Acute appendicitis – open or minimally-invasive approach

Introduction
Although laparoscopy has become the standard approach in other procedures, this technique is not generally accepted for acute appendicitis. Since the introduction of laparoscopic appendectomy by Kurt Semm in the ‘80s (1), the role of this minimally invasive surgical technique has been controversial (2). During the time, a lot of studies analyzed the advantages of this approach (e.g. lower wound infection rates (3), less postoperative pain (4) and earlier return to full activities (5) and disadvantages (e.g. higher rates of intra-abdominal abscesses (6) and sometimes severe parietal infections (7), longer operating times (8) and higher treatment costs (8,9), but the subject is still discussed. We designed a study to evaluate the results of appendectomies performed in our surgical unit by minimally-invasive approach, compared with open technique.

Material and Methods
We performed a retrospective study for a period of one year. All medical records of patients operated for acute appendicitis were reviewed. Inclusion criteria included a positive histo-logical diagnosis of acute appendicitis. Patients were divided in two groups: patients operated by open approach (OA) and patients operated by minimally invasive approach (MIA). Conversion was defined as the quit of laparoscopic procedure with removal of the trocars and the enlargement of the incision from the right abdominal quadrant or performing other incisions (e.g. mid line approach). The demographic and medical data were processed using MS Access Office XP and statistically analyzed using the SPSS software version 15.0, for Windows (Statistical Package for the Social Sciences, Chicago, Illinois, U.S.A.). Pearson Chi square and t Student tests were used to compare the groups and odd ratio (OR) to determine conversion and morbidity risk factors; statistical significance was computed for 95% probability. Average values were reported as mean ± SEM (Standard Error of Mean). We also used multivariate analysis (logistic regression in binary model) to established the odds ratio for different risk factors.

Results
A total of 200 patients were analyzed: 99 patients in OA group and 101 patients in MIA group. All open procedures were performed using a Jalaquier incision (right vertical paramedian incision). The MIA group was more heterogenic. Three different techniques have been used: 1) totally laparoscopic technique using an endo-GIA stapler to remove the appendix (1.98%; N=2); 2) video-assisted extracorporeal appendectomy – the appendix is localized during the laparoscopic abdominal exploration, exposed and, after exsufflation, the appendix is exteriorized through the right abdominal quadrant trocar site; the mesoappendix and appendix are then classically divided extra corporeally (89.1%; N=90); 3) a composite technique – the mesoappendix is treated laparoscopically using clips or electrocoagulation, the appendix is then exteriorized and extracorporeally ligated, reinserted into the abdominal cavity, divided, and removed through a trocar, in order to prevent the wound infection (8.91%; N=9). The surgical procedures were performed by surgeons with different level of expertise, from young residents to senior surgeons.
The overall men/women ratio was 112/88 (1.27), with a mean age of 31.83±1.06 years (range 10-80). There is no overall significant statistical difference between women and men regarding age (p=0.239). The analysis of demographic characteristics of the two groups revealed more women in the MIA group and more men in the OA group, but there was no statistical significant difference between groups regarding age (Table 1).
The diagnosis of acute appendicitis was established using the well known clinical signs and symptoms and laboratory tests (Table 2 ). There were more patients in the OA group with marked WBC count with neutrophils over 75% and with high values of Alvarado score (Table 2). Abdominal ultrasound exam was performed in all patients and revealed signs of acute appendicitis (thick-walled, non-compressible tubular structure in the right lower quadrant, appendoliths, pericecal fluid, free abdominal fluid) with a sensitivity of 99% (two false negatives cases) (Fig. 1).
Associated pathologies were encountered in 51% from all the patients (N=102): gynaecological diseases (ovarian cysts, pelvic inflammatory disease) 30%; chronic liver disease (steatosis, hepatitis, cirrhosis) 22%; cardiovascular diseases (coronary heart disease, hypertension, arrythmias, valvular heart disease) 18%; diabetes 12%; respiratory diseases 9%. There were more patients with comorbidities in MIA group (58.8%; N=60) then in OA group (41.2%; N=42) which proved statistically significant (p=0.016). There were also two pregnant women (weeks 8-th and 17-th, respectively) operated by open approach. Peritonitis was present in 6% from all the cases (N=12) with equal distribution in both groups. Associated surgical procedures were performed in 13 cases (6.5%), most of these (84.61%; N=11) in MIA group (p=0.025) (Table 3 ).
Mean operation time was similar in the two groups: 36.96±1.48 minutes in OA group versus 37.03±1.39 minutes in MIA group, p=0.976. As expected conversion significantly increased operating time: 49.75±2.22 minutes versus 33.89 ± 1.17 minutes in non-conversion laparoscopic cases ((p<0.001). The conversion rate was 19.81% (N=20). These were caused by: peritonitis (30%, N=6); adhesions (20%; N=4); abnormal anatomic positions of the appendix and/or caecum (20%; N=4); intraoperative bleeding (15%, N=3); instruments and technical failures (15%, N=3). The multivariate analysis of risk factors for conversion revealed the following: WBC over 10000/mm3 (OR=22.4), peritonitis (OR=9.35), associated respiratory diseases (OR=2.96), fever (OR=1.51) and male gender (OR=1.16).
The mortality rate was 0.5% (N=1): an 80-years-old male patient, with perforated appendicitis, generalized neglected peritonitis and severe sepsis; he was operated by open approach and died after 3 days with multiple organ failure.

