001). The mean number of injection courses and the mean amount of sclerosant required for variceal obliteration was also significantly (p less than 0.001) less in the alcohol-injected group. Although the total number of rebleeding episodes were significantly (p less than 0.05) less in the alcohol-injected group, the frequency of rebleeding was not significantly different between the two groups (20.8% vs 30.4%, respectively, p greater than 0.05). Two (8.1%) patients died due to rebleeding in the ethanolamine-injected group, whereas in the alcohol group, none died. There was no significant difference in the frequency of complications with the two sclerosants. Besides the relative ease of rapid injection due to its aqueous nature, alcohol is readily available and relatively economical (total cost of sclerosant per patient; alcohol US $0.50, ethanolamine US $60). In conclusion, absolute alcohol appears to be a useful alternative to 5% ethanolamine oleate as a variceal sclerosant.     

Comparative effects of 5% ethanolamine oleate versus 5% sodium morrhuate for sclerotherapy of oesphageal varices

Forty-five cirrhotic patients with oesophageal varices were randomized to receive endoscopic injection sclerotherapy with either 5% ethanolamine oleate (EO), or 5% sodium morrhuate (SM). In the EO group, there was a statistically significant higher rate of disappearance of red colour signs on the varices a week after the initial session of sclerotherapy than in the SM group (91.3% vs 45.5%, P less than 0.05). A jet-like bleeding from injection sites at the second session of sclerotherapy occurred in three patients in the SM group and they experienced blurred vision. There was no such occurrence in the EO group. Oesophageal bleeding requiring blood transfusion during the course of repeated sclerotherapy occurred only in the SM group (five patients): bleeding was from a partly thrombosed varix and in four was from oesophageal ulcers. We found that EO administered intravariceally is more efficacious than SM for sclerotherapy of oesophageal varices.     

Successful endoscopic obturation of gastric varices with butyl cyanoacrylate

In 27 patients who had bled from esophagogastric varices, large-sized and/or actively bleeding gastric varices were endoscopically obturated with the tissue adhesive butyl cyanoacrylate. Active bleeding was stopped in six patients. Rebleeding occurred in 10 patients; in four patients, rebleeding was due to ruptured gastric varices, occurred early and was successfully treated by reinjection of gastric varices; in one patient, rebleeding was attributed to ulceration on an injected gastric varix. Eight patients died: two of rebleeding (from esophageal varices or undetermined source), four of sepsis and/or liver failure and two at home of undetermined cause. No specific complication due to injection of gastric varices was observed. The results obtained in this series of patients with gastric varices obturated by injection of butyl cyanoacrylate are much more satisfactory than those obtained in previously published series of patients with gastric varices treated by injection of sclerosants.     

Sclerosants for Variceal Sclerotherapy: A Critical Appraisal

Endoscopic sclerotherapy is a well-accepted technique for the treatment of variceal bleeding. It is carried out by injecting a sclerosant into or around a varix. Sclerosants are oily or aqueous chemicals which produce sclerosis, depending on their necroinflammatory and thrombotic properties. The safety and efficacy of various sclerosants has been evaluated in experimental and human studies. However, due to the presence of a large number of variables, conflicting results have been reported. Based primarily on anecdotal experiences, sodium tetradecyl sulfate, ethanolamine oleate, polidocanol, and alcohol appear to be potent and safe sclerosants. There is great need to perform double-blind trials to identify ideal sclerosant(s) with optimum thrombogenic and minimum necroinflammatory properties.     

Studies on the damage of the cultured endothelial cells and K-562 cells by sclerosants (ethanolamine oleate, Aethoxysklerol and absolute ethanol) used in the treatment of esophageal varices

In injection sclerotherapy against esophageal varices, the damage of the endothelial cells of varices has been supposed to be most important for the formation of thrombi in the injected varices. Mechanisms of the destructive action of three sclerosants (ethanolamine oleate [EO], Aethoxysklerol [AS] & absolute ethanol [Et]) on endothelial cells of varices were studied by means of observation of morphological change of the cells and 51Cr release from the cells in a contact with these sclerosants using cultured human endothelial cells and culture cell line K-562 as target cells. Main mechanism for destructive action of EO on the endothelial cells was considered to be cytolysis through injury of cell membrane, since the cells disappeared immediately after addition of EO with marked release of 51Cr. The destructive action of AS on endothelial cells was considered to be mild cytolysis, since moderate destruction of the cells and moderate release of 51Cr were induced with AS. On the other hand, Et showed a fixative-destructive action on the cells without marked morphological change and with little release of 51Cr. Therefore, it was considered that EO and AS caused the damage of endothelial cells through their lytic action of the cell membrane, whereas Et caused it through the fixative action of the cell membrane.     

