GASTROENTEROLOGY
l!t92;103:1357-1364
SELECTED SUMMARIES Mark Feldman, M.D. Selected Summaries Editor Dallas Veterans Administration Medical Service (111) Dallas, Texas 75216
Medical Center
STAFF OF CONTRIBUTORS James L. Achord, Jackson, MS Kim E. Barrett, San Diego, CA Gary L. Davis, Gainesville, FL Grace H. Elta, Ann Arbor, MI Lawrence S. Friedman, Philadelphia, Hans Fromm, Washington, DC Hans Gerdes, New York, NY Fayez K. Ghishan, Nashville, TN
PA
John B. Gross, Jr., Rochester, MN Raymond S. Koff, Framingham, MA Benjamin Krevsky, Philadelphia, PA Loren Laine, Los Angeles, CA William M. Lee, Dallas, TX Thomas A. Miller, Houston, TX Ravinder K. Mittal, Charlottesville, VA
INTRAHEPATIC PORTACAVAL SHUNTS: A NEW ERA? Ring EJ, Lake JR, Roberts JP, et al. San Francisco, California). Using portosystemic shunts to control liver transplantation. Ann Intern
(University of California, transjugular intrahepatic variceal bleeding before Med 1992;166:304-309.
Refractory variceal hemorrhage carries a high mortality and precludes transplantation for some patients, because stability cannot be maintained long enough to allow a suitable donor to be found. The present study reports a prospective uncontrolled trial of transjugular intrahepatic portosystemic shunts (TIPS) in 13 patients with variceal hemorrhage refractory to sclerotherapy, all of whom were potential transplant candidates. The technique involves creation of a channel between hepatic and portal veins via a jugular vein approach, followed by placement of a flexible wire mesh stent, which is expanded to the proper diameter via a balloon inside the stent. Portal pressures can be measured and the stent expanded further if decompression appears inadequate. The usual internal diameter is 8-12 mm, although one can enlarge the shunt to 12 mm without difficulty. Reduction in portal pressure and cessation of bleeding occurred in all patients. No complications occurred, although two deaths secondary to septic complications, said to be unrelated to the stents, were reported. No patient developed encephalopathy. Seven patients underwent transplantation; all did well in the short term. Four have been observed without undergoing transplantation, two because of improvement in ascites and no further hemorrhage and two because of recurrent alcohol abuse. In this small series, TIPS appears to provide a safe, effective means of stopping variceal hemorrhage as a bridge to transplantation and possibly serves as definitive management for certain patients. Comment. Although endoscopic variceal sclerotherapy has largely replaced shunt operations, nothing reliably reduces portal pressure like a shunt procedure. Nevertheless, shunt operations are invasive and magnify subsequent technical hurdles for the transplant surgeon. A nonoperative shunt procedure such as that reported by Ring et al. sounds ideal and it may well be. This procedure has now been performed widely both in the United States and abroad with comparative ease and good efficacy, although
Malcolm Robinson, Oklahoma City, OK Mitchell L. Schubert, Richmond, VA Konrad Schulze-Delrieu, Iowa City, IA Fergus Shanahan, Los Angeles, CA Joseph Sweeting, New York, NY Richard C. Thirlby, Seattle, WA M. Michael Wolfe, Boston, MA
reports thus far are little more than anecdotal (Cardiovasc Intervent Radio1 1990;13:200-207; JAMA 1991;266:390-393). Rosch first introduced the concept of intrahepatic portacaval shunting in 1969 (Radiology 1969;92:1112-1114). Colapinto first applied this to a patient with portal hypertension (Can Med Assoc J 1982;126:267-268) using a Grunzig balloon dilatation to create a tract that did not remain open for long. Subsequent studies have led to development of expandable rigid stents that provide a fixed internal diameter once the stent is expanded. Initially, transhepatic portography was used to localize the site of portal vein entry; however, this is not necessary if ultrasonography is used. Stents in the biliary tract work well, and it appears that venous stents in such nonconventional locations can be equally effective. What are the advantages of this technique? First, it is a radiological procedure, usually completed within 2-3 hours. Second, a shunt within the liver is removed at the time of transplantation and requires no tedious takedown at the time of transplantation (the decompressed portal circuit makes removing the native liver easier). Finally, patients seem to stabilize quite dramatically. Indeed, bleeding stops, and