R he underwent his undergraduate medical training

CLASSICS IN THORACIC SURGERY The Nissen Fundoplication F. Henry Ellis, Jr, MD, PhD New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts The most commonly employed antireflux operation is the Nissen fundoplication. However, its origin and subsequent modifications are rarely defined. These aspects of the operation are reviewed in this article as are the results currently obtainable with the modern version of the operative procedure. (Ann Thoruc Surg 1992;54:1231-5) udolph Nissen was born in 1896 in Germany, where R he underwent his undergraduate medical training (Fig 1). His interest in thoracic surgery was greatly influenced by Professor Sauerbruch, whose assistant he became in 1921 in the surgical department of the University of Munich. He remained there until 1927, when he accompanied Sauerbruch to Berlin, eventually becoming associate professor of surgery at the University of Berlin. In 1933 he was appointed professor and head of the department of surgery at the University of Istanbul in Turkey, but came to the United States during World War I1 in 1939 where he remained during the war years and their aftermath until 1952. He was first a research fellow in surgery at the Massachusetts General Hospital, but 2 years later became chief of the surgical service at the Jewish Hospital in Brooklyn and subsequently at the Maimondes Hospital in the same city. The culmination of his career was as professor of surgery and head of the department at the University of Base1 in Switzerland in 1952, a post that he held until his retirement in 1966. Nissen died on January 22, 1981, at the age of 85 years after a long and productive career, much of it devoted to the field of thoracic surgery, particularly pulmonary surgery. Although much of Professor Nissen s original pioneering contributions to the field of pulmonary surgery have been forgotten or overlooked, his seminal contribution to the surgical management of selected patients with gastroesophageal reflux disease will long be remembered because his name has become associated with the most widely employed and successful antireflux operation currently in use. The procedure that he first described in 1956 [l](fig 2) subsequently underwent modifications by him and his colleagues as well as by others so that the term Nissen fundoplication means different things to different people [2]. It is important, therefore, when documenting his position as an innovative antireflux surgeon not only to describe in detail the procedure he originally performed and subsequently modified but also to review Address reprint requests to Dr Ellis, Suite 2C, 110 Francis St, Boston, MA 02215. the historical setting that led to the introduction of this essentially physiologically based operation. Historical Setting Before Nissen s original publication, operations for the repair of diaphragmatic hernia were based on anatomic rather than physiologic principles. It was not then recognized that reflux accounted for the symptoms of a sliding esophageal hiatus hernia, but Nissen [3] ultimately adopted the concepts proposed by Philip Allison in 1951 regarding the nature and relationship of reflux esophagitis to a sliding esophageal hiatus hernia [4]. By the early 1950s he had become dissatisfied with the results of anatomically conceived surgical techniques, including the Harrington and Allison procedures, for a review of his data revealed that 50% of his patients so treated developed either clinical or radiographic failure postoperatively [5]. He therefore sought a more effective procedure, first employing gastropexy in patients with a paraesophageal hiatus hernia in 1946 and later extending its use to elderly poor-risk individuals with a sliding hernia and reflux symptoms [6]. Accentuation of the angle of His by gastropexy was considered by him to explain the symptomatic relief that followed its use in the small number of patients with reflux on whom it was employed. However, he later abandoned the use of gastropexy alone for sliding esophageal hiatus hernia because of a high recurrence rate, 35 of 100 cases [7]. When faced in 1955 with a patient with severe reflux symptoms without a diaphragmatic hernia, Nissen recalled a 28-year-old man with a distal esophageal ulcer penetrating into the pericardium whom he had treated in 1936 by resecting the distal esophagus and proximal stomach. In an effort to protect the anastomotic suture line between esophagus