Endoscopic variceal ligation is superior to combined ligation and sclerotherapy for esophageal varices: A multicenter prospective randomized trial

Patients who have bled from varices remain at risk for rebleeding. There is interest in methods that would enable rapid eradication of varices. The present trial was designed to study whether combining ligation with sclerotherapy will allow quicker eradication of varices than either modality alone. Patients with bleeding esophageal varices were randomized into ligation or combination therapy groups. Patients in the ligation group were treated with endoscopic rubber band ligation alone. In combination group patients, each variceal column was ligated distally and 1 mL of ethanolamine was injected proximal to each ligated site. Subsequent treatment sessions were at 7- to 14-day intervals until varices were eradicated. The clinical and endoscopic characteristics of 25 patients in the ligation group were similar to those of 22 patients in the combination group. Follow-up was up to 30 months. Active bleeding was controlled in 100% of patients in the ligation group and 75% of those in combination group (P = NS). It took 3.3 +/- .4 (range, 1-7) sessions to eradicate varices with ligation and 4.1 +/- .6 (1-7) with combination therapy (P = NS). Survival (four deaths in ligation group, 8 in combination group), rebleeding rate (25% vs. 36%), and varix recurrence (16% vs. 23%) also were similar. There were more complications with combination therapy, including deep ulcers (65% vs. 20%; P < .05); dysphagia (30% vs. 0%; P < .05), with three strictures requiring dilation; and pain (30% vs. 10%; P = NS). Our results show that sclerotherapy combined with ligation offers no benefit over ligation alone. The higher complication rate with combination therapy does not warrant this approach.(Hepatology 1997 Jan;25(1):71-4)     

Long-term administration of PPI reduces treatment failures after esophageal variceal band ligation: a randomized, controlled trial

Background and purpose

Elective esophageal variceal ligation (EVL) is performed to decrease the risk of variceal hemorrhage. EVL is associated with adverse effects, including post-ligated bleeding, chest pain, and dysphagia. Proton pump inhibitors (PPIs) are the most potent pharmacological agents for inhibition of gastric acid secretion. However, the long-term effect of PPIs after EVL remains unclear. The aim of this study was to assess the efficacy of rabeprazole, a PPI, after variceal eradication by EVL.

Methods

We performed a randomized, controlled trial in Kitasato University East Hospital. The primary endpoint was treatment failure, defined as variceal hemorrhage or severe medical complications. Between July 2007 and September 2010, 43 patients were randomized into this study and followed up until September 2010.

Results

Twenty-one patients in the rabeprazole arm received 10?mg rabeprazole daily after EVL, and 22 patients in the control received no antisecretory treatment from the same stage. Baseline characteristics did not differ between the groups (median Child-Pugh score, 6; median age, 62?years; median follow-up, 18.7?months). The trial was stopped early after an interim analysis showed that the risk of bleeding and failure of rabeprazole treatment was lower than that of no antisecretory treatment with the log-rank test showing a significant difference between the groups (P?=?0.007) and a hazard ratio of 0.098 [95% confidence interval, 0.012?C0.79 (P?=?0.029)].

Conclusions

Long-term administration of PPIs reduced the risk of treatment failure after EVL. Acid suppression therapy should also be considered as a treatment option after EVL.     

A randomized control trial of bi-monthly versus bi-weekly endoscopic variceal ligation of esophageal varices

Endoscopic variceal ligation (EVL) is a safe and simple procedure now being used on a widening scale. Yet most patients who undergo endoscopic treatment for esophageal varices eventually require additional treatment for recurrent varices. In this study, we investigated and compared the efficacy and long-term results of EVL performed in three treatments with a total of sixteen O-rings at two different intervals; bi-weekly (once every 2 wk: the conventional interval) and bi-monthly (once every 2 months). A total of 63 patients with esophageal varices were randomly assigned to groups receiving bi-weekly or bi-monthly EVL treatment. Optimal medical therapy was assessed by one medical doctor who was unaware of the patients' treatment assignments. Three parameters of treatment outcome were evaluated: the rate of recurrence, rate of additional treatment, and overall survival. The overall rates of variceal recurrence and additional treatment were both higher in the bi-weekly group than in the bi-monthly group (p < 0.001). In conclusion, EVL performed for the treatment of esophageal varices at bi-monthly intervals brought about better results than the same treatment performed at bi-weekly intervals. The treatments intercalated by the longer interval obtained a higher total eradication rate, lower recurrence rate, and lower rate of additional treatment.     

