Perforated Appendicitis

Abstract

Acute perforated appendicitis is a life-threatening disease because of sepsis. We will discuss the treatment options of acute perforated appendicitis. Is the surgical treatment necessary? How can we manage the patient without surgery in acute phase? Do we need also surgical treatment in the later time? What are the risks of surgery? What are the differences in surgical treatment options between the benign and malign causes of perforation? Do we need a multidisciplinary board to discuss the management options? Do we need laparoscopy always to decide even if the radiologic examination is negative? We can discuss the all conservative and surgical treatment options for acute perforated appendicitis.

1. Introduction

Appendicitis is the most common cause of emergency surgery in the abdominal region caused by inflammation of the appendix, which is connected to the colon in the right lower quadrant [1, 2]. It occurs due to reasons such as infection or tumor [1]. It begins with a feeling of discomfort in the mid-abdominal region and progresses with pain localized to the right lower quadrant [1]. In addition to being more common in young ages and males, its overall incidence is 1 per 1000 persons per year [1, 3]. The presence of rupture complicates the appendix, while the absence of rupture can be defined as uncomplicated [1]. In this section, we aimed to provide up-to-date information on the approach in perforated appendicitis by reviewing the most recent studies in Pubmed and Google Scholar databases.

2. Causes

For many years, delay in the diagnosis or treatment of acute appendicitis was thought to be the cause of perforated appendicitis. In a multicenter study published in 2011, it was shown that delay in in-hospital treatment increases the risk of perforation in adults, and the cut-off time for over 65 s was 12 hours [4, 5]. In a meta-analysis conducted by Van Dijk in 2016, it was revealed that delaying the appendectomy until 24 hours after admission does not increase the risk of perforation [6]. Based on this study, the question of whether perforated appendicitis is caused by a delay in the treatment of appendicitis or arises as a different disease from appendicitis was again brought up for discussion. According to this second view, perforated appendicitis is a different entity from acute appendicitis, and patients already present with perforation findings at the time of admission, and early operation does not eliminate the risk of perforation. Although there are some recent studies showing that delay in the operation may be the cause of perforation, according to the existing literature, 24 hours after hospital admission is accepted as the safe time [7, 8]. Despite there is a study that states that the weakness of the longitudinal and circular muscles of the appendix makes perforation easier due to the anatomical structure of the appendix, this also explains why the tendency to perforation increases in the background of appendiceal neoplasia [9].

3. Diagnosis (blood neutrophil ratios, viewing etc.)

In a randomized controlled study on perforated appendicitis, the definition of perforation in the appendix was: (a) facilities in the abdomen, or (b) a hole in the appendix. In the same study, it was shown that the risk of intraperitoneal abscess development in the presence of purulent or gangrenous appendicitis is less than perforated appendicitis [10]. According to The American Association for the Surgery of Trauma (AAST) staging system, appendicitis is divided into five groups. Grade 1: acute inflamed, intact appendicitis, Grade 2: gangrenous intact appendicitis, Grade 3: perforated appendicitis with local contamination, Grade 4: perforated appendicitis with periappendiceal phlegmon or abscess, and Grade 5: perforated appendicitis with generalized peritonitis [11].

Since the presence of tachycardia is an indication of perforated appendicitis on admission to the hospital, it is recommended that these patients be given priority for early operation. The increase in the time between the onset of symptoms and admission to the hospital is also a risk factor for appendicitis perforation. It is thought that the time spent in the hospital after admission has no effect on appendicitis perforation [12]. In a study on the development of in-hospital perforation after admission to the hospital, it was shown that the risk of perforation increased 4.5 times in patients over the age of 46. The same study shows that leukocyte and neutrophil counts are also directly proportional to perforation [7]. A meta-analysis showed that the neutrophil/lymphocyte ratio alone is useful in both the diagnosis of acute appendicitis and the differentiation of complicated appendicitis. Accordingly, when the cut-off value in the neutrophil/lymphocyte ratio is above 8.8, complicated appendicitis can be predicted with 76.92% sensitivity and 100% specificity [13]. In the case of perforated appendicitis, regardless of the presence of an abscess, the number of WBCs has been shown to be higher than in non-perforated appendicitis [14]. Although there is a study showing that the male gender is associated with perforated appendicitis in the pediatric age group; In another study conducted in the adult age group, no relationship was found between gender and perforated appendicitis [15, 16].

