515
EDITORIALS
varices: IST, TIPS
Bleeding oesophageal EVL,
or
Emergency injection sclerotherapy (IST) via a fiberoptic endoscope is widely acknowledged as the management of choice for patients with acute oesophageal variceal bleeding,l and should preferably be done at the time of the first diagnostic endoscopy. The alternatives of surgical shunting3 or surgical staple gun oesophageal transection4 are usually reserved for patients in whom I ST fails to control acute variceal haemorrhage. One factor in the decision is the possibility of a future liver transplant; in such cases treatment should be simple and not compromise the subsequent transplantation procedure. Two new therapeutic concepts pose a challenge to I ST in the management of acute variceal bleeding: (a) endoscopic variceal ligation (EVL) or banding;5 and (b) transjugular intrahepatic portosystemic shunting (TIPS).66 I ST controls acute variceal haemorrhage in 90-95% of patients, usually with a single injection treatment (70%).1 Thus, 30% of patients require more than one injection and in 5-10% of patients bleeding is controlled by I ST. Failure of I ST has been 2
defmed as a further variceal bleed after two emergency
injection
treatments
during
a
single hospital
admission.4,7 It is recommended that such patients should have their variceal haemorrhage temporarily controlled by balloon tube tamponade and then undergo either a surgical shunt or a surgical oesophageal transection.1,4,7 EVL or TIPS may also prove valuable in this setting. A point frequently overlooked when 1ST is compared with other forms of treatment is that there are various sclerotherapy techniques not all of which are equally effective.’ The sclerosant can be administered by an intravariceal injection, a paravariceal injection, or a combination of these techniques. Numerous sclerosant agents with
different mechanisms of action are in use; the commonest agents are ethanolamine oleate 5%, sodium morrhuate 5%, sodium tetradecyl sulphate (in various concentrations), and polidocanol (1-3% concentration), and various combinations are in use. The best sclerosant and route of administration has yet to be defined. Not only are the injection techniques and sclerosant solutions different, but also I ST is applied by individuals with different levels of skill and in protocols with variable frequencies of 1ST and endoscopic review. Moreover, the incidence of the underlying diseases in the patients varies with geographic location. It is therefore not surprising that controlled comparisons of I ST and other specific therapies have yielded contradictory results. The concept of oesophageal variceal ligation (EVL) was introduced in 1988 by Stiegmann and Goff of Denver,8 and the first 146 patients were reported in 1990.9 The technique is similar to that used for banding of haemorrhoids and is carried out with a modified endoscope equipped with a preloaded elastic rubber band. The endoscope is repeatedly passed through an overtube into the oesophagus. The modified endoscope tip with a distally placed cylinder is sited over a variceal column in the lower oesophagus immediately above the oesophagogastric junction and suction is applied to draw the mucosa and the underlying varix into the cylinder. Pulling a trip wire releases the circular rubber band to encompass the base of the tissue bolus. The tissue bolus subsequently necroses to leave a superficial ulcer in the oesophagus. Minor disadvantages of the technique are the need for an overtube and the need to remove and reload the endoscope with a rubber band for each single variceal ligation. In acute variceal haemorrhage, banding is done at or around the bleeding site in the varix. This procedure is followed by banding at one or two sites for each of the remaining varices. EVL has been successful in treatment of active variceal bleeding and in long-term management to eradicate varices. EVL has even been helpful in a small group of patients after failed IST.10 A combination of EVL and simultaneous low volume 1ST may result in more rapid eradication of varices. 11 A prospective, randomised controlled clinical comparison of EVL and IST has now been published.5 129 patients with cirrhosis and proven variceal bleeding were studied; all had liver cirrhosis. Treatment was continued electively with a mean follow-up of 10 months. The primary endpoint was the incidence of complications. The two treatments were equally effective in controlling variceal bleeding. EVL had fewer treatment-related complications (2% vs 22 %) and the mortality was less (28% vs 45%) than with 1ST. Slightly more 1ST patients had recurrent haemorrhage. Eradication of varices required a lower of treatments with EVL. The mean number researchers concluded that EVL was better than 1ST, and suggested that the survival benefit of EVL results partly from fewer occurrences of bleeding and fewer