Clinical trial of prophylactic endoscopic variceal ligation for esophageal varices

Endoscopic variceal ligation is an effective therapy for variceal bleeding, and use of the method has recently been increasing. We evaluated the clinical usefulness of prophylactic endoscopic variceal ligation. Twenty-two patients with enlarged, tortuous varices and red color signs were selected. These patients were treated with ligation therapy alone and the varices were eradicated, i.e., reduced to small, straight varices without red color signs. Ligation therapy was withdrawn if the general condition of the patient worsened or if the varices could not be removed by suction. Follow-up endoscopy was performed every 4 months, and another ligation was performed if there were recurrent varices or variceal bleeding. The total reduction rate was 86.4%, and eradication required two sessions of therapy and 30 days of hospitalization on average. Complications included esophageal injury in 1 patient and treatment-induced bleeding in 1 patient; both complications were easily controlled. No variceal bleeding occurred after the eradication. There was no mortality due to gastrointestinal bleeding during the median follow-up period of 346 days. Prophylactic endoscopic variceal ligation made it possible to prevent fatal variceal bleeding with a minimum risk of complications, suggesting that this could be an alternative method for the prevention of first-time variceal bleeding.     

Endoscopic band ligation plus argon plasma coagulation versus scleroligation for eradication of esophageal varices

Background and Aim: The aim of this study was to evaluate endoscopic band ligation plus argon plasma coagulation versus scleroligation. Methods: Patients were randomized to: Group I, 50 patients subjected to endoscopic injection sclerotherapy; Group II, 50 patients subjected to variceal band ligation; Group III, 50 patients subjected to combined endoscopic sclerotherapy and band ligation; and Group IV, 50 patients subjected to endoscopic band ligation plus argon plasma coagulation. Results: A comparison of the number of therapeutic sessions showed that group III underwent significantly fewer sessions. As regards post‐treatment complications, Group I showed a high incidence of transient pyrexia, transient dysphagia and/or retrosternal pain and ulceration, while in group II a higher incidence of rebleeding was demonstrated, as well as a higher incidence of esophageal varix recurrence after eradication during the follow‐up period. A higher mortality incidence was detected in groups I and II. The follow‐up incidence did not significantly differ between the different study groups. Conclusion: Scleroligation allows very rapid eradication of varices, has a low recurrence rate, avoids the disadvantage of high recurrence of band ligation alone, and does not require special skills over sclerotherapy or band ligation. Also, band ligation plus argon plasma coagulation allows for very rapid eradication of varices, and a low recurrence rate, with no obvious recorded complications, but it has the disadvantage of being the most expensive technique and requires special equipment that is only available in a few endoscopic centers.     

Variceal band ligation and variceal band ligation plus sclerotherapy in the prevention of recurrent variceal bleeding in cirrhotic patients: a randomized, prospective and controlled trial

