Esophageal variceal ligation in the secondary prevention of variceal bleeding: result of long term follow-up

Esophageal variceal ligation in the secondary prevention of variceal bleeding: Result of long term follow-up

 

Mounia Lahbabi^1,&, Ihssane Mellouki¹, Nouredine Aqodad¹, Mohammed Elabkari¹, Mounia Elyousfi¹, Sidi Adil Ibrahimi¹, Dafr Allah Benajah¹

 

¹Department of Hepato Gastroenterology Hassan II University Hospital Fez, Morocco

 

 

^&Corresponding author
Mounia Lahbabi, department of Hepato-Gastroenterology, Hassan II university hospital, Fes, Morocco

 

 

 

 

Approximately fifty-nine percent of patients with cirrhosis develop esophageal varices, and one-third of these patients experience esophageal variceal bleeding (EVB) [1]. There is considerable morbidity with EVB and the mortality rate with each episode is up to 30% [2,3]. Recurrent bleeding is common without prophylactic treatment [4]; this risk varies between 8 and 35% within 2 years of follow up [5,6], and an early rebleeding rate of 40-60% was noted within 7 and 10 days of a controlled index episode [2,7]. This indicates that a correct therapeutic approach should be aimed not only at arresting the acute variceal bleeding episode but also at preventing an early variceal bleeding [8]. Thus, urgent treatment of the acute hemorrhage and steps to prevent rebleeding are essential. Endoscopic variceal ligation (EVL) has changed the outlook for patients with upper gastro intestinal bleeding. It is widely accepted as the optimum endoscopic treatment for esophageal variceal in the secondary prevention of EVB [9]. However, the rebleeding course and long-term outcome of patients with EVB after ligation have been poorly defined. Therefore, the aim of this retrospective study was to delineate the long term outcome of band ligation in patients with portal hypertension and who have already bled from their varices and treated by EVL.

 

 

Patients

This retrospective study was conducted in Endoscopy Unit of Department of Gastroenterology and Hepatology of Hassan II University Hospital Fez, Morocco, from December 2001 to October 2011. All adult patients with an episode of upper gastrointestinal bleeding (hematemesis or melena or both) were admitted to the emergency service, and underwent endoscopy as soon as they had been resuscitated. Patients with endoscopically proven esophageal variceal hemorrhage were treated by endoscopic variceal ligation if they had active variceal bleeding at endoscopy (spurting or oozing from esophageal varices); or if they had non bleeding varices but evidence of blood with no other potential source of gastrointestinal bleeding. Patients who were followed-up for at least 24 months were enrolled in the study. A full clinical history, physical examination, laboratory tests and ultrasonography were performed. Propranolol was initiated. The dose was increased stepwise, every two-three days, up to the maximum tolerated dose or up to 160 mg/day. The severity of liver disease was classified according to Child´s classification. The esophageal varices gradings were made as follows: 1= disappeared with air insufflation; 2= did not disappear with air insufflation; 3= occluded more than one-third of esophageal lumen [10].

Endoscopic ligation

Endoscopies were performed in a single endoscopy unit using an Olympus video endoscope GIF 160. Esophageal varices were classified according to uniform criteria. Fundal varices and portal hypertensive gastropathy were also noted. After local application of lidocaine, an endoscope was introduced, and the ligation was carried out by placing a multiple rubber band (Saeed's multiband ligator Wilson's Cook) over a varice. Application of the bands was started at the gastro-esophageal junction and progressed upward in a helical way for approximately 5-8 cm. Patients underwent regular EVL until varices eradication (disappearance of varices or being too small to be sucked in the banding device).

Follow-up

Patients were followed up from December 2001 to October 2011. Endoscopic ligation was performed every three weeks until the varices were obliterated or were reduced to a size of grade 1. In the latter instance, it was impossible to apply more bands because of the small size of the varices. The presence of ulcers, esophagitis or strictures was noted on endoscopic examination. After the varices had been obliterated or reduced in size to grade 1, patients underwent endoscopy every three months until the end of follow-up. If varices recurred and became larger or grade 2 in size, repeated ligation to obliterate was done. Patients were advised to refrain from consuming alcohol and from taking non steroidal anti-inflammatory drugs.

