Treatment of hepatocellular carcinoma with esophageal varices

This report describes 53 patients with hepatocellular carcinoma (HCC) complicated with esophageal varices. Esophageal varices were due to cirrhosis of the liver in all cases. Hepatic resection and blocking operations such as Sugiura procedure, transabdominal esophageal transection or Hassab's operation were performed for the treatment of HCC and esophageal varices in 6 cases with satisfactory results. Non-operative treatments such as TAE or arterial infusion chemotherapy for HCC and blocking operations for esophageal varices were performed in 17 cases. Late deaths were recognized in 10 cases. Causes of late deaths were carcinoma of the liver in 7 cases and ruptured varices in only 1 case. In 13 cases with severe hepatic failure, only endoscopic sclerotherapy was performed for the treatment of esophageal varices. However 8 cases of 13 had rebleeding from esophageal varices and died after sclerotherapy. We concluded that effective treatments for HCC complicated with esophageal varices were to perform both the hepatic resection and the blocking operation and these treatments prolong the long-term survival of patients with HCC with esophageal varices.     

Management of Variceal Hemorrhage in Children with Extrahepatic Portal Venous Obstruction-Shunt Surgery Versus Endoscopic Sclerotherapy

Extrahepatic portal venous obstruction (EHPVO) is a common cause of portal hypertention in children. Esophageal variceal hemorrhage is a major cause of morbidity and mortality in these patients. For many decades, portal systemic shunts were considered as the most effective treatment of variceal hemorrhage. Endoscopic injection sclerotherapy (EIS) was first introduced for emergency management of bleeding varices and subsequently as definitive treatment to prevent recurrent hemorrhage. The purpose of the study was to compare the safety and efficacy of shunt surgery and endoscopic sclerotherapy for patients with proven esophageal variceal bleeding due to EHPVO. The study was a prospective randomized study of 61 children with bleeding esophageal varices due to EHPVO carried out jointly by the department of General Surgery and Gastroenterology at Sher-i-Kashmir Institute of Medical Sciences, Srinagar, between March 2001 and September 2003. Thirty patients received surgery and other 31 patients received EIS. Overall incidence of rebleeding was 22.6% in sclerotherapy group and 3.3% in shunt surgery group. Treatment failure occurred in 19.4% patients in sclerotherapy group and 6.7% in shunt surgery group. The rebleeding rate of sclerotherapy is significantly higher than that of shunt surgery. However, the therapy failure rate of sclerotherapy is not significantly different from that of shunt surgery.     

A prospective randomized controlled trial of sclerotherapy vs ligation in the prophylactic treatment of high-risk esophageal varices

Background: Endoscopic ligation (EVL) and endoscopic sclerotherapy (EIS) are both effective in the treatment of bleeding esophageal varices, but the efficacy of the two techniques in the prophylaxis of first variceal bleeding has not been investigated. The aim of this study was to investigate the frequency of first variceal bleeding, the recurrence of varices, and survival after treatment with the two techniques, as compared to a nontreated control group. Methods: A total of 157 patients with liver cirrhosis and advanced esophageal varices with no previous history of upper gastrointestinal bleeding were randomly assigned to either an EIS group (n= 55), an EVL group (n= 52), or a nontreated control group (n= 50). After the eradication of esophageal varices in the EIS and in EVL groups and in all control patients, the endoscopic examination was performed at 3-month intervals. Results: There were no significant differences between EIS and EVL in the eradication rate of esophageal varices (85% in the EIS group versus 81% in the EVL group). The mean number of sessions required to obtain eradication was lower in the EVL group than in the EIS group (4.8 ± 1.8 versus 6.2 ± 2.0; p= 0.0003), but the recurrence of esophageal varices was higher in the EVL group (31% versus 11%; p= 0.01). Total mortality was significantly lower in the EIS patients than in the controls (20% versus 38%; p= 0.04). It was also lower, but not significantly, in the EVL patients than in the controls (23% versus 38%; p= 0.10). A significant decrease in variceal bleeding was observed both in sclerotherapy cases (20%) and controls (54%; p= 0.0005) and in ligation cases and controls (29%; p= 0.01). No significant difference in bleeding episodes was observed between the sclerotherapy and ligation cases (p= 0.29). No serious complications were observed either in the EIS or EVL groups. Conclusions: EIS and EVL are similarly effective in the prevention of first variceal bleeding. The choice between EIS and EVL depends on the skill of the endoscopic unit. For highly experienced surgeons facing no complications, sclerotherapy seems to be preferable; for all others, it is technically easier to perform ligation. Received: 29 June 1998/Accepted: 18 September 1998     