BACKGROUND: The combination treatment of band ligation plus sclerotherapy has been proposed to hasten variceal eradication. The aim of this study was to assess the efficacy of band ligation alone versus band ligation plus sclerotherapy in the prevention of recurrent variceal bleeding. METHODS: Eighty cirrhotic patients were randomized to group I (band ligation) with 41 patients or to group II (band ligation plus sclerotherapy) with 39 patients in whom polidocanol (2%) was injected 1 to 2 cm proximal to each band. RESULTS: At baseline, both groups were similar with regard to clinical, demographic and laboratory data. Mean follow-up time (standard error) for group I was 336.5 +/- 43.4 days and for group II 386.1 +/- 40.1 days (p = 0.4). No statistical differences were observed between group I and group II in relation to recurrence of bleeding (31.7% vs. 23%, p = 0.38), treatment failure (24.4% vs. 12. 8%, p = 0.18), death (39% vs. 30.8%, p = 0.44) and variceal eradication (65.8% vs. 74.4%, p = 0.40). Group II had a significantly higher number of complications than group I, 30.8% versus 7.3%, respectively (p = 0.05). The number of bleeding related deaths was higher in group I than in group II (22% vs. 10.3%, respectively; p = 0.15). CONCLUSIONS: No significant difference was observed between band ligation and band ligation plus sclerotherapy in prevention of recurrent variceal bleeding. Furthermore, there was a higher incidence of complications in the latter group.     

Bacteremia after endoscopic band ligation of esophageal varices.

In a 6-month period, 17 consecutive unselected patients undergoing emergency or elective endoscopic variceal band ligation were evaluated prospectively for clinical and bacteriological signs of bacteremia after each treatment session. None had signs of sepsis, fever, or chills; however, in one patient, a coagulase-negative Staphylococcus epidermidis was cultured from peripheral blood at 5 but not 30 min after the procedure. These data indicate that, in contrast to sclerotherapy, endoscopic variceal ligation rarely induces bacteremia.     

Comparison of endoscopic variceal injection sclerotherapy and ligation for the treatment of esophageal variceal hemorrhage: A prospective randomized trial

To determine the efficacy of endoscopic variceal sclerotherapy (EVS) and ligation (EVL) in the management of esophageal variceal bleeding, 134 cirrhotic patients were randomized to receive either treatment. The clinical and endoscopic characteristics were similar in both groups. Active bleeding was controlled with ligation (20 of 20) as efficiently as with sclerotherapy (14 of 16). Elective sclerotherapy consumed less time than ligation (7.9 ± 1.8 minutes vs. 11.5 ± 2.7 minutes, P <.001), but there was no difference between emergent sclerotherapy (14.5 ± 5.8 minutes) and ligation (14.9 ± 4.1 minutes). Ligation reduced one grade of variceal size more quickly than sclerotherapy (1.1 ± 0.4 vs. 2.0 ± 1.7 session, P < .001). The rebleeding rate was lower with ligation (13 of 67 vs. 28 of 67, P < .01). Esophageal ulcer was the most common source of rebleeding. Recurrence of varices appears more probable with ligation (P = .079). The complication rate was higher with sclerotherapy (15 of 67 vs. 3 of 67, P < .01), with esophageal stricture being the most common cause. Survival rate was the same in both groups even after stratifying patients into good and poor hepatic reserve groups. Hepatic failure was the major cause of death, followed by exsanguination. In summary, EVL was superior to EVS regarding rebleeding and complications but not in other aspects such as time consumption in elective treatment and recurrence of varices. Substantial results for long-term follow-up are required before conclusion of the treatment of choice.     

Pantoprazole reduces the size of postbanding ulcers after variceal band ligation: a randomized, controlled trial

Elective esophageal variceal ligation (EVL) is performed to decrease the risk of variceal hemorrhage. Side effects of EVL include hemorrhage, chest pain, dysphagia, and odynophagia. Because gastric acid may exacerbate postbanding ulcers and delay healing, proton pump inhibition may decrease side effects associated with EVL. The aim of this study was to assess the efficacy of pantoprazole, a proton pump inhibitor, as an adjunct to elective EVL. We performed a double-blinded, randomized, placebo-controlled trial of pantoprazole after elective EVL. Subjects in the pantoprazole arm received 40 mg pantoprazole intravenously after EVL followed by 40 mg oral pantoprazole for 9 days. Control subjects received intravenous and oral placebo. Subjects underwent upper endoscopy 10 to 14 days after banding. Primary outcomes included the size and number of ulcers and the subjects' reports of dysphagia, chest pain, and heartburn. Forty-four subjects were randomized: 42 completed the protocol. At follow-up endoscopy, the mean number of ulcers was similar in the two groups. However, the ulcers in the pantoprazole group were on average half as large as in the placebo group (37 mm(2) vs. 82 mm(2), P < .01). Chest pain, dysphagia, and heartburn scores were not significantly different. Four subjects, all in the placebo group, had adverse outcomes, including 3 who bled from postbanding ulcers and 1 with sepsis. In conclusion, subjects receiving pantoprazole after elective EVL had significantly smaller postbanding ulcers on follow-up endoscopy than subjects receiving placebo. However, the total ulcer number and patient symptoms were not different between the groups.     