Variceal rebleeding Any patient who had overt upper gastrointestinal bleeding during the study was admitted to the hospital and underwent endoscopy of the upper gastrointestinal tract within 24 hours to determine the source of bleeding. Bleeding from esophageal varices was diagnosed if active bleeding or a clot was seen on endoscopy and if there was evidence of recent bleeding in a patient with an esophageal varice and no other visible mucosal lesion. Bleeding was considered to be caused by esophageal ulcers as a result of band ligation if there was active bleeding or if there was an adherent clot on the esophageal ulcer [10].

Endpoints

The main endpoint of the study was bleeding from any source. Secondary endpoints were the number of banding sessions, the time to eradication (calculated from the first banding session), the incidence of variceal recurrence, variceal rebleeding, complications and mortality.

Statistical analysis

Data were analyzed by the Epi Info 2000. Quantitative data were expressed as means (± SD) or as medians.

Ethics

This study was approved by the local Scientific Ethics Committee.

 

 

One hundred twenty five eligible patients were included in the study. They were followed up for a mean of 31 months (range 12-107 months). Fifty-eight (46.4%) were females, and sixty seven (53.6%) were males. Mean age of patients was 49.2 years (+/-7). Medical co morbidity associated with portal hypertension was noted in 11 patients (8.8%). Diabetes (8 cases), arterial hypertension (3 cases). Portal hypertension was due to cirrhosis in 67.2 % of cases (N=84). The cause of cirrhosis was hepatitis C (HCV) alone 39,2 % (N=33), hepatitis B (HBV) alone 9.5% (N=8), combined HCV and HBV 4.7% (N=4), alcohol 1.2 % (N=1). Sixty nine (82.2 %) belonged to Child class A, twelve (14.3%) to child class B, and three patients (3.5%) were in Child class C. Propranolol was prescribed in association with esophageal variceal ligation as a secondary prophylaxis in 40.8 % of patients (N=51). The dosage was variable according to the patient (until the heart rate had fallen by 25%). The characteristics of the patients are shown in Table1. High grade varices were seen in 67 patients (53.6%) while low grade varices were noted in 58 patients (46.4%). Obliteration of the varices was achieved in 89.6% (N=112) of patients; with 3 +/-1.99 (range 1-8) endoscopy sessions; over a period of 14+/-6.8 weeks (range 3-28). The percentage of variceal recurrence during follow-up was 20.5 % (N=23). Recurrence was observed in a mean of 22 months (range 3-48). Bleeding rate from recurrent varices was 30.4 % (7/23). Rebleeding from EVL induced ulcers occurred in 5.6% (7/125) of ligation sessions. Portal hypertensive gastropathy before and after eradication of varices was 17.6% (N=22) and 44.6% (N=50) respectively; p<0.05. Fundal gastric varices was 30.4% (N=38) and 35.7% (N=40) before and after eradication of varices respectively; p>0.05. The overall mortality was 4 % (N=5). One death (0.8 %) were bleeding-related; the other causes of death were spontaneous ascites infection (2 cases), liver failure (2 cases). The results of endoscopic band ligation are shown in Table 2.

 

 

Endoscopic variceal ligation (EVL) is a purely mechanical method of obliterating varices that was introduced to preclude the undesirable effects of sclerotherapy [11]. Several studies have shown that EVL is effective and safe, requires few sessions to obliterate varices, and significantly reduces the rate of recurrent bleeding [12-14]. In the present study, EVL achieved variceal obliteration in 89,6 % of patients with 3 +/-1.99 endoscopy sessions over a period of 14+/-6.8 weeks. These findings were similar to the literature. A meta-analysis by Ko SY and others studies indicated that EVL achieved a variceal obliteration rates between 79 % and 100% [15-18]. It has been shown previously that varices can be obliterated after 4-5 endoscopic sessions given over a period of 12-24 weeks [16,17,19].

Variceal recurrence during this period of study occurred in 20,5 % (N=23) of patients. While those found by others studies ranged between 8% and 48% after banding and 2% and 50% after sclerotherapy[20-25]. Interpretation of these results is complicated by the different lengths of follow-up in the studies and by differences in the definitions of variceal recurrence. At any rate, in recent years several combinations of endoscopic treatments have been proposed to reduce variceal recurrence after band ligation, but the clinical value of this combined treatments is still unknown [26-30].