Figure 1A

Figure 1B

Figure 2

The overall postoperative morbidity rate was 12% (N=24). Complication rate was double in OA group (16 cases versus 8 cases in MIA group) but did not reach statistical significance (p=0.073). The most common postoperative complication was wound infection (4.5%; N=9). OA group has three times more cases with wound infection but due to low incidence it did not gain statistical significance (p=0.083). Other complications were urinary tract infections (4.5%; N=9), respiratory tract infections (2.5%; N=5) with similar figures in the two groups (p>0.05). We encountered one case of postoperative intraperitoneal bleeding (0.5%; N=1) in MIA group, requiring open laparotomy.
The risk factors for overall postoperative morbidity revealed by multivariate analysis were: appetite loss (OR=2.75), rebound tenderness/rigidity in RALQ (OR=1.47), fever (OR=1.64) and peritonitis (OR=36.0).
Histopathological exam revealed early acute appendicitis in 45.5% cases (N=91), suppurative appendicitis in 46.5% (N=93) and gangrenous appendicitis in 8% (N=16), with obvious more cases with early acute appendicitis in MIA group and more cases with suppurative appendicitis in OA group (p=0.017) (Fig. 2). Locally advanced disease (e.g. suppurative appendicitis) is significantly associated with postoperative morbidity: 62.5% from all cases with suppurative appendicitis (N=15) had postoperative complications; p=0.021.
The postoperative hospital stay was similar in the two groups: 4.34±0.39 days in OA versus 3.58±0.25 days in MIA group (p=0.103).

