Appendicitis: Evaluation by TC-99m leukocyte scan

ORIGINAL CONTRIBUTION appendicitis, diagnosis, TC-99m leukocyte scan; leukocyte, TC-99m, appendicitis

Appendicitis: Evaluation by TC-99m Leukocyte Scan Diagnosing appendicitis may be difficult. We report the use of a n e w technetium-99m-albumin colloid white blood cell (TAC-WBC) scan in the evaluation of appendicitis. In a synthesis requiring 75 minutes, autologous neutrophils and macrophages from 40 mL of whole blood were labelled with technetium-99m-albumin colloid and administered to 100 patients with possible appendicitis. The entire process, from labelling the cells to completion of the scan took a m a x i m u m of 5¥4 hours. Two patients had second scans on separate hospitalizations. Twenty-six patients had appendicitis; 12 had perforations, five of whom had an abscess. Eighty-five scans were read as either positive or negative for appench'ceal pathology with a sensitivity of 89%, a specificity of 92%, and an accuracy of 92% in diagnosing appendicitis. Seventeen scans were indeterminant; eight of these patients had appendicitis. The value of the TAC-WBC scan in the evaluation of appendicitis lies in its ability to be used emergently, its high negative predictive value for men and women (NPV = 97%), and its high positive predictive value for men (PPV = 93%). A t present, the scan does not appear to be reliable in diagnosing appendicitis in women (PPV = 43%). It is most useful in those patients in whom diagnosis is uncertain, and should not be used in patients with clear-cut appendicitis in whom its use will delay definitive surgical care. [Henneman PL, Marcus CS, Butler JA, Freedland ES, Wilson SE, Rothstein RJ: Appendicitis: Evaluation by TC-99m leukocyte scan. Ann Emerg Med February 1988;17:111-116.] INTRODUCTION The diagnosis of appendicitis can be difficult. In patients with abdominal pain seen in an emergency department, appendicitis has been reported as the most c o m m o n l y missed diagnosis in patients sent home and as the most common preoperative diagnosis that resulted in a negative laparotomy.i Perforation of the appendix has been reported as the most c o m m o n injury resulting in a malpractice claim against an ED.2 Accepted negative laparotomy r a t e s and perforation rates are approximately 20%. 2.6 These rates vary inversely with each other and are dependent on age, sex, and race. Black and white w o m e n between 21 and 40 years old have a negative laparotomy rate of 45%.2 Perforation rates for children less than 8 years old and adults more than 60 years old have been reported to be more than 70%.7, s Perforation significantly increases morbidity and mortality.3,8-1o Professional delay as well as parental or patient delay are responsible for these high perforation rates.7,8,11,12 There is little to acutely assist the clinical judgment of the physician in the evaluation of appendicitis. Weighted scoring systems based on history' physical examination, and laboratory data have been developed but are often cumbersome and difficult to memorize.13, ~4 Some scoring systems require computers. 13-16 More importantly, they fail in prospective application, offering no advantag~ over unaided clinical diagnosis. 16 Recently, a simplified scoring system was developed, but a prospective trial will be necessary to determine its efficacy. 17 Barium enemas are difficult to use acutely because of inadequate bowel preparation; they a r e nonspecific, and the physician cannot rely on filling of the appendix to exclude the diagnosis of appendicitis3 s Approximately 10% of normal appendices will not fill and 20% of acute nongangrenous appendices will fill completely.S Graded compression ultra17:2February 1988

Annals of Emergency Medicine

Philip L Henneman, MD* Carol S Marcus, PhD, MDt John A Butler, MD* Eric S Freedland, MD* Samuel E Wilson, MD* Torrance, California Robert J Rothstein, MD§ Bethesda, Maryland From the Department of Emergency Medicine,* Division of Nuclear Medicine,t and the Department of Surgery,~: Harbor-UCLA Medical Center, Torrance, California; and the Department of Emergency Medicine, Suburban Hospital, Bethesda, Maryland.§ Received for publication May 13, 1987. Revision received August 22, 1987. Accepted for publication November 16, 1987. This work was supported in part by E I DuPont de Nemours and Company, Inc, Bilirica, Massachusetts; and the Research and Education Institute, Inc, Harbor-UCLA Medical Center, Torrance, California. Presented at the University Association for Emergency Medicine Annual Meeting in Philadelphia, May 1987. Address for reprints: Philip L Henneman, MD, Department of Emergency Medicine, Harbor-UCLA Medical Center, 1000 W Carson Street, Torrance, California 90509.

