Introduction

Since Reginald H. Filz, anatomopathologist at Harvard, first described the disease and first introduced the term appendicitis in 1886 (1), acute appendicitis remained the most common general surgical emergency seen in most hospitals (2) and the most common cause of acute abdomen requiring surgical intervention (3). In industrialized countries, individuals have a 7% lifetime risk of developing appendicitis, with the highest frequency occurring at ages from 10 to 30 years. The risk gradually decreases until age 50, when it stabilizes (4).

Diagnosis

Typical uncomplicated cases of acute appendicitis are easy to diagnose and treat. Typical cases present classically with para-umbilical pain (visceral pain) migrating to the right lower quadrant of the abdomen (RLQ). Pain usually is associated with nausea, vomiting and low-grade fever.

Localized irritation and inflammation of the peritoneum results in pain with cough (Dunphy’s sign), tenderness and muscle guarding on palpation in the RLQ over McBurney’s point and rebound tenderness elicited by deep palpation with quick release (Blumberg sign). Unfortunately, 20-33% of the patients suspected of having acute appendicitis present with atypical findings (5-7).

Diagnostic difficulties

Accurate and timely diagnosis of atypical cases remains clinically challenging and one of the most commonly missed problems in the emergency departments. Precaution appendectomy or misdiagnosis of presumed appendicitis is an adverse outcome that leads to unnecessary surgery (8), serious interruption of patient’s daily activities and considerable waste of hospital resources (9) in addition to the recognized postoperative complications. On the other hand, delay in diagnosis may increase the morbidity and cost.

Statistics reported that 1 of 5 cases of appendicitis is misdiagnosed; however, a normal appendix is found in 15-35% of patients who have emergency appendectomy (10-12).

Variation in the position of the appendix, age of the patient and degree of inflammation make the clinical presentation of appendicitis inconsistent. Females during childbearing age present diagnostic difficulty and the incidence of misdiagnosis is increased for women of the reproductive age (13).

Variable Anatomical Positions

The base of the appendix is fairly constant and is located at the posteromedial wall of the caecum about 2.5 cm below the ileocecal valve where the taeniae converge, whereas the position of the tip varies. It is retrocaecal in 65% of the patients, pelvic in 30%, and paracaecal or post-ileal/pre-ileal in the remaining 5%.

Inflammation of a retrocacecal appendix is difficult to diagnose. Rigidity is often absent and even on deep pressure, tenderness may be lacking (silent appendix), the reason being that the cecum distended with gas prevents the pressure exerted by the hand from reaching the appendix (14). The clue to diagnosis is hip flexion that results from irritation of the psoas muscle by the inflamed appendix. Hyperextension of the hip may induce abdominal pain (psoas sign).

Inflammation of a pelvic appendix associated with early diarrhoea results from the contact between the inflamed appendix and the rectum. When the appendix lies entirely within the pelvis, there is usually complete absence of abdominal rigidity and often tenderness over McBurney’s point is lacking as well. Rectal examination is crucial for the diagnosis. Spasm of the obturator internus muscle can be sometimes demonstrated by flexion and internal rotation of the hip (obturator sign).

Postileal appendicitis presents a great diagnostic difficulty because the pain starts in the right lower abdomen and remains there (not migratory) and is usually associated with diarrhea leading to confusion with enterocolitis.

Inflammation of a maldescended or subhepatic appendix is sometimes mistaken as acute cholecystitis.

Extreme Age

Diagnostic Accuracy

Accuracy of diagnosis entitles recognition and removal of the inflamed appendix prior to perforation with a minimal number of negative appendectomies.

Many studies investigate the accuracy of clinical diagnosis, and the role of imaging techniques and laparoscopy in improving the diagnostic accuracy of the disease with conflicting results.

Clinical Diagnosis

Despite technologic advances, the diagnosis of appendicitis is still based primarily on the patient's history and the physical examination (15). It has been estimated that the accuracy of the clinical diagnosis of acute appendicitis is lying between 76% and 92%, with values correlating with the surgeon’s experience (18).

Over the years various clinical scoring systems (some of them computer assisted) have been ^{used, and, although their clinical benefits have varied, most reports describe some improvement in clinical performance with their use. The greatest beneficiaries may be junior staff, whose diagnostic accuracy increases from 58% to 71% (19).}

Alvarado scoring system is the most famous scoring system used to help with the clinical diagnosis of acute appendicitis and is very easy to apply (20). (Table 1)

Figure 1

Table 1: Alvarado scoring system

The score is based on three symptoms, three signs and one investigation as shown in Table 1. The classic Alvarado Score included left shift of neutrophil maturation (score 1) yielding a total score of 10, but Kalan et al. (18) omitted this parameter which is not routinely available in many laboratories, and produced a modified score. Patients with a score of 1-4 are considered unlikely to have acute appendicitis, those with a score of 5-6 have a possible diagnosis of acute appendicitis, not convincing enough to have urgent surgery, and those with score of 7-9 are regarded as probably having acute appendicitis.

