Best Practice & Research Clinical Gastroenterology 28 (2014) 211–224

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Best Practice & Research Clinical Gastroenterology

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Laparoscopic appendectomy: State of the art. Tailored approach to the application of laparoscopic appendectomy? Ramon R. Gorter, MD, Surgical Trainee, PhD Candidate Paediatric Surgery a, b, *,1, 2, Hugo A. Heij, MD, PhD, Professor Paediatric Surgery, Head of Paediatric Surgical Centre of Amsterdam a,1, Hasan H. Eker, MD, Surgical Trainee b, c, 3, Geert Kazemier, MD, PhD, Professor of Surgery c, 4 a

Paediatric Surgical Centre of Amsterdam, Emma Children’s Hospital AMC & VU University Medical Centre, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands Department of Surgery, Red Cross Hospital, Vondellaan13, 1942 LE Beverwijk, The Netherlands c Department of Surgery, VU University Medical Centre, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands b

a b s t r a c t Keywords: Acute appendicitis Laparoscopic appendectomy Open appendectomy

Acute appendicitis is the most common surgical emergency in developed countries. The treatment of acute appendicitis is either open or laparoscopic appendectomy. The latter has gained wide acceptance in the past years, although the debate on the true merits of laparoscopic appendectomy is still on going. Some authors prefer this approach as the gold standard for all patients, but in our opinion a tailored approach is warranted for specific patient groups. In addition, a standardised guideline on the technical aspects is still lacking. In the current article, open versus laparoscopic appendectomy and several technical aspects, such as stump closure, appendix extraction and single incision

* Corresponding author. Pediatric Surgical Centre of Amsterdam, Emma Children’s Hospital AMC and VU University Medical Centre, P. O. Box 22660, 1100 DD Amsterdam, The Netherlands. Tel.: þ31 20 444 2424; fax: þ31 20 444 2135. E-mail addresses: [email protected], [email protected] (R.R. Gorter), [email protected] (H.A. Heij), [email protected] (H.H. Eker), g. [email protected] (G. Kazemier). 1 Tel.: þ31 20 4442424; fax: þ31 20 4442135. 2 Tel.: þ31 251 263920. 3 Tel.: þ31 251 264923. 4 Tel.: þ31 20 4444781. 1521-6918/$ – see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.bpg.2013.11.016

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are discussed laparoscopic appendectomy are being addressed. In the future perspectives we will briefly discuss the third ‘newly’ introduced antibiotic treatment. Ó 2013 Elsevier Ltd. All rights reserved.

Introduction Acute appendicitis is the most common acute gastrointestinal disorder requiring surgery and hospitalization [1]. The occurrence of appendicitis is rare below the age of one year, with the peak incidence around adolescence [2]. In most cases an appendectomy is performed as surgery is considered to be the gold standard. Approximately 16.000 appendectomies are performed annually in the Netherlands [3,4]. Although the lifetime risk in the Western world of acute appendicitis is respectively 7% and 9% for females and males, the risk of undergoing an appendectomy is much higher: 23% and 12 % respectively [4]. This difference reflects a still high number of unnecessary appendectomies and incidental appendectomies. To remove the appendix, two options are available: open appendectomy (OA) through a gridiron incision; the latter first described by McBurney in 1894 and laparoscopic appendectomy (LA) first described by de Kok in 1977 and later by the gynaecologist Semm in 1983 [5–7]. Nowadays an unequivocal guideline regarding the approach for appendectomy is still lacking. The choice between OA and LA depends on the surgeon’s preference and expertise. No uniform protocol for the technique of LA is yet available [8–10]. Several (technical) aspects should be considered in the choice for the operative technique, which will be addressed further in this article. As shown in Table 1, guidelines on the aspects of laparoscopic appendectomy do not make recommendation concerning these aspects (Table 1) [8–10]. Laparoscopic appendectomy (LA); is it always the best choice? After the laparoscopic revolution in the 1980’s, the discussion about the value of LA has yet to close. In most developed countries, LA has gained wide acceptance and currently is the preferred operative technique [11]. Advantages of LA are reported to be less postoperative pain and earlier recovery, less postoperative complications, better cosmetic outcomes and its value for diagnostic opportunities (with inspection of the entire abdomen) [8–10]. During an open procedure through a gridiron incision, common surgical sense mandates appendectomy, even when the appendix is not inflamed (because of the scar that signifies appendectomy), while with laparoscopy, it is only recommended to remove the appendix when inflamed [10,12]. In 2010 Sauerland et al performed a Cochrane review including 67 studies, dated until 2010 comparing LA to OA [13]. They showed that superficial surgical-site infections (SSI) were significantly more associated with an OA (OR 0.43 (0.34–0.54)), while the chance of an intraabdominal abscess (IAA) was increased nearly twofold after LA (OR 1.77 (1.14–2.76)). Additional benefits of laparoscopy in this study were less postoperative pain, shorter hospital stay and earlier return to normal activity, although it is mentioned that the studies included for analysis showed significant heterogeneity. The authors state that the overall effects of LA are impressing and LA should be the

