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Appendicitis–A Reappraisal of an Old Problem
Appendicitis-A Reappraisal of an Old Problem JAMES L. TALBERT, M.D.* GEORGE D. ZUIDEMA, M.D., F.A.C.S.**
Any tabulation of the advances in modern surgery must include a reference to the dramatic decrease in mortality from acute appendicitis. In the year 1930, 15 of every 100,000 persons could be expected to die from this disease, whereas 30 years later this figure had decreased to one in every 100,000. 12 In most large series, the present hospital mortality from an acute attack is less than 1 per cent.n, 12, 19, 21, 30, 33, 37 As gratifying as this record must be, it does not begin to reflect the many agonizing hours of vigilant care that may be required to prevent an individual patient from succumbing to the complications of appendicitis. The increase in survival is primarily a manifestation of advances in surgical management for, unfortunately, there has been little improvement in the early recognition of this condition. 29 , 38 The incidence of perforation of the appendix in a number of reported series has shown relatively little fluctuation in the past 30 years, occurring in as many as one-third of the cases. 5 , 6, 11, 19,29,30 In spite of the many obvious advances in surgical management of appendicitis, a surprising number of aspects in the treatment of this condition remain inadequately recognized and poorly understood. The present dicsussion is offered, not as a comprehensive review of the subject, but rather as a clarification of those points in diagnosis and treatment which may still prove troublesome for the physician. From the Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland * Assistant Professor of Surgery and Garrett Scholar in Pediatric Surgery, The Johns Hopkins University School of Medicine ** Professor and Director of the Department of Surgery, The Johns Hopkins University School of Medicine; Surgeon-in-Chief, The Johns Hopkins Hospital; John and Mary R. Markle Scholar in Academic Medicine
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PITFALLS IN DIAGNOSIS
Not every doctor can be so fortunate as to have patients seek his consultation with the diagnosis as clearly defined as in the case of the N ewfoundland Eskimo. Surgeons working in the Grenfell Mission Hospital at St. Anthony, Newfoundland, report that Eskimos attempt to relieve themselves of pain by painting the offending part of the body. Thus it happens that when they present with appendicitis they frequently appear with a circle painted around the umbilicus and an arrow pointing to the right lower quadrant. Pitfalls in the diagnosis of acute appendicitis are encountered most frequently at the extremes of age, during pregnancy, or in the presence of other systemic disease. Appendicitis in the infant or young child may present a diagnostic dilemma, even for the experienced pediatrician or pediatric surgeon. S3 For the physician who may be less adept at handling children, the problem may be compounded by a lack of familiarity with the techniques of examining atients in this age group. I t is the rare youngster who is willing to lie on a table and quietly submit to the poking and probing of a stranger in a white coat. The successful examination of any child must include a preliminary attempt to win his trust and confidence. Kindness and gentleness will often break the barrier of natural distrust and allow a satisfactory examination. In other cases, however, all efforts to establish rapport will be repulsed. An alternative in the young child is to have the mother hold him in her arms while the physician, standing behind the child and facing the mother, explores the abdomen with his fingers while the child is quiet in the security afforded by his parent. Gentleness is' the watchword in the examination of any child with an acute abdominal condition. Roughness will lead only to the massive tensing of abdominal muscles, effectively masking any of the more subtle features of involuntary guarding. Light percussion of the abdomen may help in resolving the question of peritoneal irritation. Allowing the child to place his hand beneath that of the doctor is another method that may be of value. In any case, the examination should proceed from the area of least involvement to that which is suspected of being the primary site of disease, in most instances the right lower quadrant. Although abdominal auscultation is often difficult to interpret in the young child, this is the one aspect of physical examination which he may recognize and trust, and may offer an opportunity for confirmation of the presence or absence of tenderness. As a final resort, in some cases it may be necessary to sedate the child with pentobarbital (2.5 mg./lb.) in order to obtain enough relaxation to differentiate peritoneal irritation from voluntary guarding. so. 33 Any fear that sedation, in doses of this order of magnitude, will obscure the signs of true intra-abdominal disease is unfounded.
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As stated previously, however, the diagnosis of acute appendicitis in the young child or infant may seem impossible even in the most experienced hands. This fact is reflected in the increase in average duration of symptoms, frequency of perforation and, finally, mortality that has been reported from most pediatric centers.19, 33 Between 70 and 80 per cent of the patients under two years of age will have developed perforation of the appendix by the time of surgical exploration. 29 , 30 Changes in the infant's behavior pattern as manifested by irritability and restlessness may be the first warning of an acute abdominal condition. Sleeplessness and failure to respond to the usual comforting devices of feeding, diaper changing, cuddling, etc., will often alert a suspicious parent of impending danger. An inability of the infant to verbalize his complaints contributes to the high incidence of perforation in this age group. Other causes which have been incriminated include the liberal use of cathartics by well-meaning parents, an anatomical limitation in the normal "policing" role of the omentum because of its underdevelopment in this age group, and the relatively high position of the cecum and appendix, a point which may confuse the physician who relies on the classic sign of tenderness over McBurney's point.8 At the opposite extreme is the difficulty in establishing a diagnosis of acute appendicitis in the elderly patient. 23 , 43 In general, associated gastrointestinal symptoms may be minimal in these patients. Abdominal pain and tenderness, sometimes seemingly insignificant, may be the only indication of underlying pathologic change. The frequent association of other intraabdominal lesions and systemic illness may further complicate the picture. Other manifestations of disease, including elevations in white cell count and temperature, may be absent. (A differential smear may disclose a relative leukocytosis in such circumstances.) As a result, surgical treatment in the majority of elderly patients is delayed 24 hours or longer after the onset of symptoms. It is not unexpected, therefore, that the incidence of perforation is correspondingly increased. The frequency of complicated disease and an increase in associated systemic illnesses are reflected in a concomitant elevation in mortality rate. A third condition which may interfere with an accurate diagnosis is pregnancy. Appendicitis is the most frequent extrauterine surgical complication of pregnancy.28 Although ectopic pregnancy must be excluded, the signs and symptoms of appendicitis do not differ significantly in early pregnancy from those usually anticipated in the adult female. Later in gestation there is a natural tendency for the gravid uterus to displace the cecum upward and laterally. The abdominal wall musculature also relaxes, interfering with its normal response to peritoneal irritation. The omentum may be thwarted in any attempt to wall off the inflammatory process. A physiological elevation in white blood cell count may obscure any response to disease. All these factors contribute to the unfamiliar picture of acute appendicitis in late pregnancy. Abdominal pain and tenderness are unusually intense and, indeed, may be localized entirely. to the right flank. Muscle guarding may be