During the study period, bleeding rate from recurrent varices was 30.4 % (7/23). Others studies found rates ranged between 10% and 50% [31-33]. A relatively wide variation in rates of recurrent bleeding may be due, at least in part, to technical differences among studies, such as variations in the interval between sessions or in the number of bands placed during each session [34]. Whether these or other technical differences can affect the outcome has not been adequately investigated. Other possible confounding factors, such as the time since the initial bleeding episode, alcohol use or non-use, and the treatment used to stop the bleeding, may also affect the results of treatment. Among different trials, there may be differences in the characteristics of the population treated, such as the cause or the severity of hypertension, or in the definition of end points such as recurrent bleeding [35-40].

During the study period, the incidence of bleeding from treatment-induced ulcers was 5,6 %. In others published studies, variceal ulcers have been reported between 3.3% and 36 % [41,42]. However, to our knowledge, most of these studies interested patient who underwent EVL for hemostasis of acute variceal bleeding. There is few data correlating the indication of EVL to the bleeding rate of ligation ulcers. One study recently published showed that bleeding from ligation ulcers occurred in 7.1% of cases after emergency ligation and in 0.5% of cases after electively performed banding ligation [43].

In this study, band ligation influences the development of portal hypertensive gastropathy (17,6% versus 44.6% before and after EVL respectively; p< 0.05). Some studies have shown that EVL results in an increase in the incidence and worsening of portal hypertensive gastropathy [44-47]. Others studies have shown that EVL influences also the development of gastric varices [48-50]. We in our study, contrary to these finding, haven't objectified the same results. A possible explanation on the key role of EVL in the development of Hypertensive gastropathy may be based on alteration of hemodynamics in patients with cirrhosis [51]. Kanke K et al concluded that cirrhotic gastric mucosa is in congestive condition [52], and EVL makes it more congestive soon after the procedure [53]. In addition, Korula J et al concluded that after EVL there is an increase in portal pressure gradient [54] which is transformed in worsening of portal hypertensive gastropathy and development of fundal varices [46].

In this study we were confronted with some limitations. First, our study is retrospective which make it difficult to compare to other studies generally prospective. Second, portal hypertensive gastropathy wasn't classified using the Baveno scoring system to classify its severity. And finally, the follow up time for these patients had varied from one year to ten years.

 

 

In our population, endoscopic variceal ligation was an effective technical approach for variceal obliteration with low rates of variceal recurrence, rebeeding and development of fundal gastric varices. Furthermore, it was associated with frequent development of portal hypertensive gastropathy.

 

 

The authors declare that they have no competing interests

 

 

All authors analyzed, interpreted, wrote and approved the final manuscript.

 

 

1. Blei AT. Portal hypertension and its complications. Curr Opin Gastroenterol. 2007;23(3): 275-282. PubMed | Google Scholar


2. Graham DY, Smith JL. The course of patients after variceal hemorrhage. Gastroenterology. 1981;80(4):800-809. PubMed | Google Scholar


3. Stanley AJ, Hayes PC. Portal hypertension and variceal haemorrhage. Lancet. 1997; 350(9086):1235-1239. PubMed | Google Scholar


4. Augustin S, González A, Genescà J. Acute esophageal variceal bleeding: Current strategies and new perspectives. World J Hepatol. 2010;2(7):261-274. PubMed | Google Scholar


5. North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices. Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices. A prospective Multicenter Study. N Engl J Med. 1988;319(15):983-989. PubMed | Google Scholar


6. De Franchis R. Endoscopy critics vs. endoscopy enthusiasts for primary prophylaxis of variceal bleeding. Hepatology. 2006; 43(1):24-26. PubMed | Google Scholar


7. Thomsen BL, Moller S, Sorensen TIA. Copenhagen Esophageal Varices Sclerotherapy Project. Optimized analysis of recurrent bleeding and death in patients with cirrhosis and esophageal varices. J Hepatol. 1994;21(3):367-375. PubMed | Google Scholar


8. D'Amico G, Luca A. Natural history. Clinical-haemodynamic correlations. Prediction of the risk of bleeding. Bailliere's Clinical Gastroenterology. 1997;11(2):243-255. PubMed | Google Scholar


9. Sarin SK, Govil A, Jain AK, Guptan RC, Issar SK, Jain M, Murthy NS.Prospective randomized trial of endoscopic sclerotherapy versus variceal band ligation for esophageal varices: influence on gastropathy, gastric varices and variceal recurrence. J Hepatol. 1997;26(4):826-832. PubMed | Google Scholar