Table 1 Guidelines for LA [8–10]. SAGES [8]

IPEG [9]

Guideline The Netherlands [10]

Number of trocars Appendiceal Stump closure

3 –

– –

Extraction of the appendix

Port extraction (no recommendation)

3 Endo-loops, Endostapler, Endoscopic sutures, Extracorporeally Umbilical port extraction or retrieval bag

–

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preferable approach in centres where surgical expertise and equipment is available. However a remark is made that this recommendation may not be applicable in cases of gangrenous or perforated appendicitis [13]. Inconsistent results about the possible superiority of LA are still being published. Ingraham et al published an multicentre study, including over 30,000 patients [14]. LA was associated with less SSI, wound disruption and sepsis or septic shock and shorter hospital stay [11]. Kouhia et al found that LA resulted in less postoperative complications and earlier return to work in their long-term follow up study [15]. Tzavaros et al however performed an RCT and they only identified a significant difference in operating time, while morbidity, mortality, hospital stay, pain and return to normal activities were comparable to OA [16]. Khalil et al randomised 160 patients and found no difference in postoperative complications but laparoscopy was associated with less pain [17]. It is remarkable that, whereas the minimally invasive approach for cholecystectomy is generally accepted without too much scientific evidence, the debate about the approach for appendectomy still continues. In our opinion, the added value of LA does exist for specific indications and patient groups. For instance, the diagnostic advantage is evident. Criticism on the above mentioned studies is that the results are obtained from the general population while in our opinion, the treatment strategy of appendicitis should be individualised. Nowadays we see more and more RCTs focussing on specific patient groups [18–23]. We have conducted a literature search trying to identify valuable metaanalyses published after the meta-analysis in 2010 by Sauerland [13].The search strategy that has been added in Addendum #1 revealed nine articles (Table 2) [24–32].

Specific patient groups Complex appendicitis in adults Three meta-analyses in the general population have been published after Sauerland’s review [13,29–31]. All three authors conclude that LA has considerable advantages over OA in terms of postoperative complications and recovery. In the opinion of all three authorgroups, LA should be the treatment of choice as none of the studies reported a higher incidence of IAA after this procedure [29– 31]. These findings are in contrast to the findings of Sauerland et al [13]. Possible explanations for the different findings could be found in the heterogeneity of the studies included, the definition of IAA, different laparoscopic techniques or selection bias. The risk of developing an IAA after LA is related to

Table 2 LA versus OA (overview of the meta-analyses) [24–32]. Study population

Overall Othani (2012) [30] Li (2011) [31] Liu (2010) [29] Elderly Southgate (2012) [27] Children Markar (2012) [24]

Obese Woodham (2012) [25] Markar (2011) [26] Complicated Markides (2010) [32] Pregnancy Wilasrusmee (2012) [28]