ascites is mobilized as well. The TIPS appears to function as a side-to-side shunt, and diuresis has been reported in all patients who have ascites. If patients have no more bleeding or ascites, nutritional recovery may occur and transplantation may no longer be necessary. According to all studies to date, encephalopathy has not been observed. This seems incredible, and it is likely that a longer experience with more patients with TIPS shunts will disclose significantly increased encephalopathy over time. If encephalopathy is not a problem with TIPS, then we need to rethink our understanding of why other types of shunt operations are associated with so much encephalopathy. There is no evidence thus far that significant antegrade portal flow is maintained through the sinusoids; however, portal hypertension is not fully resolved by TIPS. Thus, we have created a small bore shunt that may be more effective than an extrahepatic shunt in maintaining sinusoidal perfusion and work to limit the hepatic atrophy associated with the postshunt situation. Over time, a thick neointima develops, limiting any flow directly through the shunt walls. Nevertheless, with significant resistance across the shunt, perfusion of the remaining portal veins is apparently well maintained. The disadvantages of this type of shunt would include the catastrophic possibility of puncture of portal vein or gall bladder wall as well as the potential for infection, with the metal stent serving as nidus. One wonders whether the shunt in any way was involved in the deaths of the two patients in the present study, because it is made clear that in both instances the infection was already underway before TIPS placement. Does this all sound too good to be true? Maybe. TIPS certainly seems like a genuine advance in management of portal hyperten-
1358 SELECTED SUMMARIES
GASTROENTEROLOGY
sion that may finally make the operative portacaval shunt procedure a dinosaur. It may even replace injection sclerotherapy if safety and uniformity of function over a long period can be assured. One patient in whom bleeding recurred and in whom a partial stent occlusion was shown was treated by placement of a second stent, which was expanded inside the first. Transplantation was accomplished shortly thereafter. TIPS appears to provide at least an effective bridge to hepatic transplantation, although its widespread application has not been observed. One cautionary note: the present small study represented consecutive but uncontrolled results. Before we get ahead of ourselves, TIPS should be subjected to a head-to-head trial with sclerotherapy or banding. Otherwise, TIPS is likely to become a strong consideration as definitive therapy for variceal hemorrhage before adequate data are available. Please somebody, start a controlled trial right now! Technology once more has triumphed in the porta hepatis, and we welcome this potentially important and far-reaching discovery. It is fascinating to speculate why such “simple” advances take so long to evolve. W. M. LEE.M.D.
INJECTION THERAPY FOR BLEEDING ULCERS: WHICH SOLUTION IS BEST? Lin HI, Cban CY, Lee FY, et al. (Departments of Medicine and Emergency, Veterans General Hospital, Taipei, Taiwan). Endoscopic injection to arrest peptic ulcer hemorrhage: a prospective, randomized controlled trial; preliminary results. Hepatogastroenterology 1991;38:291-294 (August). Eighty-four patients presenting with melena or hematemesis, undergoing endoscopy within 12 hours of arrival, and found to have an ulcer with active bleeding or a nonbleeding visible vessel were randomly assigned to receive endoscopic injection therapy with absolute alcohol, 50% glucose (D5OW), 3% saline (3%S), or normal saline (NS). Patients could receive a maximum of 5 mL of alcohol, 15 mL of D50W, 25 mL of 3%S, or 25 mL of NS. If hemostasis was not achieved with these volumes, injection was considered a failure and heater probe or surgical treatment was used. Rebleeding was defined as blood in the stomach 24 hours after therapy; bleeding in the ulcer base at endoscopy; unstable vital signs (not specifically defined); and continued melena, hematochezia, or hematemesis after therapy (it is unclear how many of these features were required for the diagnosis of rebleeding). Repeat endoscopy was performed for unstable vital signs or if melena or hematochezia continued. All patients had repeat endoscopy at 72 hours and, if no blood clot or hemorrhage was seen, patients were discharged. About one fourth of the patients had systolic blood pressure ~100 mm Hg and heart rate ~100 beats/min; 29% had nonbleeding visible vessels and the remainder active bleeding. Hemostasis was successful initially in 90% treated with alcohol, 80% treated with D5OW, 87% given 3%S, and 85% receiving NS. Overall, persistent or recurrent bleeding after treatment was seen in 24% of the alcohol group, 25% of the D50W group, 35% of the 3% NS group, and 20% of the NS group (differences not significant). The volume of blood transfused and days in hospital were not significantly different in the four groups, and,