10. De Franchis R, BavenoV faculty. Revising consensus in portal hypertension: Report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol. 2010;53(4):762-768. PubMed | Google Scholar


11. Baron TH, Wong Kee, Song LM. Endoscopic variceal band ligation. Am J Gastroenterol. 2009; 104(5):1083-1085. PubMed | Google Scholar


12. Geraci G, Arnone E, Lo Nigro C, Sciuto A, Modica G, Sciumè C. Endoscopic rubber band ligation in treatment of esophageal varices bleeding. Personal experience. G Chir. 2011;32(3):113-117. PubMed | Google Scholar


13. Hsu YC, Chung CS, Wang HP. Application of Endoscopy in Improving Survival of Cirrhotic Patients with Acute Variceal Hemorrhage. Int J Hepatol. 2011; 2011:893973. PubMed | Google Scholar


14. Villanueva C, Minana J, Ortiz J, Gallego A, Soriano G, Torras X, Sáinz S, Boadas J, Cussó X, Guarner C, Balanzó J. Endoscopic ligation compared with combined treatment with nadolol and isosorbide mononitrate to prevent recurrent variceal bleeding. N Engl J Med. 2001;345(9):647-655. PubMed | Google Scholar


15. De la Peña J, Rivero M, Sanchez E, Fábrega E, Crespo J, Pons-Romero F. Variceal ligation compared with endoscopic sclerotherapy for variceal hemorrhage: prospective randomized trial. Gastrointestinal endoscopy. 1999;49(4 pt. 1):417-423. PubMed | Google Scholar


16. Ouakaa-Kchaou A, Kharrat J, Mir K, Houda B, Abdelli N, Ajmi S, Azzouz M, Ben Abdallah H, Ben Mami N, Bouzaidi S, Chouaib S, Golli L, Melki W, Najjar T, Saffar H, Belhadj N, Ghorbel A. Variceal band ligation in the prevention of variceal bleeding: A multicenter trial. The saudi journal of gastroenterology. 2011;17(2):105-109. PubMed | Google Scholar


17. Altinta? E, Sezgin O, Kaçar S, Tunç B, Parlak E, Altiparmak E, Sarita? U. Esophageal variceal ligation for acute variceal bleeding: Results of three years' follow-up. Turk J Gastroenterol. 2004;15(1):27-33. PubMed | Google Scholar


18. Ko SY, Kim JH, Choe WH, Kwon SY, Lee CH. Pharmacotherapy alone vs endoscopic variceal ligation combination for secondary prevention of oesophageal variceal bleeding: meta-analysis. Liver Int. 2011 Dec 2; doi: 10.1111/j.1478-3231.2011.02681.x. PubMed | Google Scholar


19. Roberts L, Kamath PS. Pathophysiology and treatment of variceal hemorrhage. Mayo Clinic Proceedings. 1996;71(10):973-983. PubMed | Google Scholar


20. Stiegmann GV, Goff JS, Michaletz-Onody PA, Korula J, Lieberman D, Saeed ZA, Reveille RM, Sun JH, Lowenstein SR. Endoscopic sclerotherapy as compared with endoscopic ligation for bleeding esophageal varices. N Engl J Med. 1992;326 (23) :1527-1532. PubMed | Google Scholar


21. Hou MC, Lin HC, Kuo BI, Chen CH, Lee FY, Lee SD. Comparison of endoscopic variceal injection sclerotherapy and ligation for the treatment of esophageal variceal hemorrhage: a prospective randomized trial. Hepatology. 1995;21(6):1517-1522. PubMed | Google Scholar


22. Fakhry S, Ömer M, Nouh A. Endoscopic sclerotherapy versus endoscopic variceal ligation in the management of bleeding esophageal varices: a preliminary report of a prospective randomized study in schistosomal hepatic fibrosis [Abstract]. Hepatology. 1995; 22: 251. PubMed | Google Scholar


23. Avgerinos A, Armonis A, Manolakopoulos S, Avgerinos A, Armonis A, Manolakopoulos S, Poulianos G, Rekoumis G, Sgourou A, Gouma P, Raptis S. Endoscopic sclerotherapy versus variceal ligation in the long-term management of patients with cirrhosis after variceal bleeding. A prospective randomized trial. J Hepatol. 1997;26(5):1034-1041. PubMed | Google Scholar