Studies included

Outcome

Hospital stay (days)

SSI

IAA

LA: OR 0.46 (0.34–0.62) LA: OR 0.45 (0.34–0.59) LA: OR 0.51 (0.36–0.73)

No difference No difference -

LA: 0.79 (1.06 to 0.52) LA: 0.6 (0.85 to 0.36) LA:0.82 (0.93 to 0.70

No difference

No difference

LA: 0.51 (0.64 to 0.37)

Simple: No difference Complex: LA OR 0.42 (0.27–0.67)

Simple: No difference Complex: LA OR 1.32 (1.15–1.5)

Simple: LA: 1.18 (1.61 to 0.74) Complex: LA: 0.67 (0.95 to 0.4)

7 (2428) 6 (2309)

LA: OR 0.34 (0.16–0.66) No difference

No difference No difference

Shorter in LA group LA: 1.26 (2.36 to 0.16)

12 (16516)

LA: OR 0.43 (0.34–0.55)

No difference

LA: 1.05 (1.56 to 0.53)

11 (3415)

No difference

–

LA: 0.49 (1.76 to 0.78)

39 (5896) 44 (5292) 16 (3261) 6 (15852) 18 (73150)

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the complexity of the appendicitis [24,33–35]. The hypothesis for this increased risk is threefold. Firstly the insufflation of carbon dioxide can lead to spread of purulent fluid throughout the abdomen making it a more generalised abdominal problem. Secondly, the dissection of the appendix is performed intraabdominally with the potential risk of contamination. Thirdly, suction after irrigation of purulent fluids may contribute to spreading of microorganisms in the abdominal cavity, this might even be associated with a higher IAA rate [24,36,37]. In case of complex appendicitis, it has been shown in a systematic review that the rate of IAA after LA was not increased [32]. LA is associated with shorter length of hospital stay and earlier return to normal activities, which may reflect the benefits of minimally invasive surgery. We need to keep in mind however that the clinical relevance of an overall reduction ranging from 0.6 to 0.82 days is low [29–31]. Pregnancy Appendicitis during pregnancy is most common in the second trimester [28]. The most important risk of appendectomy during pregnancy is foetal loss. It has been reported that foetal loss usually occurs in women with complex appendicitis during the first trimester [28,38]. Although in 2008 Walsh et al reported that the risk of foetal loss en preterm delivery was comparable among the three trimesters [39]. Wilasrusmee et al in a review of the literature reported a significantly higher risk of foetal loss after laparoscopy, which was almost twofold compared to OA [28]. This outcome was mainly determined by the outcomes of the study of McGory et al [40]. When this study was excluded from analysis, no significant differences could be found [28,40]. The effects of increased intra-abdominal pressure and the effect of carbon dioxide during pregnancy still remain unclear. Increased intraabdominal pressure may lead to impaired venous return and subsequently maternal hypotension [41,42] and carbon dioxide may lead to foetal acidosis [43], which could not be supported in a later study [44]. Although the conclusion from these authors is that LA results in an increased risk of foetal loss, others emphasize the need for better data and wonder if pregnancy is a true contraindication for laparoscopy [21,45]. In our opinion LA is feasible in the first and second trimester. In the third trimester LA can be cumbersome because of space occupied by the enlarged uterus. The obese and the elderly Two groups that might benefit from the laparoscopic approach particularly are obese and elderly patients. These patient groups are at higher operative risk due to the associated comorbidities. Southgate et al found in adults over 60 years old that the overall postoperative mortality and morbidity was significantly lower in the LA group [27]. They state that this patient group benefits more from a less invasive procedure [27]. Both meta-analyses in the obese patients also favour LA, reducing the length of hospital stay and postoperative complications [25,26]. However conclusion from these meta-analyses should be interpreted with care as the included studies are limited by the quality of the available studies i.e. comparative studies, non-blinded RCTs and the heterogeneity of the included studies. However, until date this is the highest level of evidence yet available to us, although we emphasize the requirements of high-powered RCT focussing on these specific patient groups. Children In children, LA is still not widely accepted as the standard approach. Differences between children and adults preclude extrapolation of adult data. Markar et al have recently published a review of the available literature and performed a pooled analysis [24]. Their results showed no significant differences in terms of SSI, IAA and overall complications for children with simple appendicitis with a significant shorter hospital stay in favour of LA. In case of complex appendicitis, although LA was associated with significantly fewer overall complications, SSI and reduction in hospital stay, it was also associated with a higher risk of IAA and longer operative time than OA [24]. Conclusion In our opinion the discussion of the preferred operative technique for acute appendicitis remains open and definitive conclusions are hard to make based on the available data. For diagnostic purposes,

