Figure 71-6. Completed perfusion circuit (closed abdomen technique), with dual inflow and outflow cannulas.

Most experienced centers approach to peritoneal dissemination from appendiceal tumors has been

aggressive cytoreduction surgery, with the goal of removal of all gross disease if feasible. Selection

criteria should include a resectable primary lesion, resectable peritoneal disease, freedom from extraabdominal disease, and good performance status. The resection typically entails peritonectomy

procedures, omentectomy and potentially multivisceral resection (if the peritoneal disease cannot be

stripped from the organ). The cytoreductive phase is followed by hyperthermic intraperitoneal

chemotherapy (HIPEC), see figure. Mitomycin is the standard agent used in the perfusate, with

perfusions running for 30 to 120 minutes depending upon the center. This is typically administered with

mild hyperthermia (40 to 43°C), as elevated temperatures are associated with enhanced antineoplastic

effect in vivo, and help maintain normothermia after cytoreduction. After completion of the HIPEC, the

patient is definitively closed. If complete cytoreduction is achieved, at an initial procedure, if the

disease recurs, selected patients may undergo repeat exploration and perfusion as dictated by their

performance status and symptoms.127 Patient selection and the demands of cytoreduction have

significant learning curves and are best not performed by the occasional operator.128,129 Patients with

low-grade disease who undergo complete cytoreduction and HIPEC have 10-year survival rates in the

70% to 80% range.129–131 These cytoreductive procedures can be formidable procedures, and have been

associated with considerable morbidity, however more recent experience from major centers suggests

improvements and complication rates which are in keeping with those expected for major procedures on

patients with disseminated malignancy.128,129,132,133

Systemic chemotherapy for peritoneal surface disease from low-grade appendiceal neoplasms is

largely ineffective. This is due to both the inability of systemically delivered drugs to reach effective

intraperitoneal concentrations, and the slow-growth kinetics of the malignant cells. A phase II study in

advanced unresectable low-grade appendiceal primaries, with concurrent mitomycin C and capecitabine,

showed a “response” in 38% of the patients in the form of either stabilization or radiologic reduction in

the volume of disease.134 For high-grade lesions it seems that systemic chemotherapy improves

progression-free survival, even after a HIPEC with complete cytoreduction.135,136 Chemotherapy with

FOLFOX, in the preoperative setting for high-grade appendiceal mucinous lesions, was found to have

progression of disease in 50% of the patients, and significant tumor response observed in 29% of

cases.137 In addition, several groups have evaluated a number of alternative treatment modalities

including photodynamic therapy,138 and external beam radiation therapy.119 None of these treatments

have significantly altered the clinical course of these patients.

Carcinoids

Approximately one-third of all appendiceal neoplasms are carcinoids, which are tumors of

neuroendocrine/neural crest origin. Of all carcinoid tumors within the GI tract, approximately half arise

within the appendix. Carcinoid tumors of the appendix are usually found incidentally on pathologic

examination of the inflamed appendix. Most appendiceal carcinoids are <2 cm in size and arise in or

near the tip, thus they rarely cause obstruction. These tumors have a characteristic firm yellow

appearance, and when advanced, may be associated with a surrounding desmoplastic reaction.

Approximately 25% of cases present with nodal metastases and 10% with distant metastases.139–141

Tumor markers (such as CEA, chromogranin, or urinary hyroxyindole acetic acid) may be useful for

following up carcinoid cases, and should be obtained prior to resection.

1902

In regard to treatment and prognosis, the key feature is the size of the tumor. Most carcinoids are

small and those <1 cm in diameter, are adequately treated by simple appendectomy. Lesions between 1

and 2 cm have a 7.5% risk of nodal disease and a 4% risk of distant metastasis, while those larger than

2 cm have a 33% risk of nodal disease, and a 12% risk of distant metastasis.142 For lesions 2 cm in size

or greater, a right hemicolectomy is indicated, principally for the attendant lymphadenectomy.142 For

lesions between 1 and 2 cm, right colectomy is considered for high-grade malignant lesions with a high

mitotic index, mesoappendiceal invasion, lymphovascular invasion, tumors located at the base of the

appendix with positive margins, and goblet cell adenocarcinoid tumors.143 Overall survival at 5 years

approaches 100% for node-negative lesions <3 cm, 85% for node-positive lesions and 30% for

metastatic lesions.144 Appendiceal carcinoids are associated with liver metastases, and in these cases the

carcinoid syndrome may be present. The number and location of liver lesions, as well as the associated

symptoms, dictates treatment in these cases.142,144

Carcinoid syndrome is typically treated with somatostatin analogs as well as systemic chemotherapy.