In a multicenter prospective study comparing the use of Magnetic resonance imaging (MR) with the combined use of Computerized tomography (CT) and ultrasonography (USG) in the diagnosis of perforated appendicitis, it was observed that MR did not have any superiority in terms of sensitivity, specificity, positive predictive value and negative predictive value. The use of both MR and combined CT, ultrasonography evaluated about half of the perforated appendicitis as simple uncomplicated appendicitis. In this respect, it should be noted that the positive predictive value of imaging methods is generally low [17]. When ultrasonography is used alone, it is insufficient both in the diagnosis of appendicitis and in the differentiation of complicated and uncomplicated appendicitis. The sensitivity of CT in providing discrimination has been reported between 64 and 88% and specificity between 85 and 99% in different studies [18]. Among the CT findings, the findings with the highest specificity for complicated appendicitis are extraluminal appendicitis, abscess, presence of extraluminal air, contrast involvement defect in the appendix wall, and presence of ileus. Of these findings, only the presence of an involvement defect in the appendix wall has a moderate sensitivity with a rate of 59%. The sensitivity of others is below 50% [19]. It should be noted that CT without contrast has no place in both the diagnosis of acute appendicitis and the diagnosis of complicated appendicitis.

It has been observed that the incidence of appendicitis has increased during the Covid-19 pandemic process [20]. At the same time, it was observed that the symptoms of the patients worsened, and the perforation rate increased compared to the pre-pandemic period. As a result, the pandemic has caused delays in the diagnosis of appendicitis [4, 5].

4. Surgical vs. conservative approach

According to conservative approach, in the presence of appendicitis, treatment is done by intravenous antibiotics and surgery is postponed or not performed at all. While the conservative approach is almost avoided in the presence of generalized peritonitis due to perforated appendicitis, the clinical approach in perforated appendicitis with phlegmon or abscess is still controversial and there is no standard guideline recommendation. In a 2010 meta-analysis comparing the conservative approach to surgery, it was shown that the overall complication rate was lower in patients with the conservative approach. According to this meta-analysis, there were fewer wound infections, abdominal/pelvic abscesses, and ileus in the conservative treatment group [21]. In a recent meta-analysis involving randomized controlled trials, the hospital stay was 1 day shorter in the laparoscopic appendectomy group than in the conservatively followed group. In terms of general complications, it is seen that there is no difference between the two groups [22]. In the absence of equipment and an experienced team for laparoscopic surgery, conservative follow-up with perforated drainage should be preferred instead of open surgery for perforated appendicitis with phlegmon and abscess [23].

5. Open vs. laparoscopic surgery

Today, laparoscopic appendectomy is recommended over open appendectomy wherever there is equipment and an experienced team for both non-complicated and complicated appendicitis. McBurney is the most preferred incision in the open appendectomy method. However, in some patients or in rare cases, median or paramedian incisions may be preferred. In classical three-port laparoscopic appendectomy, left lower quadrant, suprapubic and umbilical trocars are used. A 5 mm umbilical trocar can be used if a 5 mm laparoscope is available. For closure of the appendix stump, linear stapler, simple intracorporeal ligation, extracorporeal prepared loop, or polymeric clip can be used, as well as ready-made industrial Endoloop. In the choice of surgical technique, classical three-port laparoscopic appendectomy should be preferred instead of single-port laparoscopic appendectomy because of both less postoperative pain and less wound infection [23]. In the presence of perforated appendicitis, the rate of conversion to open is significantly higher than those without perforation. In the presence of an abscess, the probability of opening increases 7.4 times, while it is 5.5 times in perforated appendicitis without an abscess [14].

6. Decision to wash or not

In patients who underwent appendectomy due to perforated appendicitis, it was observed that the operation time was prolonged when irrigation and aspiration were compared with only aspiration. However, peritoneal washing does not reduce the development of postoperative intra-abdominal abscess [24, 25]. Moreover, it is thought that peritoneal irrigation increases the risk of intra-abdominal abscess development in the pediatric age group [25].

Anderson et al. showed that irrigation with povidone-iodine after appendectomy moderately reduced the development of an intra-abdominal abscess. In this study, right upper, right lower quadrants and pelvis were washed after appendectomy using povidone-iodine diluted with SF at a ratio of 1:9, and after waiting for 1 minute, they were aspirated [26]. Povidone-iodine wash is promising for the development of intra-abdominal abscess after perforated appendicitis.

7. Whether to use a drain

According to the Cochrane meta-analysis, it is thought that the use of drains in patients undergoing surgery for complicated appendicitis has no effect on preventing intraperitoneal abscess [27]. There are also more recent studies that support this [28]. It has been shown that the use of drains has no effect in terms of wound infection [27]. There is also a study showing that the use of drains increases patient morbidity and health expenditures [29]. In addition, the use of drains causes prolongation of hospital stay [27].

According to a retrospective cohort study, if an intra-abdominal abscess develops due to perforated appendicitis, the length of hospital stay is prolonged and the overall cost increases by increasing hospitalization costs, medication costs and imaging costs [30]. For all these reasons, it is not recommended to place a drain during surgery for perforated appendicitis [23]. However, since there is no sufficient literature data on the use of drains in elderly patients, there are authors recommending drain placement as an expert recommendation [31].