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insignificant. The only consistent clue may be a complaint of right-sided abdominal pain, which is aggravated by lying on that side and relieved by turning to the left.4 Pyelonephritis frequently mimics this picture in late pregnancy and must be excluded. Every effort must be made to establish a correct diagnosis and in the presence of reasonable doubt exploratory laparotomy must be performed. It is as true today as 65 years ago that "the mortality of appendicitis complicating pregnancy is the mortality of delay."3 This mortality, it must be remembered, involves both fetus and mother. In simple appendicitis there is little risk that a carefully performed appendectomy will result in interruption of the pregnancy. This danger, however, increases precipitously with perforation and peritonitis. Another group of patients in whom diagnosis may prove difficult and in whom utmost caution must be exercised not to overlook appendicitis are those suffering from concurrent systemic disease, especially those receiving treatment with steroids or antimetabolites. Signs and symptoms of appendicitis may be masked under these circumstances. The known association of gastrointestinal symptoms with certain chemotherapeutic agents may falsely allay any suspicion of appendiceal involvement. At times the correct diagnosis has been established only when a peritoneal tap revealed purulent fluid. A final group of patients in whom problems of diagnosis may be encountered are those complaining of recurrent attacks of abdominal pain. The term "chronic appendicitis" is unsavory to the modern surgeon, but recurrent attacks of acute appendicitis are a recognized entity. An outstanding example of this syndrome is the frequent early recurrence of disease in those cases of appendiceal abscess which have been treated by simple drainage only. 7 It seems perfectly logical, therefore, that in a certain number of patients the original disease may have been aborted only to recur later. Any busy practicing surgeon can recall patients who seem to fit into this category and, indeed, have proved to have acute appendicitis at exploration. The importance of this point is to emphasize the danger of excluding a diagnosis of appendicitis on the basis of a history of previous attacks of abdominal pain which have subsided with nonoperative treatment. The indications for surgical intervention in each instance must be based entirely on the criteria presented by the current episode. QUESTIONS OF SURGICAL MANAGEMENT
Adequate Preoperative Preparation The "typical" patient with appendicitis has a relatively brief history of symptoms and little evidence of systemic reaction. If an adequate period has elapsed since the ingestion of food, surgical management in these instances is simple and straightforward. There is no necessity for extensive
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preparation and appendectomy may be performed immediately. An excellent operative result with a short convalescence can be anticipated. Repeated experiences of this type may induce an unwarranted. complacency in managing all cases of appendicitis. In spite of frequent warnings in the recent medical literature, there remains a lack of appreciation of the importance of adequate preoperative preparation in the treatment of toxic patients. ss . S6 The urgency of surgical intervention, which has been stressed for the early, nonperforated case, too often has been mistakenly applied to this latter category as well. In any large series of appendectomies a certain proportion of the mortality can be attributed to injudicious surgery performed before optimal preparation has been achieved. The responsibility for this phase of the patient's care is shared not only by the surgeon who undertakes definitive treatment, but also by the referring practitioner. A tragic example of a failure in this chain of responsibility is the case of a seven year old girl who had a history typical of appendicitis. The diagnosis was made and she was transferred immediately to The Johns Hopkins Hospital. Unfortunately a nasogastric tube was not inserted to remove the stomach contents, and in transit by ambulance she vomited and aspirated the vomitus. Cardiac arrest ensued and she arrived too late for resuscitation. This death could easily have been prevented by the simple measure of nasogastric intubation and suction. Adequate preoperative stabilization of the critically ill patient involves re-expansion of intravascular volume, restoration of electrolyte imbalance, resolution of fever, and antibiotic administration when inflammatory complications are suspected. ss • S6 Children are particularly susceptible, and may quickly develop dehydration and high fever. A useful guideline in these instances is to postpone surgery until the temperature has been reduced to less than 38.7° C. (rectal) and the pulse rate is less than 120/min. so Experience has emphasized that the hypovolemic, febrile child is a poor operative risk. Ideally the patient should be sufficiently hydrated so that he will void preoperatively, but this is not always practical. The immediate objective of fluid therapy should be adequate expansion of intravascular volume and correction of gross discrepancies in serum electrolytes and pH.n Complete correction of all abnormalities may require days rather than hours, but the above criteria may be satisfied by intensive treatment, requiring a maximum of four to six hours. As indicated, the patient's vital signs and clinical response form the ultimate test of satisfactory response. Great help may also be obtained through the use of monitoring techniques which have proved so important in the management of other forms of acute surgical disease, that is, venous pressure monitoring, blood volume studies, serial determinations of hematocrit and serum proteins, and urinary outputs and specific gravities. The usefulness of these ancillary measures is not limited solely to the preoperative period, but extends throughout the period of the operation and immediate convalescence as well. In febrile cases the patient's temperature
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should be followed during surgery by means of indwelling esophageal or rectal monitoring probes. A cooling mattress should be available for treatment if any tendency to hyperthermia is observed. Transfusions of whole blood are rarely required, but in no sense are they contraindicated. Indeed, much of the present-day decrease in mortality from acute appendicitis can be traced to the period of introduction of whole blood and plasma transfusions. 5 • 11 This method still provides the most reliable and effective means for restoring deficits in intravascular volume, whatever the etiology. Nonoperative treatment has been proposed in patients with evidence of sepsis and spread of the inflammatory process. 14 • 33 Emphasis on adequate preoperative preparation of the patient should not be confused with this so-called "conservative" mode of therapy. Indeed, procrastination may be as disastrous as ill-advised hastiness. There is practically no instance in which adequate preoperative preparation cannot be achieved within the specified four to six hours, and in the vast majority of cases a far shorter period is required. The nonoperative approach can be justified at present only in the case of chronic abscess which appears to be resolving with antibiotic treatment, or in those rare instances of associated systemic disease, such as hemophilia, in which the morbidity of emergent operative intervention may exceed that of prolonged antibiotic therapy.u The progression of acute appendicitis to perforation and peritonitis in the face of antibiotic treatment has been documented repeatedly, and it is difficult to believe that any form of so-called "nonoperative treatment" can approximate the low morbidity and mortality recorded with modern surgical methods. 6 • 23. 39 Reliance on the normal body defense mechanisms to localize the disease is risky at best, and is particularly unsound in the young child or pregnant woman in whom anatomical variations impede this process. 19 • 28