Vol. 103, No. 4
apparently, only 3 patients died. No perforations occurred despite mean volumes injected of 3.2 mL alcohol, 10.8 mL D50W, 19.2 mL 3%S, and 16.7 mL NS. Fourteen patients failing injection therapy had heater probe treatment: 11 had permanent hemostasis and 3 required surgery. Four other patients had surgery after injection failed, and 2 patients with metastatic cancer died without further therapy. Comment. Numerous randomized, controlled trials have documented that endoscopic injection therapy is an effective hemostatic treatment for bleeding peptic ulcers (Lancet 1987;2:1292Endoscopy 1989;21:53-55). A 1294;BrMedJ 1988;296:1631-1633; variety of injection solutions have been used in these trials. The most common agents studied are absolute alcohol, epinephrine l:lO,OOO, and epinephrine followed by a sclerosing agent such as polidocanol. However, little information is available regarding the relative efficacies of the different injection methods, and, at present, no specific injection solution is clearly the agent of choice. Studies of injection solutions in animal models have yielded results much less impressive than those seen in clinical trials. Several studies have indicated that, unlike thermal methods, injection therapy usually does not stop bleeding in the experimental ulcer model or in bleeding canine mesenteric arteries with any solution tested [Gastroenterology 1989:97:610-621; GastroinGastroenterology 1991;100:A170 test Endosc 1991;37:305-309; (abstr)], although the rate of bleeding is decreased. Absolute alcohol and sclerosing agents are reported to be better than epinephrine or saline by some investigators [Gastroenterology 1989; 96:1274-1281; Gastroenterology 199l;lOO:Al70 (abstr)]. Also, Rutgeerts et al. suggested that, although epinephrine is at least as good at stopping acute bleeding, it is less likely to prevent further bleeding because of its failure to induce thrombosis (Gastroenterology 1989;97:610-621). Many physicians have questioned whether local tamponade by an injected solution can effectively halt bleeding independently of vasoconstrictive or sclerosing effects, and results in experimental settings are conflicting. Whittle et al. reported that NS caused a significant decrease in blood flow compared with no treatment (Gastrointest Endosc 1991;37:305-309), whereas Swain and Kalabakas found no significant difference between saline and control [Gastroenterology 1991;lOO:A170 (abstr)]. Randall et al. (Gastroenterology 1989;96:1274-1281) reported that epinephrine was not significantly better than saline in achieving arterial coagulation, but Chung et al. showed that epinephrine causes a decrease in blood loss from experimental ulcers and a decrease in gastric blood flow compared with injection with an equal volume of vehicle [Gastrointest Endosc 1988;34:174-175 (abstr); Dig Dis Sci 1990;35:1008-loll]. Data comparing different injection solutions in humans are also limited and conflicting. The Hong Kong group reported that the addition of tetradecyl to epinephrine did not improve outcome (Gastrointest Endosc 1990;36:194); this group routinely repeats endoscopy in all patients at 24 hours and retreats -lo%-20% who have evidence of rebleeding. Rutgeerts, on the other hand, found that epinephrine plus polidocanol is superior to epinephrine alone (Lancet 1989;2:1164-1167) and later reported that absolute alcohol is at least as effective as epinephrine plus polidocanol [Gastroenterology 1990;98:A115 (abstr)]. Finally, a preliminary communication from Italy reported that absolute alcohol and epinephrine were similar in efficacy [Gastroenterology 1989;96:A86 [abstr)]. How does the paper by Lin et al. fit into this confusing and contradictory group of studies? Lin et al. studied patients with high-risk endoscopic features, although high-risk clinical characteristics were not required for entry (only one fourth of patients
