**3. Pathology**

Several factors are claimed to predispose to acute inflammation of the appendix, including faecolith, food residues, lymphoid hyperplasia (in children) and the presence of a carcinoid tumour. Specific viral and bacterial inflammation can also affect the appendix. In addition the appendix can be involved by ulcerative colitis and Crohn's disease. In early acute appendicitis there is acute inflammation of the mucosa which undergoes ulceration. Pus may be present in the lumen. At this stage the patient experiences an ill defined central abdominal pain. Microscopically, the appendix is usually swollen and the overlying vessels are dilated and prominent. As the acute inflammation develops, it spreads through the full thickness of the appendix wall to reach the serosal surface. This causes a localised acute peritonitis, which is perceived as a sharp pain localised to the right iliac fossa. At this stage the appendix microscopically shows dilated serosal vessels and a rough, yellow, fibrinous exudate on the surface. By this stage the inflammation and the infection has spread to involve all layers of the appendix wall. The build up of fluid exudate within the wall increases tissue pressure and this, together with the toxic damage to blood vessels and subsequent thrombosis can lead to superimposed ischemia. In addition the muscle layer is replaced by an acute inflammatory infiltrate with degranulation of neutrophils contributing to toxic damage. Both the ischemia, toxic products and infection contribute to weakness of the wall of the appendix and the distal part of the appendix can become gangrenous and perforate. This liberates bowel contents in to the peritoneal cavity and causes generalised peritonitis which leads to severe deterioration in the clinical condition. If the general condition of the patient is satisfactory, the omentum might cover the site of perforation and local abscess formation follows. Infiltration into blood vessels and lymphatics leads to the consequences of blood spread which is suppurative pylephlebitis (inflammation and thrombosis of the portal vein), liver abscess and septicaemia. The inflammation can also become chronic, or obstruction to the neck of the appendix may lead to mucus retention in its lumen causing a mucocoele of the appendix. This does not often give rise to clinical problems but on rare occasions may rupture and disseminate mucus secreting epithelial cells in to the peritoneal cavity – pseudomyxoma peritonei.

The presence of gangrene or perforation seems to be associated with the presence of faecoliths. These are intraluminal laminated appendiceal calculi. They result from dehydration and compaction of faecal pellets. Approximately 50% of cases of gangrenous or perforated appendicitis are associated with a faecolith in contrast with uncomplicated appendicitis in which a faecolith is rarely present. It is thought that a faecolith increases the likelihood of obstruction of the appendix and thereby allows the accumulation of pus. Overall about 20% of all patients with acute appendicitis have perforation at the time of operation. At the extremes of age (below 5 and above 60 years) the rate of perforation is in the region of 60%.

Perforation rates of 20% to 30% have been reported consistently over the past 70 years despite the technologic advances over this interval. Recent evidence suggesting that perforation precedes surgical evaluation in the majority of cases indicates that reduction of perforation rates will have to be addressed through encouraging earlier evaluation and greater access to care. However, modern surgical therapy has been responsible for reducing

of referral, infrastructure, and surgical treatment strategy on the incidence of acute appendicitis. Therefore, there is a strong need for good prospective studies with high-

Several factors are claimed to predispose to acute inflammation of the appendix, including faecolith, food residues, lymphoid hyperplasia (in children) and the presence of a carcinoid tumour. Specific viral and bacterial inflammation can also affect the appendix. In addition the appendix can be involved by ulcerative colitis and Crohn's disease. In early acute appendicitis there is acute inflammation of the mucosa which undergoes ulceration. Pus may be present in the lumen. At this stage the patient experiences an ill defined central abdominal pain. Microscopically, the appendix is usually swollen and the overlying vessels are dilated and prominent. As the acute inflammation develops, it spreads through the full thickness of the appendix wall to reach the serosal surface. This causes a localised acute peritonitis, which is perceived as a sharp pain localised to the right iliac fossa. At this stage the appendix microscopically shows dilated serosal vessels and a rough, yellow, fibrinous exudate on the surface. By this stage the inflammation and the infection has spread to involve all layers of the appendix wall. The build up of fluid exudate within the wall increases tissue pressure and this, together with the toxic damage to blood vessels and subsequent thrombosis can lead to superimposed ischemia. In addition the muscle layer is replaced by an acute inflammatory infiltrate with degranulation of neutrophils contributing to toxic damage. Both the ischemia, toxic products and infection contribute to weakness of the wall of the appendix and the distal part of the appendix can become gangrenous and perforate. This liberates bowel contents in to the peritoneal cavity and causes generalised peritonitis which leads to severe deterioration in the clinical condition. If the general condition of the patient is satisfactory, the omentum might cover the site of perforation and local abscess formation follows. Infiltration into blood vessels and lymphatics leads to the consequences of blood spread which is suppurative pylephlebitis (inflammation and thrombosis of the portal vein), liver abscess and septicaemia. The inflammation can also become chronic, or obstruction to the neck of the appendix may lead to mucus retention in its lumen causing a mucocoele of the appendix. This does not often give rise to clinical problems but on rare occasions may rupture and disseminate mucus secreting epithelial