Surgical Treatment of Inflammatory Complications In addition to deciding the question of operative versus nonoperative treatment the surgeon must be prepared to handle a variety of other problems once laparotomy has been undertaken. Indeed, this responsibility reflects the basic reason why it is important to have a trained, qualified specialist perform so simple an operation. An uncomplicated appendectomy may be a relatively easy technical procedure, one which is within the capability of many physicians. Any person accepting this responsibility, however, must be equally prepared and capable of handling all unsuspected conditions that may be encountered. The qualified surgeon possesses not only technical skill, but also experience and knowledge which allow him to cope with unforeseen conditions. One of the many questions which may confront the surgeon is the proper management of the perforated appendix. In general the dictum has been accepted that localization of perforation in the form of an abscess represents a desirable defense mechanism which should be encouraged rather than disturbed. I • 36 Accordingly, dissection should be limited in these
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instances, and the adhesions between omentum and bowel, a part of the natural walling off process, should be preserved whenever possible. In most instances it will still be feasible to carry out a definitive appendectomy and, particularly in small children, the indications for simple drainage are few.30, 33 In the occasional critical patient, however, simple drainage may still be preferable. Adequate drainage of the abscess cavity as well as the wound is imperative in all cases. 38 If definitive appendectomy is deferred, six weeks is probably a reasonable waiting period before the procedure is carried out electively.7 The recorded incidence of recurrent disease has been relatively high even with this brief delay. Some authors have suggested that the dangers of recurrent disease are minimal, and an interim appendectomy may not be necessary, but their experience contrasts sharply with the overwhelming body of surgical literature, and does not seem justifiable in view of the extremely low morbidity of simple appendectomy.6, 7 The question of peritoneal drainage in the presence of generalized peritonitis has proved more controversial. In general there is little objective evidence to support drainage of the free peritoneal cavity under such circumstances. l This experience contrasts sharply with that of abscess drainage in which clear-cut statistical benefit is evident,l9, 32, 36, 38 Indeed, there have been suggestions that free peritoneal drains may be detrimental, not only perpetuating the inflammatory process through foreign body reaction, but also serving as a nidus for intra-abdominal adhesions, eventually leading to intestinal obstruction. Yates in 1905 demonstrated that the free peritoneal cavity could not be satisfactorily drained because walling off occurs within a few hours. 45 These findings have been confirmed by many and refuted by none. Adult general surgeons as a consequence have seemed to abandon this approach. A number of pediatric surgeons on the other hand feel strongly that drainage is advantageous in the young child because of restrictions in the ability of the omentum to wall off the inflammatory process.30, 33 Unfortunately, there is inadequate clinical evidence on this problem and any scientific evaluation must await a true prospective investigation in which all aspects are equally weighed. 32 Certainly it does seem more important to carry out definitive appendectomy in small children at the time of initial exploration, and at least one series suggests an increased mortality when such a policy has not been followed. 33 A brief flurry of interest in intraperitoneal instillation of drugs has followed the introduction of each of the modem forms of chemotherapy, only to subside and be discarded. Currently it is recognized that certain medications, of which neomycin is an outstanding example, may produce respiratory depression when instilled intraperitoneally at the time of operation. 17 To avoid this problem the latest techniques of intraperitoneal chemotherapy involve placement of a transabdominal catheter through which medications may be administered once the patient has fully recovered from the anesthetic agent. 2 Experimental studies in animals have
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suggested some benefit from this approach, and further clinical experience with the method seems justified.l8 The use of prophylactic antibiotics for treatment of the case of nonperforated appendicitis has absolutely no foundation on the basis of published experience. 5 , 11, 15, 19 The incidence of inflammatory complications has not varied significantly in treated or nontreated groups. Similarly, antibiotics have not seemed to alter the frequency of superficial wound infections in cases of peritoneal soiling and primary wound closure. 15 , 41 This experience emphasizes the necessity in such cases for either concomitant drainage or delayed closure of the skin incision. There is no question, however, that the addition of antibiotics to the treatment regimen of patients with perforated appendicitis has contributed significantly to the decrease in mortality and intra-abdominal complications. 5 , 11 Although the organisms which are most frequently isolated from the peritoneal cavity in cases of appendiceal perforation are those which would ordinarily be considered penicillin resistant, Altemeier has emphasized the importance of retaining this antibiotic in the treatment regimen. 1 Most cases of secondary peritonitis develop from a mixed flora, even though a single organism, usually E. coli, may be the predominant one reported. Each of these organisms by itself is usually innocuous, but in combination with others seems to exert a synergistic action with a high degree of pathogenicity. Some of these bacteria, particularly gram-positive cocci and bacilli, are sensitive to penicillin, and their eradication will not only decrease the total bacterial count but also interfere with the perpetuation of this synergism. The addition of a drug with specific action against gramnegative organisms, such as chloramphenicol, kanamycin or tetracycline, will provide adequate antibiotic coverage in most instances. Occasionally this regimen. may need to be altered on the basis of reported bacterial sensitivities and clinical response. This latter index is by far the more important, and no change in treatment should be contemplated in the patient who clinically demonstrates satisfactory progress. Conditions Simulating Appendicitis
Any differential diagnosis is simply a recognition that more than one disease process is capable of producing a specific clinical picture. A number of other conditions may simulate appendicitis, but those of intestinal origin that may demand definitive surgery include regional ileitis, cecal diverticulitis, Meckel's diverticulitis and various tumors. The question of whether to proceed with an appendectomy in the presence of previously suspected regional ileitis has remained perplexing. Any decision not to remove the appendix accepts the calculated risk of a subsequent attack of true appendicitis being misinterpreted as recurrent ileitis. On the other hand, the seemingly frequent development of cutaneous wound fistulas following appendectomy in these cases would suggest that this procedure is contraindicated. Fortunately this question has been
