A better mousetrap LANDWAIlKS I1 HEPATOLOGY A Better Mousetrap lood spurts as from a geyser, and prompt action is required. With its familiar hiss, suction is applied, and an expanding redness comes into view, like a vermilion Carolina moon waxing in accelerated time. The knob is turned, and a satisfying muffled click is felt more than heard. Warily, the vacuum is released and the knuckle of once gushing mucosa, now ensnared with a shiny black rubber ring, recedes slowly from sight like the jettisoned stage of a spacecraft. Another bleeding varix, temporarily staunched only weeks ago with a styptic in- jection, has finally been successfully obliterated (Fig. 1) l . It seems a little surprising now that the occurrence of esophagogastric varices in cirrhosis and their propensity to bleed became widely appreciated only late in the his- tory of hepatology, after the turn of the 20th century.2 Although modern estimates do range widely, we know that the prevalence of varices in cirrhosis, their risk of bleeding and rebleeding and the consequent mortality, are all in the 20% to 80% range, depending upon the variables in the study and the particular stratification used.3 Nonetheless, William Osler, who recognized the existence of esophageal varices4 and had himselfwitnessed a fatality therefrom,5 had personal experience of only two cases by the time he published his famous textbook in 1892, in which, forsooth, he also wrote that hemorrhage from gastric varices was seldom f a d 6 The existence of esophageal varices had actually been clearly established 50 years earlier, in 1840, by William Power of Maryland, who reported on the autopsy of a 50-year-old man of robust frame, intemperate habits, and deficient intelli- gence.7 The patient, who died of gastrointestinal hemor- rhage, was found to have “Varicose veins of the oesophagus” that Power had never met with before, nor had he found a similar case recorded. Power wondered, “. . .whether the presence ofvarices to such an extent, and death caused by their rupture, be not-something as yet unheard of in pathological anatomy.”7 Power’s discovery was later confirmed in a report from France,8 but even so this was still the only experience of that entity for Friedrich Theodor von Frerichs, the founder of modern hepatology, by the time his own textbook was written.’ Admittedly it was well nigh impossible then to diagnose in life the presence of varices-silent or otherwise-in the years before Adolf Kussmaul performed the first really practical esophagoscopy in Freiburg in 1868, using an ~ ~~~~ ~ ~~ Copyright 0 2004 by the American Association fir the S d y of Liver Diseases. Published online in Wiley Interscience (www. interscience. wiley.com). DOI 10.1002lhep.20449 endoscope designed for the urethra and bladder by Anto- nin J. Dtsormeaux of the Acadtmie de Mkdecine in Paris, and with the skillful cooperation of his intrepid first sub- ject, a visiting sword swallower who was performing at a local inn.’” The development of flexible fiber-optic en- doscopy by Basil Hirschowitz and others in the 195Os,l1 culminating in the first reports of its clinical use, initially in May 1961 ,l2,13 conveniently expanded the patient pool to include less-supple individuals (than Kussmaul’s itin- erant showman), for whom this procedure would be fea- sible, thereby illuminating the way for the endoscopic evaluation and treatment of varices that we enjoy today. Preble’s report,2 at the beginning of the 20th century, of 60 patients with cirrhosis and fatal gastrointestinal bleeding, of whom 80% had esophageal varices, foretold an era of intensive investigation of portal hypertension14 and a de- mand for effective therapies to combat this most lethal com- plication of cirrhosis, either by decompressing the portal system and/or diverting variceal blood flow elsewherel5 or simply by obliterating the varices in the hope that the prob- lem would go away. From the mid 1940s, and for the longest while, shunt surgery was king, with its peak popularity in the 1970s followed by the development of selective shunts and devascularization procedures in the next decade or so, be- cause of dissatisfaction with the morbidity of surgically in- duced encephalopathy and liver failure. With the growth of successfd liver transplantation and the development of non- surgical methods for treating bleeding varices, enthusiasm for shunt surgery has been tempered in favor of pharmaco- logical, endoscopic, and interventional radiological treat- ment, while selective shunts are reserved for patients with good liver h c t i o n (especially those with portal hyperten- sion without cirrhosis) and, in some cases, shunts and devas- cularization procedures may be used when other treatments fail.17-20 In this context, the idea of obliterating varices rather than bypassing them with a surgically created shunt dates back more than 50 years to a w e report that described si- multaneous variceal suture ligation and injection with a scle- rosing solution at thoracotomy, through an esophagus that had been split open almost from stem to stern, from the level of the aortic arch to the diaphragm.21 Thereafter, the tech- niques of vascular