516
that the preliminary results of two other controlled trials accord with this view. Does this mean that EVL should replace 1ST in the management of bleeding oesophageal varices? These results must be accepted with caution. The sclerosant used in the study, sodium tetradecyl sulphate, is not necessarily the best solution for IST,l so the results of comparisons of EVL with other IST techniques are important. A survival difference was only found in the better risk Child’s A and B category patients and not in the few (one-fifth of the series) poor risk Child’s C patients. These poor risk patients pose the main difficulty in management. Portosystemic shunting was formerly achieved only by major surgery. The trans jugular intrahepatic portosystemic shunt (TIPS) is a new simple nonoperative interventional radiological technique.6 In principle, a catheter is passed into the hepatic vein via the jugular vein and a tract is opened into a major portal brach with a rigid needle followed by a guidewire. The tract is dilated with a 8 mm or 10 mm angioplasty balloon catherter and patency is maintained by an expandable metal stent. Several techniques with stents are being evaluated .6,12,13 This procedure, which has the advantage of being applicable to poor risk patients, was described in 196914 and first used in man in 1982.15 The use of an expandable metallic stent, to maintain patency of the shunt in animals, 16,17 led to the successful introduction in man.6,12,13 Ring and colleagues6 have placed this shunt and controlled acute variceal bleeding in all of 13 patients referred for liver transplantation, without complications.6 7 of these patients subsequently underwent successful liver transplantation and 3 are being treated conservatively long-term. Shunt occlusion, due to neo-intimal hyperplasia, developed in 1 patient and was treated by dilatation and the placement of a further stent before liver transplantation. No long-term follow-up after TIPS is available. Although the reported encephalopathy rate has been very low, unpublished figures indicate the development of encephalopathy in some patients. TIPS has been successfully applied in poor risk patients before liver transplantation, but its long-term use requires further evaluation and comparison with 1ST, especially in controlled trials. The narrow diameter of the shunt in TIPS may be advantageous in the light of the successful long-term surgical shunting reported by Sarfeh and colleagueslg who used similar sized surgically placed portacaval shunts. If the TIPS occludes it can be reopened by percutaneous catheter dilatation or a further shunt. For now, I ST is the best primary therapy for bleeding oesophageal varices.
complications. They point
out
J, Burroughs AK, Hobbs KEF. Controversies in the management of bleeding esophageal varices. N Engl J Med 1989; 320:
1. Terblanche
1393-98, 1469-75. 2.
Westaby D, Hayes PC, Gimson AES, Polson RJ, Williams R. Controlled clinical trial of injection scleropathy for active variceal bleeding. Hepatology 1989; 9: 274-47.
3. Cello JP, Grendell JH, Crass RA, Weber TE, Trunkey DD. Endoscopic scleropathy versus portacaval shunt in patients with severe cirrhosis and acute variceal hemorrhage. Long-term follow-up. N Engl J Med
1987; 316: 11-15.
Burroughs AK, Hamilton G, Phillips A, Mezzanotte G, McIntyre N, Hobbs KEF. A comparison of scleropathy with staple transection of the esophagus for the emergency control of bleeding from esophageal varices. N Engl J Med 1989; 321: 857-62. 5. Stiegmann GV, Goff JS, Michaletz-Onody PA, et al. Endoscopic scleropathy as compared with endoscopic ligation for bleeding esophageal varices. N Engl J Med 1992; 326: 1527-32. 6. Ring EJ, Lake JR, Roberts JP, et al. Using transjugular intrahepatic portosystemic shunts to control variceal bleeding before liver transplantation. Ann Intern Med 1992; 116: 304-09. 7. Bornman PC, Terblanche J, Kahn D, Jonker MA, Kirsch RE. Limitations of multiple injection scleropathy sessions for acute variceal bleeding. S Afr Med J 1986; 70: 34-36. 8. Stiegmann GV, Goff JS. Endoscopic esophageal varix ligation (EDL): preliminary clinical experience. Gastrointest Endosc 1988; 34: 105-08. 9. Goff JS. Esophageal variceal ligation. Can J Gastroenterol 1990; 4: 4.