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LEUKOCYTESCAN Hennemanet al

VERTEBRAL MARROW

MIIIVIwC ~ A FIGURE 1. A) A normal anterior view of the lower abdomen and pelvis obtained two hours following IV injection of 4.0 mCi TAC-WBC. There is no evidence of an inflammatory process (negative scan). B) A schematic diagram of a negative scan. sound may offer some benefit but requires a vigilant, experienced ultrasonographer because nonvisualization of the appendix implies the absence of appendicitis. 19 We report a new labelled leukocyte scan that can be used in the diagnosis of appendicitis.

MATERIALS A N D METHODS Between March and N o v e m b e r 1986, 100 patients were scanned with technetium-99m-albumin colloid (Microlite ®, EI DuPont de Nemours and Co, Inc, Bilirica, Massachusetts) white blood cells (TAC-WBC) in the evaluation of possible appendicitis at Harbor-UCLA Medical Center. These were not consecutive patients being evaluated for appendicitis because the scan was not available at night and on weekends. Patients admitted when the scan was not available with the diagnosis of appendicitis underwent prompt exploration. All patients with possible appendicitis seen in the Department of Emergency Medicine, and hospitalized patients requiring obser-

20/112

~

~

BLADDER

1B

vation to exclude the diagnosis of appendicitis, were eligible for study if scanning facilities were available. Two male patients underwent second scans on separate hospitalizations. Autologous leukocytes, separated from 40 mL of heparinized, whole blood, were incubated for 15 minutes at 37 C with 220 to 300 MBq (6 to 8 mCi) TAC; macrophages and neutrophils were labelled, presumably by phagocytosis. After centrifuging, the final 150 to 220 MBq (4 to 6 mCi) TAC-WBC preparation contained approximately equal activity of macrophages and neutrophils. A small amount of TAC was associated with red blood cells and l y m p h o c y t e s . About 50% of the TAC was either unphagocytized or loosely bound and could be removed with repeated washings; these washings were not performed in the routine preparation as loose TAC is involved in the early uptake at an i n f l a m m a t o r y site. The entire labelling procedure required 75 minutes. A total of 300,000 count images of the lower anterior abdomen and pelvis were obtained with a scintillation camera beginning five minutes following the IV administration of 150 to 220 MBq (4 to 6 mCi} TAC-WBC. Images of the anterior abdomen and pelvis were obtained every five minutes for the first 30 minutes, at which time images were obtained of the posterior Annals of Emergency Medicine

lower a b d o m e n and pelvis, liver, spleen, lungs, and head. Anterior views of the lower abdomen and pelvis were obtained again at one, two, three, and four hours. Studies were often terminated early if they were positive. Patients were encouraged to void frequently during the imaging period in order to avoid having a large, radioactive bladder on the scan, which might have obscured an abnormal focus of activity. Scans were interpreted as negative, positive, or indeterminant for appendicitis (Figures 1, 2, and 3). A negative study was one in which a focus of activity was not observed within the appendix zone by four hours. Positive scans had increased activity of TAC localized to the right abdomen and no other areas of increased activity that could confuse the diagnosis of appendicitis. Indeterminant scans were abnormal. They were indeterminant if they were consistent with appendicitis as well as other pathology (eg, diffuse uptake of TAC in the peritoneum without localization). Scans that were negative or indeterminant for appendiceal pathology might have been positive for other pathological causes of abdominal pain (eg, colitis, gastroenteritis, pancreatitis, pelvic inflammatory disease, pyelonephritis, and tubo-ovarian abscess). Laparotomy and histological exam-

17:2February1988

TABLE 1. Clinical presentation of study population

Duration of abdominal pain (days)* Pain migration to right lower quadrant Right lower quadrant tenderness Right lower quadrant rebound Temperature (C)* Temperature > 37.8 C WBC count ( x 103/mm3)* WBC count > 13,000/mm3 (102 scans on 100 patients) •Plus-minus values are means _+ SEM.