Discussion
For more then 100 years the open appendectomy is the standard procedure with continuously improved results (10,11). On the other hand, laparoscopic appendectomy was, from the beginning, a subject of debates and didn’t become a gold standard for acute appendicitis, as compared with laparoscopic cholecystectomy. More so, in most surgical training programs appendectomy is considered an “easy operation”, frequently a first surgical procedure for young residents, very often using an open approach (12).
There is a variety of technical approaches’ using a laparos-copic environment, three of them used in our surgical unit and previously described. We need to stress that these are not the only alternatives and as such we prefer the term of minimally invasive appendectomy instead of laparoscopic appendectomy. Much more, the appendectomy performed using the last technological developments (NOTES (13) and single port surgery (14)) could be included in this terminology.
In our study we showed some demographic differences between OA and MIA groups – more women in MIA group and more men in OA probably due to a theoretical benefit of laparoscopic diagnostic in women. Different randomized trials didn’t report statistically significant demographic differences between groups (5,15,16,17) but some prospective trials excluded women patients in order to avoid the impact of diagnostic laparoscopy (18,19). Nevertheless it is important to stress that all the retrospective studies revealed a higher incidence of women for laparoscopic appendectomy group which varied from 50-60% (20,21) to over 75% (22,23). Otherwise, the rate of “laparoscopic appendectomy” for other pathologies is about 2% in men and 11% in women (24), with a specificity of laparoscopic appendectomy of 97.6% in women and 100% in men (8).
The mean age of our study group (31.83±1.0 years old) was similar with those reported in literature and reflects the age related incidence of the acute appendicitis reflected from randomized trials and meta-analysis (5,11,16,19); it is a marked discrepancy with the majority of the retrospective studies that report series with younger patients, with a mean age of about 20 years (21,22,23,24,25).
There are few data in literature comparing Alvarado score in OA versus MIA; we found a significantly increased value in OA group. The values are similar with others reported series (26,27,28). The lower value of Alvarado score in MIA group is probably explained by the impact of diagnostic laparoscopy; otherwise, Andersson M and Andersson RE prefer the laparos-copic approach or more complex imagistic evaluation for the patients’ with “an indeterminate scoring result” who represents 37% from that series (29). In the same line EAES guidelines recommend “Patients with symptoms and diagnostic findings suggestive of acute appendicitis should undergo diagnostic laparoscopy and, if the diagnosis is confirmed, laparoscopic appendectomy” (30). The rate of comorbidities, increased in MIA group, is also probably explained by the impact of diagnostic laparoscopy. However, in our study, the rate of cardiovascular diseases, respiratory diseases and diabetes is twice, three and respectively fourth times higher then in other series (16). We should also underline that the major drawback of such retrospective studies is the variability of surgical expertise among teams, regarding both general experience as well as laproscopic skills. In our study acute appendicitis associated with pregnancy was managed only by open approach which appears to be safer then the laparoscopic approach, as in the other reports from the literature (31).
The value of abdominal ultrasound exam in the diagnosis of acute appendicitis is not well established; some studies revealed “no advantage of ultrasound over the Alvarado score” (32). However most of the authors noted the importance of ultrasound exam in doubtful cases for decreasing the rate of negative laparotomy (33,34). The sensitivity and specificity of ultrasound exam in our study is over the rates noted in the literature (34,35) probably due to the retrospective type of analysis we performed as in other series (36). We have no experience in the use of CT scan abdominal examination for cases with acute appendicitis. Some authors noted a superior sensitivity of CT scan compared to abdominal ultrasound (37); however the CT scan seems to be overused in some countries and ultrasound exam could avoid a useless CT scan exam and radiation exposure (38).