Application of Alvarado scoring system in diagnosis of acute appendicitis can provide a high degree of positive predictive value and thus diagnostic accuracy. The positive predictive value of Alvarado score is reported as high as 85.3%, 87.5% and 87.4% in many studies (20-22).

The accuracy of clinical diagnosis of suspected cases of acute appendicitis can further be improved by repeated clinical examination and adoption of what is called active observation. Patients under active observation are kept fasting and re-evaluated for progression or regression of their symptoms and signs by repeated clinical examination every 2-3 hours (preferably by the same physician) and repeated estimation of while blood count and C-reactive protein.

Active observation confirms intraperitoneal pathology which requires surgical intervention or further investigation in a small group of patients. It also excludes those found to have medical illness, e.g., UTI. In 30-40% of patients, a firm diagnosis is not possible; those patients can benefit from a further period of active observation with or without further investigation depending on whether the symptoms are persisting or improving. Active observation results in a substantial fall in negative appendicectomy rate (9) and is widely considered as safe and effective approach to the management of patients with equivocal features of acute appendicitis (23).

Laboratory investigations

The white blood cell (WBC) count is elevated (more than 10 x10⁹ per L) in 80 percent of all cases of acute appendicitis (24). ^{Unfortunately, the WBC is elevated in up to 70 percent of patients with other causes of right lower quadrant pain (25). Thus, an elevated WBC has a low predictive value. Serial WBC measurements (over 4 to 8 hours) in suspected cases may increase the specificity, as the WBC count often increases in acute appendicitis (15). In addition, 95 percent of patients have neutrophilia (26).}

Many studies evaluated the role of C-reactive protein in diagnosis of acute appendicitis with conflicting results. Although the predictive value of high C-reactive protein in patients with acute appendicitis is low, current literature would suggest that a normal pre-operative CRP level is not likely to be associated with acute appendicitis.

An elevated C-reactive protein level in combination with an elevated WBC count and neutrophilia are highly sensitive (97 to 100 percent). Therefore, if all three of these findings are absent, the chance of appendicitis is low (27).

Ultrasound

Graded compression Sonography is relatively inexpensive, rapid, non-invasive, ^{and requires no patient preparation or contrast material administration. Unfortunately, graded compression sonography is operator-dependent and requires a high level of skill and expertise. Sonography is also a dynamic investigation, and photographs of sonographic images cannot be reliably re-evaluated (28).}

An inflamed appendix appears on ultrasound as a non-compressible tubular structure, more than 6 mm in diameter, with a thickened wall (figures 1&2).

Ultrasonography may significantly improve the diagnostic accuracy in patients with suspected acute appendicitis and should be performed in some patients in whom the clinical diagnosis is equivocal. The overall sensitivity, specificity and accuracy of ultrasonography in the diagnosis of acute appendicitis were 78%, 92% and 87%, respectively (29).

Another limitation of ultrasound in the diagnosis of acute appendicitis is the fact that patients cannot be safely be sent home after a negative result unless there are good clinical grounds for their discharge (2).

Ultrasound is helpful in young females in diagnosis of some gynecological conditions like torsion of ovarian cyst and ectopic pregnancy which may be confused with acute appendicitis.

Figure 2

Figure 1: An inflamed appendix appears on ultrasound as non-compressible tubular structure, more than 6 mm in diameter, with thickened wall and peri-appendicular inflammation

Figure 3

Figure 2: Ultrasound of the same patient as above

Contrast-Enhanced CT

CT is a well-established ^{technique in the study of acute abdominal pain and has shown high sensitivity and specificity for diagnosing and differentiating appendicitis, providing an accurate diagnosis in the early stages of disease (30).}

CT is readily available, is ^{supposed to be operator-independent, is relatively easy to perform, and has results that are easy to interpret. Helical CT has reported sensitivities of 90-100%, specificities of 91-99%, accuracies of 94-98%, positive predictive values of 92-98%, and negative predictive values of 95-100% (31-32). Studies have proven that CT without the administration of contrast material in the setting of suspicion of acute appendicitis can be as accurate as those techniques in which oral, rectal, or IV contrast medium is administered.}

The typical CT finding of an inflamed appendix is a thickened wall and a non-filling appendix associated with periappendicular inflammatory fluid (figures 3&4).

CT scanning of patients with suspected appendicitis may reduce the number of patients admitted for observation and decrease the rate of negative appendectomy (33).