639-42. 10. Saeed ZA, Michaletz PA, Winchester CB, et al. Endoscopic variceal ligation in patients who have failed endoscopic scleropathy. Gastrointest Endosc 1990; 36: 572-74. 11. Reveille RM, Goff JS, Stiegmann GV, Stauffer JT. Combination
12.
endoscopic variceal ligation (EVL) and low-volume endoscopic scleropathy (ES) for bleeding esophageal varices: a faster route to variceal eradication? Gastrointest Endosc 1991; 37: 243 (abstr). Richter GM, Noeldge G, Palmaz JC, et al. Transjugular intrahepatic portacaval shunt: preliminary clinical results. Radiology 1990; 174:
1027-30. 13. Zemel G, Katzen BT, Becker GJ, Benenati JF, Sallee DS. Percutaneous transjugular portosystemic shunt. JAMA 1991; 266: 390-93. 14. Rosch J, Hanafee WN, Snow H. Transjugular portal venography and radiologic portocaval shunt: an experimental study. Radiology 1969; 92: 1112-14. 15. Colapinto RF, Stronell RD, Birch SJ, et al. Creation of an intrahepatic portosystemic shunt with a Gruntzig balloon catheter. Can Med Assoc J 1982; 126: 267-68. 16. Palmaz JC, Sibbitt RR, Reuter SR, Garcia F, Tio FO. Expandable intrahepatic shunt stents: early experience in the dog. Am J Roentgenol 1985; 145: 821-25. 17. Rosch J, Uchida BT, Putnam JS, Buschman RW, Law RD, Hershey AL. Experimental intrahepatic portocaval anastomosis: use of expandable Gianturco stents. Radiology 1987; 162: 481-85. 18. Sarfeh IJ, Rypins EB, Mason GR. A systematic appraisal of portacaval H-grafts diameters. Clinical and hemodynamic perspectives. Ann Surg 1986; 204: 356-63.
Cytoreduction Is
cytoreductive
in ovarian
cancer
surgery-"debulking"-
warranted in patients with ovarian cancer? The benefits include relief of symptoms and improvement in the quality of life, but it is uncertain whether maximum cytoreductive surgery improves outlook. Hunter et all resorted to meta-analysis to see whether surgery was an independent determinant of prognosis. As these researchers note, the favourable outlook of patients with small amounts of residual tumour may be another example of the "Will Rogers phenomenon", in which reclassification of patients improves the survival of new subgroups without altering the survival of the whole population. In the meta-analysis, survival of groups with high and low percentages of patients undergoing maximum cytoreductive surgery were compared. The conclusion from fifty-eight suitable studies was that, for the group as a whole, only a small median survival advantage can be expected from cytoreductive surgery. A randomised trial to confirm or refute this
EDITORIALS
varices: IST, TIPS
Bleeding oesophageal EVL,
or
Emergency injection sclerotherapy (IST) via a fiberoptic endoscope is widely acknowledged as the management of choice for patients with acute oesophageal variceal bleeding,l and should preferably be done at the time of the first diagnostic endoscopy. The alternatives of surgical shunting3 or surgical staple gun oesophageal transection4 are usually reserved for patients in whom I ST fails to control acute variceal haemorrhage. One factor in the decision is the possibility of a future liver transplant; in such cases treatment should be simple and not compromise the subsequent transplantation procedure. Two new therapeutic concepts pose a challenge to I ST in the management of acute variceal bleeding: (a) endoscopic variceal ligation (EVL) or banding;5 and (b) transjugular intrahepatic portosystemic shunting (TIPS).66 I ST controls acute variceal haemorrhage in 90-95% of patients, usually with a single injection treatment (70%).1 Thus, 30% of patients require more than one injection and in 5-10% of patients bleeding is controlled by I ST. Failure of I ST has been 2
defmed as a further variceal bleed after two emergency
injection
treatments
during
a
single hospital
admission.4,7 It is recommended that such patients should have their variceal haemorrhage temporarily controlled by balloon tube tamponade and then undergo either a surgical shunt or a surgical oesophageal transection.1,4,7 EVL or TIPS may also prove valuable in this setting. A point frequently overlooked when 1ST is compared with other forms of treatment is that there are various sclerotherapy techniques not all of which are equally effective.’ The sclerosant can be administered by an intravariceal injection, a paravariceal injection, or a combination of these techniques. Numerous sclerosant agents with