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laparoscopy is recommended in case of an inconclusive diagnosis preoperatively. We can state that LA is as good as OA and might have several advantages, especially in specific patient groups, like the obese and the elderly. We recommend LA when the experience and equipment is present to perform LA especially in case of an inconclusive diagnosis preoperatively.

Single incision laparoscopic appendectomy (SILA): moving forward or wanting too much? After the introduction of LA, numerous modifications in order to further reduce surgical trauma have been proposed. Nowadays, the next evolution seems to be ‘scarless’ surgery. It was Pelosi in 1992 who reported the first LA through a single incision [46]. The fundamental of SILA is the single incision, although in general three techniques have been described: [47,48]  Unassisted SILA: Single skin with single/multiple facial incisions with placement of either a special or improvised (glove) single port device with special or conventional laparoscopic equipment [47,49]  Assisted SILA: Any technique with a single skin incision with additional use of percutaneous sutures or wires. [47,49]  ‘Hybrid’ approaches: Exteriorised appendix using a single incision with laparoscopic assistance and subsequent division using a conventional open technique [47,48,50–52] The benefits of SILA over LA are reported to be reduced surgical trauma, shorter hospital stay, avoidance of injury to the bladder and inferior epigastric vessels, fewer complications, less postoperative pain and better cosmetic results [48,53–57]. It is considered a good and safe technique [48,53–57]. Critics however raise their concerns about presumed higher costs, longer operative time, higher complication rates and technical difficulties [58]. In addition concern exists with the use of SILA in specific patient groups, like obese patients, as the increased distance to the target organs from the umbilicus limit its use [51,58–60]. In 2011 Rehman et al published a Cochrane review, comparing SILA with conventional LA. Although their search yielded 77 articles up to December 2010, none were RCTs, and no solid conclusions could be drawn from this review [48]. Since then, three reviews have been published focussing on SILA of which two also performed a pooled analysis [56,61,62]. In 2012 Gill et al performed a systematic review with pooled analysis of nine adult studies (seven retrospective, two prospective non-randomised) [61]. No differences were detected between SILA and conventional LA in terms of operative time, length of hospital stay, overall complications, secondary bowel obstruction, SSI rate, IAA rate, and postoperative pain. Although results should be interpreted with care, the authors conclude that SILA is comparable to conventional LA [61]. These results are supported by the latest review from Pisanu et al who also could not detect any significant differences [56]. No analysis was conducted on the cosmetic effects as only two studies included reported their results [56] Pisanu et al conclude that SILA is a good alternative for conventional LA, however it is noted that there are no real observed benefits of SILA [56] These reviews are limited by the low-quality studies included leading to heterogeneity and also the possibility of selection, allocation, interventional bias. RCTs until then were scarce. We have repeated the search strategy of the Cochrane review using the pubmed database, identifying four RCTS (Addendum #2) [48,52,63–65]. To extent our search, we also screened the reference lists of the three reviews [56,61,62]. Another potential RCT was identified although due to lack of adequate description of the randomization process and no sample size calculation, we decided to exclude this study [66] Characteristics of the studies are displayed in Tables 3 and 4. We want to point out three things. First SILA techniques are comparable to conventional LA. Not even was there a significant difference in postoperative pain in the meta-analyses. Of the RCTS only Frutos et al found less postoperative pain in the SILA group [63–65]. Some studies even reported more postoperative pain with SILA due to the longer fascia incision and skin irritation due to insertion of multiple surgical instruments through one incision [67,68]. Cosmetic results were impossible to meta-analyse, although it has been reported that SILA is associated with better cosmetic results [64–66]. Conclusions