Figure 4

Figure 3: CT scan. The arrow points to a distended appendix with thickened walls which do not fill with colonic contrast agent, together with peri-appendicular inflammation.

Figure 5

Figure 4: CT scan of the same patient as above, the arrow shows the appendix with the same findings.

Diagnostic Laparoscopy

Several authors have advocated the use of laparoscopy as a diagnostic modality in the evaluation of a patient suspected of having acute appendicitis. Diagnostic laparoscopy should be viewed as an invasive procedure requiring general anesthesia and having a risk similar to appendectomy. For this reason, it is not preferred as a diagnostic tool. There is a lot of debate whether to remove a normal-looking appendix during diagnostic laparoscopy or to leave it. Naturally, many surgeons prefer not to come out empty-handed regardless of the gross appearance of the appendix, especially if no other pathology is identified. Many authors advocate removal of appendix regardless of the gross appearance as they believe not all normal-looking appendices are not inflamed and the inflammation may be limited to the mucosa (endo-appendicitis); however, the routine removal of a normal appendix is not a complication-free technique even in laparoscopy. Kraemer et al. reviewed the literature for the years 1978 to 1998 to analyze the negative appendectomy rates, complication rates, the accuracy of laparoscopic appendix assessment, and the incidence of false negative diagnosis of appendicitis, at surgical and gynaecological laparoscopy. He concluded that, contrary to general opinion, there is no substantial evidence to support the assumption that the macroscopic diagnosis of appendicitis is unreliable. High rates of conflicting diagnoses of excision specimens suggest that endo-appendicitis has little clinical significance. At present, negative appendectomy rates are considerably higher for laparoscopic appendectomy than for the open approach. The role of diagnostic laparoscopy in suspected appendicitis should be reconsidered. It may be useful in particular subgroups of patients, but it is no substitute for good clinical judgement. (34). Walker et al. reported that 3.2% of the intra-operatively normal-appearing appendices demonstrated acute inflammation after pathological examination (35).

Furthermore, Van den Broek prospectively evaluated 109 diagnostic laparoscopies for suspected appendicitis with normal-looking appendices in 100 cases. After a median follow-up of 4.4 years, only two patients had acute appendicitis and nine had some recurrent pain He suggested that it is safe to leave a normal-looking appendix in place when a diagnostic laparoscopy for suspected appendicitis is performed, even if another diagnosis cannot be found at laparoscopy. (36) Diagnostic laparoscopy may be helpful in equivocal cases or in women of childbearing age, while therapeutic laparoscopy may be preferred in certain subsets of patients (e.g., women, obese patients, athletes) (37), but it should not be advocated as a routine diagnostic procedure to replace the classical pre-operative work-up usually performed for clinically suspected appendicitis, because it has its own morbidity and in most cases requires general anesthesia.

Management

Surgical management

Medical management

Appendicular Mass

An appendix mass is a common surgical clinical entity, encountered in 2-6% of patients presenting with acute appendicitis (47, 48, 49).

Patients presenting late in the course of acute appendicitis are complicated by the development of an inflammatory mass in right iliac fossa (49). This inflammatory mass is composed of the inflamed appendix, omentum and bowel loops (figures 5&6).

At the beginning of the 20th century, Ochsner (1901) proposed non-operative management for the appendix mass (50), followed by interval appendectomy 6-8 weeks after successful conservative management as proposed by Murphy at the beginning of the 20^th century (51). This approach became a traditional management of appendicular mass.

Conservative treatment (Ochsner–Sherren regimen) comprises hospitalization, intravenous fluids, antibiotics, analgesics and a strict watch on the vitals and general state of the patient. In 90-80% of the patients, the mass resolves without complications. The remaining 10-20% need emergency operation due to spreading infection (figure 5-7), which is comparatively more difficult (52, 53).

Figure 6

Figure 5: Appendicular mass (arrow).

Figure 7

Figure 6: Appendicular mass lignifying to form an appendicular abscess

Figure 8

Figure 7: CT scan of the same patient as above (coronal view)

Advocates of initial conservative approach claim a lower rate of complications compared to early operative approach (54, 55). In the recent years, the treatment of the appendicular mass took a turn from the traditional approach of initial conservative treatment followed by interval appendectomy to immediate appendectomy (56, 57). However, this change is not widely accepted and a large number of surgeons still continue to adopt the same traditional conservative approach (58). It is obvious thqt controversy exists as to the best approach towards this problem and the opinion is divided about the management of appendicular masses.

Many studies showed that early surgical intervention is known to be an effective alternate to conservative therapy for a long time as it considerably reduces the total hospital stay and obviates the need for a second admission (59). At present, there is no agreed consensus on the management of appendiceal masses. There is a need to develop a protocol for the management of this common problem (60).