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clarified recently by the demonstration that in the absence of cecal disease these fistulas arise from the diseased ileum rather than from the appendiceal stump.34 It would appear, therefore, that appendectomy per se is not the critical element in the development of this complication. As a result, most authorities appear to agree that in the absence of cecal involvement a definitive appendectomy should be performed at the time of the initial diagnostic celiotomy. IS Cecal diverticulitis is another condition in which the symptoms may mimic those of an acute attack of appendicitis. Differentiation of this disease from a perforating tumor may be difficult grossly and the most expeditious and safest course is usually to carry out a right hemicolectomy, although simple resection of the appendix and diverticulum has been advocated. 10 In the event that multiple diverticula are present, a more extensive procedure is required. Meckel's diverticulitis is a classic source of confusion with acute appendicitis and should be sought in any instance in which exploration reveals a normal appendix.24 This lesion is always located within the terminal 6 feet of ileum. Again, intestinal resection may be the easiest procedure, although simple excision occasionally is feasible. Finally, various tumors of the cecum or appendix may be encountered unexpectedly. Appendiceal tumors may be a source of misdiagnosis, either by simulating the picture of appendicitis or by actually inducing that disease by obstructing the lumen. Neoplasms involving the appendix include mucoceles, carcinoids, adenocarcinomas and lymphomas; endometriosis may also involve the appendix. 16 Mucocele of the appendix is a condition in which great care must be exerted to remove the tumor intact in order to prevent peritoneal contamination and secondary implants. 9 • 42 The malignant potential of these lesions may be difficult to assess, even on histological examination, and adequate excision may require a right hemicolectomy. Even in cases of prior perforation with pseudomyxoma peritonei, excision of the primary neoplasm with removal of as much as possible of the pseudomucinous peritoneal disease may result in arrest of the condition. Carcinoids of the appendix have been thought to have less malignant potential than those arising at other sites in the gastrointestinal tract." Although it is now recognized that these tumors may metastasize, the majority are discovered as incidental findings on examination of specimens removed for acute appendicitis. 16 In the absence of local invasion or regional lymph node metastases, simple appendectomy usually results in permanent cure. Even in the presence of hepatic metastases, it is extremely rare for these appendiceal tumors to be associated with the "serotonin syndrome" of cutaneous Hushing, hyperactivity of the bowel and valvular heart lesions. 36 • " Primary adenocarcinoma of the appendix is rare, but is usually manifested early on the basis of secondary appendicitis developing because of
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lumen obstruction. 22 , 35 Any suspiciousnoiules which are recognized at the time of appendectomy should be subjected immediately to frozen-section examination, and a right hemicolectomy performed on confirmation of carcinoma. 4o In most instances, however, the correct diagnosis will become apparent only on routine histological examination of the specimen. In such circumstances re-exploration with right hemicolectomy is advised. These lesions are slow-growing and, frequently, can be completely excised. Primary malignant lymphoma of the appendix is another condition which is rarely encountered. Thorough exploration for intra-abdominal metastases and multicentric lesions of the gastrointestinal tract must be carried out at the time of laparotomy. The possibility of associated hematologic disease must also be excluded. The recommended treatment for localized tumors is surgical removal of the lesion and adjacent lymph nodes by right hemicolectomy, followed by radiotherapy to the affected area. In one series of primary lymphomas of the colon and appendix treated in this manner, 74 per cent of the patients survived five years. 20 Endometriosis of the appendix as an isolated disease is uncommon, but it can be expected to respond satisfactorily to local excision,21 Rarely, lumen obstruction with secondary mucocele formation has been noted. 26 The Management of Postoperative Complications
The management of the postoperative complications of appendicitis is an extensive subject in itself, and has been reviewed recently in this journa1. 31 The successful development of techniques for dealing with the inflammatory complications of appendiceal perforation has played a major role in decreasing the mortality and morbidity of this disease. A prolonged convalescence, marked by persistent elevations in pulse rate, temperature and leukocyte count, is usually indicative of residual infection. 1 The most frequent sites of such involvement are the abdominal wound and the pelvis. These areas are readily accessible to careful rectal, pelvic and abdominal :examination. Probing the wound or drain site with a sterile gloved finger while the patient is heavily sedated may disclose the source of infection and satisfactorily drain the process. Obscure sites of infection which may not be readily apparent on examination include the subphrenic and subhepatic .spaces. The diagnosis of subphrenic and subhepatic abscesses may be sug·gested by a tender, enlarged liver or by pain on percussion over the lower costal margin. The development of improved diagnostic techniques, including contrast studies of the upper gastrointestinal tract, chest fluoroscopy and radioscans of the liver, has simplified greatly the accurate recognition of these processes. Pylephlebitis is an inflammatory complication which is rarely encountered at present. Because of its rarity, however, the physician may fail to recognize the development of this serious condition. As a result, unlike other complications of appendicitis, the mortality and morbidity of pylephlebitis have remained distressingly high.25 A rapid fatal termination may quickly follow the onset of symptoms. Recurrent chills, high fever and
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jaundice are the most frequent manifestations of this problem. 1 Although 70 per cent of these cases are secondary to acute appendicitis, the relationship may be obscure and the true etiology may become apparent only on postmortem examination. The importance of early exploration with the rapid institution of massive and prolonged antibiotic therapy has been emphasized recently in a report from this institution. 26
SUMMARY The dramatic decrease in the morbidity and mortality of acute appendicitis is a reflection of major advances in surgical diagnosis and treatment. A discussion has been presented of some of the problems in management which must be recognized and understood if this improvement is to be perpetuated.
REFERENCES 1. Altemeier, W. A. and Culbertson, W. R.: Complications of appendectomy. In Complications in Surgery and Their Management (C. P. Artz and J. D. Hardy, Eds.). Philadelphia, W. B. Saunders Co., 1960, pp. 750-763. 2. Artz, C. P., Barnett, W. O. and Grogan, J. B.: Further studies concerning the pathogenesis and treatment of peritonitis. Ann. Surg. 155: 756,1962. 3. Babler, E. A.: Perforative appendicitis complicating pregnancy: With report of successful case. J.A.M.A. 51: 1310,1908. 4. Baker, T. H.: Appendicitis in pregnancy. J. Kentucky M. A. 6S: 944,1964. 5. Barnes, B. A., Behringer, G. E., Whellock, F. C. and Wilkins, E. W.: Surgical sepsis: Analysis of factors associated with sepsis following appendectomy (1937-1959). Ann. Surg. 156: 703, 1962. 6. Barnes, B. A., Behringer, G. E., Whellock, F. C. and Wilkins, E. W.: Treatment of appendicitis at Massachusetts General Hospital 1937-1959. J.A.M.A. 180: 122, 1962. 7. Befeler, D.: Recurrent appendicitis: Incidence and prophylaxis. Arch. Surg. 89: 666, 1964. 8. Benson, C. D., Coury, J. J., Jr. and Hagge, D. R.: Acute appendicitis in infants. Arch. Surg. 64: 561,1952. 9. Bernhardt, H. and Young, J. M.: Mucocele and pseudomyxoma peritonei of appendiceal origin. Am. J. Surg. 109: 235,1965. 10. Botsford, T. W. and Curtis, L. E.: Diverticulitis coli. New EnglandJ. Med. S65: 618, 1961. 11. Cantrell, J. R. and Stafford, E. S.: The diminishing mortality from appendicitis. Ann.Surg. 141:749, 1955. 12. Clements, N., Olson, J. E. and Powers, J. H.: Acute appendicitis in a rural community. IV. Ann. Surg. 161: 231, 1965.. 13. Colcock, B. P.: Regional enteritis. In Current Problems in Surgery, June, 1965. 14. Coldrey, E.: Five years of conservative treatment of acute appendicitis. J. Internat. Coll. Surgeons 3S: 255, 1959. 15. Cole, W. R. and Bernard, H. R.: A reappraisal of the effects of antimicrobial therapy on the course of appendicitis in children. Am. Surgeon Ifl: 29, 1961. 16. Collins, D. C.: 71,000 human appendix specimens; A final report summarizing forty years' study. Am. J. Proctol. 14: 365, 1963. 17. Craig, H. V., Guillet, G. G., Walker, J. A. and Artz, C. P.: Respiratory depression related to intraperitoneal neomycin. Am. SUrgeon 38: 27,1966.