Combination treatment of transjugular retrograde obliteration and endoscopic embolization for portosystemic encephalopathy with esophageal varices

The treatment of chronic portosystemic encephalopathy with esophageal varices has not yet been established. We were able to control a case of chronic portosystemic encephalopathy with esophageal varices using a combination treatment of transjugular retrograde obliteration and endoscopic embolization. A 57-year-old man came to our hospital in a confused, apathetic and tremulous state. The grade of encephalopathy was II. The plasma ammonia level was abnormally elevated to 119 microg/dL, and the ICGR15 was 59%. Endoscopic examination revealed nodular esophageal varices with cherry-red spots. There were no gastric varices. Ultrasonography and CT revealed liver cirrhosis with a splenorenal shunt. We first applied endoscopic embolization for the esophageal varices before transjugular retrograde obliteration. We injected 5% ethanolamine oleate with iopamidol retrogradely into the esophageal varices and their associated blood routes under fluoroscopy and obliterated the palisade vein, the cardiac venous plexus and left gastric vein. Transjugular retrograde obliteration was performed 14 days after endoscopic embolization. Retrograde shunt venography visualized the splenorenal shunt and communicating route to the retroperitoneal vein. There was no communicating route to the azygos vein. After obliteration of the communicating route to the retroperitoneal vein with absolute ethanol, 5% ethanolamine oleate with iopamidol was injected into the splenorenal shunt as far as the root of the posterior gastric vein. After transjugular retrograde obliteration, the encephalopathy improved to grade 0 even without the administration of lactulose and branched-chain amino acid. The plasma ammonia level and ICGR15 were reduced to 62 microg/dL and 26%. We conclude that combination treatment of transjugular retrograde obliteration and endoscopic embolization is a rational, effective and safe treatment for chronic portosystemic encephalopathy complicated with esophageal varices.     

A case of gastric varices with gastropericardiac shunt successfully treated by balloon-occluded retrograde transvenous obliteration via the pericardiophrenic vein using a microballoon catheter

Gastric fundal varices developed in a 72-year-old female patient with liver cirrhosis due to hepatitis C virus infection after endoscopic injection sclerotherapy for esophageal varices. Three-dimensional computed tomography (CT) imaging demonstrated that gastrorenal shunts were absent as the drainage vessels of the varices, and the blood flows drained mainly into the pericardiophrenic vein. Balloon-occluded retrograde transvenous obliteration (B-RTO) was performed using a microballoon catheter to prevent bleeding from the gastric varices. The left inferior phrenic vein detectable as the second drainage vessel by venography was embolized with metallic coils and ethanolamine oleate solution was injected into the varices following occlusion of blood flow with a microballoon located in the pericardiophrenic vein. CT examination performed 7 days following B-RTO therapy revealed that the blood flow had disappeared with thrombus formation in the varices. B-RTO therapy with a microballoon catheter may be a useful therapy for gastric fundal varices even in cases without gastrorenal shunts, if the main drainage vessels are determined.     

小剂量硬化剂加固对食管静脉曲张术后的影响

目的探讨在密集套扎疗法的基础上进行硬化加固治疗对于食管静脉曲张复发的防治作用。方法对食管静脉曲张套扎治疗后食管曲张静脉消失或基本消失的患者进行硬化剂加固治疗,从齿状线开始依次向上在残存小曲张静脉内与血管旁粘膜下层注射5％鱼肝油酸钠,每点注射1—2ml,每次共注射10—14ml。观察其对静脉曲张消失后复发的预防作用。结果加固治疗组49例共行硬化治疗132次,平均2．7次,最多治疗4次。随访12～25个月,平均18个月。结果40例（81．9％）患者未发现食管静脉曲张再出现,原有细小静脉明显减轻或消失,9例复发。加固组与单纯套扎组再出血率有明显差异（10．2％对23．4％,P〈0．05）;超声内镜检查显示加固治疗组食管曲张静脉发现率明显低于单纯套扎组（42．9％对76．6％,P〈0．01）;加固治疗组与单纯套扎组穿通支血管检出率无明显差异（42．8％对57．4％,P〉0．05）。治疗后未发现严重并发症。结论套扎治疗后小剂量硬化剂加固治疗可显著减少套扎术后残留的食管曲张静脉、防止闭塞消失的静脉再通、预防再出血,有助于提高结扎术的长期疗效,延缓静脉曲张的复发。     

门脉CTA及内镜对胃静脉曲张诊断及疗效评估的比较研究

目的探讨多层螺旋CT血管造影（门脉CTA，简称CTPA）在诊断门脉高压胃静脉曲张及内镜下胃静脉曲张黏合剂联合硬化剂治疗疗效评估中的作用。方法对20例内镜下证实存在胃静脉曲张的患者予以黏合剂联合硬化剂治疗，治疗前后分别进行多层螺旋CT血管门脉造影检查。结果20例门脉CTA检查均发现胃静脉曲张。GOV-型门脉CTA示血流来源以胃左静脉为主，GOV-2型则由胃左静脉、胃短／胃后静脉混合供血，IGV-型以胃短／胃后静脉供血为主，此型分流发生率较高。经内镜下黏合剂联合硬化剂治疗，孤立性瘤状胃静脉曲张（IGV-型）10例，总体有效率为90．00％，而非孤立性瘤状胃静脉曲张（GOV-型和GOV-型）9例，总体有效率为44．45％。结论门脉CTA能准确、直观、立体地显示血管解剖特点，为门脉高压胃静脉曲张的诊断、治疗方案的选择提供重要依据，并且可作为评估内镜下胃静脉曲张黏合剂联合硬化剂治疗疗效的一种重要手段。     