The current role of devascularization and transection procedures in portal hypertension]

It is not clear which theory should be used in patients with bleeding esophageal varices that are not controlled by emergency endoscopic sclerotherapy. Definitive hemostasis is the key to successful therapy of variceal bleeding. Recurrence of haemorrhage in patients with portal hypertension is the most feared life threatening complication. Based on our management of 658 patients with esophageal varices and the availability of treatment options at our institution, the strategy of management of uncontrollable variceal haemorrhage by endoscopic sclerotherapy has evolved. Bleeding was controlled in 64 liver cirrhosis (100%) by devascularization and transection procedures and 50 patients (78%) survived to leave the hospital including 43 of 64 patients (67%) with Child grade C liver cirrhosis. Cumulative rebleeding rate at 10 years following emergency surgery was 3% (2/64). It is associated with a lower morbidity and mortality as well as a lower incidence of subsequent encephalopathy. We suggest that emergency transection and devascularization is an effective salvage treatment for the endoscopic sclerotherapy failed group.     

Endoscopic sclerotherapy

Various sclerotherapy techniques have proved successful in the management of acute variceal bleeding and in long-term control of patients after a variceal bleed. We prefer either an intravariceal or a combined intravariceal and paravariceal technique using ethanolamine oleate, but we advocate that individual units utilize the technique with which they have the most experience. The use of an unmodified flexible endoscope has been almost universally accepted. Once active variceal bleeding is diagnosed on emergency endoscopy, immediate emergency sclerotherapy should be performed. When this is not possible, bleeding should be controlled by balloon-tube tamponade with subsequent delayed emergency sclerotherapy after resuscitation. Patients with variceal bleeding that has stopped at the time of the diagnostic endoscopy can either be treated by immediate sclerotherapy or be observed initially and subsequently treated using the long-term management policy of the unit concerned. Over 90% of actively bleeding patients should be controlled using emergency sclerotherapy. Failures are defined as patients who have more than two acute variceal bleeds during a single hospital admission. Such patients should be identified early and treated either by simple staple-gun transection or by an emergency portosystemic shunt. Repeated injection sclerotherapy using a flexible endoscope and the technique with which the group concerned has the most experience is recommended as the primary form of treatment for the majority of patients after a proven esophageal variceal bleed. Repeat injection treatments should probably be performed at weekly intervals until the esophageal varices are eradicated, with follow-up at 6-month or yearly intervals thereafter. Recurrent varices should be treated similarly. Failures of sclerotherapy are defined as patients who have either recurrent bleeds or in whom varices are difficult to eradicate. They require either a portosystemic shunt or a devascularization and transection operation. All patients presenting with cirrhosis and variceal bleeding should be evaluated for liver transplantation; unfortunately, however, few variceal bleeders are candidates for transplantation. Prophylactic sclerotherapy in patients with esophageal varices that have not bled remains unjustified outside of controlled trials. Available trials have produced conflicting data.     

Present status of sclerotherapy and surgical treatment for esophageal varices in Japan. Japanese Research Society for Portal Hypertension and Japanese Research Society for Sclerotherapy of Esophageal Varices.