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18. Di Vincenti, F. C. and Cohn, 1., Jr.: Intraperitoneal kanamycin in advanced peritonitis. Am. J. Surg. 111: 147,1966. 19. Foster, J. H. and Edwards, W. H.: Acute appendicitis in infancy and childhood: A twenty year study in a general hospital. Ann. Surg. 146: 70, 1957. 20. Glick, D. D. and Soule, E. H.: Primary malignant lymphoma of colon or appendix: Report of 27 cases. Arch. Surg. 92: 144, 1966. 21. Harbitz, H. F., and Sandvig, F. L.: Present day mortality and cause of death in acute appendicitis. Acta chir. scandinav. (Suppl.) 253: 118, 1960. 22. Hesketh, K. T.: The management of primary adenocarcinoma of the vermiform appendix. Gut 4: 158, 1963. 23. Hubbell, D. S., Barton, W. K. and Solomon, O. D.: Appendicitis in older people. Surg. Gynec. & Obst. 110: 289, 1960. 24. Johns, T. N. P., Wheeler, J. R. and Johns, F. S.: Meckel's diverticulum and Meckel's diverticulum disease. Ann. Surg. 150: 241, 1959. 25. Klinefelter, H. F., Jr., Grose, W. E. and Crawford, H. J.: Pylephlebitis. Bull. Johns Hopkins Hosp. 106: 65, 1960. 26. Kohout, E.: Mucocele of the appendix caused by endometriosis. Am. J. Obst. & Gynec. 79: 1181, 1960. 27. Lane, R. E.: Endometriosis of the vermiform appendix. Am. J. Obst. & Gynec. 79: 372, 1960. 28. Lee, R. A., Johnson, C. F. and Symmonds, R. F.: Appendicitis during pregnancy. J.A.M.A. 193: 966, 1965. 29. Liechti, R. E. and Snyder, W. H., Jr.: Acute appendicitis under age two. Am. Surgeon 29: 92,1963. 30. Longino, L. A., Holder, T. M. and Gross, R. E.: Appendicitis in childhood. A study of 1,358 cases. Pediatrics 22: 238, 1958. 31. Madden, J. L.: Immediate complications following appendectomy. S. CLIN. NORTH AMERICA 44: 411, 1964. 32. Maddox, J. R., Jr., Johnson, W. W. and Sergeant, C. K.: AppendectOInies in a children's hospital. A five year survey. Arch. Surg. 89: 223, 1964. 33. Martin, L. W.: Appendicitis. In Pediatric Surgery (C. D. Benson, et aI., Eds.). Chicago, Year Book Medical Publishers, Inc., 1962, pp. 790-S01. 34. Marx, F. W., Jr.: Incidental appendectomy with regional enteritis. Arch. Surg. 88: 546,1964. 35. McGregor, J. K. and McGregor, D. D.: Adenocarcinoma of the appendix. Surgery 48: 925, 1960. 36. Moore, F. D.: Acute appendicitis. In Surgery (R. Warren, Ed.). Philadelphia, W. B. Saunders Co., 1963, pp. 783-787. 37. Ross, F. P., Zarem, H. A. and Morgan, A. P.: Appendicitis in a community hospital. Arch. Surg. 85: 1036, 1962. 38. Stafford, E. S. and Scott, H. W., Jr.: The mortality of appendical perforation. South. M. J. 41: 834, 1948. 39. Stanley-Brown, E. G.: Acute appendicitis during first five years of life. Am. J. Dis. Child. 108: 134, 1964. 40. Tarasidis, G. C., Goodall, H. M. and Farringer, J. L., Jr.: Adenocarcinoma of the vermiform appendix. Surg. Gynec. & Obst. 115: 287, 1962. 41. Vinnicombe, J.: Appendectomy wound infection, drainage and antibiotics. Brit. J. Surg. 51: 32S, 1964 42. Wesser, D. R. and Edelman, S.: Experiences with mucocele of the appendix. Ann. Surg. 153: 272, 1961. 43. Williams, J. S. and Hale, H. W.: Acute appendicitis in the elderly: Review of 83 cases. Ann. Surg. 162: 208, 1965. 44. Wilson, H., Storer, E. H. and Star, F. J.: Carcinoid tumors. A study of 78 cases. Am.J. Surg. 105:35,1963. 45. Yates, J. L.: Experimental study of local effects of peritoneal drainage. Surg. Gynec. & Obst. 1: 473, 1905. Department of Surgery The Johns Hopkins Hospital BaJ.timore, Maryland 21205
Any tabulation of the advances in modern surgery must include a reference to the dramatic decrease in mortality from acute appendicitis. In the year 1930, 15 of every 100,000 persons could be expected to die from this disease, whereas 30 years later this figure had decreased to one in every 100,000. 12 In most large series, the present hospital mortality from an acute attack is less than 1 per cent.n, 12, 19, 21, 30, 33, 37 As gratifying as this record must be, it does not begin to reflect the many agonizing hours of vigilant care that may be required to prevent an individual patient from succumbing to the complications of appendicitis. The increase in survival is primarily a manifestation of advances in surgical management for, unfortunately, there has been little improvement in the early recognition of this condition. 29 , 38 The incidence of perforation of the appendix in a number of reported series has shown relatively little fluctuation in the past 30 years, occurring in as many as one-third of the cases. 5 , 6, 11, 19,29,30 In spite of the many obvious advances in surgical management of appendicitis, a surprising number of aspects in the treatment of this condition remain inadequately recognized and poorly understood. The present dicsussion is offered, not as a comprehensive review of the subject, but rather as a clarification of those points in diagnosis and treatment which may still prove troublesome for the physician. From the Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland * Assistant Professor of Surgery and Garrett Scholar in Pediatric Surgery, The Johns Hopkins University School of Medicine ** Professor and Director of the Department of Surgery, The Johns Hopkins University School of Medicine; Surgeon-in-Chief, The Johns Hopkins Hospital; John and Mary R. Markle Scholar in Academic Medicine
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PITFALLS IN DIAGNOSIS
Not every doctor can be so fortunate as to have patients seek his consultation with the diagnosis as clearly defined as in the case of the N ewfoundland Eskimo. Surgeons working in the Grenfell Mission Hospital at St. Anthony, Newfoundland, report that Eskimos attempt to relieve themselves of pain by painting the offending part of the body. Thus it happens that when they present with appendicitis they frequently appear with a circle painted around the umbilicus and an arrow pointing to the right lower quadrant. Pitfalls in the diagnosis of acute appendicitis are encountered most frequently at the extremes of age, during pregnancy, or in the presence of other systemic disease. Appendicitis in the infant or young child may present a diagnostic dilemma, even for the experienced pediatrician or pediatric surgeon. S3 For the physician who may be less adept at handling children, the problem may be compounded by a lack of familiarity with the techniques of examining atients in this age group. I t is the rare youngster who is willing to lie on a table and quietly submit to the poking and probing of a stranger in a white coat. The successful examination of any child must include a preliminary attempt to win his trust and confidence. Kindness and gentleness will often break the barrier of natural distrust and allow a satisfactory examination. In other cases, however, all efforts to establish rapport will be repulsed. An alternative in the young child is to have the mother hold him in her arms while the physician, standing behind the child and facing the mother, explores the abdomen with his fingers while the child is quiet in the security afforded by his parent. Gentleness is' the watchword in the examination of any child with an acute abdominal condition. Roughness will lead only to the massive tensing of abdominal muscles, effectively masking any of the more subtle features of involuntary guarding. Light percussion of the abdomen may help in resolving the question of peritoneal irritation. Allowing the child to place his hand beneath that of the doctor is another method that may be of value. In any case, the examination should proceed from the area of least involvement to that which is suspected of being the primary site of disease, in most instances the right lower quadrant. Although abdominal auscultation is often difficult to interpret in the young child, this is the one aspect of physical examination which he may recognize and trust, and may offer an opportunity for confirmation of the presence or absence of tenderness. As a final resort, in some cases it may be necessary to sedate the child with pentobarbital (2.5 mg./lb.) in order to obtain enough relaxation to differentiate peritoneal irritation from voluntary guarding. so. 33 Any fear that sedation, in doses of this order of magnitude, will obscure the signs of true intra-abdominal disease is unfounded.