Patients With Appendicitis (26 patients, 27 scans)

P

2.3 +_ 0.6

NS

Patients Without Appendicitis (74 patients, 75 scans) 2.9 _+ 0.8

67% (18/27)

< ,005

31% (23/75)

96% (26/27)

NS

93% (70/75)

63% (17/27) 37.8 _+ 0.2 37% (10/27) 15.5 _+ 0.8 74% (20/27)

< .005 NS NS NS NS

27% (20/75) 37.6 +_ 0.1 33% (25/75) 14.6 _+ 0.7 63% (47/75)

FIGURE 2. Postive scan for appendicitis. Focal right lower quadrant collection with diffuse peritoneal uptake of TAC seen on anterior view of the lower abdomen and pelvis. This image was obtained two hours, 40 minutes following the IV administration of 5.2 mCi TAC-WBC. Surgery revealed a perforated appendix.

2 ination were necessary to make a diagnosis of appendicitis. Patients who did not undergo laparotomy and completely resolved their signs and symptoms in the hospital and at follow-up were considered not to have appendicitis. Scans that were interpreted as positive or negative for appendiceal pathology were used to determine the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the technetium-99m leukocyte scan in the diagnosis of appendiceal pathology. Comparison of frequencies was by chi-square or Fisher's exact test, and of means by t test with significance defined as a P < .05.

RESULTS One hundred patients (55 men, 45

17:2 February1988

women) ranging in age from 9 to 80 years were included in the study (Figure 4). Ninety-six percent of the patients were between 10 and 49 years old. The clinical presentation of patients is shown (Table.l). Patients with appendiceal pathology differed significantly from patients without appendiceal pathology in the frequency of pain migration from the periumbilical region to the right lower quadrant (67% c o m p a r e d with 31%, respectively; P < .005) and of rebound tendemess (63% compared with 27%, respectively; P < .005). Duration of abdominal pain, presence of right lower quadrant tendemess, oral temperature, and white blood count were not significantly different between patients with and without appendicitis. Twenty-six p a t i e n t s had appen-

Annals of Emergency Medicine

FIGURE 3. Indeterminant scan. Diffuse peritoneal uptake of TAC without focal collection seen on anterior view of the lower abdomen and pelvis. This image was obtained four hours following IV administration of 4.7 m C i TAC-WBC. The patient's right lower quadrant tenderness resolved spontaneously and was of un. known etiology. dicitis (19 men, seven women); 12 had perforations (nine men, three women), five of whom had an abscess. Laparoto m y findings were compared w i t h scan results (Table 2). Scans were abnormal in 93% of the patients with appendiceal pathology. The results of the 102 labelled leukocyte scans are listed (Table 3). The scan was positive in 22 patients; 17 had appendicitis. Ten patients had a perforated appendix, four of w h o m had an abscess. The areas of increased activity of TAC for the true-positive scans were combined to form the appendicitis zone (Figure 5). There were five false-positive scans (one man, four

113/21

LEUKOCYTE SCAN Henneman et al

40fj.)

35-

Iz

30-

I--] M A L E

25-

[]

m

Q..

FEMALE

20t~ 1 5 LLI m t0::D

Z

5-

O_

0-9

10-19 20-2!

~ ~

T ITTTI ......