A nationwide survey on the treatment for esophageal varices was performed in 1990 jointly by the Japanese Research Society for Portal Hypertension and the Japanese Research Society for Sclerotherapy of Esophageal Varices to clarify the present status and strategy of this treatment in Japan. A total of 12,675 cases, including 4,159 cases of nonshunting procedures and 7,612 cases of sclerotherapy, were collected from 101 institutions. The number of patients had greatly increased in the first half of the 1980s. With regard to the therapeutic strategy, surgical procedures were not recommended in either emergency or prophylactic cases in terms of the timing of the operation, or in Child C cases in terms of the degree of hepatic insufficiency. Endoscopic injection sclerotherapy became the leading method of treatment and in 1988 only 16% of 1,528 cases were treated by surgical procedures. The strategy for the same group of patients differed between medical and surgical institutions. With regard to sclerotherapy, repeated intravariceal injection and combined intra- and paravariceal injection were the two main techniques and 10-year cumulative survival rates were 62.8% in Child A cases, 47.7% in Child B cases, and 13.2% in Child C cases. With regard to surgical procedures, 10-year survival rates were 50.6% in esophageal transection, 42.5% in gastric transection, 53.1% in cardiectomy, and 43.0% in selective shunt procedures. We are quite convinced that this report will prove useful in determining the future strategy for treating esophageal varices.     

Rupture of rectal varices treated with endoscopic variceal ligation

We report here 3 cases of rectal varices treated with endoscopic variceal ligation and discuss the pathogenesis, treatment, and prognosis of rectal varices with referring to previous reports. Of the 3 patients, 2 had been diagnosed as liver cirrhosis and 1 as extrahepatic portal hypertension. All of the 3 patients had previously undergone treatment of esophagogastric varices. The rupture of rectal varices appeared to have some relationship with the treatment of esophageal varices. In previous reports, 73% of patients with ruptured rectal varices treated with endoscopic injection sclerotherapy or endoscopic variceal ligation had undergone treatments of esophageal varices. The endoscopic treatments resulted in a favorable prognosis in 2 patients. Although no fatality from endoscopic injection sclerotherapy or endoscopic variceal ligation has been reported, 1 of the present 3 cases died of liver failure.     

Esophageal motility: effects of injection sclerotherapy

The purpose of this project was to evaluate the acute and chronic effects of sclerotherapy on esophageal motility and function. We studied motility in eight patients before and after injection sclerotherapy of esophageal varices. We injected the varices with 5% sodium morrhuate twice during the first week and then at 1, 2, 3, and 6 months. Lower esophageal sphincter pressure, contraction wave amplitude, and duration were not altered by sclerotherapy. However, the length of the high-pressure zone increased significantly from 3.6 +/- 0.3 cm to 4.2 +/- 0.2 cm during the first 3 days after initial treatment, and sclerotherapy caused considerable distortion of peristaltic wave form. Also, esophageal peristaltic velocity decreased in three patients who complained of dysphagia and subsequently developed esophageal stricture. The strictures have responded well to dilatation, and in two patients velocity has even returned toward the baseline value. Reflux esophagitis has not been a problem. Esophageal motility is altered by sclerotherapy of esophageal varices. Stricture formation seems to be reversible after sclerotherapy is stopped or discontinued.     

Surgical versus non-surgical treatment in patients with esophageal varices--a prospective randomized study]

In Japan, non-shunting procedures and selective shunt such as esophageal transection (ET), and distal splenorenal shunt (DSRS) have been widely performed. A prospective randomized trial was done to assess the effects of EIS and DSRS for treating patients with esophageal varices. Ninety-six Japanese with good liver function (Child A or B) and large esophageal varices were randomly assigned to one of three groups given different treatments; (EIS, n = 32), (ET, n = 32) and (DSRS, n = 32). Five patients (15.6%) of the DSRS group has to be excluded from this study, because of severe chronic pancreatitis. No patient died within 30 days of the treatments. The 5-year cumulative bleeding rates were 0%, 4.3% and 12.1% in the EIS, ET and DSRS groups, respectively, with no statistical significances. In no case in the three groups did the death occur because of variceal bleeding. Nineteen patients died mainly due to the underlying liver disease; 5 in the EIS, 5 in the ET and 9 in the DSRS group. There was no statistically significant difference in the survival rates among the three groups. We conclude that EIS is a satisfactory alternative to ET or DSRS for the management of patients with large esophageal varices.     