Prophylactic banding ligation of high-risk esophageal varices in patients with cirrhosis: a prospective, randomized trial.

BACKGROUND/AIMS: Injection sclerotherapy has been used to prevent the first episode of variceal hemorrhage, but the results are controversial. The value of banding ligation in the prophylaxis of the first episode of variceal bleeding has not yet been completely evaluated. This study was conducted to determine whether prophylactic banding ligation is beneficial for cirrhotic patients with high-risk esophageal varices. METHODS: A total of 127 cirrhotic patients with endoscopically-assessed high-risk esophageal varices but no history of bleeding were randomized to undergo banding ligation (64 patients) or to serve as controls (63 patients). Ligation was performed at 3-week intervals until variceal obliteration was obtained. RESULTS: During a median follow-up of 29 months, 14 patients (21.8%) in the ligation group and 22 patients (34.9%) in the control group experienced upper gastrointestinal bleeding (p = 0.15). Variceal bleeding occurred in eight patients (12.5%) in the ligation group and 14 patients (22.2%) in the control group (p = 0.22). Blood transfusion requirements were fewer in the EVL group than in the control group (0.6+/-0.4 units vs. 1.2+/-0.8 units, p<0.001). Furthermore, variceal bleeding was significantly reduced in Child-Pugh class B patients treated with ligation compared with the control group (p<0.05). Sixteen patients (25%) in the ligation group and 23 patients (36.5%) in the control group died. Comparison of Kaplan-Meier estimates of time to death for the two groups did not show significant differences (p = 0.19). More patients died of uncontrollable variceal bleeding in the control group (7 patients, 11%) than in the ligation group (3 patients, 4.7%) (p = 0.15). CONCLUSIONS: Although prophylactic ligation did not significantly reduce the first episode of bleeding from esophageal varices in cirrhotic patients with high-risk esophageal varices, a subgroup of patients (Child-Pugh class B) had a reduced frequency of the first episode of esophageal variceal bleeding after prophylactic banding ligation. Furthermore, there was a trend of reducing mortality from variceal bleeding in patients receiving prophylactic ligation. Prophylactic ligation is a promising treatment, but requires further investigation.     

Adjuvant sclerotherapy after ligation for the treatment of esophageal varices: a prospective, randomized long-term study

BACKGROUND: To assess the efficacy of adjuvant sclerotherapy after banding for the treatment of esophageal varices, a randomized trial was carried out of endoscopic variceal ligation (EVL) alone with sequential sclerotherapy versus sequential ligation-sclerotherapy (SLS) after banding with respect to variceal eradication, associated complications, and recurrence of varices. METHODS: One hundred patients qualified for this study. Fourteen patients were not included for the following reasons: 6 chose not to participate, 4 had fundal varices, and 4 had some form of cancer. Of the remaining 86 patients in the study, 42 underwent EVL alone and the other 44 SLS. Variceal ligation was begun in the region of the gastroesophageal junction, with subsequent ligatures applied cephalad 3 to 5 cm; ligation was repeated every 2 weeks until variceal obliteration. For SLS, ligation was also begun in the region of the gastroesophageal junction and repeated until varices were reduced to F1 size. Subsequently, these patients underwent sclerotherapy with between 6 and 8 mL of sodium tetradecyl sulfate (free hand technique). RESULTS: No significant differences were found between EVL alone and SLS with regard to variceal eradication, development of associated complications, and recurrent bleeding during a follow-up of 2 years. The probability of variceal recurrence requiring further treatment after 1 year was 14% for the SLS group and 26% for EVL group patients. Another year later, the probability of variceal recurrence was 24% and 45%, respectively, for the SLS and EVL groups. CONCLUSIONS: Because a significantly lower rate of variceal recurrence was found for SLS patients, sequential sclerotherapy followed by ligation to eradicate those varices too small to easily band may be a better procedure.     