Treatment of gastric fundal varices by balloon-occluded retrograde transvenous obliteration

Although less common than oesophageal varices in portal hypertension, gastric fundal varices carry a higher mortality rate when they rupture. They are less amenable to sclerotherapy. We have developed a minimally invasive balloon-occluded retrograde transverse obliteration (B-RTO) procedure to treat gastric fundal varices. B-RTO involves inserting a balloon catheter into an outflow shunt (gastric-renal or gastric-vena caval inferior) via the femoral or internal jugular vein. Blood flow is then blocked by inflating the balloon, and 5% ethanolamine oleate iopamidol is injected in a retrograde manner. The embolized gastric varix subsequentlyl disappears. B-RTO was performed in 32 patients with gastric varices. Follow-up endoscopies were performed at intervals of 2–4 months for an average observation period of 14 months. Eradication of the varices has been confirmed in 31 of 32 patients. No recurrence occurred in any patients in the follow-up period. There were no significant changes in liver function after the procedure. We conclude that B-RTO is a safe and effective procedure for the treatment of gastric fundal varices.     

Prospective Randomized Comparison of Sodium Tetradecyl Sulfate and Polidocanol as Variceal Sclerosing Agents

A prospective randomized controlled study was designed to evaluate differences in efficacy and complication rate between the two most commonly used sclerosing agents, sodium tetradecyl sulfate (STD) and polidocanol. Of 52 patients with esophageal variceal bleeding, 26 were randomized to receive sclerotherapy with 1.5% STD and 26 to receive 1% polidocanol at weekly intervals. Eradication of varices was achieved in 88% patients each of the STD and polidocanol group. There was no significant difference between patients injected with STD and polidocanol with regard to re-bleeding (27% vs. 15%) and mortality (11.5% in both). The use of STD, in contrast to polidocanol, was associated with a higher incidence of complications in terms of severe retrosternal pain (27% vs. 4%), deep ulceration (53% vs. 23%), dysphagia (88% vs. 46%), and stricture formation (27% vs. 8%). It was concluded that these two agents were similar in efficacy. However, polidocanol was superior due to a lower incidence of complications.     

Variceal injection sclerotherapy

With the development and widespread use of flexible endoscopes, injection sclerotherapy of oesophageal varices has advanced beyond the early stages. Although slightly different techniques and different sclerosants are used, the results are not strikingly different. The cumulative rate of adverse effects is in the range of 20 to 40%, with a procedure-related mortality of around 1 to 2%. Sclerotherapy is the best available treatment for haemostasis of acute oesophageal variceal bleeding. However, as a long-term therapy it is less effective in the prevention of recurrent gastrointestinal bleeding events, since obliteration of all varices often takes several months. Furthermore, extra-oesophageal bleeding is not amenable to sclerotherapy. Thus, if repeated injections fail to prevent recurrent bleeding, other options such as shunt surgery, transection, chronic medical portal decompression with beta-blockers or even liver transplantation should be considered according to the needs of the individual patient. Prophylaxis of first variceal haemorrhage was beneficial in selected patients with a high bleeding risk. It cannot, however, be generally recommended at present.     

Prediction of oesophageal varices in patients with compensated cirrhosis: A novel scoring system

Background and study aimsPatients with liver cirrhosis are recommended to undergo an evaluation of oesophageal varices to assess their risk of bleeding. Predicting the presence of oesophageal varices through non-invasive means may reduce the number of unnecessary endoscopies. This study was designed to develop a predictive model for varices in patients with Child-Pugh A liver cirrhosis.Patients and methodsRetrospective analysis was performed on 70 patients with compensated cirrhosis. Clinical and laboratory parameters Child-Pugh class and platelet count were assessed. Ultrasonographic characteristics of splenic axis and portal vein diameter were noted. The data were assessed by univariate analysis and a multivariate logistic regression analysis.ResultsWe found the prevalence of oesophageal varices in patients with child A liver cirrhosis to be 64.3%. Platelet count, splenic axis, portal vein diameter, platelet count/splenic axis ratio, portal vein congestive index, and renal resistive index were found to be significantly associated with the presence of oesophageal varices on univariate analysis. A platelet count of 100,000, platelet count/splenic axis ratio <900, renal resistive index ?0.68, and a portal vein congestive index of ?0.07 had the highest discriminating value, at which the number of true positive patients was highest and the number of false positive patients was lowest (50% and 3%, 63% and 13%, 41% and 0%, 57% and 1%, respectively). Multivariate analysis identified platelet count, platelet count/splenic axis ratio, renal resistive index, portal vein congestive index as independent factors for the presence of oesophageal varices.ConclusionOur data suggest that a new score system composed of some laboratory and ultrasonographic parameters may predict the presence of varices in patients with Child-Pugh A cirrhosis, and that the score system may help physicians to identify patients who would most likely benefit from screenings for oesophageal varices.