Endoscopic resection of carcinoma in situ of the esophagus accompanied by esophageal varices

Summary A case of carcinoma in situ of the esophagus accompanied by esophageal varices was treated by endoscopic mucosal resection using a transparent tube (EMRT) following eradication of the varices via injection sclerotherapy (EIS). Intravariceal injection sclerotherapy was performed for esophageal varices, and after eradication of the varices had been achieved, half of the circumferential esophageal mucosal resection of the cancer lesion was carried out. No serious complication such as perforation or mass bleeding was observed. Cancer-involved mucosa was completely resected and all specimens contributed well to accurate histopathological study, being diagnosed as intraepithelial squamous-cell carcinoma. The artificial ulcer recovered completely, showing no stenotic changes. Our conclusion from this experience is that EIS + EMRT is a valuable and minimally invasive treatment for patients exhibiting this disease, providing an accurate histopathological diagnosis.     

Gastric bleeding after endoscopic injection sclerotherapy for esophageal varices may be fatal.

Among 457 Japanese cirrhotic patients with esophageal varices, 28 (6%) bled from the upper gastrointestinal tract after the initial session of endoscopic injection sclerotherapy (EIS); 13 bled during the course of repeated EIS and 15 bled mainly from gastric lesions after eradication of the varices. Of these 28 patients, bleeding from gastritis occurred in 13 (46%), from esophageal varices in 10 (36%), from gastric varices in 4 (14%) and from gastric ulcer in one (4%). Six of 13 patients with gastritis-related bleeding and 3 of 4 patients with gastric variceal bleeding died of uncontrollable hemorrhage complicated liver failure, while 9 of 10 patients with esophageal variceal bleeding were controlled and reinjection was feasible. Ten (36%) of the 28 patients, with Child's grade B or C and severe ascites, died, mainly following bleeding from gastric lesions. This study shows that bleeding from gastric lesions after EIS can be uncontrollable and fatal in patients with poor liver function.     

内镜下硬化与套扎治疗食管静脉曲张破裂出血疗效比较

目的：对比内镜下硬化治疗（EIS）、套扎治疗（EVL）及套扎联合硬化治疗（ESL）3种方法对食管静脉曲张破裂出血的临床疗效。方法：回顾分析中日友好医院消化内科2001—2005年内镜下治疗肝硬化单纯食管静脉曲张破裂出血149例,其中EIS46例、EVL32例、ESL71例,对3种方法的止血率、静脉曲张消失率及再出血率进行比较。结果：3种治疗方法止血率均在90%以上;静脉曲张消失率分别为EIS80.4%、EVL68.8%、ESL87.3%;2年内再出血率分别为EIS52.2%、EVL59.3%、ESL43.6%,差异无统计学意义（P〉0.05）。结论：内镜下EIS、EVL及ESL治疗肝硬化食管曲张静脉出血均可达到较好效果,临床实践中可结合患者实际情况综合考虑后选择。     

The use of sclerotherapy for the management of oesophageal varices in portal hypertension

Summary Although sclerotherapy is currently the most widely used treatment for the management of both acute variceal bleeding and the long-term management of patients with varices, its definitive role in the treatment of these patients has yet to be finally proven. Sclerotherapy appears to be the most effective treatment for the majority of patients with acute variceal bleeding. Failures require either a shunt or a transection and/or devascularisation procedure. Current evidence favours simple staple gun transection or a shunt (either a portacaval shunt or a side-to-side narrow diameter polytetrafluoroethylene graft between the portal vein and vena cava). In long-term management of patients after a variceal bleed the currently favoured treatment is repeated sclerotherapy. However, failures should be identified early. We define failures as patients who present with varices that are either difficult to eradicate by sclerotherapy or who have repeated life-threatening variceal bleeds during the course of repeated injection sclerotherapy. Such patients should have either a portal-to-systemic shunt or a transection and devascularisation operation. Further controlled trials are required to define the specific indications for the individual forms of therapy. Prophylactic treatment for varices that have not yet bled is unjustified at present. Based on a presentation to the International Congress on Surgical Endoscopy, Ultrasound, and Interventional Techniques, Berlin 1988     