and stomach, he embedded the esophageal stump into the wall of the stomach as in a Witzel gastrostomy [8]. Sixteen years later it was possible to reexamine the patient, and to Nissen s surprise there was no evidence of esophagitis. Thus in December 1955 when confronted with a 49-year-old woman with a 3-year history of reflux esophagitis without a hiatus hernia, he performed a similar type of procedure through a transabdominal approach by mobilizing the distal esophagus and wrapping the distal 6 cm of esophagus with gastric fundus in an effort to correct gastroesophageal reflux. Few details regarding the technique of the operation were provided in his original article [l] (see Fig 2), but subsequent publications in English [9], French [lo], and German [ll] provided detailed descriptions of the operative procedure (Fig 3). The phrenoesophageal membrane was divided and the 0 1992 by The Society of Thoracic Surgeons 0003-4975/92/$5.00

1232 CLASSICS ELLIS Ann Thorac Surg 1992;54:1231-5 being restricted only to patients with a paraesophageal hiatus hernia [9]. Another important modification of the original procedure subsequently became routine practice. In one of the reports by Nissen and Rossetti [7], only the anterior wall of the stomach was used to encircle the distal esophagus in extremely obese patients. This technical modification was described in detail by Rossetti in 1968 [13] and became the procedure of choice in Nissen s clinic. By 1977 Rossetti and Hill [14] were able to report 1,400 cases, many of them operated on using only the anterior wall of the stomach for the wrap. The long-term results in 590 cases were evaluated and symptomatic relief was achieved in 90% of cases. Some time later Rossetti and Hitz [15] further modified the procedure in patients with hyperacidity by performing a vagotomy of the esophagogastric junctional area and bringing the wrap between the vagal trunk and the esophagus. Fig 1. Rudolf Nissen, MD. (Reproduced from Nissen R. Reminiscences-reflux esophagitis and hiatal hernia. Rev Surg 1970;27:307-14, with the permission of the publisher.) esophagus mobilized to provide a substantial intraabdominal esophageal segment. The gastrohepatic ligament was divided and, if necessary, so was the left gastric artery, but the short gastric vessels were not divided. Then, using the right hand, the gastric fundus was passed behind the stomach and through the opening provided by the divided gastrohepatic ligament to permit encirclement of the distal 6 cm of esophagus. The posterior and anterior walls of the esophagus were then approximated with four or five interrupted sutures, one or more of which also incorporated part of the anterior wall of the esophagus. The wrapping procedure was performed around a largebore indwelling intraesophageal stent. Technical Modifications by Nissen and Associates Although the transabdominal approach was preferred by Nissen, he did not hesitate to use the transthoracic approach under certain circumstances such as a previous failed operation, the presence of a short esophagus, and when other intrathoracic disorders requiring a transthoracic approach were present such as an esophageal ulcer or an epiphrenic diverticulum [12]. Nor did he hesitate to leave the wrap in the chest if it could not be reduced intrabdominally. Although the first operation did not include a gastropexy, the combined operation became the procedure of choice [6] but was gradually abandoned because fundoplication alone proved beneficial. By 1962 gastropexy was no longer combined with fundoplication, Other Modifications of the Nissen Fundoplication There have been many other modifications of the Nissen fundoplication, most of which were designed to avoid some of the complications of the procedure, which include postoperative dysphagia, disruption of the wrap, and the gas bloat syndrome, complications related for the most part to the formation of too tight a wrap. Nissen himself originally advocated the use of an indwelling Aue der chirurgischen UniversitAteklinik Bawl Vorsteher : Prof. R. Nieeen Eiae einirehe Operation zur Beeidussung der Reflaxoewphqilis Vm R. Nissen Abb. 1. Gastroplicatio ziir Vrrliiiideruiig des o~ophepalcn 1Clagciisnftrc~fluxrrr. Fig 2. Title page of Nissen s original article describing his operation and Figure 1 of that article. (Reproduced from Nissen R. Eine einfache Operation zur Beeinflussung der Refluxoesophagitis. Schweiz Med Wochenschr 1956;86:590-2, by permission.)