The value of interval appendicectomy has been increasingly questionable. The principal reasons for justifying interval appendicectomy are firstly to prevent recurrence of acute appendicitis and secondly to avoid misdiagnosing an alternative pathology such as a malignancy (61).

Kaminski et al. (2005) identified 1012 patients over a 13-year period with an appendix mass that had successful initial non-operative treatment. Eight hundred and sixty-four did not have interval appendicectomy performed. Thirty-nine of the 864 (5%) had a recurrence at a mean follow-up of 48 months. The mean time to recurrence was 10±15 months. They concluded that interval appendicectomy was not justified as the vast majority (95%) of patients successfully managed conservatively will not develop a recurrence (62, 63).

Willemsen et al. studied 233 patients who had interval appendectomy after successful initial conservative management of an appendicular mass. He found that histological examination of resection specimen showed a normal appendix without signs of previous inflammation in 30% of cases. In addition, complications due to interval appendectomy were seen in 18% of patients, including sepsis, bowel perforation, small bowel ileus, and various wound abscesses. He concluded that interval appendectomy seems unnecessary in patients who respond well to initial conservative treatment (64).

The incidence of misdiagnosing an appendix mass varies between 0% and 10%. Following non-operative management of an appendix mass, most authors consider further investigations as mandatory (65, 66, and 67). CT has been shown to be effective in diagnosing alternative pathologies that had clinically been diagnosed as an appendix mass (68).

Ahmed et al. review recent literature on interval appendicectomy; they concluded that interval appendicectomy is unnecessary in the majority of patients presenting with an appendix mass; 86-95% of the patients with an appendix mass whose symptoms resolve following conservative management will not experience a recurrence. If recurrence does occur it is likely to occur within one year and is usually associated with a milder clinical course amenable to both operative and non-operative approaches (63).

Summary

Acute appendicitis remains the most common general surgical emergency seen in most hospitals and the most common cause of acute abdomen requiring surgical intervention. Typical uncomplicated cases of acute appendicitis are easy to diagnose and to treat. Diagnosis of atypical appendicitis is a difficult task and remains a clinical challenge that may test the diagnostic skills of even the most experienced surgeons. Difficulties of diagnosis of atypical cases result from variation of the anatomical position of the appendix, appendicitis occurring at extremes of age and in females during child bearing age.

Despite technologic advances, the diagnosis of appendicitis is still based primarily on the patient's history and the physical examination. Diagnostic accuracy can be improved by using various clinical scoring systems. The Alvarado scoring system is the most famous scoring system used to help with the clinical diagnosis of acute appendicitis and is very easy to apply. The positive predictive value of Alvarado score is reported as high as 85.3%, 87.5%, and 87.4% in many studies. Accuracy of diagnosis can also be improved by adoption of an active observation policy.

Laboratory investigations including WBCC and serum reactive proteins help in supporting the diagnosis of acute appendicitis rather than excluding it.

Ultrasonography may significantly improve the diagnostic accuracy in patients with suspected acute appendicitis and should be performed in some patients in whom the clinical diagnosis is equivocal. The overall sensitivity, specificity and accuracy of ultrasonography in the diagnosis of acute appendicitis were 78%, 92% and 87%, respectively.

CT scanning of patients with suspected appendicitis may reduce the number of patients admitted for observation and decrease the rate of negative appendectomy. Helical CT has reported ^{sensitivities of 90-100%, specificities of 91-99%, accuracies of 94-98%, positive predictive values of 92-98%, and negative predictive values of 95-100%.}

There is a lot of controversy associated with laparoscopy as a diagnostic modality in the evaluation of a patient suspected of having acute appendicitis, including the question whether to remove a normal looking appendix during diagnostic laparoscopy or to leave it.

Appendectomy is the only curative treatment for acute appendicitis. Many studies claimed that laparoscopic appendectomy, compared with open surgery, reduces postoperative pain, length of hospitalisation, analgesic doses and surgery-associated complications.

Medical treatment of acute appendicitis may be helpful in isolated environments where there are no surgical capabilities until surgical resources become available. Although some studies indicated that antibiotics are an appropriate first-line treatment for adults with appendicitis without obvious signs of intra-abdominal perforation, more studies are needed to establish the role of antibiotic as a primary treatment of non-complicated appendicitis.

In the recent years the treatment of an appendicular mass took a turn from the traditional approach of initial conservative treatment to immediate appendectomy. Many studies showed that early surgical intervention is known to be an effective alternate to conservative therapy as it considerably reduces the total hospital stay and obviates the need for a second admission.

The value of interval appendicectomy has been increasingly questionable and there is strong evidence from various studies that there are no needs for interval appendicetomy after successful conservative management of an appendicular mass.