shunting, sclerotherapy, and ligation evolved along parallel (and occasionally intersecting) paths, each with its fervent advocates vying for the favors ofpatients with portal hypertension and varices that had bled or were doomed to do so. Surgeons began to divert the flow of blood from the portal to the systemic circulation in patients with portal hypertension, even before they fully understood the dis- 1023 1024 REUBEN HEPATOLOGY, October 2004 pioneered temporizing balloon tamponade techniques for acute variceal bleeding2* From the 1970s to the 1990s, total portal decompressive shunts gave way to selective shunts and eventually to partial portal shunts, using graded interposition conduits.25 For a while it seemed that there were countless ways for surgeons to bypass var- ices and/or decompress the portal venous system, as they used all of their anatomical ingenuity. Unfortunately, while the need to prevent variceal bleeding by surgery was well fulfilled, all such operations, in greater or lesser mea- sure, were wanting with respect to patient morbidity, due to encephalopathy and liver failure, and mortality. Physi- cians desired better overall results for their patients and not just the cessation of hemorrhage. And as historian, philosopher, and guru of invention Henry Petroski theo- rizes, it is the desire to improve on the failings of existing technology that drives innovation and not simply that there is a need to innovate.26 Want, says Petroski, and not necessity, is the mother of invention. This principle and its corollary that no invention is perfect and that every- thing is susceptible to change and improvement in time is Fig. 1. Bleeding esophageal varices. (A) In an endoscopic photograph - of the esophagus of a 56-year-old alcoholic man with massive hemate- mesis, blood can be seen spurting from a ruptured varix (arrow). (B) After very well exemplified by the successive and continuing innovation in the treatment of portal hypertension and injection sclerotherapy of the variceal trunk and immediate hemostasis, . . . . .. the source of bleeding was revealed as a white nipple, which represents VarlCed bleeding. what was thought to be a fibrin-platelet plug (arrow). Endoscopic variceal ligation was performed for recurrent bleeding from the same source three weeks after the initial episode. (C) The white object (arrow) is the remnant of a banded varix. Reproduced with permission from Navarro and Reuben.l ease and its complications of ascites and variceal hemor- rhage that they hoped to cure.16 Portosystemic shunts were performed in patients in the early part of the 20th century, in the years before the First World War- based on the surgical anastomosis between the portal vein and the inferior vena cava in dogs, described by Nikolai Vlad- imirovich Eck in Moscow in 1 87722-to replace the then- fashionable operation of splenectomy that was combined with the curious procedure of omentopexy, in which the omentum was sewn to the parietal peritoneum to produce portosystemic collaterals. l6 That William Mayo strongly favored splenectomy (as did Harvey Cushing and William Halsted before him) and omentopexy, and that 7 of Eck's 8 canine patients died of the operation (while the survivor was allowed to run away by a careless technician) 16 did not dampen the enthusiasm of pathfinding shunt surgeons in those days. Interest in Eck's fistula was revived by Archibald McIndoe, as a result of his detailed pathological vascular studies in cirrhosis in the late 192Os,l5 and the idea was enthusiastically and variously adapted by Allen Oldfather Whipple and his many disciples at Columbia- Presbyterian in New York City,23 who incidentally also The desire to create a portosystemic shunt and yet avoid the deleterious effects of surgery, usually but not exclusively expressed by nonsurgeons,17 gave rise to the familiar radiologically created transjugular intrahepatic portosystemic shunt (TIPS) that is ubiquitous t0day.~7 First achieved crudely by dragging a Gruntzig balloon, inflated in the portal vein, through liver tissue to create a track to the hepatic vein,28 the predictable failure of this early method due to track closure has been remedied, partially at least, by deploying a metal conduit between the portal and hepatic veins29-31 as predated by experi- mental efforts in dogs more than 30 years ag0.3~ Variceal sclerotherapy has passed through many itera- tions too, since the first description of an endoscopic ap- proach by a thoracic surgeon and otolaryngologist in 1939 who used an quinine-uretan sclerosant and an idea borrowed from the treatment of rectal hemorrhoids.33 Although later the percutaneous transhepatic approach to both ~clerotherapy3~J5 and variceal embolization36 was short-lived, the technique of endoscopic sclerotherapy progressed from using a rigid esophagoscope or fiber-op- tic endoscope with a flexible oversheath, both under gen- eral anesthesia,37 to performing the procedure electively or in an emergency with an unmodified modern video endoscope under conscious sedation, using any one of the many sclerosants a~ailable,3~,39 including cyanoacrylate in some c o ~ n t r i e s . * ~ Despite the