8. Antibiotherapy use

Escherichia coli was the most grown bacteria in culture in both perforated and non-perforated acute appendicitis and was grown in all patients. The second most common bacterium is Bacteroides fragilis. However, Pseudomonas aeruginosa is the second most common bacteria growing in ASST Grade 5, that is, perforation with generalized peritonitis [32]. Considering this situation in the use of postoperative antibiotic therapy, regimens containing at least two drugs are generally preferred to cover these types. In a retrospective study conducted in the pediatric age group in postoperative antibiotherapy, the use of once-daily ceftriaxone and single-dose metronidazole, daily use of 4x1 ampicillin, 3x1 gentamicin and 4x1 clindamycin were compared, and it was shown that the use of single-dose ceftriaxone and metronidazole is a simple and sufficient combination and more cost-effective [33]. Although the use of piperacillin-tazobactam has come to the fore due to its antipseudomonal effect, retrospective cohort studies in the pediatric age group have shown that piperacillin-tazobactam combination is not superior to the ceftriaxone + metronidazole regimen. Therefore, routine use of antipseudomonal antibiotics is not recommended [34, 35]. It is recommended to start ceftriaxone and metronidazole after the diagnosis, before the operation and to continue after the operation [36]. However, it has been shown that the time from hospital admission to the initiation of antibiotic therapy does not increase the perforation rate [7].

9. Discharge

Postoperative discharge criteria of the patient include an afebrile course (<38°C for 24 hours, toleration by eating more than 50% of the normal diet for two consecutive meals, pain control with oral analgesics or ketorolac, benign examination, and mobilization). Prescribing oral antibiotics at discharge is still controversial. In a cohort study conducted in the pediatric population, oral antibiotics were not prescribed if there was no leukocytosis or left shift in the blood drawn on the day of discharge, and it was shown that the rate of surgical site infection or re-admission to the hospital did not increase in these patients [36].

10. What if it’s a mucinous cyst?

When the pathologies of patients who underwent appendectomy with the diagnosis of acute appendicitis were examined retrospectively, the rate of appendiceal tumoral lesions was reported to be between 0.2% and 0.87%. Accumulation of mucinous acid in the abdominal cavity and associated complications may occur in low-grade appendiceal mucinous neoplasia, high-grade appendiceal mucinous neoplasia, or rupture of adenocarcinoma; this condition is defined as pseudomyxoma peritonei [37]. In the case of complicated appendicitis, when interval appendectomy was performed, the rate of appendiceal neoplasm was found to be higher in specimens than in early appendectomy. According to one review, the rate of neoplasia in interval appendectomy is 11%. Of these, 43% were appendiceal mucinous neoplasia, 29% were adenocarcinoma, 21% were neuroendocrine neoplasia, 13% were goblet cell carcinoma, and 20% were adenoma or serrated lesions [38]. The narrow lumen diameter of the appendix leads to premature occlusion of the lumen in the presence of neoplasm. In the presence of mucinous neoplasia, after lumen occlusion, the appendix becomes distended due to mucin and desquamated cells, which increases the tendency to appendicitis and perforation. In a retrospective study involving 3744 patients, the perforation rate was 80% in the presence of appendiceal neoplasm. Weakness of the longitudinal and circular muscle layer of the appendix causes the submucosa and peritoneum layers to be close to each other and the early spread of the lesion. Although perforation provides early clinical diagnosis and intervention, it causes intraperitoneal spread of tumor cells [9]. Some authors recommend a screening program with colonoscopy and CT to detect hidden pathologies, especially in patients over 40 years of age, if the decision to follow-up without surgery in complicated appendicitis is made. Despite this, appendiceal neoplasms rarely show signs before surgery, and therefore they are diagnosed either intraoperatively incidentally or by pathology in the postoperative period [38]. Previously, appendiceal mucinous neoplasms were treated with right hemicolectomy. Over time, it was seen that ileocolic lymph node dissection together with right hemicolectomy in appendiceal mucinous neoplasms with peritoneal metastases did not have a survival advantage and routine right hemicolectomy was abandoned. The concept of radical appendectomy has emerged in the treatment of these tumors, and it has been written that removal of the appendix with adjacent soft tissues and lymph nodes is sufficient. If necessary, it is recommended to switch from laparoscopic to open surgery [39]. In the presence of pseudomyxoma peritonei, the current treatment modality is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). In a recent cohort study, it was shown that HIPEC administered with mitomycin + cisplatin or oxaliplatin + fluorouracil/leucovorin combinations increased overall survival compared to the group that did no [40].