Ann Thorac Surg 1992;54:1231-5 CLASSICS ELLIS 1233 NISSEN FUNDOFLICATION Fig 3. Detailed illustrations of the Nissen fundoplication. (Reproduced from Nissen R. The treatment of hiatal hernia and esophageal reflux by fundoplication. In: Nyhus LM, Harkins HH, eds. Hernia. Philadelphia: J.B. Lippincott, 1964:488-96, by permission.) stent during the performance of the wrap, and this maneuver is currently employed by most surgeons performing the operation, although the size of the stent varies with the operator. I employ a 46F to 50F Maloney dilator depending on the size of the patient, but some advocate using a larger stunt, up to 60F [16]. Although the original Nissen procedure did not involve division of the short gastric and posterior gastric vessels, complete mobilization of the fundus by division of these vessels is now preferred by most surgeons to provide as loose a wrap as possible in an effort to avoid the complications just mentioned. The advantages of a loose, "floppy" wrap in avoiding the gas bloat syndrome have been well documented [17]. Division of the gastrohepatic ligament, advocated by Nissen, is now rarely performed not only to preserve the hepatic branch of the vagus nerve but to prevent caudal migration of the wrap. Some prefer to exclude one or both vagus nerves from the wrap [15, 18, 191. Whereas Nissen's original wrap extended over 6 cm of the distal esophagus, most surgeons now prefer a shorter wrap as recommended by DeMeester and associates [ZO], the wrap enveloping only 1 to 2 cm of the distal esophagus. Other modifications include narrowing of the esophageal hiatus [21], anchoring of the plication sutures to the preaortic fascia [22] to prevent mediastinal migration of the wrap, concomitant performance of parietal cell vagotomy (not only to reduce gastric acidity, but also to simplify performance of the fundoplication) [23], and decreasing the degree of the fundal wrap to encircle less than 360 degrees of the esophageal tube. The partial wrap was proposed in an effort to minimize the risk of postoperative gas bloat syndrome. The names of Guarner [24], Dor [25], and Toupet [26] have become associated with such procedures depending on whether the partial wrap is applied anterior to the esophagus or posterior to it. Other modifications include the cut or uncut Collis- Nissen procedures for reflux associated with a shortened esophagus and the Thal-Nissen for relief of obstruction and reflux in the presence of a peptic esophageal stricture. Mechanism of Action of Fundoplication It is not clear from Nissen's articles how he believed his fundoplication prevented reflux. Esophageal manometry was not part of his preoperative or postoperative workup and apparently never became so. Certainly restoration of normal anatomy was not his goal, as it was for Belsey and Hill with their procedures, although both accomplish a modified wrap. Perhaps he thought he was fashioning a "flutter valve," a mechanism suggested by others [27]. However, regardless of which modification of the Nissen fundoplication is employed, the mechanism by which the wrap accomplishes its antireflux function is probably the same. A variety of explanations for its mode of action have been suggested. Most postoperative manometric studies identify an increase in amplitude and length of the high-pressure zone after the performance of fundoplication [28-301. This has been explained on the basis of

1234 CLASSICS ELLIS Ann Thorac Surg 1992;54 1231-5 purely mechanical factors by the experimental studies of Condon and associates [31]. In addition to the mechanical effect of fundoplication there is a return to normal of the adaptive response of the response of the lower esophageal sphincter (LES) to graded increases in intragastric pressure suggesting a return of the normal physiology of the sphincter mechanism [32]. Furthermore, the subnormal response of the hypotensive LES to gastrin administered parenterally is restored to normal after clinical fundoplication and experimental fundoplication [33], suggesting that the smooth muscle of the gastric fundus behaves in a manner similar to the smooth muscle of the LES, a concept supported by the anatomic studies of Liebermann-Meffert [34]. Lipschutz and associates [35] have suggested that alteration in the length tension characteristics of the LES produced by the surgical repair is an important factor in preventing reflux. It has also been suggested that antireflux operations may interrupt distracting forces on the LES by limiting tension at the gastroesophageal junction [36]. Thus there are a multiplicity of explanations for the successful antireflux function of fundoplication procedures, none of which have been convincingly proved to be the true mechanism. In all likelihood, a variety of factors are involved in the success of fundoplication procedures in preventing reflux. Suffice it to say, Nissen was the first of the