l!t92;103:1357-1364
SELECTED SUMMARIES Mark Feldman, M.D. Selected Summaries Editor Dallas Veterans Administration Medical Service (111) Dallas, Texas 75216
Medical Center
STAFF OF CONTRIBUTORS James L. Achord, Jackson, MS Kim E. Barrett, San Diego, CA Gary L. Davis, Gainesville, FL Grace H. Elta, Ann Arbor, MI Lawrence S. Friedman, Philadelphia, Hans Fromm, Washington, DC Hans Gerdes, New York, NY Fayez K. Ghishan, Nashville, TN
PA
John B. Gross, Jr., Rochester, MN Raymond S. Koff, Framingham, MA Benjamin Krevsky, Philadelphia, PA Loren Laine, Los Angeles, CA William M. Lee, Dallas, TX Thomas A. Miller, Houston, TX Ravinder K. Mittal, Charlottesville, VA
INTRAHEPATIC PORTACAVAL SHUNTS: A NEW ERA? Ring EJ, Lake JR, Roberts JP, et al. San Francisco, California). Using portosystemic shunts to control liver transplantation. Ann Intern
(University of California, transjugular intrahepatic variceal bleeding before Med 1992;166:304-309.
Refractory variceal hemorrhage carries a high mortality and precludes transplantation for some patients, because stability cannot be maintained long enough to allow a suitable donor to be found. The present study reports a prospective uncontrolled trial of transjugular intrahepatic portosystemic shunts (TIPS) in 13 patients with variceal hemorrhage refractory to sclerotherapy, all of whom were potential transplant candidates. The technique involves creation of a channel between hepatic and portal veins via a jugular vein approach, followed by placement of a flexible wire mesh stent, which is expanded to the proper diameter via a balloon inside the stent. Portal pressures can be measured and the stent expanded further if decompression appears inadequate. The usual internal diameter is 8-12 mm, although one can enlarge the shunt to 12 mm without difficulty. Reduction in portal pressure and cessation of bleeding occurred in all patients. No complications occurred, although two deaths secondary to septic complications, said to be unrelated to the stents, were reported. No patient developed encephalopathy. Seven patients underwent transplantation; all did well in the short term. Four have been observed without undergoing transplantation, two because of improvement in ascites and no further hemorrhage and two because of recurrent alcohol abuse. In this small series, TIPS appears to provide a safe, effective means of stopping variceal hemorrhage as a bridge to transplantation and possibly serves as definitive management for certain patients. Comment. Although endoscopic variceal sclerotherapy has largely replaced shunt operations, nothing reliably reduces portal pressure like a shunt procedure. Nevertheless, shunt operations are invasive and magnify subsequent technical hurdles for the transplant surgeon. A nonoperative shunt procedure such as that reported by Ring et al. sounds ideal and it may well be. This procedure has now been performed widely both in the United States and abroad with comparative ease and good efficacy, although
Malcolm Robinson, Oklahoma City, OK Mitchell L. Schubert, Richmond, VA Konrad Schulze-Delrieu, Iowa City, IA Fergus Shanahan, Los Angeles, CA Joseph Sweeting, New York, NY Richard C. Thirlby, Seattle, WA M. Michael Wolfe, Boston, MA
reports thus far are little more than anecdotal (Cardiovasc Intervent Radio1 1990;13:200-207; JAMA 1991;266:390-393). Rosch first introduced the concept of intrahepatic portacaval shunting in 1969 (Radiology 1969;92:1112-1114). Colapinto first applied this to a patient with portal hypertension (Can Med Assoc J 1982;126:267-268) using a Grunzig balloon dilatation to create a tract that did not remain open for long. Subsequent studies have led to development of expandable rigid stents that provide a fixed internal diameter once the stent is expanded. Initially, transhepatic portography was used to localize the site of portal vein entry; however, this is not necessary if ultrasonography is used. Stents in the biliary tract work well, and it appears that venous stents in such nonconventional locations can be equally effective. What are the advantages of this technique? First, it is a radiological procedure, usually completed within 2-3 hours. Second, a shunt within the liver is removed at the time of transplantation and requires no tedious takedown at the time of transplantation (the decompressed portal circuit makes removing the native liver easier). Finally, patients seem to stabilize quite dramatically. Indeed, bleeding stops, and ascites is