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Table 3 Characteristics of four randomized controlled trials [52,63–65]. Author

Age (range)

Number of cases

Type of procedure

Blinded

Primary outcome

Cosmetic results included?

Peter [52] Lee [63]

Children (–) Adults (16–78)

N ¼ 360 N ¼ 229

‘Hybrid’ SILA unassisted

No No

No No

Teoh [64] Frutos [65]

Adults (–) Children þ adults (12–71)

N ¼ 195 N ¼ 184

SILA unassisted SILA unassisted

Yes No

SSI Postoperative complications Overall pain score Postsurgical complications

Yes No

concerning cosmetic results should be interpreted with care, as most authors only report the short term results and results are related to age, sex, ethnicity, socio-economic status and expectations. Secondly it has been reported that SILA is associated with increased costs although the differences disappeared when staplers were excluded from the charges [52]. Due to the fact that operating time and length of hospital stay are equal in both groups, the higher cost of SILA is solely related to higher cost of the surgical instruments used [56,61]. Interestingly when no specially designed surgical device or instruments are used, the cost of SILA appears to be equal to conventional LA [61,69]. Thirdly, several SILA techniques have been described in the literature. Only one literature review reports that SILA unassisted techniques were associated with the highest intraoperative and postoperative complication rates [47]. Further reduction of trauma to the abdominal wall could be achieved by use of NOTES (natural orifice translumenal endoscopic surgery) to perform appendectomy. Two orifices are commonly mentioned in the literature; transgastric and transvaginal [70,71]. The latter is associated with less postoperative analgesia and more rapid return to normal activity level with no dyspareunia complaints and comparable pre- and postoperatively sexual function [71]. Reports however in the literature are scarce, only on specific patients, its feasibility in children is highly doubtful and in our opinion due to its technological limitations, learning curve will not be generally accepted. In our opinion, there is not enough evidence in literature supporting superiority of SILA or NOTES appendectomy compared to conventional OA or LA. Stump closure: to staple, loop or clip? A crucial part of the LA is to ensure adequate closure of the appendiceal stump. Semm’s treatment of the appendiceal stump consisted of an endoligature with a surgical knot combined with a purse string suture [7]. This approach requires not only skill, experience, and time, but may also lead to the development of mucocele and anatomical changes of the caecum affecting a possible later colonoscopy [72]. Various techniques to ensure adequate stump closure nowadays entail, among

Table 4 Results from the four RCTs on SILA versus conventional laparoscopic appendectomy (CLA) [52,63–65]. Author

Peter [52] Lee [63] Teoh [64] Dolores Frutos [65]

Operative time in minutes Mean  SD SILA CLA SILA CLA SILA CLA SILA CLA

35.2 29.8 43.8 35.8 63 60.2 38.1 32.1

       

14.5 11.6 21.3 18.9 27.2 31.7 13.5 12.4

SSI N (%)

IAA N (%)

Visual analogue pain score (24 hours after operation)

Length of hospital stay (in hours

6/180 (3.3%) 4/180 (1.7)% 6/116 (5.1%) 12/113(10.6%) 8/98 (8.1%) 5/97 (5.2%) 0/91 0/93

0/180 1/180 (0.6%) 6/116 (5.1%) 2/113 (1.8%) 4/98 (4.1%) 3/97 (3.1%) 0/91 0/93

–

22.7 22.2 72 72 84.7 76.8 18.9 21.3

2.2 2.3 5.6 5.1 2.8 3.8

   

2.2 2.2 1.6 1.8

 6.2  6.8

   