exceptional success of en- doscopically delivered injection sclerotherapy in control- HEPATOLOGY, Vol. 40, No. 4 , 2004 REUBEN 1025 ling acute variceal hemorrhage and the achievement of a significant reduction in bleeding r e c ~ r r e n c e , ~ ’ this form of variceal therapy has its shortcomings too, in terms of patient morbidity. Sclerotherapy can produce mucosal ulcers that bleed, esophageal stenosis, the rare case of esophageal perforation, and other unpleasant misadven- tures such as adult respiratory distress syndrome, bronch- oesophageal fistula, chylothorax, pneumothorax, and media~tinitis.3~ Besides, brandishing a naked needle loaded with sclerosant in the vicinity of a bleeding varix that must be speared, no more than a fingerbreadth from the heart, lungs and great vessels, in a bucking patient, is not for the faint-hearted. By the mid 1980s, the moment was ripe for another leap forward in variceal therapy. This came as the exquisitely simple but effective remedy of endoscopic variceal band ligation that was first published in 1988 in two landmark a r t i ~ l e s ~ ~ 3 ~ 3 from the Mile High City of Denver, not far from the Rocky Mountains in the Centennial State of Colorful Colorado. Compared to the many innovations over the years of sur- gical and radiological portosystemic shunting, sclerotherapy, and pharmacotherapy for portal hypertensive variceal bleed- ing, there had been little progress in variceal ligation since the surgical operations of the 1950s, except that ligation could be accomplished via a small rather than large esophageal inci- sion by pulling on the pliable mucosa to bring the varices into view from both the esophagus and ~tomach.4~,~5 Even in the early 1970s, ligation was still being performed surgically for acute variceal bleeding, with good results for Child-Tur- cotte-Pugh Class A patients and moderate success for Class B patients, but almost certain demise (90% mortality) for Class C patients, who also suffered the morbidity of fistulae at the esophageal suture line more frequently (20%) than the other patients.46 Like Clarence Crafoord and Paul Frenckner 50 years before him,33 Gregory Van Stiegmann, then Assistant Professor of Surgery at the University of Colorado School of Medicine (where he is now Professor of Surgery and Associ- ate Dean and Vice-president for Clinical AfEairs), was in- spired to improve the treatment of esophageal varices while gazing at rectal hemorrhoids that he was treating. Stiegmann had had considerable experience with endoscopic esophageal sclerotherapy from his training in surgery and surgical endos- copy during a brief sojourn in Cape Town, South Africa. He wondered whether the nonoperative rubber-band ligation procedure that he was using on the hemorrhoids, and that had superseded sclerotherapy for that purpose, could be adapted to treat esophageal varices too. By producing a “suc- tion polyp” of the pliable esophageal mucosa to “grasp the varix,” so to speak, he reasoned that it should then be possible to apply the ligating rubber bands in the esophagus. Using personal funds accrued from consulting fees, Stiegmann commissioned engineers of the machine shop at the Univer- Fig. 2 . (A) The original endoscopic ligating device. The instrument was carved from stainless steel and screwed onto the endoscope in place of the lens cap. A single black rubber “0” ring is shown in place over the distal end of the device. (B) The trip wire and the components used to assemble and load the ligator. Photographs generously provided by the inventor, Dr. Greg Van Stiegmann. sity to fashion a stainless steel ligator, consisting of an outer cylinder and an inner cylinder, which was screwed onto the tip of an endoscope instead of its lens cap (Fig. 2A, 2B).47 Using a single latex “0” ring and a trip wire, the efficacy of Stiegmann’s gadget was first established using a canine model of varices.42 Then he and John Goff, a colleague and friend in the Division of Gastroenterology in Denver, showed that the procedure was feasible, safe, and effective clinically by performing 132 varix ligations during 44 sepa- rate sessions in 14 consecutive patients under topical anes- thesia and/or conscious sedation, using an over-tube and a single-fire te~hnique.~3 In the 10 patients who completed the course of treatment (2 died of unrelated causes and 2 were noncompliant), all achieved complete variceal eradication after a mean of 3.9 sessions, and there were no major com- plications. These excellent results were subsequently borne out in numerous studies thereafter by Stiegmann48 and oth- ers,49 and superiority over sclerotherapy was established. True to Petroski‘s predictions, the Stiegmann-Goff tech- nique has been modified to improve performance and re- duce failures due to complications, such as trauma caused by the over-tube50 that was needed for the single-fire device. Translucent plastic ligators that fit snuggly over the tip of the endoscope have been developed, with repeat-fire capabili- ties51 that obviate the need for repeated intubation and the use of an over-tube. Incidentally, Stephen Perry of the rubber manufacturing company Messrs Perry and Co., London, England, would