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As stated previously, however, the diagnosis of acute appendicitis in the young child or infant may seem impossible even in the most experienced hands. This fact is reflected in the increase in average duration of symptoms, frequency of perforation and, finally, mortality that has been reported from most pediatric centers.19, 33 Between 70 and 80 per cent of the patients under two years of age will have developed perforation of the appendix by the time of surgical exploration. 29 , 30 Changes in the infant's behavior pattern as manifested by irritability and restlessness may be the first warning of an acute abdominal condition. Sleeplessness and failure to respond to the usual comforting devices of feeding, diaper changing, cuddling, etc., will often alert a suspicious parent of impending danger. An inability of the infant to verbalize his complaints contributes to the high incidence of perforation in this age group. Other causes which have been incriminated include the liberal use of cathartics by well-meaning parents, an anatomical limitation in the normal "policing" role of the omentum because of its underdevelopment in this age group, and the relatively high position of the cecum and appendix, a point which may confuse the physician who relies on the classic sign of tenderness over McBurney's point.8 At the opposite extreme is the difficulty in establishing a diagnosis of acute appendicitis in the elderly patient. 23 , 43 In general, associated gastrointestinal symptoms may be minimal in these patients. Abdominal pain and tenderness, sometimes seemingly insignificant, may be the only indication of underlying pathologic change. The frequent association of other intraabdominal lesions and systemic illness may further complicate the picture. Other manifestations of disease, including elevations in white cell count and temperature, may be absent. (A differential smear may disclose a relative leukocytosis in such circumstances.) As a result, surgical treatment in the majority of elderly patients is delayed 24 hours or longer after the onset of symptoms. It is not unexpected, therefore, that the incidence of perforation is correspondingly increased. The frequency of complicated disease and an increase in associated systemic illnesses are reflected in a concomitant elevation in mortality rate. A third condition which may interfere with an accurate diagnosis is pregnancy. Appendicitis is the most frequent extrauterine surgical complication of pregnancy.28 Although ectopic pregnancy must be excluded, the signs and symptoms of appendicitis do not differ significantly in early pregnancy from those usually anticipated in the adult female. Later in gestation there is a natural tendency for the gravid uterus to displace the cecum upward and laterally. The abdominal wall musculature also relaxes, interfering with its normal response to peritoneal irritation. The omentum may be thwarted in any attempt to wall off the inflammatory process. A physiological elevation in white blood cell count may obscure any response to disease. All these factors contribute to the unfamiliar picture of acute appendicitis in late pregnancy. Abdominal pain and tenderness are unusually intense and, indeed, may be localized entirely. to the right flank. Muscle guarding may be
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insignificant. The only consistent clue may be a complaint of right-sided abdominal pain, which is aggravated by lying on that side and relieved by turning to the left.4 Pyelonephritis frequently mimics this picture in late pregnancy and must be excluded. Every effort must be made to establish a correct diagnosis and in the presence of reasonable doubt exploratory laparotomy must be performed. It is as true today as 65 years ago that "the mortality of appendicitis complicating pregnancy is the mortality of delay."3 This mortality, it must be remembered, involves both fetus and mother. In simple appendicitis there is little risk that a carefully performed appendectomy will result in interruption of the pregnancy. This danger, however, increases precipitously with perforation and peritonitis. Another group of patients in whom diagnosis may prove difficult and in whom utmost caution must be exercised not to overlook appendicitis are those suffering from concurrent systemic disease, especially those receiving treatment with steroids or antimetabolites. Signs and symptoms of appendicitis may be masked under these circumstances. The known association of gastrointestinal symptoms with certain chemotherapeutic agents may falsely allay any suspicion of appendiceal involvement. At times the correct diagnosis has been established only when a peritoneal tap revealed purulent fluid. A final group of patients in whom problems of diagnosis may be encountered are those complaining of recurrent attacks of abdominal pain. The term "chronic appendicitis" is unsavory to the modern surgeon, but recurrent attacks of acute appendicitis are a recognized entity. An outstanding example of this syndrome is the frequent early recurrence of disease in those cases of appendiceal abscess which have been treated by simple drainage only. 7 It seems perfectly logical, therefore, that in a certain number of patients the original disease may have been aborted only to recur later. Any busy practicing surgeon can recall patients who seem to fit into this category and, indeed, have proved to have acute appendicitis at exploration. The importance of this point is to emphasize the danger of excluding a diagnosis of appendicitis on the basis of a history of previous attacks of abdominal pain which have subsided with nonoperative treatment. The indications for surgical intervention in each instance must be based entirely on the criteria presented by the current episode. QUESTIONS OF SURGICAL MANAGEMENT
Adequate Preoperative Preparation The "typical" patient with appendicitis has a relatively brief history of symptoms and little evidence of systemic reaction. If an adequate period has elapsed since the ingestion of food, surgical management in these instances is simple and straightforward. There is no necessity for extensive
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preparation and appendectomy may be performed immediately. An excellent operative result with a short convalescence can be anticipated. Repeated experiences of this type may induce an unwarranted. complacency in managing all cases of appendicitis. In spite of frequent warnings in the recent medical literature, there remains a lack of appreciation of the importance of adequate preoperative preparation in the treatment of toxic patients. ss . S6 The urgency of surgical intervention, which has been stressed for the early, nonperforated case, too often has been mistakenly applied to this latter category as well. In any large series of appendectomies a certain proportion of the mortality can be attributed to injudicious surgery performed before optimal preparation has been achieved. The responsibility for this phase of the patient's care is shared not only by the surgeon who undertakes definitive treatment, but also by the referring practitioner. A tragic example of a failure in this chain of responsibility is the case of a seven year old girl who had a history typical of appendicitis. The diagnosis was made and she was transferred immediately to The Johns Hopkins Hospital. Unfortunately a nasogastric tube was not inserted to remove the stomach contents, and in transit by ambulance she vomited and aspirated the vomitus. Cardiac arrest ensued and she arrived too late for resuscitation. This death could easily have been prevented by the simple measure of nasogastric intubation and suction. Adequate preoperative stabilization of the critically ill patient involves re-expansion of intravascular volume, restoration of electrolyte imbalance, resolution of fever, and antibiotic administration when inflammatory complications are suspected. ss • S6 Children are particularly susceptible, and may quickly develop dehydration and high fever. A useful guideline in these instances is to postpone surgery until the temperature has been reduced to less than 38.7° C. (rectal) and the pulse rate is less than 120/min. so Experience has emphasized that the hypovolemic, febrile child is a poor operative risk. Ideally the patient should be sufficiently hydrated so that he will void preoperatively, but this is not always practical. The immediate objective of fluid therapy should be adequate expansion of intravascular volume and correction of gross discrepancies in serum electrolytes and pH.n Complete correction of all abnormalities may require days rather than hours, but the above criteria may be satisfied by intensive treatment, requiring a maximum of four to six hours. As indicated, the patient's vital signs and clinical response form the ultimate test of satisfactory response. Great help may also be obtained through the use of monitoring techniques which have proved so important in the management of other forms of acute surgical disease, that is, venous pressure monitoring, blood volume studies, serial determinations of hematocrit and serum proteins, and urinary outputs and specific gravities. The usefulness of these ancillary measures is not limited solely to the preoperative period, but extends throughout the period of the operation and immediate convalescence as well. In febrile cases the patient's temperature