70.1 56.6 9.8 11.7

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them endo-loops, endostaplers and metal/non-metal clips [73–94]. All of these have their own advantages and disadvantages. A recent survey performed amongst German surgeons demonstrated that in children endo-loops were still the most commonly used (57%) with endostapler on the second place with 39% [11]. Endo-loops versus endostapler Endo-loops are commonly used for appendiceal stump closure. In the early days of LA this was the preferred approach [73]. An alternative approach for this procedure is the endostapler. Possible disadvantages of endo-loops are a higher incidence of rupture of the appendix during manipulation, slippage of the endo-loop, and IAA due to exposure of the remaining contaminated mucosa to the abdominal cavity [74–76]. Endo-loops are also not usable when the base of the appendix is heavily inflamed. In addition the placement and tightening of the endo-loop around the appendicular base requires experience in order to avoid local necrosis or even transsection [74,76,77] Even though it has been suggested that routine placement of two loops at the appendiceal stump is mandatory [78], Beldi et al demonstrated in an RCT that appendiceal stump closure can safely be done with one endo-loop [77] This is comparable to the technique of the OA, where the stump is closed with one single ligature. Endostaplers on the other hand can lead to small bowel obstruction when staples are left behind and they are more expensive. However their use requires less dexterity, and they are safer when the base of the appendix is heavily inflamed or perforated [74,79,80]. To answer which closure device should be used preferentially, two meta-analyses have been conducted. In 2006, Kazemier et al published a systematic review (including four RCTs) and found that the operating time was reduced when using stapler routinely and SSI and small bowel obstruction were significantly less when endostapler was used with no difference in the rate of IAA in contrast to the findings of Beldi [74,77]. The authors concluded that despite the higher cost, endostapler should be preferred. In a later review by Sajid et al however, including five RCTs, no significant differences between endostapler and endo-loops were found in terms length of hospital stay, peri-operative complications and IAA formation, although they too showed significantly longer operating time with endo-loops [80]. They concluded that endo-loops may be used safely and are preferred to secure the appendicular stump, with a remark that it is unclear if endo-loops can be used in all stages or types of appendicitis [80]. Even though Sajid et al included an extra RCT, it must be mentioned that both authors draw contrary conclusions [74,80]. This might be due to the poor-tomoderate quality of the included studies as stated by both authors [74,80]. Reports after the metaanalyses are still mostly consistent of non-concurrent cohort studies of prospectively acquired data. When both approaches are safe with comparable complication rate, cost-effectiveness is of additional value and future studies should focus to finally elucidate this question. In children, three studies need extra attention. Miyano et al described two prospective cohort studies in children with both uncomplicated and complicated appendicitis. Although the used technique was according to personal preference leading to selection bias, it showed that both techniques were comparable in terms of operating time, hospital stay and postoperative complications, with endoloops being cheaper [81,82]. These findings were supported by a retrospective study from Safavi et al [83]. They even found a higher rate of IAA after endostapler, which is in contrast to the earlier mentioned studies [74,77,83]. Endoclips In 1991, Cristalli described their technique of appendiceal stump closure using metal clips [84]. This method was considered more simple and quicker than the intracorporeal suture placement. Although its use is limited by the severity of the inflammation and the diameter of the base of the appendix, it is considered a viable alternative for endo-loop placement [84]. Metallic clips for stump closure however are still not generally accepted for stump closure. In recent years it has been shown, in small cohort studies, that metallic clips can be used safely to ensure an appendiceal stump closure, reducing costs [85,86]. Two recent RCTs have shown the benefits of metallic clips compared to the intracorporeal knot-tying suture in terms of significantly shorter operation time, lower costs and comparable