There is a role for debulking of metastases, which may result in improved quality of life and overall

survival for those with the paraneoplastic carcinoid syndrome.

References

1. Major RH. Classic Descriptions of Disease. 3rd ed. Springfield, IL: Charles C. Thomas; 1945.

2. Wakeley CP. The position of the vermiform appendix as ascertained by an analysis of 10,000 cases.

J Anat 1933;67(Pt 2):277–283.

3. Wangensteen OH, Dennis C. Experimental proof of the obstructive origin of appendicitis in man.

Ann Surg 1939;110(4):629–647.

4. Bennion RS, Thompson JE, Baron EJ, et al. Gangrenous and perforated appendicitis with peritonitis:

treatment and bacteriology. Clin Ther 1990; 12(suppl C):31–44.

5. Buckius MT, McGrath B, Monk J, et al. Changing epidemiology of acute appendicitis in the United

States: study period 1993–2008. J Surg Res 2012;175(2):185–190.

6. Flum DR, Koepsell T. The clinical and economic correlates of misdiagnosed appendicitis: nationwide

analysis. Arch Surg 2002;137(7):799–804; discussion 804.

7. Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intraabdominal infection in adults and children: guidelines by the Surgical Infection Society and the

Infectious Diseases Society of America. Surg Infect (Larchmt). 2010;11(1):79–109.

8. Andersson RE. Meta-analysis of the clinical and laboratory diagnosis of appendicitis. Br J Surg

2004;91(1):28–37.

9. Wagner JM, McKinney WP, Carpenter JL. Does this patient have appendicitis? JAMA

1996;276(19):1589–1594.

10. Bundy DG, Byerley JS, Liles EA, et al. Does this child have appendicitis? JAMA 2007;298(4):438–

451.

11. Yen K, Karpas A, Pinkerton HJ, et al. Interexaminer reliability in physical examination of pediatric

patients with abdominal pain. Arch Pediatr Adolesc Med 2005;159(4):373–376.

12. Kharbanda AB, Fishman SJ, Bachur RG. Comparison of pediatric emergency physicians’ and

surgeons’ evaluation and diagnosis of appendicitis. Acad Emerg Med 2008;15(2):119–125.

13. Alvarado A. A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med

1986;15(5):557–564.

14. Samuel M. Pediatric appendicitis score. J Pediatr Surg 2002;37(6):877–881.

15. Kharbanda AB, Taylor GA, Fishman SJ, et al. A clinical decision rule to identify children at low risk

for appendicitis. Pediatrics 2005;116(3):709–716.

16. Lintula H, Kokki H, Pulkkinen J, et al. Diagnostic score in acute appendicitis. Validation of a

diagnostic score (Lintula score) for adults with suspected appendicitis. Langenbeck’s Arch Surg

2010;395(5):495–500.

17. Rezak A, Abbas HM, Ajemian MS, et al. Decreased use of computed tomography with a modified

clinical scoring system in diagnosis of pediatric acute appendicitis. Arch Surg 2011;146(1):64–67.

18. Farahnak M, Talaei-Khoei M, Gorouhi F, et al. The Alvarado score and antibiotics therapy as a

corporate protocol versus conventional clinical management: randomized controlled pilot study of

1903

approach to acute appendicitis. Am J Emerg Med 2007;25(7):850–852.

19. Flum DR, McClure TD, Morris A, et al. Misdiagnosis of appendicitis and the use of diagnostic

imaging. J Am Coll Surg 2005;201(6):933–939.

20. Flum DR, Morris A, Koepsell T, et al. Has misdiagnosis of appendicitis decreased over time? A

population-based analysis. JAMA 2001;286(14):1748–1753.

21. Doria AS, Moineddin R, Kellenberger CJ, et al. US or CT for diagnosis of appendicitis in children

and adults? A meta-analysis. Radiology 2006; 241(1):83–94.