mobilized as well. The TIPS appears to function as a side-to-side shunt, and diuresis has been reported in all patients who have ascites. If patients have no more bleeding or ascites, nutritional recovery may occur and transplantation may no longer be necessary. According to all studies to date, encephalopathy has not been observed. This seems incredible, and it is likely that a longer experience with more patients with TIPS shunts will disclose significantly increased encephalopathy over time. If encephalopathy is not a problem with TIPS, then we need to rethink our understanding of why other types of shunt operations are associated with so much encephalopathy. There is no evidence thus far that significant antegrade portal flow is maintained through the sinusoids; however, portal hypertension is not fully resolved by TIPS. Thus, we have created a small bore shunt that may be more effective than an extrahepatic shunt in maintaining sinusoidal perfusion and work to limit the hepatic atrophy associated with the postshunt situation. Over time, a thick neointima develops, limiting any flow directly through the shunt walls. Nevertheless, with significant resistance across the shunt, perfusion of the remaining portal veins is apparently well maintained. The disadvantages of this type of shunt would include the catastrophic possibility of puncture of portal vein or gall bladder wall as well as the potential for infection, with the metal stent serving as nidus. One wonders whether the shunt in any way was involved in the deaths of the two patients in the present study, because it is made clear that in both instances the infection was already underway before TIPS placement. Does this all sound too good to be true? Maybe. TIPS certainly seems like a genuine advance in management of portal hyperten-
1358 SELECTED SUMMARIES
GASTROENTEROLOGY
sion that may finally make the operative portacaval shunt procedure a dinosaur. It may even replace injection sclerotherapy if safety and uniformity of function over a long period can be assured. One patient in whom bleeding recurred and in whom a partial stent occlusion was shown was treated by placement of a second stent, which was expanded inside the first. Transplantation was accomplished shortly thereafter. TIPS appears to provide at least an effective bridge to hepatic transplantation, although its widespread application has not been observed. One cautionary note: the present small study represented consecutive but uncontrolled results. Before we get ahead of ourselves, TIPS should be subjected to a head-to-head trial with sclerotherapy or banding. Otherwise, TIPS is likely to become a strong consideration as definitive therapy for variceal hemorrhage before adequate data are available. Please somebody, start a controlled trial right now! Technology once more has triumphed in the porta hepatis, and we welcome this potentially important and far-reaching discovery. It is fascinating to speculate why such “simple” advances take so long to evolve. W. M. LEE.M.D.
INJECTION THERAPY FOR BLEEDING ULCERS: WHICH SOLUTION IS BEST? Lin HI, Cban CY, Lee FY, et al. (Departments of Medicine and Emergency, Veterans General Hospital, Taipei, Taiwan). Endoscopic injection to arrest peptic ulcer hemorrhage: a prospective, randomized controlled trial; preliminary results. Hepatogastroenterology 1991;38:291-294 (August). Eighty-four patients presenting with melena or hematemesis, undergoing endoscopy within 12 hours of arrival, and found to have an ulcer with active bleeding or a nonbleeding visible vessel were randomly assigned to receive endoscopic injection therapy with absolute alcohol, 50% glucose (D5OW), 3% saline (3%S), or normal saline (NS). Patients could receive a maximum of 5 mL of alcohol, 15 mL of D50W, 25 mL of 3%S, or 25 mL of NS. If hemostasis was not achieved with these volumes, injection was considered a failure and heater probe or surgical treatment was used. Rebleeding was defined as blood in the stomach 24 hours after therapy; bleeding in the ulcer base at endoscopy; unstable vital signs (not specifically defined); and continued melena, hematochezia, or hematemesis after therapy (it is unclear how many of these features were required for the diagnosis of rebleeding). Repeat endoscopy was performed for unstable vital signs or if melena or hematochezia continued. All patients had repeat endoscopy at 72 hours and, if no blood clot or hemorrhage was seen, patients were discharged. About one fourth of the patients had systolic blood pressure ~100 mm Hg and heart rate ~100 beats/min; 29% had nonbleeding visible vessels and the remainder active bleeding. Hemostasis was successful initially in 90% treated with alcohol, 80% treated with D5OW, 87% given 3%S, and 85% receiving NS. Overall, persistent or recurrent bleeding after treatment was seen in 24% of the alcohol group, 25% of the D50W group, 35% of the 3% NS group, and 20% of the NS group (differences not significant). The volume of blood transfused and days in hospital were not significantly different in the four groups, and,