24. Baroncini D, Milandri GL, Borioni D, Piemontese A, Cennamo V, Billi P, Dal Monte PP, D'Imperio N. A prospective, randomized trial of sclerotherapy versus ligation in the elective treatment of bleeding esophageal varices. Endoscopy. 1997;29(4):235-240. PubMed | Google Scholar


25. Masci E, Norberto L, D'Imperio N. Prospective multicentric randomized trial comparing banding ligation with sclerotherapy of esophageal varices. Hepatogastroenterology. 1999 May-Jun;46(27):1769-73. PubMed | Google Scholar


26. Masumoto H, Toyonaga A, Oho K. Ligation plus low-volume sclerotherapy for high-risk esophageal varices: comparisons versus ligation therapy or sclerotherapy alone. J Gastroenterol. 1998;33(1):1-5. PubMed | Google Scholar


27. Saeed ZA, Stiegmann GV, Ramirez FC, Reveille RM, Goff JS, Hepps KS, Cole RA. Endoscopic variceal ligation is superior to combined ligation and sclerotherapy for esophageal varices: a multicenter prospective randomized trial. Hepatology. 1997;25(1):71-74. PubMed | Google Scholar


28. Grgov S, Stamenkovi? P. Does sclerotherapy of remnant little oesophageal varices after endoscopic ligation have impact on the reduction of recurrent varices? Prospective study. Srp Arh Celok Lek. 2011;139(5-6):328-332. PubMed | Google Scholar


29. Lo GH, Lai KH, Cheng JS, Lin CK, Huang JS, Hsu PI, Huang HC, Chiang HT. The additive effect of sclerotherapy to patients receiving repeated endoscopic variceal ligation: a prospective randomized trial. Hepatology. 1998;28(2):391-395. PubMed | Google Scholar


30. Hokari K, Kato M, Katagiri M. A new combined therapeutic method for esophageal varices: endoscopic variceal ligation followed by mucosa-fibrosing with microwave [Abstract]. Gastroenterology. 1998; 114(1): L0242. PubMed | Google Scholar


31. Garcia-Pagan JC, De Gottardi A, Bosch J. Review article: The modern management of portal hypertension ? primary and secondary prophylaxis of variceal bleeding in cirrhotic patients. Aliment Pharmacol Ther. 2008;28(2):178?186. PubMed | Google Scholar


32. Silvanou S, Potenza I, Debernardi Venon W. Endoscopic variceal ligation for prophylaxis of esophageal variceal bleeding: Technical aspects and outcome. Dig Liv Dis. 2009; 41S:167. PubMed | Google Scholar


33. Chandrasekhara V, Yepuri J, Sreenarasimhaiah J. Clinical predictors for recurrence of esophageal varices after obliteration by Endoscopic Band ligation. Gastrointest Endosc. 2007;65(5):148. PubMed | Google Scholar


34. Nguyen KC, Nguyen TH. Efficacy of endoscopic multi-site band ligation in eradicating esophageal varices. Gastrointest Endosc. 2009;69(5):222. PubMed | Google Scholar


35. Spaander MC, Darwish Murad S, van Buuren HR, Hansen BE, Kuipers EJ, Janssen HL. Endoscopic treatment of esophagogastric variceal bleeding in patients with noncirrhotic extrahepatic portal vein thrombosis: A long-term follow-up study. Gastrointest Endosc. 2008; 67(6):821?827. PubMed | Google Scholar


36. Zargar SA, Javid G, Khan BA, Shah OJ, Yattoo GN, Shah AH, Gulzar GM, Singh J, Shah NA, Shafi HM. Endoscopic ligation vs. sclerotherapy in adults with extrahepatic portal venous obstruction: A prospective randomized study. Gastrointest Endosc. 2005; 61(1):58?66. PubMed | Google Scholar


37. De Franchis R. Evolving consensus in portal hypertension report of the Baveno IV consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol. 2005; 43(1):167?176. PubMed | Google Scholar


38. Garcia-Tsao G, Sanyal AJ, Grace ND. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007; 46(3): 922?938. PubMed | Google Scholar