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should be followed during surgery by means of indwelling esophageal or rectal monitoring probes. A cooling mattress should be available for treatment if any tendency to hyperthermia is observed. Transfusions of whole blood are rarely required, but in no sense are they contraindicated. Indeed, much of the present-day decrease in mortality from acute appendicitis can be traced to the period of introduction of whole blood and plasma transfusions. 5 • 11 This method still provides the most reliable and effective means for restoring deficits in intravascular volume, whatever the etiology. Nonoperative treatment has been proposed in patients with evidence of sepsis and spread of the inflammatory process. 14 • 33 Emphasis on adequate preoperative preparation of the patient should not be confused with this so-called "conservative" mode of therapy. Indeed, procrastination may be as disastrous as ill-advised hastiness. There is practically no instance in which adequate preoperative preparation cannot be achieved within the specified four to six hours, and in the vast majority of cases a far shorter period is required. The nonoperative approach can be justified at present only in the case of chronic abscess which appears to be resolving with antibiotic treatment, or in those rare instances of associated systemic disease, such as hemophilia, in which the morbidity of emergent operative intervention may exceed that of prolonged antibiotic therapy.u The progression of acute appendicitis to perforation and peritonitis in the face of antibiotic treatment has been documented repeatedly, and it is difficult to believe that any form of so-called "nonoperative treatment" can approximate the low morbidity and mortality recorded with modern surgical methods. 6 • 23. 39 Reliance on the normal body defense mechanisms to localize the disease is risky at best, and is particularly unsound in the young child or pregnant woman in whom anatomical variations impede this process. 19 • 28
Surgical Treatment of Inflammatory Complications In addition to deciding the question of operative versus nonoperative treatment the surgeon must be prepared to handle a variety of other problems once laparotomy has been undertaken. Indeed, this responsibility reflects the basic reason why it is important to have a trained, qualified specialist perform so simple an operation. An uncomplicated appendectomy may be a relatively easy technical procedure, one which is within the capability of many physicians. Any person accepting this responsibility, however, must be equally prepared and capable of handling all unsuspected conditions that may be encountered. The qualified surgeon possesses not only technical skill, but also experience and knowledge which allow him to cope with unforeseen conditions. One of the many questions which may confront the surgeon is the proper management of the perforated appendix. In general the dictum has been accepted that localization of perforation in the form of an abscess represents a desirable defense mechanism which should be encouraged rather than disturbed. I • 36 Accordingly, dissection should be limited in these
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instances, and the adhesions between omentum and bowel, a part of the natural walling off process, should be preserved whenever possible. In most instances it will still be feasible to carry out a definitive appendectomy and, particularly in small children, the indications for simple drainage are few.30, 33 In the occasional critical patient, however, simple drainage may still be preferable. Adequate drainage of the abscess cavity as well as the wound is imperative in all cases. 38 If definitive appendectomy is deferred, six weeks is probably a reasonable waiting period before the procedure is carried out electively.7 The recorded incidence of recurrent disease has been relatively high even with this brief delay. Some authors have suggested that the dangers of recurrent disease are minimal, and an interim appendectomy may not be necessary, but their experience contrasts sharply with the overwhelming body of surgical literature, and does not seem justifiable in view of the extremely low morbidity of simple appendectomy.6, 7 The question of peritoneal drainage in the presence of generalized peritonitis has proved more controversial. In general there is little objective evidence to support drainage of the free peritoneal cavity under such circumstances. l This experience contrasts sharply with that of abscess drainage in which clear-cut statistical benefit is evident,l9, 32, 36, 38 Indeed, there have been suggestions that free peritoneal drains may be detrimental, not only perpetuating the inflammatory process through foreign body reaction, but also serving as a nidus for intra-abdominal adhesions, eventually leading to intestinal obstruction. Yates in 1905 demonstrated that the free peritoneal cavity could not be satisfactorily drained because walling off occurs within a few hours. 45 These findings have been confirmed by many and refuted by none. Adult general surgeons as a consequence have seemed to abandon this approach. A number of pediatric surgeons on the other hand feel strongly that drainage is advantageous in the young child because of restrictions in the ability of the omentum to wall off the inflammatory process.30, 33 Unfortunately, there is inadequate clinical evidence on this problem and any scientific evaluation must await a true prospective investigation in which all aspects are equally weighed. 32 Certainly it does seem more important to carry out definitive appendectomy in small children at the time of initial exploration, and at least one series suggests an increased mortality when such a policy has not been followed. 33 A brief flurry of interest in intraperitoneal instillation of drugs has followed the introduction of each of the modem forms of chemotherapy, only to subside and be discarded. Currently it is recognized that certain medications, of which neomycin is an outstanding example, may produce respiratory depression when instilled intraperitoneally at the time of operation. 17 To avoid this problem the latest techniques of intraperitoneal chemotherapy involve placement of a transabdominal catheter through which medications may be administered once the patient has fully recovered from the anesthetic agent. 2 Experimental studies in animals have
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suggested some benefit from this approach, and further clinical experience with the method seems justified.l8 The use of prophylactic antibiotics for treatment of the case of nonperforated appendicitis has absolutely no foundation on the basis of published experience. 5 , 11, 15, 19 The incidence of inflammatory complications has not varied significantly in treated or nontreated groups. Similarly, antibiotics have not seemed to alter the frequency of superficial wound infections in cases of peritoneal soiling and primary wound closure. 15 , 41 This experience emphasizes the necessity in such cases for either concomitant drainage or delayed closure of the skin incision. There is no question, however, that the addition of antibiotics to the treatment regimen of patients with perforated appendicitis has contributed significantly to the decrease in mortality and intra-abdominal complications. 5 , 11 Although the organisms which are most frequently isolated from the peritoneal cavity in cases of appendiceal perforation are those which would ordinarily be considered penicillin resistant, Altemeier has emphasized the importance of retaining this antibiotic in the treatment regimen. 1 Most cases of secondary peritonitis develop from a mixed flora, even though a single organism, usually E. coli, may be the predominant one reported. Each of these organisms by itself is usually innocuous, but in combination with others seems to exert a synergistic action with a high degree of pathogenicity. Some of these bacteria, particularly gram-positive cocci and bacilli, are sensitive to penicillin, and their eradication will not only decrease the total bacterial count but also interfere with the perpetuation of this synergism. The addition of a drug with specific action against gramnegative organisms, such as chloramphenicol, kanamycin or tetracycline, will provide adequate antibiotic coverage in most instances. Occasionally this regimen. may need to be altered on the basis of reported bacterial sensitivities and clinical response. This latter index is by far the more important, and no change in treatment should be contemplated in the patient who clinically demonstrates satisfactory progress. Conditions Simulating Appendicitis
Any differential diagnosis is simply a recognition that more than one disease process is capable of producing a specific clinical picture. A number of other conditions may simulate appendicitis, but those of intestinal origin that may demand definitive surgery include regional ileitis, cecal diverticulitis, Meckel's diverticulitis and various tumors. The question of whether to proceed with an appendectomy in the presence of previously suspected regional ileitis has remained perplexing. Any decision not to remove the appendix accepts the calculated risk of a subsequent attack of true appendicitis being misinterpreted as recurrent ileitis. On the other hand, the seemingly frequent development of cutaneous wound fistulas following appendectomy in these cases would suggest that this procedure is contraindicated. Fortunately this question has been