Vol. 103, No. 4
apparently, only 3 patients died. No perforations occurred despite mean volumes injected of 3.2 mL alcohol, 10.8 mL D50W, 19.2 mL 3%S, and 16.7 mL NS. Fourteen patients failing injection therapy had heater probe treatment: 11 had permanent hemostasis and 3 required surgery. Four other patients had surgery after injection failed, and 2 patients with metastatic cancer died without further therapy. Comment. Numerous randomized, controlled trials have documented that endoscopic injection therapy is an effective hemostatic treatment for bleeding peptic ulcers (Lancet 1987;2:1292Endoscopy 1989;21:53-55). A 1294;BrMedJ 1988;296:1631-1633; variety of injection solutions have been used in these trials. The most common agents studied are absolute alcohol, epinephrine l:lO,OOO, and epinephrine followed by a sclerosing agent such as polidocanol. However, little information is available regarding the relative efficacies of the different injection methods, and, at present, no specific injection solution is clearly the agent of choice. Studies of injection solutions in animal models have yielded results much less impressive than those seen in clinical trials. Several studies have indicated that, unlike thermal methods, injection therapy usually does not stop bleeding in the experimental ulcer model or in bleeding canine mesenteric arteries with any solution tested [Gastroenterology 1989:97:610-621; GastroinGastroenterology 1991;100:A170 test Endosc 1991;37:305-309; (abstr)], although the rate of bleeding is decreased. Absolute alcohol and sclerosing agents are reported to be better than epinephrine or saline by some investigators [Gastroenterology 1989; 96:1274-1281; Gastroenterology 199l;lOO:Al70 (abstr)]. Also, Rutgeerts et al. suggested that, although epinephrine is at least as good at stopping acute bleeding, it is less likely to prevent further bleeding because of its failure to induce thrombosis (Gastroenterology 1989;97:610-621). Many physicians have questioned whether local tamponade by an injected solution can effectively halt bleeding independently of vasoconstrictive or sclerosing effects, and results in experimental settings are conflicting. Whittle et al. reported that NS caused a significant decrease in blood flow compared with no treatment (Gastrointest Endosc 1991;37:305-309), whereas Swain and Kalabakas found no significant difference between saline and control [Gastroenterology 1991;lOO:A170 (abstr)]. Randall et al. (Gastroenterology 1989;96:1274-1281) reported that epinephrine was not significantly better than saline in achieving arterial coagulation, but Chung et al. showed that epinephrine causes a decrease in blood loss from experimental ulcers and a decrease in gastric blood flow compared with injection with an equal volume of vehicle [Gastrointest Endosc 1988;34:174-175 (abstr); Dig Dis Sci 1990;35:1008-loll]. Data comparing different injection solutions in humans are also limited and conflicting. The Hong Kong group reported that the addition of tetradecyl to epinephrine did not improve outcome (Gastrointest Endosc 1990;36:194); this group routinely repeats endoscopy in all patients at 24 hours and retreats -lo%-20% who have evidence of rebleeding. Rutgeerts, on the other hand, found that epinephrine plus polidocanol is superior to epinephrine alone (Lancet 1989;2:1164-1167) and later reported that absolute alcohol is at least as effective as epinephrine plus polidocanol [Gastroenterology 1990;98:A115 (abstr)]. Finally, a preliminary communication from Italy reported that absolute alcohol and epinephrine were similar in efficacy [Gastroenterology 1989;96:A86 [abstr)]. How does the paper by Lin et al. fit into this confusing and contradictory group of studies? Lin et al. studied patients with high-risk endoscopic features, although high-risk clinical characteristics were not required for entry (only one fourth of patients