different mechanisms of action are in use; the commonest agents are ethanolamine oleate 5%, sodium morrhuate 5%, sodium tetradecyl sulphate (in various concentrations), and polidocanol (1-3% concentration), and various combinations are in use. The best sclerosant and route of administration has yet to be defined. Not only are the injection techniques and sclerosant solutions different, but also I ST is applied by individuals with different levels of skill and in protocols with variable frequencies of 1ST and endoscopic review. Moreover, the incidence of the underlying diseases in the patients varies with geographic location. It is therefore not surprising that controlled comparisons of I ST and other specific therapies have yielded contradictory results. The concept of oesophageal variceal ligation (EVL) was introduced in 1988 by Stiegmann and Goff of Denver,8 and the first 146 patients were reported in 1990.9 The technique is similar to that used for banding of haemorrhoids and is carried out with a modified endoscope equipped with a preloaded elastic rubber band. The endoscope is repeatedly passed through an overtube into the oesophagus. The modified endoscope tip with a distally placed cylinder is sited over a variceal column in the lower oesophagus immediately above the oesophagogastric junction and suction is applied to draw the mucosa and the underlying varix into the cylinder. Pulling a trip wire releases the circular rubber band to encompass the base of the tissue bolus. The tissue bolus subsequently necroses to leave a superficial ulcer in the oesophagus. Minor disadvantages of the technique are the need for an overtube and the need to remove and reload the endoscope with a rubber band for each single variceal ligation. In acute variceal haemorrhage, banding is done at or around the bleeding site in the varix. This procedure is followed by banding at one or two sites for each of the remaining varices. EVL has been successful in treatment of active variceal bleeding and in long-term management to eradicate varices. EVL has even been helpful in a small group of patients after failed IST.10 A combination of EVL and simultaneous low volume 1ST may result in more rapid eradication of varices. 11 A prospective, randomised controlled clinical comparison of EVL and IST has now been published.5 129 patients with cirrhosis and proven variceal bleeding were studied; all had liver cirrhosis. Treatment was continued electively with a mean follow-up of 10 months. The primary endpoint was the incidence of complications. The two treatments were equally effective in controlling variceal bleeding. EVL had fewer treatment-related complications (2% vs 22 %) and the mortality was less (28% vs 45%) than with 1ST. Slightly more 1ST patients had recurrent haemorrhage. Eradication of varices required a lower of treatments with EVL. The mean number researchers concluded that EVL was better than 1ST, and suggested that the survival benefit of EVL results partly from fewer occurrences of bleeding and fewer
516
that the preliminary results of two other controlled trials accord with this view. Does this mean that EVL should replace 1ST in the management of bleeding oesophageal varices? These results must be accepted with caution. The sclerosant used in the study, sodium tetradecyl sulphate, is not necessarily the best solution for IST,l so the results of comparisons of EVL with other IST techniques are important. A survival difference was only found in the better risk Child’s A and B category patients and not in the few (one-fifth of the series) poor risk Child’s C patients. These poor risk patients pose the main difficulty in management. Portosystemic shunting was formerly achieved only by major surgery. The trans jugular intrahepatic portosystemic shunt (TIPS) is a new simple nonoperative interventional radiological technique.6 In principle, a catheter is passed into the hepatic vein via the jugular vein and a tract is opened into a major portal brach with a rigid needle followed by a guidewire. The tract is dilated with a 8 mm or 10 mm angioplasty balloon catherter and patency is maintained by an expandable metal stent. Several techniques with stents are being evaluated .6,12,13 This procedure, which has the advantage of being applicable to poor risk patients, was described in 196914 and first used in man in 1982.15 The use of an expandable metallic stent, to maintain patency of the shunt in animals, 16,17 led to the successful introduction in man.6,12,13 Ring and colleagues6 have placed this shunt and controlled acute variceal bleeding in all of 13 patients referred for liver transplantation, without complications.6 7 of these patients subsequently underwent successful liver transplantation and 3 are being treated conservatively long-term. Shunt occlusion, due to neo-intimal hyperplasia, developed in 1 patient and was treated by dilatation and the placement of a further stent before liver transplantation. No long-term follow-up after TIPS is available. Although the reported encephalopathy rate has been very low, unpublished figures indicate the development of encephalopathy in some patients. TIPS has been successfully applied in poor risk patients before liver transplantation, but its long-term use requires further evaluation and comparison with 1ST, especially in controlled trials. The narrow diameter of the shunt in TIPS may be advantageous in the light of the successful long-term surgical shunting reported by Sarfeh and colleagueslg who used similar sized surgically placed portacaval shunts. If the TIPS occludes it can be reopened by percutaneous catheter dilatation or a further shunt. For now, I ST is the best primary therapy for bleeding oesophageal varices.
complications. They point
out
J, Burroughs AK, Hobbs KEF. Controversies in the management of bleeding esophageal varices. N Engl J Med 1989; 320:
1. Terblanche
1393-98, 1469-75. 2.