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postoperative complication rates (SSI and IAA) [87,88]. When using endoclips, the surgeon should keep in mind that their efficacy is limited with larger diameter appendices and when the appendiceal base is heavily inflamed. There has to be a zone of healthy tissue at the base to place the clip safely [89]. Secondly, the possible difficulties when applying metallic clips such as rupture of the appendix due to twisting, partial or complete transection, and slippage of a clip should be taken into consideration [85]. An alternative for metallic clips are non-absorbable non-metallic clips which are commonly used during nephrectomy to secure the ureter and vascular structures [90,91,95]. Several studies compare non-metallic clips with another technique of appendiceal stump closure [89–94]. In all six studies, the authors conclude that use of non-absorbable clips shortens operating time, results in comparable complication rates, and reduces costs compared to other stump closure techniques [89–94]. Although the same remarks need to be made as for the metallic clips, it appears to be that non-absorbable clips are more generally accepted, mostly because of presumed better grip on the tissue and less risk of slippage. In most cases, although the literature is rather inconsistent, there appears to be a tendency to the placement of a single clip [89,92,93].

Conclusion Based upon the available literature endo-loops, endostapler and clips can all be used to ensure adequate stump closure in acute appendicitis, although each technique has its own benefits and hazards. The technique of appendiceal stump closure should be left to the discretion of the surgeon. In our opinion when money plays no part in the decision making or when the base of the appendix is involved in the inflammation, appendiceal stump closure should be done with endostapler. High quality evidence for the superiority of either of the techniques however is lacking as literature shows significant heterogeneity both in results and methods of stump closure. Extraction of the appendix; is an endobag always necessary? The main advantage of LA is the decreased incidence of SSI [13]. This is possibly due to the fact that the abdominal wall is not exposed to the inflamed appendix and the small incisions [12,13]. Protection of the abdominal wall can be done in several ways. An endobag can be introduced through a 10–12 mm port, opened in the abdomen and after placement of the appendix closed and removed [96]. A major disadvantage of this device is its costs. Other cheaper alternatives have been proposed [97–99]. Bhandakar et al introduced a technique in which the appendix, after its division, is grasped by an instrument inserted through the supra-umbilical trocar and pushed into the trocar at the umbilicus. As the appendix passes through the flap valve, the appendix is removed from the umbilical trocar using a Kelly clamp [97]. They make no comment on the incidence of SSI associated with this technique. They do however recognize its limitation as this method is only suitable for thin non-fragile appendices [97]. Saad et al introduced the fisherman’s technique, entailing the placement of a third endo-loop around the appendix, leaving it uncut, and grabbing the endo-loop with an instrument retracting it in the umbilical port [98]. They state that all appendices can be removed using this technique without any chance of fragmentation and subsequently abdominal contamination [98]. Two articles use a homemade endobag, which consist of a piece of a surgical glove [99]. A recent nationwide survey in Germany showed that the majority of surgeons removes the appendix through the port, with only 18% using an endobag [11]. To our knowledge there is no study investigating the superiority of either one of the techniques in terms of the incidence of SSI and cost-effectiveness. In conclusion in our opinion the manner of appendix extraction during LA should respect the idea of abdominal wall protection. Currently no evidence is available in literature to support routine use of an endobag. To evaluate different extraction techniques, an RCT with cost-effectiveness analysis should be conducted. Until then the manner of extraction should be at the discretion of the surgeon, based upon the size of the appendix and the severity of the inflammation. The costs associated with the use of devices should be kept in mind. We recommend the usage of an endobag when the appendix does not fit into one of the trocars.