One theoretical advantages of minimally invasive approach in acute appendicitis is a shorter operating time (39). Few studies revealed a shorter operative time for minimally invasive appendectomy (3,4,16,40). Most meta-analysis studies (6,11,25), prospective trials (5,12,15,17,18,19,41) and retros-pective studies (42) demonstrate that a longer operative time is required for laparoscopic appendectomy. In our study the mean operating time was similar in both groups (37 minutes) and that was shorter compared to other reported series (4,8,11,12,15,16,19,22,23,40,41,42,43). The longest mean operating time for laparoscopic appendectomy was reported by Pokala (43) (100.5±36.2 minutes); similar operating time has been previously reported in the ‘90s by Martin LC (44) (102.2 minutes).
The conversion rate varies in the literature; most prospective randomized trials reported nil conversion rates or under 2% (4,12,16,17,18,19,40). However, some retrospective studies reported higher conversion rates: 3.6% (20), 7.6% (45), 18.6% (42) and even 19.1% (46). In our study conversion rate was high 19.81% probably due to lack of experience of young trainees as well as technical limitations and financial restriction. We should add that most teams are not trained in advanced laparoscopic colonic surgery, hence the decision to convert in most cases where a full mobilization of the right colon is required. That certainly influences the figures, but in the mean time it reflects a reality at least in our geographical area.
The overall postoperative complications rate for laparos-copic appendectomy is about 10% (11,12,16,19,47). In our study we found similar figures, with no statistical difference between OA and MIA group. The overall wound infection rate was 4.5% similar with other series (11,19); most studies report wound infection rates smaller in laparoscopic approach. In the largest retrospective study which includes over 40,000 patients operated for acute appendicitis, Guller U et al (47) reported a significant lower number of infectious complications in laparoscopic group versus open approach (0.8% versus 1.9%, respectively, p<0.0001). This discrepancy may be due to a very liberal conversion policy, demonstrated by a very high conversion rate in our series.
Some meta-analysis revealed a higher risk for intra-abdominal postoperative abscesses for the laparoscopic approach (8,11,25). Some authors discussed as risk factor for intra-abdominal abscesses intraoperative surgical maneuvers and carbon dioxide insufflation (16), and others the usage of Roeders loop instead of stapler devices (48). However, in recent studies there are no difference between open and laparoscopic approaches from the point of view of postoperative deep abdominal infections (4,15,49). In our series we didn’t encounter any intra-abdominal abscess, and staplers were used in only two cases.
The postoperative mortality rate is generally considered under 0.5% (9). Guller U et al (47) reported 0.05% death rate for laparoscopic appendectomy versus 0.3% for open approach. In our series we noted one fatality (OA): elderly patient with complicated appendicitis, sepsis and multiple organs failure. Similar isolated cases are reported in literature (12,46). Although we can reduce mortality we agree with Bastien J (50): “we don’t believe we can reduce mortality to zero”.
The postoperative hospital stay is shorter for laparoscopic approach then for OA in many studies (3,6,16,25,47); however many authors failed to find any difference between open and laparoscopic approaches (4,5,8,9,11,15,17,18,19). In our series, patients operated by MIA had a shorter postoperative stay, but without statistical significance.
We recognize some of the limitations of our study. Although we reported and statistical analyzed a series of clinical, biological and operative parameters, we didn’t asses some postoperative relevant factors such as postoperative pain and quality of life, time until the bowel movements, time until the return to routine daily activities and cosmetic results. Unfortunately these parameters are impossible to be assessed in a retrospective study. The cost evaluation of MIA versus OA was not computed for two main reasons: 1. most of our MIA operations were performed using the video-assisted method (3) which is less expensive compared with the totally laparos-copic approach; 2. Our unit budget is calculated using diagnosis-related grouping (DRG) method. As such cases with more comorbidities and associated surgical procedures (as was the case in the MIA group in our study) generate an increased Case Mix Index (CMI) and are better reimbursed. Also prices in laparoscopic appendectomy differ significantly according to the type of instruments used (single use versus disposable), number of laparoscopic procedures per unit and expected lifetime of instruments.