have been gratified to learn that Stiegmann has extended the utility of the rubber band, which he in- vented originally to hold papers or envelopes together and patented in 1845. Endoscopic variceal ligation is now recommended by many a~thorities38,4~,5~,53 as first-line treatment for bleeding esophageal varices and to prevent rebleeding. Its widespread 1026 REUBEN HEPATOLOGY, October 2004 use has not been adopted yet, possibly in part due to the cost of the disposable equipment,39 which local ingenuity in some less-afffuent parts of the world has overcome by using what the authors describe as indigenous s~bstitutes.5~ By substituting bands used for hemorroidal ligation and fash- ioning an introducer (to slip the “0” ring on the cylinder) from a glass pipette and a tripwire from the wire used to string tennis raquets, the authors saved thousands of ru- pees.54 The next logical step in this saga will probably be to recommend prophylactic banding to prevent the first hem- orrhage,55,56 although for some doubters the notion of this motion is still controversial.57 “If a man can write a better book, preach a better sermon or make a better mousetrap, than his neighbor, though he build his house in the woods, the world will make a beaten path to his door.” Whether or not these words were ever uttered or written by the American essayist, poet, and philosopher Ralph Waldo Emerson is still a matter for ~ o n j e c t u r e , 5 ~ a but the sentiment that quality prevails in the marketplace is clearly true for Stiegmann’s invention. Parenthetically, it must be noted that the Patent Office has issued over 4,000 mousetrap patents, although none have surpassed the quality of the trap invented by John Mast of Lititz, PA, in 1899.59 Whereas a path may not have been beaten to Greg Stiegmann’s door, partly because his invention has never really been eponymous and partly because of the high altitude of his mountainous retreat, it is unquestionably one of the better traps that has yet been devised to ensnare that most elusive mouse, the bleeding esophageal varix. Acknowledgments: The author thanks Dr. Gregory Van Stiegmann for generously imparting the story of his invention of endoscopic variceal band ligation and for providing the photographs of his prototypic device. Mar- gie Myers continues to provide skilled manuscript prepa- ration and literature retrieval. ADRIAN REUBEN, M.B.B.S., F.R.C.P. Professo r o f Medicine Division of Gastroenterology and Hepatology Department ofMedicine Medical University of South Carolina Charleston, SC While this sentence has never been found in Emerson i. works, he is believed t o have used it in a lecture either at San Francisco or Oakland, Calfornia, in 1871. Borrowings was an anthology compiled by women of the First Unitarian Church of Oakland, and Sarah Yule contributed this sentence, which she had copiedfiom an address years b&ore. There has been some controversy because others, including Elbert Hubbard have claimed authorship. (Source: Respectjidly quoted: a dictio- navy of quotations requested fiom the Congressional Research Service. Edited by Suzy Plan. Washington: Libravy o f Cong-ess, US GPO, 1989.) References 1. Navarro V, Reuben A. Bleeding esophageal varices. N Engl J Med 1994; 331:1129. 2. Preble PB. Conclusions based on sixty cases of fatal gascrointestinal hem- orrhage due to cirrhosis of the liver. 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Stiegmann GV, Goff JS, Michaletz-Ohody PA, Korula J, Lieberman D, Saeed ZA, et al. Endoscopic sclerotherapy as compared with endoscopic ligation for bleeding esophageal varices. N Engl J Med 1992;326:1527- 1532. 49. Laine L, Cook D. Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding: a meta-analysis. Ann Intern Med 1995;123:280-287. 50. Hoepffner N , Foerster E, Menzel J, Gillessen A, Domschke W . Severe complications arising from oesophageal varix ligation with the Stiegmann- Goff set. Endoscopy 1995;27:345. 51. Saeed ZA. The Saeed six-shooter: a prospective study of a new endoscopic multiple rubber band ligator for the treatment of varices. Endoscopy 1996; 28:559-564. 52. Grace ND. Diagnosis and treatment of gastrointestinal bleeding secondary to portal hypertension. Am J Gastroenterol 1997;921081-1091. 53. Sharara AI, Rockey DC. Gastrointestinal variceal hemorrhage. N Engl J Med 2001;345:669--681. 54. Nanivadekar SA, Satarkar RP, Dave UR, Sawant P, Chopda N. Use of indigenous and economical substitutes for variceal band ligation accesso- ries. Indian J Gastroenterol 1995;14:1-8. 55. Imperiale TF, Chalasani N. A meta-analysis of endoscopic variceal ligation for primary prophylaxis of esophageal variceal bleeding. HEPATOLOGY 2001;33:802-807. 56. Van Stiegmann G. Motion-prophylactic banding of esophageal varices is useful: arguments for the motion. Can J Gastroenterol. 2002;16:689- 692. 57. Kowdley KV. Motion-prophylactic banding of esophageal varices is use- ful: arguments against the motion. Can J Gastroenterol 2002; 16:693- 695. 58. Ladies of the First Unitarian Church of Cortland, California. Borrowings. San Francisco, CA: CA Murdock and Co., 1889:38. 59. Hope JA. A better mousetrap. Am Herit 1996: 90-97. 179:35-38.