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Future perspectives Recently an alternative to the surgical treatment of acute appendicitis has been reintroduced; antibiotic treatment. Due to evidence from epidemiological, radiological and pathological studies, acute appendicitis is no longer considered to be an irreversible progressive disease. Rather it appears that acute appendicitis varies along a spectrum ranging from simple appendicitis to complex appendicitis [100–102]. This has led to the proposal of antibiotic treatment for acute appendicitis. Hansson et al provoked many reactions with his RCT in 2009 [103] Nowadays several meta-analyses have been published comparing initial antibiotic treatment with an immediate appendectomy [104–106]. The general conclusion is that the overall efficacy of antibiotic treatment is lower compared to appendectomy, although initial antibiotic treatment appears to be safe and associated with fewer complications [104–106]. In case of complex appendicitis (with the formation of an appendicular abscess or phlegmone) two meta-analyses have demonstrated the benefits of non-surgical treatment (consisting of antibiotic treatment combined with percutaneous drainage procedures) compared to a direct appendectomy in terms of fewer complications, SSI and IAA [107,108]. In children no RCT has been conducted yet. In our opinion, treatment of acute appendicitis will evolve over time. The type of appendicitis, its clinical presentation and co-morbidity of the patient will all influence the choice of treatment strategy. Antibiotic treatment alone can be the initial treatment choice for those patients with simple appendicitis or those with complex appendicitis and a well-defined appendicular abscess or phlegmone, provided that the clinical condition of the patient allows this. In cases of generalized peritonitis, in septic patients or those with significant co-morbidities, the clinical condition might still mandate direct surgical intervention.

Summary LA is safe and effective to treat acute appendicitis. Both LA and OA can be used, although LA might be especially beneficial in certain specific patient groups, for instance, obese and elderly patients. Even though SILA was introduced as the new approach for LA, results from the literature fail to show clear advantage. Stump closure during LA can be performed safely by endo-loops, endostapler or endoclips. Endostapler are safe but expensive. In cases of severe inflammation and involvement of the appendicular base, endostaplers should be preferred. For the extraction of the appendix the general principle of protection of the abdominal wall needs to be followed and this can be done with either an endobag or by extraction through a trocar. In the future, treatment of appendicitis will be personalized. Appendectomy might only be reserved for those patients not responding to antibiotic treatment, presenting with generalized peritonitis or who are septic on presentation and other specific patient groups.

Practice points  Both LA and OA are safe and effective in treating patients with acute appendicitis, but LA appears to have more benefits in obese and elderly patients  SILA appears to have no merits over conventional LA  Endo-loops, endostapler and endoclips can all be used to achieve adequate appendiceal stump closure, although it is recommend to use endostapler in case of severe inflammation and when the base in involved  Extraction for the appendix during LA should follow the principle of abdominal wall protection.  Initial antibiotic treatment is safe and associated with less complications, although its efficacy is lower than an appendectomy

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Research agenda  The benefits of LA compared to OA in specific patient groups needs to be evaluated  The possible less postoperative pain and better cosmetic outcomes of SILA should be evaluated  Cost-effectiveness of the closure devices and method of appendix extraction should be investigated  The safety and effectiveness of initial antibiotic treatment for acute appendicitis should be evaluated in specific patient groups i.e. children, obese patients

Conflict of interest statement None. Addendum #1 Search strategy for meta-analysis focussing on laparoscopic versus open appendectomy. Database: Pubmed database. Search date: 17th of May 2013. Key words:  (Open or laparoscopy or laparoscopic) AND  (Appendectomy or appendicectomy) AND  (Review or Pooled analysis or Systematic review or Mata-analysis) Identification of 176 studies. Analysis of Title and Abstract on: Inclusion criteria were: -

Meta-analysis/pooled analysis Comparing open versus laparoscopic appendectomy Full text available English written

Identification of nine included meta-analysis. Addendum #2 Search strategy for RCT focussing on single incision laparoscopic appendectomy versus conventional laparoscopic appendectomy. Database: Pubmed database. Search date: 17th of May 2013. Key words  (Appendectomy or Appendicectomy or Appendicitis) AND  (Laparoscopy or Laparoscopic) AND  (Single port or Single incision or Single site OR One port OR Incisionless OR Scarless) AND Identification of. Analysis of Title and Abstract on: 19. Inclusion criteria were: - Randomised Controlled Trial - Comparing SILA versus conventional laparoscopic appendectomy

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-

221

Full text available English written Adequate description of randomisation process Sample size calculation

Identification of four RCTs.

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