antireflux surgeons to attempt to restore normal physiology, not normal anatomy. Current Results of the Modified Nissen Fundoplication It is difficult to evaluate the reported results of the modified Nissen fundoplication because of differences in methods of reporting, varying patient populations, and the subtle variations in the surgical techniques employed. In general, however, successful alleviation of reflux symptoms has been achieved in from 85% to 90% of patients (20, 321. Negre [37], however, has drawn attention to the high frequency of complications following this operation. Of 226 patients followed up, 19% had persistent or recurrent reflux and only 24% were totally without symptoms. Such findings have not been the universal experience, however, as suggested by another recent study which followed up 350 patients up to 20 years after the Nissen fundoplication and found a low incidence of complications, only 5.7% of patients exhibiting the gas bloat syndrome, 2.9% complaining of dysphagia, and only 4.8% having recurrent reflux [38]. A number of studies, some of which were prospective and randomized, have compared the results of the Nissen procedure with those of other antireflux operations such as the Belsey, Hill, and Toupet procedures. With few exceptions [3941], these studies have found Nissen fundoplication to be superior to the other operations in restoring LES function and preventing reflux [29, 42441. Even more important is a recent study involving a longterm randomized comparison of the results of medical therapy with the Nissen fundoplication for patients with complicated gastroesophageal reflux disease. The conclu- sion from this study was that operation was significantly more effective than medical therapy in improving the symptoms and endoscopic signs of esophagitis [45]. In summarizing the pertinent recent literature on the results of the modified Nissen fundoplication, one is drawn to the conclusion that with proper patient selection and the use of meticulous surgical technique emphasizing a short loose total wrap, the Nissen fundoplication will provide relief of symptoms in approximately 90% of patients with a low incidence of serious side effects. Whether the indications for surgical therapy will persist at the present level now that H2 receptor antagonists and omeprazole (Prilosec), an effective proton pump inhibitor, are available remains to be seen. A recent report from a major surgical referral center in Great Britain describes an 87.5% reduction in the numbers of patients being referred for antireflux operation since the introduction of H, receptor antagonists [46]. All the same, as long as there are medical failures and uncertainties regarding potential adverse effects of long-term administration of the new antisecretory drugs, modifications of Nissen's originally proposed operation will be the procedure of choice to provide reflux control in appropriately selected patients with the complications of gastroesophageal reflux disease. The assistance of Professor Andre P. Naef and Paul A. Kirschner in the preparation of the historical aspects of this review is gratefully acknowledged. References 1. Nissen R. Eine einfache Operation zur Beeinflussung der Refluxoesophagitis. Schweiz Med Wochenschr 1956;86: 590-2. 2. Jamieson GG, Duranceau A. What is a Nissen fundoplication? Surg Gynecol Obstet 1984;159:591-3. 3. Nissen R. Beiziehungen zwischen Hiatushernie und Refluxoesophagitis. Munchen Med Wochenschr 1960;102:1472-4. 4. Allison R. Reflux esophagitis, sliding hiatal hernia and anatomy of repair. Surg Gynecol Obstet 1951;92:419-31. 5. Nissen R. Gastropexy as lone procedure in surgical repair of hiatus hernia. Am J Surg 1956;92:389-92. 6. Nissen R. Gastropexy and "fundoplication" in surgical treatment of hiatal hernia. Am J Dig Dis 1961;6:95441. 7. Nissen R, Rossetti M. Surgery of hiatal and other diaphragmatic hernias. J Int Coll Surg 1965;43:663-74. 8. Nissen R. Die transpleurael Resektion der Kardia. Deutsche Z Chir 1937;249:3114. 9. Nissen R. The treatment of hiatal hernia and esophageal reflux by fundoplication. In: Nyhus LM, Harkins HH, eds. Hernia. Philadelphia: J.B. Lippincott, 1964:48%96. 10. Nissen R, Rossetti M. La fundoplicatio et la gastropexie dans le traitement chirurgical de I'insuffisance du cardia et de la hernie hiatal. Ann Chir 1962;16:825-36. 11. Nissen R, Rossetti M. Die Behandlung von Hiatushernien 12. 13. 14. und Refluxoesophagitis mit Gastropexie und Fundoplication. Stuttgart: Thieme, 1959. Nissen R. Transthorakale Fundusrafflung zur Beeinflussung besonderer Formen von Refluxoesophagitis. Langenbechs Arch Klin Chir 1960;293:365-72. Rossetti M. Zur Technic der Fundoplicatio. Actuelle Chir 1968;3:29. Rossetti M, Hell K. Fundoplication for the treatment of gastroesophageal reflux in hiatal hernia. World J Surg 1977; 1:439.