:.30-39 4 0 - 4 9 ,50-59 6 0 - 6 9 7 0 - 7 9 8 0 - 8 9

AGE

FIGURE 4. Age and sex distribution of the study population. FIGURE 5. The appendicitis zone represents the c o m b i n e d areas of increased activity of TAC on the anterior view of the lower abdomen and pelvis of the 17 true-positive scans. women). None of the patients with false-positive scans u n d e r w e n t lapar o t o m y and all improved clinically; one of these patients received metronidazole hydrochloride for presumed amebiasis with complete resolution of diffuse abdominal pain. Three patients h a d a b d o m i n a l p a i n of u n c l e a r etiology, and the last was given the discharge diagnosis of gastroenteritis. All remained asymptomatic at followup. Sixty-three scans were interpreted as negative; there were two false-negative scans (one man, one woman). Both required histologic examination to diagnose early appendicitis. There were 61 tree-negative scans on 60 patients. A b d o m i n a l pain of u n c l e a r etiology accounted for 50%, and gastroenteritis for 25% of the patients. Seven percent of patients had a ruptured ovarian cyst; pelvic inflammatory disease and urinary tract infections each accounted for 5% of the patients with tree-negative scans. ' There was one case of each of the following diagnoses: cholecystitis, diverticulitis, omental adhesions, ovarian carcinoma, and periumbilical hernia. T h e p a t i e n t w i t h o m e n t a l adhesions had two negative TAC-WBC 22/114

5

TABLE 2. Operative finch'ngs and TAC-WBC results for appendicitis

Scan Results Negative Positive Indeterminant Total

Non-Perforated Appendicitis

Perforated Appendixt

Appendiceal Abscess

Total

2 7 6

0 6 1

0 4 1

2 17 8

15*

7

5

27¢

*One patient underwent two scans; the initial scan was indeterminant and the second scan, three months later, was positive. 1-Perforated appendix without abscess information. :i:Total of 27 scans in 26 patients with appendicitis.

scans. A b a r i u m e n e m a p e r f o r m e d during a second hospitalization was read as a periappendiceal abscess. No abscess was f o u n d at l a p a r o t o m y ; omental adhesions and a normal appendix were removed. One other patient u n d e r w e n t a negative laparoto o m y after a negative scan. One male patient with a negative scan for appendicitis had a focal collection of TAC in the left lower quadrant consistent with an abscess and at operation was found to have a normal appendix and a rectus sheath abscess. Eighty-five scans were read as either positive or negative for appendiceal pathology (Table 4). The sensitivity, specificity, and accuracy of the leukocyte scan for these patients was 89%, 92%, and 92%, respectively. W h e n data were divided by sex, the scan had a sensitivity, specificity, and accuracy of 93%, 97%, and 96%, respectively, Annals of Emergency Medicine

for men, and 75%, 88%, and 86%, respectively, for women. The predictive value of a positive scan was 93% in m e n and 43% in w o m e n , giving a combined value of 77%. The predictive value of a negative scan was 97% for both men and women. The scan was indeterminant in 17 cases. Eight of these patients (47%) had appendicitis; the appendix was perforated in two and nonperforated in six. Six of the eight i n d e t e r m i n a n t scans on patients w i t h appendicitis had diffuse abdominal uptake of technetium-99m-albumin colloid without localization consistent with peritoneal reaction from any cause. One of these patients was given metronidazole hydrochloride for p r e s u m e d amebiasis with complete resolution of abdominal pain, fever, and l e u k o c y t o s i s . Three m o n t h s later, this patient returned with a similar clinical picture, 17:2 February 1988

TABLE 3. Results of TAC-WBC scan

Male Patients Female Patients Total

No. Scans

True-Positive

57 45 102

Indeterminant (Appendicitis)

False-Positive

True-Negative

False-Negative

14

1

33

1

8 (5)

3

4

28

1

17

5

61

2

9 (3) 17 (8)

TABLE 4. Computed results of TAC-WBC scan

Male Patients (n = 49) Female Patients (n = 36) Combined (N = 85)