22. Solomkin JS. Evaluating evidence and grading recommendations: the SIS/IDSA guidelines for the

treatment of complicated intra-abdominal infections. Surg Infect 2010;11(3):269–274.

23. Krajewski S, Brown J, Phang PT, et al. Impact of computed tomography of the abdomen on clinical

outcomes in patients with acute right lower quadrant pain: a meta-analysis. Can J Surg

2011;54(1):43–53.

24. Hlibczuk V, Dattaro JA, Jin Z, et al. Diagnostic accuracy of noncontrast computed tomography for

appendicitis in adults: a systematic review. Ann Emerg Med 2010;55(1):51–59 e51.

25. Lee CC, Golub R, Singer AJ, et al. Routine versus selective abdominal computed tomography scan

in the evaluation of right lower quadrant pain: a randomized controlled trial. Acad Emerg Med

2007;14(2):117–122.

26. Walker S, Haun W, Clark J, et al. The value of limited computed tomography with rectal contrast

in the diagnosis of acute appendicitis. Am J Surg 2000;180(6):450–454; discussion 454–455.

27. Williams RF, Blakely ML, Fischer PE, et al. Diagnosing ruptured appendicitis preoperatively in

pediatric patients. J Am Coll Surg 2009;208(5):819–825; discussion 826–818.

28. Kentsis A, Lin YY, Kurek K, et al. Discovery and validation of urine markers of acute pediatric

appendicitis using high-accuracy mass spectrometry. Ann Emerg Med 2010;55(1):62–70 e64.

29. Muenzer JT, Jaffe DM, Schwulst SJ, et al. Evidence for a novel blood RNA diagnostic for pediatric

appendicitis: the riboleukogram. Pediatr Emerg Care 2010;26(5):333–338.

30. Murphy CG, Glickman JN, Tomczak K, et al. Acute appendicitis is characterized by a uniform and

highly selective pattern of inflammatory gene expression. Mucosal Immunol 2008;1(4):297–308.

31. Burford JM, Dassinger MS, Smith SD. Surgeon-performed ultrasound as a diagnostic tool in

appendicitis. J Pediatr Surg 2011;46(6):1115–1120.

32. Leeuwenburgh MM, Lameris W, van Randen A, et al. Optimizing imaging in suspected appendicitis

(OPTIMAP-study): a multicenter diagnostic accuracy study of MRI in patients with suspected acute

appendicitis. Study Protocol. BMC Emerg Med. 2010;10:19.

33. Kim SY, Lee KH, Kim K, et al. Acute appendicitis in young adults: low- versus standard-radiationdose contrast-enhanced abdominal CT for diagnosis. Radiology 2011;260(2):437–445.

34. Hsieh CH, Lu RH, Lee NH, et al. Novel solutions for an old disease: diagnosis of acute appendicitis

with random forest, support vector machines, and artificial neural networks. Surgery

2011;149(1):87–93.

35. DeFrances CJ, Podgornik MN. 2004 National hospital discharge survey. Adv Data 2006;(371):1–19.

36. Addiss DG, Shaffer N, Fowler BS, et al. The epidemiology of appendicitis and appendectomy in the

United States. Am J Epidemiol 1990;132(5):910–925.

37. McBurney C. IV. The incision made in the abdominal wall in cases of appendicitis, with a

description of a new method of operating. Ann Surg 1894;20(1):38–43.

38. Tingstedt B, Johansson J, Nehez L, et al. Late abdominal complaints after appendectomy–

readmissions during long-term follow-up. Dig Surg 2004;21(1):23–27.

39. Coursey CA, Nelson RC, Patel MB, et al. Making the diagnosis of acute appendicitis: do more

preoperative CT scans mean fewer negative appendectomies? A 10-year study. Radiology

2010;254(2):460–468.

40. Rao PM, Rhea JT, Rattner DW, et al. Introduction of appendiceal CT: impact on negative

appendectomy and appendiceal perforation rates. Ann Surg 1999;229(3):344–349.

41. Simpson J, Samaraweera AP, Sara RK, et al. Acute appendicitis–a benign disease? Ann R Coll Surg

Engl 2008;90(4):313–316.

42. Mason RJ. Surgery for appendicitis: is it necessary? Surg Infect 2008;9(4):481–488.

43. Eriksson S, Granstrom L. Randomized controlled trial of appendicectomy versus antibiotic therapy

1904