Endoscopic variceal ligation for primary prophylaxis of oesophageal variceal bleed: preliminary report of a randomized controlled trial

BACKGROUND: Prevention of variceal bleeding, a major cause of morbidity and mortality, is an important goal in the management of patients with portal hypertension (PHT). Although propranolol has been found useful in preventing the first episode of variceal bleeding (primary prophylaxis) in cirrhotic PHT, it has limitations which include side effects, contraindications, non-compliance and failure in some patients. Endoscopic variceal ligation (EVL) has not been used for primary prophylaxis. METHODS: Thirty cirrhotic patients with PHT, grade III to IV oesophageal varices, hepatic venous pressure gradient > or = 12 mmHg and no prior history of upper gastrointestinal bleeding were randomized to receive propranolol (to reduce their pulse rate by 25% from baseline, n = 15) and EVL (weekly to fortnightly until variceal eradication, n = 15). The two groups were comparable. All the patients in EVL group had variceal eradication during 3.8 +/- 2.2 sessions. RESULTS: There was no major complication or interval bleeding. During a follow-up period of 17.6 +/- 4.7 months, varices recurred in three, two of which bled (successfully treated by EVL). In contrast, during this period of follow up one patient in the propranolol group had variceal bleeding (P=NS). Side effects of propranolol included symptomatic bradycardia requiring reduction of dose in one of 15 patients. CONCLUSIONS: Although sample size in this study is small, it seems that EVL may be a good option for primary prophylaxis for variceal bleeding in patients with cirrhotic PHT; further studies on a larger number of patients and longer follow up are required.     

Prospective randomized trial: Endoscopic follow up 3 vs 6 months after esophageal variceal eradication by band ligation in cirrhosis

Background and objectivesEndoscopic variceal ligation (EVL) is recommended to treat esophageal varices (EV) in cirrhosis and portal hypertension. A program of endoscopic surveillance is not clearly established. The aim of this prospective randomized trial was to assess the most effective timing of endoscopic monitoring after variceal eradication and its impact on the patient's outcome and on the costs.MethodsA hundred and two cirrhotic patients with esophageal varices treated by EVL were evaluated. After variceal eradication patients were randomized to receive first endoscopic control at 3 (Group 1) and 6 (Group 2) months respectively.ResultsVariceal obliteration was achieved in all patients. Variceal recurrence was observed in 28 cases at the first control (29.1%) without difference between the two groups (32% vs 29% in group 1 and 2 respectively, p = 0.75). The incidence of large varices is similar in the two groups (33% vs 38% respectively). Using a multivariate analysis, medical therapy with B blockers was the only independent predictor of lowest risk of variceal recurrence [OR 2.30, 95% CI (1.68–3.26)]. Bleeding related to recurrent varices occurred in 3.1% of cases and was associated with portal thrombosis. Child Pugh score ≥ 8 was the only predictor of mortality (p = 0.0002).ConclusionsRecurrence of varices after banding ligation is not rare but it is associated with a low risk of variceal progression and bleeding. Accordingly, a first endoscopic control at 6 months after variceal eradication associated with a good risk stratification might be a cost-effective strategy of monitoring.     