% Sensitivity

% Specificity

% Accuracy

% Positive Predictive Value

93

97

96

93

97

75

88

86

43

97

89

92

92

77

97

a positive TAC-WBC scan, and an inflamed, nonperforated appendix. One patient with diarrhea had right lower quadrant activity on his scan consistent with appendicitis but also had increased activity of TAC within the bowel consistent with gastroenteritis. At laparotomy, he had a nonperforated, inflamed appendix. Four patients had abdominal pain of unclear etiology and another developed hemorrhagic pancreatitis as the cause for diffuse abdominal uptake of TAC. Scans on five patients localized pathology to the pelvis but could not differentiate an appendiceal abscess from a tubo-ovarian abscess (one); or appendicitis (one) from pelvic inflammatory disease (two); or a ruptured ovarian cyst (one). Eight of the 100 patients also underwent barium enemas. Two patients had appendiceal pathology. TAC-WBC scans were positive in both; barium enemas were suggestive in one and false-negative in the other. In the six patients w i t h o u t appendiceal pathology, TAC-WBC scans were indeterminant in one, negative in four, and false-positive in one; barium enemas were indeterminant in three, negative in two, and false-positive in one. DISCUSSION The value of TAC-WBC scan in the evaluation of appendicitis appears to 17:2 February 1988

be threefold: the ability to scan patients emergently; the high negative predictive value for men and women (NPV = 97%); and the high positive predictive value for men (PPV = 93% ) in diagnosing appendicitis. This is the first labelled leukocyte scan that can be performed on an emergency basis. The labelling of leukocytes with t e c h n e t i u m takes 75 minutes, and the majority of patients with appendicitis will have a positive scan within two hours of administration of TAC-WBC. Indium-Ill leukocyte imaging has been evaluated in 32 patients with possible appendicitis. The accuracy and rate of indeterminant scans were similar to TAC-WBC scan but indium- 111 imaging required 24 hours for completion. 2° Indium-Ill leukocyte scans generally require 16 to 24 hours to complete. Technetium-99m leukocytes are less expensive, require shorter preparation time, have lower radiation absorbed dose, and result in superior images compared with indium-Ill leukocytes. 21 The absorbed radiation dose in TAC-WBC scan for the spleen, which is the target organ, is 0.14 mGy/MBq (0.50 rad/mCi). This is less than that absorbed by the spleen with computerized tomography and standard cuts. The liver and red marrow are approximately equivalent secondary target organs, each receiving 20% of the Annals of Emergency Medicine

% Negative Predictive Value

spleen dose. 2~ The estimated patient cost of a TAC-WBC scan is $400. We r e c o m m e n d that TAC-WBC scan be used for patients in whom the diagnosis of appendicitis is unclear. Patients with definite appendicitis should undergo prompt exploration without diagnostic studies that delay definitive care. Stable patients with negative TAC-WBC scans can probably be sent home with a scheduled follow-up within 24 hours and strict instructions to retum if symptoms get worse. Men w i t h positive scans should probably undergo prompt exploration. Negative laparotomy rates for men can be expected to be approximately 7%, which is acceptable in light of reported negative laparotomy rates for appendicitis. Surgical judgment, however, is still critical as falsepositives and false-negatives do occur. Not all TAC-WBC scans can be interpreted as positive or negative for appendicitis. Some scans may be abnormal, but the uptake of TAC will not be specific enough to diagnose or exclude appendicitis. In our series 17% of scans were indeterminant. Indeterminant scans have a moderate probability of appendicitis. Patients with indeterminant scans probably should be admitted for further evaluation and observation. At present, the TAC-WBC scan does not appear to be reliable in diagnosing 115/23