39. Laine L, el-Newihi HM, Migikovsky B, Sloane R, Garcia F. Endoscopic ligation compared with sclerotherapy for the treatment of bleeding esophageal varices. Ann Intern Med. 1993; 119(1):1-7. PubMed | Google Scholar


40. Jensen DM, Kovacs TO, Randall GM. Initial results of a randomized prospective study of emergency banding vs sclerotherapy for bleeding gastric or esophageal varices [Abstract]. Gastrointest Endosc 1993; 39: 279. Google Scholar


41. Lo GH, Lai KH, Cheng JS, Lin CK, Huang JS, Hsu PI, Chiang HT. Emergency banding ligation versus sclerotherapy for the control of active bleeding from esophageal varices. Hepatology 1997;25(5):1101-1104. Google Scholar


42. Gimson AE, Ramage JK, Panos MZ, Hayllar K, Harrison PM, Williams R, Westaby D. Randomised trial of variceal banding ligation versus injection sclerotherapy for bleeding oesophageal varices. Lancet 1993; 342(8868): 391-394. Google Scholar


43. Petrasch F, Grothaus J, Mössner J, Schiefke I, Hoffmeister A. Differences in bleeding behavior after endoscopic band ligation: a retrospective analysis. BMC Gastroenterology. 2010; 10: 5. PubMed | Google Scholar


44. Misra SP, Misra V, Dwivedi M. Effect of esophageal variceal band ligation on hemorrhoids, anorectal varices, and portal hypertensive colopathy. Endoscopy. 2002; 34(3): 195-198. PubMed | Google Scholar


45. Lo GH, Lai KH, Cheng JS, Hsu PI, Chen TA, Wang EM, Lin CK, Chiang HT. The effects of endoscopic variceal ligation and proprano-lol on portal hypertensive gastropathy: a prospective, controlled trial. Gastrointest Endosc. 2001;53(6):579-584. PubMed | Google Scholar


46. Sarwar S, Khan AA, Alam A, Butt AK, Shafqat F, Malik K, Ahmad I, Niazi AK. Effect of band ligation on portal hypertensive gastropathy and development of fundal varices. J Ayub Med Coll Abbottabad. 2006; 18(1): 32-35. PubMed | Google Scholar


47. Schepke M, Biecker E, Appenrodt B, Heller J, Sauerbruch T. Coexisting gastric varices should not preclude prophylactic ligation of large esophageal varices in cirrhosis. Digestion. 2009; 80(3): 165-169. PubMed | Google Scholar


48. Zanasi G, Rossi A, Grosso C, Bini M, Gambitta P, Pirone Z, Arcidiacono R. The effect of endoscopic sclerotherapy of esophageal varices on the development of gastric varices. Endoscopy. 1996; 28(2):234-238. PubMed | Google Scholar


49. Samiullah S, Memon MS, Memon HG, Ghori A. Secondary gastric varices in hepatic cirrhosis. J Coll Physicians Surg Pak. 2011; 21(10): 593-596. PubMed | Google Scholar


50. De la Pena J, Rivero M, Sanchez E. Variceal ligation compa-red with endoscopic sclerotherapy for variceal hemorrhage: prospective randomized trial. Gastrointest Endosc. 1999; 49(4 pt 1): 417-423. PubMed | Google Scholar


51. Sato M. Effects of endoscopic variceal ligation on systemic and splanchnic hemodynamics in patients with cirrhosis. Kurume Med J. 1997; 44(3): 191-199. PubMed | Google Scholar


52. Kanke K, Ishida M, Yajima N, Saito M, Suzuki Y, Masuyama H, Hiraishi H, Terano A. Gastric mucosal congestion following endoscope-ic variceal ligation analysis using reflectance spectrophotom-etry. Nippon Shokakibyo Gakkai Zasshi. 1996;93(10):701-706. PubMed | Google Scholar


53. Tayama C, Iwao T, Oho K, Toyonaga A, Tanikawa K. Effect of large fundal varices on changes in gastric mucosal hemodynamics after endoscopic variceal ligation. Endoscopy. 1998; 30(1): 25-31. PubMed | Google Scholar


54. Korula J, Ralls P. The effects of chronic endoscopic variceal sclerotherapy on portal pressure in cirrhotics. Gastroenterology. 1991;101(3):800-805. PubMed | Google Scholar