Conclusions
Minimally invasive appendectomy is a safe procedure and can be performed even in patients with comorbidities, although these associations may increase the conversion and postoperative morbidity rates. We didn't find any statistical significant difference regarding postoperative morbidity; however, the overall number of complicated cases was double in OA group versus MIA group and it may be considered practically significant. The postoperative hospital stay was similar in both groups.
Laparoscopic exploration is probably the most important benefit of MIA in acute abdomen and should be done more frequently with a probable decrease in number of conversions with the added experience and technological improvements.

Authors Disclosures
Drs. Radu Moldovanu, Nutu Vlad, Eugen Târcoveanu, Gabriel Dimofte, Viorel Filip, Cristian Lupaşcu, Costel Bradea, Ghiocel Rãileanu, Bogdan Tutuianu and Felicia Crumpei, have no conflicts of interest or financial ties to disclose.

References
1. Semm K. Endoscopic appendectomy. Endoscopy. 1983; 15(2): 59-64.
2. Litynski GS. Kurt Semm and the fight against skepticism: endoscopic hemostasis, laparoscopic appendectomy, and Semm's impact on the "laparoscopic revolution". JSLS. 1998; 2:309-313.
3. Malik AM, Talpur AH, Laghari AA. Video-assisted laparoscopic extracorporeal appendectomy versus open appendectomy. J Laparoendosc Adv Surg Tech A. 2009;19(3):355-9.
4. Wang YC, Yang HR, Chung PK, Jeng LB, Chen RJ. Laparos-copic appendectomy in the elderly. Surg Endosc. 2006; 20(6): 887-9. Epub 2006 May 11.
5. Wei HB, Huang JL, Zheng ZH, Wei B, Zheng F, Qiu WS, et al. Laparoscopic versus open appendectomy: a prospective randomized comparison. Surg Endosc. 2009. [Epub ahead of print]
6. Bennett J, Boddy A, Rhodes M. Choice of approach for appendicectomy: a meta-analysis of open versus laparoscopic appendicectomy. Surg Laparosc Endosc Percutan Tech. 2007; 17(4):245-55.
7. Svaton R, Neumann C, Hanslianová M. Necrotizing fasciitis--a rare complication of laparoscopic appendectomy. Rozhl Chir. 2009;88(1):35-9. Czech
8. Kum CK, Ngoi SS, Goh PMY, Tekant Y, Isaac JR. Randomised controlled trial comparing laparoscopic and open appendicectomy. Br J Surg. 1993;80(12):1599-600.
9. Köckerling F, Schug-Pass C, Grund S. Laparoscopic appendectomy: The new standard? Chirurg. 2009;80(7):594-601. Review. German
10. McBurney C. The incision made in the abdominal wall in cases of appendicitis. Ann Surg. 1894;20(1):38-43.
11. Fingerhut A, Millat B, Borrie F. Laparoscopic versus open appendectomy: time to decide. World J Surg. 1999;23(8): 835-45.
12. Cueto J, D'Allemagne B, Vázquez-Frias JA, Gomez S, Delgado F, Trullenque L, et al. Morbidity of laparoscopic surgery for complicated appendicitis: an international study. Surg Endosc. 2006;20(5):717-20. Epub 2006 Mar 16.
13. Horgan S, Cullen JP, Talamini MA, Mintz Y, Ferreres A, Jacobsen GR, et al. Natural orifice surgery: initial clinical experience. Surg Endosc. 2009;23(7):1512-8. Epub 2009 Apr 3
14. Nguyen NT, Reavis KM, Hinojosa MW, Smith BR, Stamos MJ. A single-port technique for laparoscopic extended stapled appendectomy. Surg Innov. 2009;16(1):78-81. Epub 2009 Jan 13.
15. Katkhouda N, Mason RJ, Towfigh S, Gevorgyan A, Essani R. Laparoscopic versus open appendectomy. A prospective randomized double-blind study. Ann Surg. 2005;242(3):439-48; discussion 448-50
16. Kehagias I, Karamanakos SN, Panagiotopoulos S, Panagopoulos K, Kalfarentzos F. Laparoscopic versus open appendectomy: Which way to go? World J Gastroenterol. 2008;14(31):4909-14.
17. Williams MD, Collins JN, Wright TF, Fenoglio ME. Laparoscopic versus open appendectomy. South Med J. 1996; 89(7):668-74
18. Mutter D, Vix M, Bui A, Evrard S, Tassetti V, Breton JF, et al. Laparoscopy not recommended for routine appendectomy in men: results of a prospective randomized study. Surgery. 1996; 120(1):71-4.
19. Ignacio RC, Burke R, Spencer D, Bissell C, Dorsainvil C, Lucha PA. Laparoscopic versus open appendectomy: what is the real difference? Results of a prospective randomized double-blinded trial. Surg Endosc. 2004;18(2):334-7. Epub 2003 Dec 29.
20. Champault A, Polliand C, Mendes da Costa P, Champault G. Laparoscopic appendectomies: retrospective study of 2074 cases. Surg Laparosc Endosc Percutan Tech. 2008;18(2):168-72.
21. Cariati A, Brignole E, Tonelli E, Filippi M, Guasone F, De Negri A, et al. Laparoscopic or open appendectomy. Critical review of the literature and personal experience. G Chir. 2001; 22(10):353-7. Review. Italian
22. Fogli L, Brulatti M, Boschi S, Di Domenico M, Papa V, Patrizi P, et al. Laparoscopic appendectomy for acute and recurrent appendicitis: retrospective analysis of a single-group 5-year experience. J Laparoendosc Adv Surg Tech A. 2002;12(2):107-10.