LEUKOCYTE SCAN Henneman et al

appendicitis in w o m e n (PPV = 43%) but our n u m b e r s were s m a l l and n o n e of t h e false-positives w e r e s u r g i c a l l y confirmed. A l t h o u g h no studies have been published d o c u m e n t i n g a rate of s p o n t a n e o u s r e s o l u t i o n of a c u t e appendicitis, such a possibility has b e e n proposed.22, 23 T h i s study i n c l u d e d our earliest experience w i t h the T A C - W B C scan in the diagnosis of a p p e n d i c i t i s . Understandably, the decision to operate was less affected by scan results early in our experience. We have c o n t i n u e d to i m p r o v e our t e c h n i q u e and interpretation of scans. Presently, the T A C - W B C scan is an accepted diagnostic modality at our i n s t i t u t i o n in the e v a l u a t i o n of patients w i t h possible appendicitis. T h e h i g h perforation rate (46%) in our s t u d y p o p u l a t i o n appeared to be related to t h e d u r a t i o n of s y m p t o m s prior to p r e s e n t a t i o n (mean, 3.9 days for p a t i e n t s w i t h p e r f o r a t i o n c o m pared w i t h 0.9 days for p a t i e n t s w i t h out perforation, P < .02) and perhaps to delay in operation. A l t h o u g h t h e t i m e f r o m E D visit to l a p a r o t o m y was not significantly different for patients w i t h and w i t h o u t perforation, it t o o k a m e a n of 31.8 hours (SEM, 1.5 hours) f r o m initial v i s i t to o p e r a t i o n . T h i s delay in definitive care m a y have been due to the diagnostic d i l e m m a s t h e s e patients posed, and probably played a role in the rate of perforation. T h e risk of perforation was not related to age in our study, p r o b a b l y b e c a u s e w e had few patients at the e x t r e m e s of age. T h e diagnostic accuracy for appendicitis has n o t changed for 50 years. 6 Clinical instinct has remained the m o s t reliable m e t h o d for d i a g n o s i n g appendicitis, albeit an i m p e r f e c t one. Retrospective analyses have defined those features in the history, physical examination, and laboratory data that help instinct, but w e i g h t e d or c o m p u t erized scoring systems have not proved helpful. 16 T h r e e diagnostic m o d a l i t i e s n o w exist to aid c l i n i c a l j u d g m e n t : b a r i u m enema, graded compression ultrasound, and l e u k o c y t e scans. A l t h o u g h barium e n e m a s have been reported to have an accuracy as high as 98% in c h i l d r e n , a c c u r a c i e s as l o w as 79% have b e e n reported.Is, 24 Perhaps t h i s is w h y barium e n e m a s are used infrequently. G r a d e d c o m p r e s s i o n u l t r a sound has recently been d e m o n s t r a t e d

24/116

in a c o n v e n i e n c e s a m p l e of 90 patients to h a v e a s e n s i t i v i t y of 89%, a specificity of 95%, and an accuracy of 9 3 % i n d i a g n o s i n g a p p e n d i c i t i s . 2s T h e s e results are similar to our results with the TAC-WBC scan. Further studies are needed to c o m p a r e scoring systems, graded compression ultrasound, b a r i u m enemas, and l e u k o c y t e scans, and to d e t e r m i n e if and w h e n t h e y i m p r o v e clinical accuracy in the diagnosis of appendicitis. CONCLUSION O n e h u n d r e d p a t i e n t s w e r e evaluated for appendicitis w i t h a n e w techn e t i u m - 9 9 m l e u k o c y t e scan. Eightyf i v e s c a n s w e r e read as p o s i t i v e or n e g a t i v e for a p p e n d i c e a l p a t h o l o g y w i t h a s e n s i t i v i t y of 89%, a specificity of 92%, and an accuracy of 92% in diagnosing appendicitis. Seventeen s c a n s w e r e i n d e t e r m i n a n t ; e i g h t of t h e s e p a t i e n t s had appendicitis. T h e value of T A C - W B C scan in the evaluation of appendicitis lies in its ability to be used emergently, its high negat i v e p r e d i c t i v e v a l u e for m e n a n d w o m e n (NPV = 97%), and its h i g h positive predictive value for m e n (PPV = 93%). A t present, t h e T A C - W B C scan does n o t appear to be reliable in diagnosing appendicitis in women (PPV = 43%). It is m o s t useful in patients in w h o m the diagnosis is uncertain, and s h o u l d n o t be u s e d in pat i e n t s w i t h c l e a r - c u t a p p e n d i c i t i s in w h o m it w i l l delay definitive surgical care. The authors thank the housestaff of the Departments of Emergency Medicine and Surgery at Harbor-UCLA Medical Center for their care of these patients, and Sara Marini for preparation of the manuscript.