Ann Thorac Surg 1992;541231-5 CLASSICS ELLIS 1235 15. Rossetti M, Hitz P. Intravagale Fundoplicatio und kardiofundale Vagotomie: eine Technisch-physiologische Variante in der Refluxchirurgie. Helv Chir Acta 1989;55:559-64. 16. DeMeester TR, Stein HJ. Minimizing the side effects of antireflux surgery. World J Surg 1992;16:3354. 17. Donahue PE, Samelson S, Nyhus LM, Bombeck CT. The floppy Nissen fundoplication: effective long term control of pathologic reflux. Arch Surg 1985;120:663-7. 18. Herrington JL Jr, Meacham PW, Hunter RM. Gastric ulceration after fundic wrapping. Vagal nerve entrapment, a progressive causative factor. Ann Surg 1982;195:574-81. 19. Siewert JR, Feussner H, Walker SJ. Fundoplication: how to do it? Peri-esophageal wrapping as a therapeutic principle in gastro-esophageal reflux prevention. World J Surg 1992;16: 326-34. 20. DeMeester TR, Bonavina L, Albertucci M. Nissen fundoplication for gastroesophageal reflux disease: evaluation of primary repair in 100 consecutive patients. Ann Surg 1986; 204:9-20. 21. Ellis FH Jr. Nissen fundoplication. In: Braasch JW, et a1 eds. Atlas of abdominal surgery. Philadelphia: Saunders, 1990: 10-6. 22. Codiano C, Revere GQ, Agugiaro S, et al. Technical modification of the Nissen fundoplication procedure. Surg Gynecol Obstet 1976;143:977-8. 23. Jordan PH Jr. Parietal cell vagotomy facilitates fundoplication in the treatment of reflux esophagitis. Surg Gynecol Obstet 1978;147593-5. 24. Guarner V, Martinez N, Gavino JF. Ten year evaluation of posterior fundoplasty in the treatment of gastroesophageal reflux: long term and comparative study of 135 patients. Am J Surg 1980;139:200-3. 25. Dor J, Humbert P, Dor V, Figarella J. L interet de la technique de Nissen modifiee la prevention du reflux aprh cardiomyotomie extra muqueuse de Heller. Mem Acad Chir 1962;88: 877233. 26. Toupet A. Technique d oesophagogastroplastie avec phrenogastropexie appliquee dans la cure radicale des hernia hiatales et comme complement de l operation de Heller dans les cardiospasmus. Mem Acad Chir 1963;89:374-9. 27. Matikainen M, Kaukinen L. The mechanism of Nissen fundoplication. Acta Chir Scand 1984;150:653-5. 28. Ellis FH Jr, El-Kurd MF, Gibb SP. The effect of fundoplication on the lower esophageal sphincter. Surg Gynecd Obstet 1976; 143: 1-5. 29. DeMeester TR, Johnson FF, Kent AH. Evaluation of current operations for the prevention of gastroesophageal reflux. Ann Surg 1974;180:511-23. 30. Csendes A, Braghetto J, Korn 0, Cortes C. Late subjective and objective evaluations of antireflux surgery in patients with reflux esophagitis. Analysis of 215 patients. Surgery 1989;105:374-82. 31. Condon RE, Kraus MA, Wolheim D. Cause of increase in lower esophageal sphincter pressure after fundoplication. J Surg Res 1976;20:445-50. 32. Ellis FH Jr, Crozier RE. Reflux control by fundoplication: a clinical and manometric assessment of the Nissen operation. Ann Thorac Surg 1984;38:387-92. 33. Siewert R, Jennewein HM, Waldeck F, et al. Experiementelle und klinische Untersuchungen zum Wirkungsmechanismus der Fundoplicatio. Langenbecks Arch Chir 1973;333:519-22. 34. Liebermann-Meffert D. Architecture of the musculature of the gastroesophageal junction and in the fundus. Chir Gastroenterol 1975;9:425-9. 35. Lipshutz WH, Eckert RJ, Gaskins RD, et al. Normal lower esophageal sphincter function after surgical treatment of gastroesophageal reflux. N Engl J Med 1974;291:1107-10. 36. Anderson KW, Bombeck CT. Why anti-reflux surgery works. Surg Rounds 1987;11:49. 37. Negre JB. Post-fundoplication symptoms: do they restrict the success of Nissen fundoplication? Ann Surg 1983;198:698-700. 38. Shiraz SS, Schulze K, Soper RT. Long term follow-up for treatment of complications of reflux oesophagitis. Arch Surg 1987;122:54&52. 39. Fenaris VA, Sube J. Retrospective study of the surgical management of reflux esophagitis. Surg Gynecol Obstet 1981;152:17-21. 40. Tho; KBA, Selander T. A long term randomized prospective trial of the Nissen procedure versus a modified Toupet technique. Ann Surg 1989;210:719-24. 41. Stipa S, Fegiz G, Iascone C, et al. Belsey and Nissen operations for gastroesophageal reflux. Ann Surg 1989;210:58%9. 42. Nicholson DA, Nohl-Oser HC. Hiatus hernia: a comparison between two methods of fundoplication by evaluation of the long term results. J Thorac Cardiovasc Surg 1976;72:93843. 43. Dilling EW, Peyton MD, Cannon SP, et al. Comparison of Nissen fundoplication and Belsey Mark IV in the management of gastroesophageal reflux. Am J Surg 1973;134:73&3. 44. Sillin LF, Condon RE, Wilson SD, Worman LW. Effective surgical therapy of esophagitis: experience with Belsey, Hill and Nissen operations. Arch Surg 1979;114:53640. 45. Spechler SJ. Comparison of medical and surgical therapy for complicated gastroesophageal reflux disease in veterans. N Engl J Med 1992;326:786-92. 46. Macintyre IMC, Goulbourne IA. Long term results after Nissen fundoplication: a 5-15 year review. J R Coll Surg Edinb 1990;35:159-62.