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clarified recently by the demonstration that in the absence of cecal disease these fistulas arise from the diseased ileum rather than from the appendiceal stump.34 It would appear, therefore, that appendectomy per se is not the critical element in the development of this complication. As a result, most authorities appear to agree that in the absence of cecal involvement a definitive appendectomy should be performed at the time of the initial diagnostic celiotomy. IS Cecal diverticulitis is another condition in which the symptoms may mimic those of an acute attack of appendicitis. Differentiation of this disease from a perforating tumor may be difficult grossly and the most expeditious and safest course is usually to carry out a right hemicolectomy, although simple resection of the appendix and diverticulum has been advocated. 10 In the event that multiple diverticula are present, a more extensive procedure is required. Meckel's diverticulitis is a classic source of confusion with acute appendicitis and should be sought in any instance in which exploration reveals a normal appendix.24 This lesion is always located within the terminal 6 feet of ileum. Again, intestinal resection may be the easiest procedure, although simple excision occasionally is feasible. Finally, various tumors of the cecum or appendix may be encountered unexpectedly. Appendiceal tumors may be a source of misdiagnosis, either by simulating the picture of appendicitis or by actually inducing that disease by obstructing the lumen. Neoplasms involving the appendix include mucoceles, carcinoids, adenocarcinomas and lymphomas; endometriosis may also involve the appendix. 16 Mucocele of the appendix is a condition in which great care must be exerted to remove the tumor intact in order to prevent peritoneal contamination and secondary implants. 9 • 42 The malignant potential of these lesions may be difficult to assess, even on histological examination, and adequate excision may require a right hemicolectomy. Even in cases of prior perforation with pseudomyxoma peritonei, excision of the primary neoplasm with removal of as much as possible of the pseudomucinous peritoneal disease may result in arrest of the condition. Carcinoids of the appendix have been thought to have less malignant potential than those arising at other sites in the gastrointestinal tract." Although it is now recognized that these tumors may metastasize, the majority are discovered as incidental findings on examination of specimens removed for acute appendicitis. 16 In the absence of local invasion or regional lymph node metastases, simple appendectomy usually results in permanent cure. Even in the presence of hepatic metastases, it is extremely rare for these appendiceal tumors to be associated with the "serotonin syndrome" of cutaneous Hushing, hyperactivity of the bowel and valvular heart lesions. 36 • " Primary adenocarcinoma of the appendix is rare, but is usually manifested early on the basis of secondary appendicitis developing because of
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lumen obstruction. 22 , 35 Any suspiciousnoiules which are recognized at the time of appendectomy should be subjected immediately to frozen-section examination, and a right hemicolectomy performed on confirmation of carcinoma. 4o In most instances, however, the correct diagnosis will become apparent only on routine histological examination of the specimen. In such circumstances re-exploration with right hemicolectomy is advised. These lesions are slow-growing and, frequently, can be completely excised. Primary malignant lymphoma of the appendix is another condition which is rarely encountered. Thorough exploration for intra-abdominal metastases and multicentric lesions of the gastrointestinal tract must be carried out at the time of laparotomy. The possibility of associated hematologic disease must also be excluded. The recommended treatment for localized tumors is surgical removal of the lesion and adjacent lymph nodes by right hemicolectomy, followed by radiotherapy to the affected area. In one series of primary lymphomas of the colon and appendix treated in this manner, 74 per cent of the patients survived five years. 20 Endometriosis of the appendix as an isolated disease is uncommon, but it can be expected to respond satisfactorily to local excision,21 Rarely, lumen obstruction with secondary mucocele formation has been noted. 26 The Management of Postoperative Complications
The management of the postoperative complications of appendicitis is an extensive subject in itself, and has been reviewed recently in this journa1. 31 The successful development of techniques for dealing with the inflammatory complications of appendiceal perforation has played a major role in decreasing the mortality and morbidity of this disease. A prolonged convalescence, marked by persistent elevations in pulse rate, temperature and leukocyte count, is usually indicative of residual infection. 1 The most frequent sites of such involvement are the abdominal wound and the pelvis. These areas are readily accessible to careful rectal, pelvic and abdominal :examination. Probing the wound or drain site with a sterile gloved finger while the patient is heavily sedated may disclose the source of infection and satisfactorily drain the process. Obscure sites of infection which may not be readily apparent on examination include the subphrenic and subhepatic .spaces. The diagnosis of subphrenic and subhepatic abscesses may be sug·gested by a tender, enlarged liver or by pain on percussion over the lower costal margin. The development of improved diagnostic techniques, including contrast studies of the upper gastrointestinal tract, chest fluoroscopy and radioscans of the liver, has simplified greatly the accurate recognition of these processes. Pylephlebitis is an inflammatory complication which is rarely encountered at present. Because of its rarity, however, the physician may fail to recognize the development of this serious condition. As a result, unlike other complications of appendicitis, the mortality and morbidity of pylephlebitis have remained distressingly high.25 A rapid fatal termination may quickly follow the onset of symptoms. Recurrent chills, high fever and
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jaundice are the most frequent manifestations of this problem. 1 Although 70 per cent of these cases are secondary to acute appendicitis, the relationship may be obscure and the true etiology may become apparent only on postmortem examination. The importance of early exploration with the rapid institution of massive and prolonged antibiotic therapy has been emphasized recently in a report from this institution. 26
SUMMARY The dramatic decrease in the morbidity and mortality of acute appendicitis is a reflection of major advances in surgical diagnosis and treatment. A discussion has been presented of some of the problems in management which must be recognized and understood if this improvement is to be perpetuated.
REFERENCES 1. Altemeier, W. A. and Culbertson, W. R.: Complications of appendectomy. In Complications in Surgery and Their Management (C. P. Artz and J. D. Hardy, Eds.). Philadelphia, W. B. Saunders Co., 1960, pp. 750-763. 2. Artz, C. P., Barnett, W. O. and Grogan, J. B.: Further studies concerning the pathogenesis and treatment of peritonitis. Ann. Surg. 155: 756,1962. 3. Babler, E. A.: Perforative appendicitis complicating pregnancy: With report of successful case. J.A.M.A. 51: 1310,1908. 4. Baker, T. H.: Appendicitis in pregnancy. J. Kentucky M. A. 6S: 944,1964. 5. Barnes, B. A., Behringer, G. E., Whellock, F. C. and Wilkins, E. W.: Surgical sepsis: Analysis of factors associated with sepsis following appendectomy (1937-1959). Ann. Surg. 156: 703, 1962. 6. Barnes, B. A., Behringer, G. E., Whellock, F. C. and Wilkins, E. W.: Treatment of appendicitis at Massachusetts General Hospital 1937-1959. J.A.M.A. 180: 122, 1962. 7. Befeler, D.: Recurrent appendicitis: Incidence and prophylaxis. Arch. Surg. 89: 666, 1964. 8. Benson, C. D., Coury, J. J., Jr. and Hagge, D. R.: Acute appendicitis in infants. Arch. Surg. 64: 561,1952. 9. Bernhardt, H. and Young, J. M.: Mucocele and pseudomyxoma peritonei of appendiceal origin. Am. J. Surg. 109: 235,1965. 10. Botsford, T. W. and Curtis, L. E.: Diverticulitis coli. New EnglandJ. Med. S65: 618, 1961. 11. Cantrell, J. R. and Stafford, E. S.: The diminishing mortality from appendicitis. Ann.Surg. 141:749, 1955. 12. Clements, N., Olson, J. E. and Powers, J. H.: Acute appendicitis in a rural community. IV. Ann. Surg. 161: 231, 1965.. 13. Colcock, B. P.: Regional enteritis. In Current Problems in Surgery, June, 1965. 14. Coldrey, E.: Five years of conservative treatment of acute appendicitis. J. Internat. Coll. Surgeons 3S: 255, 1959. 15. Cole, W. R. and Bernard, H. R.: A reappraisal of the effects of antimicrobial therapy on the course of appendicitis in children. Am. Surgeon Ifl: 29, 1961. 16. Collins, D. C.: 71,000 human appendix specimens; A final report summarizing forty years' study. Am. J. Proctol. 14: 365, 1963. 17. Craig, H. V., Guillet, G. G., Walker, J. A. and Artz, C. P.: Respiratory depression related to intraperitoneal neomycin. Am. SUrgeon 38: 27,1966.
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