Westaby D, Hayes PC, Gimson AES, Polson RJ, Williams R. Controlled clinical trial of injection scleropathy for active variceal bleeding. Hepatology 1989; 9: 274-47.
3. Cello JP, Grendell JH, Crass RA, Weber TE, Trunkey DD. Endoscopic scleropathy versus portacaval shunt in patients with severe cirrhosis and acute variceal hemorrhage. Long-term follow-up. N Engl J Med
1987; 316: 11-15.
Burroughs AK, Hamilton G, Phillips A, Mezzanotte G, McIntyre N, Hobbs KEF. A comparison of scleropathy with staple transection of the esophagus for the emergency control of bleeding from esophageal varices. N Engl J Med 1989; 321: 857-62. 5. Stiegmann GV, Goff JS, Michaletz-Onody PA, et al. Endoscopic scleropathy as compared with endoscopic ligation for bleeding esophageal varices. N Engl J Med 1992; 326: 1527-32. 6. Ring EJ, Lake JR, Roberts JP, et al. Using transjugular intrahepatic portosystemic shunts to control variceal bleeding before liver transplantation. Ann Intern Med 1992; 116: 304-09. 7. Bornman PC, Terblanche J, Kahn D, Jonker MA, Kirsch RE. Limitations of multiple injection scleropathy sessions for acute variceal bleeding. S Afr Med J 1986; 70: 34-36. 8. Stiegmann GV, Goff JS. Endoscopic esophageal varix ligation (EDL): preliminary clinical experience. Gastrointest Endosc 1988; 34: 105-08. 9. Goff JS. Esophageal variceal ligation. Can J Gastroenterol 1990; 4: 4.
639-42. 10. Saeed ZA, Michaletz PA, Winchester CB, et al. Endoscopic variceal ligation in patients who have failed endoscopic scleropathy. Gastrointest Endosc 1990; 36: 572-74. 11. Reveille RM, Goff JS, Stiegmann GV, Stauffer JT. Combination
12.
endoscopic variceal ligation (EVL) and low-volume endoscopic scleropathy (ES) for bleeding esophageal varices: a faster route to variceal eradication? Gastrointest Endosc 1991; 37: 243 (abstr). Richter GM, Noeldge G, Palmaz JC, et al. Transjugular intrahepatic portacaval shunt: preliminary clinical results. Radiology 1990; 174:
1027-30. 13. Zemel G, Katzen BT, Becker GJ, Benenati JF, Sallee DS. Percutaneous transjugular portosystemic shunt. JAMA 1991; 266: 390-93. 14. Rosch J, Hanafee WN, Snow H. Transjugular portal venography and radiologic portocaval shunt: an experimental study. Radiology 1969; 92: 1112-14. 15. Colapinto RF, Stronell RD, Birch SJ, et al. Creation of an intrahepatic portosystemic shunt with a Gruntzig balloon catheter. Can Med Assoc J 1982; 126: 267-68. 16. Palmaz JC, Sibbitt RR, Reuter SR, Garcia F, Tio FO. Expandable intrahepatic shunt stents: early experience in the dog. Am J Roentgenol 1985; 145: 821-25. 17. Rosch J, Uchida BT, Putnam JS, Buschman RW, Law RD, Hershey AL. Experimental intrahepatic portocaval anastomosis: use of expandable Gianturco stents. Radiology 1987; 162: 481-85. 18. Sarfeh IJ, Rypins EB, Mason GR. A systematic appraisal of portacaval H-grafts diameters. Clinical and hemodynamic perspectives. Ann Surg 1986; 204: 356-63.
Cytoreduction Is
cytoreductive
in ovarian
cancer
surgery-"debulking"-
warranted in patients with ovarian cancer? The benefits include relief of symptoms and improvement in the quality of life, but it is uncertain whether maximum cytoreductive surgery improves outlook. Hunter et all resorted to meta-analysis to see whether surgery was an independent determinant of prognosis. As these researchers note, the favourable outlook of patients with small amounts of residual tumour may be another example of the "Will Rogers phenomenon", in which reclassification of patients improves the survival of new subgroups without altering the survival of the whole population. In the meta-analysis, survival of groups with high and low percentages of patients undergoing maximum cytoreductive surgery were compared. The conclusion from fifty-eight suitable studies was that, for the group as a whole, only a small median survival advantage can be expected from cytoreductive surgery. A randomised trial to confirm or refute this