Portal hypertension management

Summary Injection sclerotherapy is the mainstay of treatment for acute variceal bleeding and for long-term management after a variceal bleed. In those few patients in whom sclerotherapy fails to control acute bleeding, either a surgical shunt or a simple esophageal transection is recommended. A surgical shunt or a more extensive esophagogastric evascularization and transection operation is advocated for the failures of long-term sclerotherapy management. The role of pharmacological agents in acute variceal bleed management remains in question, and the use of propranolol in long-term management, either as an alternative to sclerotherapy or in combination with sclerotherapy, is controversial. The definitive roles of the newly described variceal banding and transjugular intrahepatic portosystemic shunts (TIPS) procedures have yet to be established. All patients presenting with end-stage liver disease and esophageal variceal bleeding should be evaluated for a liver transplant, although few will qualify. A possible future transplant should be kept in mind when emergency treatment is planned. Any form of prophylactic therapy for patients with esophageal varices that have not yet bled will remain unjustified until those patients at high risk of a first variceal bleed can be identified. The gastric mucosal lesion, portal hypertensive gastropathy, has been underdiagnosed in the past. Although bleeding does occur, it is seldom a major clinical problem. When necessary, bleeding can be controlled by propranolol or a surgical shunt.     

Has sclerotherapy altered the management of patients with variceal bleeding?

Sclerotherapy is currently the primary treatment of choice for the majority of patients who present with esophageal variceal bleeding. Although it has altered the management of these patients, unanswered questions and controversies remain. Patients with acute variceal bleeding should preferably be treated in a specialized center. The primary treatment should be immediate sclerotherapy, when possible. Portosystemic shunts and esophageal transection should be reserved for the 5% to 10% of patients in whom sclerotherapy fails to control acute bleeding. There are several treatment options for long-term management after a variceal bleeding episode. Sclerotherapy is one option and has become the primary treatment in most major centers. All patients with end-stage liver disease must be considered for liver transplantation, and sclerotherapy should be the primary method of treatment in those who are selected. Pharmacologic therapy remains controversial. I propose that portosystemic shunts and devascularization and transection operations be reserved for those few patients in whom sclerotherapy fails to eradicate the varices and to prevent recurrent variceal bleeding. Patients in whom sclerotherapy is unsuccessful should be identified and treated early.     

Injection sclerotherapy for esophageal varices.

Thirty-five consecutive patients with bleeding esophageal varices were treated by repeated endoscopic injection sclerotherapy. During each session the varices were injected with 14 +/- 4.2 ml (mean +/- SD) of 5% ethanolamine oleate submucosally or intravariceally. The varices were obliterated in 31 (89%) patients. On average 3.3 +/- 2.4 sclerotherapy sessions were required for eradication of the varices. Mild fever was noticed almost in every patient after sclerotherapy. Mediastinitis was a complication in one (2.8%) patient. Esophageal stricture ensued in two (5.7%) patients which did not require treatment. The cumulative survival rates at 1, 2, 3, 4 and 5 years were 83%; 65%; 52%; 52% and 47% respectively. The corresponding 95% confidence intervals were (0.7, 0.96); (0.48, 0.8); (0.34, 0.7); (0.3, 0.74) and (0.22, 0.7). Sclerotherapy is an effective and safe method to treat bleeding esophageal varices.     