A prospective, randomized controlled trial of chronic esophageal variceal sclerotherapy

The results of a prospective, randomized controlled trial of chronic esophageal variceal sclerotherapy conducted over a 38-month period are presented. One-hundred twenty patients were randomized following variceal bleeding, 63 to esophageal variceal sclerotherapy and 57 to control. Mean follow-up was similar in both groups (esophageal variceal sclerotherapy, 12.5 +/- 8.8 months; control, 14.9 +/- 6.6 months). Twenty-one percent of the patients in each group were lost to follow-up. Esophageal variceal sclerotherapy decreased rebleeding as evidenced by a decrease in the mean bleeding risk factor, transfusion requirement and by an increase in bleeding free interval; differences between the treated and control groups in these parameters were especially significant after variceal obliteration. A high incidence of asymptomatic ulceration and low frequency of strictures were notable effects of esophageal variceal sclerotherapy. Cumulative life table analysis revealed no differences in survival between esophageal variceal sclerotherapy and control groups. However, when patients who received portal-systemic shunt surgery (esophageal variceal sclerotherapy, 6%; control, 28%) were removed from the analysis at the time the shunt surgery was performed (defining the shunt as an endpoint, a significant difference in survival (p less than 0.05, F ratios) in favor of esophageal variceal sclerotherapy was observed.     

心得安对食管曲张静脉套扎后再出血的影响

目的:观察心得安对食管曲张静脉套扎后再出血的影响.方法:7 8 例门脉高压性食管静脉曲张(esophageal varices, EV)患者, 分成单独套扎组(39例, 作为对照组)和心得安组(39例, 套扎后给予心得安, 10 mg, 3次/d, po). 比较两组套扎后12 mo内再出血率, 同时12 mo后复查胃镜,比较两组患者门脉高压性胃病及胃底曲张静脉发生率.结果:套扎12 mo后再出血率心得安组明显低于对照组(38.70% vs 54.54%, P<0.05). 心得安组门脉高压性胃病发生率、胃底静脉发生率,食管静脉再发率均明显低于对照组(32.25% vs57.57%, 25.80% vs 42.42%, 29.03% vs 39.39%,均P<0.05).结论:心得安可降低食管曲张静脉套扎后再出血, 其原因是心得安能够降低套扎后的门脉高压性胃病和食管、胃底静脉曲张的发生.     

Endoscopic injection sclerotherapy with ligation versus endoscopic injection sclerotherapy alone in the management of esophageal varices: a prospective randomized trial

BACKGROUND/AIMS: Endoscopic injection sclerotherapy with ligation is a technique by which endoscopic injection sclerotherapy is first carried out for a target esophageal varix using an endoscope equipped with a device for endoscopic variceal ligation, and subsequently, endoscopic variceal ligation is performed for the varix together with the injection site of the sclerosing agent. The aim of this prospective, randomized trial was to compare endoscopic injection sclerotherapy with ligation with endoscopic injection sclerotherapy techniques in utility for patients with esophageal varices. METHODOLOGY: Twenty-four patients with esophageal varices who were to undergo either an elective treatment of bleeding esophageal varices or a prophylactic treatment of non-bleeding esophageal varices underwent endoscopic injection sclerotherapy with ligation (n = 12) or without ligation (n = 12). The patients were followed for a mean of 19.9 +/- 8.1 months in the endoscopic injection sclerotherapy with ligation (EISL) group and 19.5 +/- 5.4 months in the Endoscopic injection sclerotherapy (EIS) group. RESULTS: The red color sign disappeared in 10 patients in the EISL group and 3 in the EIS group (P = 0.004) after initial treatment. The length of time required for initial treatment was 16.3 +/- 4.7 min for the EISL group and 27.2 +/- 6.2 min for the EIS group (P = 0.0003). For treatment-related complications, no significant difference was noted between the 2 groups and no serious complication were noted in the 2 groups. The total quantity of ethanolamine oleate used to attain the endpoint was 17.3 +/- 7.9 mL for the EISL group and 25.2 +/- 9.7 mL for the EIS group (P < 0.05). The cumulative non-relapse rate for 2 years following attainment of the endpoint [F1, RC(-)] was 81.5% for the EISL group and 47.5% for the EIS group, producing no significant difference between the 2 groups. The cumulative non-bleeding and survival rates were 100% in the 2 groups. CONCLUSIONS: Endoscopic injection sclerotherapy with ligation is more useful for esophageal varices than endoscopic injection sclerotherapy alone.