The presence of gangrene or perforation seems to be associated with the presence of faecoliths. These are intraluminal laminated appendiceal calculi. They result from dehydration and compaction of faecal pellets. Approximately 50% of cases of gangrenous or perforated appendicitis are associated with a faecolith in contrast with uncomplicated appendicitis in which a faecolith is rarely present. It is thought that a faecolith increases the likelihood of obstruction of the appendix and thereby allows the accumulation of pus. Overall about 20% of all patients with acute appendicitis have perforation at the time of operation. At the extremes

Perforation rates of 20% to 30% have been reported consistently over the past 70 years despite the technologic advances over this interval. Recent evidence suggesting that perforation precedes surgical evaluation in the majority of cases indicates that reduction of perforation rates will have to be addressed through encouraging earlier evaluation and greater access to care. However, modern surgical therapy has been responsible for reducing

of age (below 5 and above 60 years) the rate of perforation is in the region of 60%.

cells in to the peritoneal cavity – pseudomyxoma peritonei.

quality data.

**3. Pathology** 

the mortality of appendicitis from 26% overall to less than 1% over the same period. The mortality rate of 0.08% reported is testament to the benefits of advancing technology in managing a persistent rate of perforation and its attendant complications. Perforation continues to disproportionately affect those individuals at the extremes of age. This is most likely due to delays in presentation and diagnosis related to an inability to communicate in the younger population. In the older population, a combination of delayed presentation, confounding medical conditions and a decreased index of suspicion may contribute to this observation.

Emergency appendectomy was originally advocated because of the very high mortality of perforated appendicitis and the assumption that acute appendicitis evolved to perforated disease, a pathophysiologic hypothesis that has never been proven. This notion was first proposed by Reginald Fitz, the originator of the term appendicitis, in 1886. Fitz was the first to identify inflammation of the appendix as a cause for right lower quadrant infections, previously known as thyphilitis. In making the argument that the appendix causes this entity, however, Fitz incidentally noted that one-third of patients undergoing autopsy in the pre-appendectomy era had evidence of prior appendiceal inflammation, suggesting that appendicitis often resolved spontaneously without surgery. Later evidence from submariners who developed appendicitis while at sea and received delayed surgical therapy has shown that in most cases the acute disease can resolve with non-operative antibiotic and supportive therapy.

Perforated and non-perforated appendicitis have followed radically different epidemiologic trends over the past 2 decades. While perforated appendicitis slowly but steadily increased in incidence, non-perforated appendicitis stabilised or declined. If perforated appendicitis was simply the result of appendicitis that was not surgically treated early enough, the trends should have been more nearly parallel throughout all the time periods studied. Time series analysis showed that on a year-to-year basis, there was a significant positive correlation between perforated and non-perforated appendicitis for men but not for women. These unassociated epidemiologic trends suggest that the pathophysiology of these diseases is different. If true, it might follow that many patients presenting with non-perforated appendicitis might experience spontaneous resolution without perforation. There is historical, clinical, and immunologic evidence to support this hypothesis.

An alternative hypothesis suggests that several factors (ie, prehospital time, availability of operating room for emergency surgery, time of presentation) have been shown to be significantly associated with perforated appendicitis. Compared with uncomplicated appendicitis, perforated appendicitis is associated with a two- to tenfold increase in mortality