REFERENCES 1. Brewer RJ, Golden GT, Hitch DC, et al: Abdominal pain: An analysis of 1,000 consecutive cases in a university hospital emergency room. Am J Surg 1976;131:219-223. 2. Trautlein JJ, Lambert RL, Miller J: Malpractice in the emergency department -- review of 200 cases. Ann Emerg Med 1984;13:709-711, 3. Lewis FR, Holcroft JW, Boey J, et al: Appendicitis. A critical review of diagnosis and treatment in 1,000 cases. Arch Surg 1975;110: 677-684. 4. Hobson T, Rosenman LD: Acute appendicitis -- when is it right to be wrong. A m I Surg 1964; 108:306-312. 5. Weigelt J: Diagnosis of appendicitis, in Me-

Annals of Emergency Medicine

Clellan RN, Gewertz BL, Fry WJ (eds): Selected Readings in General Surgery, vol 7. Dallas, University of Texas, 1980, p 1-14. 6. Berry J, Malt RA: Appendicitis near its centenary. Ann Surg 1984;200:567-575. 7. Throbjarnarson B, Loehr WJ: Acute appendicitis in patients over the age of sixty. Surg Gynecol Obstet 1967~125:1277-1280. 8. Stone HH, Sanders JL, Martin JD: Perforated appendicitis in children. Surgery 1971;69: 673-679. 9. Scher KS, Coil JA: The continuing challenge of perforated appendicitis. Surg Gynecol Obstet 1980; 150:535-538. 10. Janik JS, Firor HV: Pediatric appendicitis. Arch Surg 1979;114:717-719. 11. Owens BJ, Hamit HF: Apendicitis in the elderly. Ann Surg 1978;187:392-396. 12. Savrin RA, Clatsworthy HW: Appendiceal rapture: A continuing diagnostic problem. Pediatrics 1979;63:37-43. 13. Teicher I, Landa B, Cohen M, et al: Scoring systems to aid in diagnosis of appendicitis. Ann Surg 1983;198:753-759. 14. Grahm DF: Computer-aided prediction of gangrenous and perforating appendicitis. Br Med [ 1977;2:1375-1377. 15. DeBombal FT, Leaper DJ, Horrocks JC, et al: Human and computer aided diagnosis of abdominal pain: Further report with emphasis on the performance of clinicians. Br Med J 1974; 1:376-380. 16. Van Way III CW, Murphy JR, Dunn EL, et al: A feasibility study of computer aided diagnosis in appendicitis. Surg GynecoI Obstet 1982; t55:685-688. 17. Alvarado A: A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med 1986;15:557-564. 18. Rajagopalan AE, Mason JH, Kennedy M, et al: The value of barium enema in the diagnosis of acute appendicitis. Arch Surg 1977;112: 531-533. 19. Puylaert JBCM: Acute appendicitis: US evaluation using graded compression. Radiology 1986;158:355-360. 20. Navarro DA, Weber PM, Kang IY, et al: Indium-Ill leukocyte imaging in appendicitis. AJR 1987;148:733-736. 21. Marcus CS, Kuperus JH, Salk RD, et al: Clinical applications of Tc-99m Microlite leukocytes (abstract). Clin Nucl Med 1986;11/9S: Pll. 22. Collins DC: Mechanisms and significance of obliteration of the lumen of the vermiform appendix. Ann Surg 1936;104:199-211, 23. Crile G Jr, Fulton JR: Appendicitis with emphasis on use of penicillin. Naval Medical Bulletin 1945;45:464-473. 24. Lewin GA, Mikity V, Wingert WA: Barium enema: An outpatient procedure in the early diagnosis of acute appendicitis. ] Pediatr 1978; 92:451-453. 25. Jeffrey RB, Laing FC, Lewis FR: Acute appendicitis: High resolution real-time US findings. Radiology 1987;163:11-14.

17:2 February 1988