23. Panzera F, Ghisio S, Grosso A, Vigezzi P, Vitale M, Cariaggi RM, et al. Laparoscopic appendectomy. Retrospective analysis of our experience compared with the literature. Minerva Chir. 2000;55(9):577-80. Review. Italian
24. Nana AM, Ouandji CN, Simoens C, Smets D, Mendes da Costa P. Laparoscopic appendectomies: results of a monocentric prospective and non-randomized study. Hepatogastroenterology. 2007;54(76):1146-52.
25. Sauerland S, Lefering R, Neugebauer EA. Laparoscopic versus open surgery for suspected appendicitis. Cochrane Database Syst Rev. 2004;(4):CD001546. Review
26. Tade AO. Evaluation of Alvarado score as an admission criterion in patients with suspected diagnosis of acute appendicitis. West Afr J Med. 2007;26(3):210-2.
27. Subotić AM, Sijacki AD, Dugalić VD, Antić AA, Vuković GM, Vukojević VS, et al. Evaluation of the Alvarado score in the diagnosis of acute appendicitis. Acta Chir Iugosl. 2008; 55(1):55-61
28. Jang SO, Kim BS, Moon DJ. Application of alvarado score in patients with suspected appendicitis. Korean J Gastroenterol. 2008;52(1):27-31. Korean.
29. Andersson M, Andersson RE. The appendicitis inflammatory response score: a tool for the diagnosis of acute appendicitis that outperforms the Alvarado score. World J Surg. 2008; 32(8):1843-9.
30. Sauerland S, Agresta F, Bergamaschi R, Borzellino G, Budzynski A, Champault G, et al. Laparoscopy for abdominal emergencies. Evidence-based guidelines of the European Association for Endoscopic Surgery. Surg Endosc. 2006; 20(1):14-29. Epub 2005 Oct 24.
31. Walsh CA, Tang T, Walsh SR. Laparoscopic versus open appendicectomy in pregnancy: a systematic review. Int J Surg. 2008;6(4):339-44. Epub 2008 Feb 1.
32. Stephens PL, Mazzucco JJ. Comparison of ultrasound and the Alvarado score for the diagnosis of acute appendicitis. Conn Med. 1999;63(3):137-40.
33. John H, Neff U, Kelemen M. Does sonography help in the diagnosis of appendicitis? Helv Chir Acta. 1991;57(5):671-7. German
34. Zoller WG, Kellner H, Schwerk WB. Value of ultrasound in diagnosis of acute appendicitis. Bildgebung. 1996;63(2):78-82. Review. German
35. Amgwerd M, Röthlin M, Candinas D, Schimmer R, Klotz HP, Largiadèr F. Ultrasound diagnosis of appendicitis by surgeons - a matter of experience? A prospective study. Langenbecks Arch Chir. 1994;379(6):335-40. German
36. Kiyak G, Korukluoğlu B, Ozgün Y, Devay AO, Kuşdemir A. Evaluation of Ohmann and Eskelinen scores, leukocyte count and ultrasonography findings for diagnosis of appendicitis. Ulus Travma Acil Cerrahi Derg. 2009;15(1):77-81. Turkish
37. Al-Khayal KA, Al-Omran MA. Computed tomography and ultrasonography in the diagnosis of equivocal acute appendicitis. A meta-analysis. Saudi Med J. 2007;28(2):173-80.
38. Wong KK, Cheung TW, Tam PK. Diagnosing acute appendicitis: are we overusing radiologic investigations? J Pediatr Surg. 2008; 43(12):2239-41.
39. Tarcoveanu E. Tehnici chirurgicale. Iaşi: Ed. Polirom; 2003.
40. Yau KK, Siu WT, Tang CN, Yang GP, Li MK. Laparoscopic versus open appendectomy for complicated appendicitis. J Am Coll Surg. 2007;205(1):60-5
41. Khan MN, Fayyad T, Cecil TD, Moran BJ. Laparoscopic versus open appendectomy: the risk of postoperative infectious complications. JSLS. 2007;11(3):363-7.
42. Pokala N, Sadhasivam S, Kiran RP, Parithivel V. Complicated appendicitis - is the laparoscopic approach appropriate? A comparative study with the open approach: outcome in a community hospital setting. Am Surg. 2007;73(8):737-41; discussion 741-2.
43. Shalak F, Almulhim SI, Ghantous S, Yazbeck S. Laparoscopic appendectomy: burden or benefit? A single-center experience. J Laparoendosc Adv Surg Tech A. 2009;19(3):427-9
44. Martin LC, Puente I, Sosa JL, Bassin A, Breslaw R, McKenney MG, et al. Open versus laparoscopic appendectomy. A prospective randomized comparison. Ann Surg. 1995; 222(3):256-61; discussion 261-2
45. Wullstein C, Barkhausen S, Gross E. Results of laparoscopic vs. conventional appendectomy in complicated appendicitis. Dis Colon Rectum. 2001;44(11):1700-5.
46. François, GF, Giuly J. Cinq mille trente quatre appendicectomies. Résultats. e-mémoires de l'Académie Nationale de Chirurgie 2006;5:61-70.
47. Guller U, Hervey S, Purves H, Muhlbaier LH, Peterson ED, Eubanks S, et al. Laparoscopic versus open appendectomy: outcomes comparison based on a large administrative database. Ann Surg. 2004;239(1):43-52.
48. Kazemier G, in't Hof KH, Saad S, Bonjer HJ, Sauerland S. Securing the appendiceal stump in laparoscopic appendectomy: evidence for routine stapling? Surg Endosc. 2006;20(9):1473-6. Epub 2006 Jul 3.
49. Kouwenhoven EA, Repelaer van Driel OJ, van Erp WF. Fear for the intraabdominal abscess after laparoscopic appendectomy: not realistic. Surg Endosc. 2005;19(7):923-6. Epub 2005 May 12.
50. Bastien J, Leconte P, Leconte D. Reflections on a series of 5,000 appendectomies. Ann Chir. 1986;40(6):368-80. French