Therapeutic modality for esophago-gastric varices analyzed by endoscopic ultrasonography]

For 64 cases with portal hypertensive disease, we investigated the intramural and extramural structure of the stomach and esophagus by endoscopic ultrasonography (EUS). Variously developed intra- or extra-mural vascular structures had a relationship to the endoscopic variceal form, and the communicating (inflow) vessels to varices were found in 35 of 50 primary treated cases (70%). We classified the esophago-gastric varices into three types according to the vascular structure, such as the esophageal type, the esophago-gastric type and the solitary gastric type. From the analyses of these collateral structures, we should select a treatment as follows. In the esophageal type which has a few inflow vessels, it is easy to eliminate the varices by obturating the inflow vessels by endoscopic injection sclerotherapy (EIS). In the esophago-gastric type, which has many enlarged inflow vessels, the Hassab operation is effective to devascularize extramural inflow vessels, and the combination of EIS is necessary to sclerous the intramural varices. In the solitary gastric type which is a part of the downward porto-systemic shunt, Hassab operation is recommended to prevent the rupture of varices for the subtype with intramural running vessels, but conservative therapy is enough for the subtype without intramural running vessel.     

Treatment of patients with hepatoma and esophageal varices

Fifty-nine patients with hepatoma associated with advanced esophageal varices who received a variety of therapeutic modalities in the past 10 years at our department were reviewed. Our therapeutic modalities are hepatic resection, hepatic artery ligation (HAL) and trans-arterial embolization (TAE) for those with hepatoma and non-shunting treatment (NST; esophageal transection or Hassab's procedure) and endoscopic sclerotherapy (ST) for those with esophageal varices. A patient selection was made by our own criterial developed by a multiple regression analysis for the hepatoma and KICG value for esophageal varices. Out of 59.16 underwent hepatic resection and NST. Eight survived more than 2 years. The longest survivor has been living for 4 yr and 4 months. Two-year survival rate is 69.8%. Another 16 underwent HAL and NST. Two-year survival was 14.6%. Another 7 underwent ST following hepatic resection or HAL. Five of the 7 received an emergency ST. Hemostasis was achieved in all of them. Two-year survival was 21.8%. The remaining 20 underwent ST and TAE; 13 received an emergency ST with 85% of hemostasis rate. None of them survived more than 2 years. From these data, it is suggested that a proper selection of patients for a proper therapeutic modality improves the prognosis even in those with hepatoma associated with advanced esophageal varices.     

Evaluation of propranolol for prevention of recurrent bleeding from esophageal varices between sclerotherapy sessions

Forty-one patients admitted with first episode of bleeding from esophageal varices were enrolled in a trial of the efficacy of oral propranolol to prevent rebleeding during the course of endoscopic sclerotherapy until obliteration. Single-blind randomization to sclerotherapy alone or with propranolol was used. At monthly endoscopy the varices were injected with 1% Aethoxysclerol until obliteration. If bleeding recurred, additional sclerotherapy was given. There was no intergroup difference in time to eradication of varices (8.1 vs. 7.7 months). The cumulative number of bleedings from varices and from distal esophageal ulcerations was identical in the two study groups. Five patients in the control group but only one in the propranolol group died of bleeding in the study period, a difference of only borderline significance (chi 2 = 4.08, df = 1). There were no specific side effects of propranolol. Thus propranolol did not significantly reduce the frequency of rebleeding until variceal obliteration, but could have had some influence on the gravity of rebleeding.     

Selection of the treatment for esophagogastric varices

Summary In 57 cases with portal hypertensive disease, we investigated the intramural and extramural structure of the stomach and the esophagus by endoscopic ultrasonography (EUS). Variously developed intra- and extramural vascular structures had a relationship to the endoscopic variceal form, and communicating (inflow) vessels to varices were found in 28 of the 43 primary cases treated (65%). We then classified the esophagogastric varices into three types according to the vascular structure, such as the esophageal type, esophagogastric type, and solitary gastric type. Based on the analysis of these collateral structures, we selected the treatment as follows. In the esophageal type, which has a few inflow vessels, it is easy to eliminate the varices by obturating the inflow vessels by endoscopic injection sclerotherapy (EIS). In the esophagogastric type, which has many enlarged inflow vessels, the Hassab operation is effective in devascularizing the extramural inflow vessels, and the combination of EIS is necessary to sclerose the intramural varices. In the solitary gastric type, which is a part of the downward portosystemic shunt, the Hassab operation is recommended to prevent rupture of the varices for the subtype with intramural running vessels, but conservative therapy is enough for the subtype without.