Prevalence and clinical implications of diverticulosis of the vermiform appendix

Abstract

Objective

The epidemiology and the aetiology of inflammatory diseases of the vermiform appendix remain poorly understood. The prevalence of appendiceal diverticulosis and diverticulitis in patients undergoing appendectomy for suspected acute appendicitis was investigated.

Methods

A retrospective study was completed on patients who underwent appendectomy for suspected acute appendicitis. Pathology reports of all patients were screened for diverticula of the vermiform appendix. Patients with either diverticulitis of the vermiform appendix or normal appendicitis were compared.

Results

Out of two sets of consecutive patients (n = 1073), nine (0.8%) were identified with diverticulosis of the vermiform appendix. Two of these patients had diverticulitis of the vermiform appendix without appendicitis, three had diverticulitis with consecutive localized appendicitis, and four had proper acute appendicitis with a noninflamed diverticulum of the vermiform appendix. One patient had perforated appendicitis. Two patients had an obstructing neuroendocrine carcinoid which may have caused diverticular formation.

Conclusions

Diverticula of the vermiform appendix are rare. If inflamed, they mimic acute appendicitis and are treated by appendectomy. If not inflamed, and diagnosed intraoperatively, incidental appendectomy is recommended.

Introduction

The epidemiology and aetiology of inflammatory diseases of the vermiform appendix remain poorly understood.^1,2 Appendiceal diverticulosis was first described in 1893, although there are few published studies relating to this disease. ³ The prevalence of appendiceal diverticulosis in patients undergoing appendectomy is ∼1% of all examined cases. ⁴ Diverticulitis in appendiceal diverticulosis may mimic normal acute appendicitis, although these are distinct clinical entities. ⁴ Diverticulitis in appendiceal diverticulosis appears to affect older patients (mean age, 60 years) more often than younger patients, and the clinical evolution of symptoms appears to be slower, compared with normal acute appendicitis.^4,5

The present study investigated the prevalence of appendiceal diverticulosis, the clinical significance of diverticulitis of the vermiform appendix, and levels of inflammatory markers in patients undergoing appendectomy for suspected acute appendicitis.

Patients and methods

Study population

The present retrospective study was completed on two sets of consecutive patients undergoing appendectomy for suspected acute appendicitis at the hospital of Liestal (Liestal, Switzerland) between June 2003 and June 2008, and at the hospital of Tafers (Tafers, Switzerland) between June 1998 and June 2008. Inclusion criteria were appendectomy or ileo–caecal resection for suspected acute appendicitis. Exclusion criteria were appendectomy or ileocecal resection for reasons other than suspected acute appendicitis. As this study was retrospective and based on existing pathology reports, the need for approval by an ethics committee was waived. For the same reasons, the patients were not required to provide written or verbal informed consent.

Examination of tissue samples

In all cases, the resected specimens were fixed in 4% neutral buffered formalinand examined by a pathologist (N.W.). Macroscopic analysis of the tissue was followed by standard paraffin-wax embedding, for histological examination. At least two paraffin-wax blocks per tissue sample were used to cut 3–4-µm-thick sections for staining with haematoxylin and eosin. A longitudinal section of the tip of the vermiform appendix and a transverse section of the vermiform appendix at the dissection margin were cut from the first standard block. Three transverse sections of the vermiform appendix were cut from the second standard block. Additional blocks (with optional staining of tissue sections with Elastica van Gieson or periodic acid Schiff) were prepared in cases of suspected perforation, presence of tumour or diverticula, and in the absence of inflammation. The specific histological features used to classify tissues were: (I) existence of inflammation in lumen, mucosa, lamina propria, fatty tissue, serosa; (II) type of inflammation (granulocytic, lymphocytic, granulomatous, eosinophilic); (III) type, extension and intensity of inflammation (appendicitis catarrhalis, ulcerosa, ulcero-phlegmonosa, ulcero-gangraenosa, neurogenic appendicopathy); (IV) tumour presence (adenoma/carcinoma/neuroendocrine tumour/mucinous tumour of the appendix etc.) and tumour extension (infiltration of mucosa and submucosa/lamina propria/fatty tissue and serosal surface); (V) presence of parasites; (VI) anatomical abnormalities (mucosal protrusion through the muscle layer, fibrolipomatous obliteration, endometriosis, endosalpingiosis).

In the presence of a diverticulum of the vermiform appendix, proper appendicitis without inflammation of the diverticulum was differentiated from diverticulitis of the vermiform appendix with or without consecutive localized appendicitis at the neck of the diverticulum. Negative appendectomy was defined as nonincidental appendectomy for suspected appendicitis, without specific histological features of inflammation in the specimen.

Analysis of inflammatory markers

Data from patients with a diverticulum of the vermiform appendix were retrospectively analysed for the presence of inflammatory markers. Venous blood samples had been taken from each patient in the emergency room, before any infusion therapy was started. All analyses were performed immediately following blood collection. Circulating leucocyte levels were measured in blood mixed with ethylenediaminetetra-acetic acid (1.8 mg/l) as anticoagulant, in tubes of 5 ml, using an automatic blood-cell counter. Levels of C-reactive protein were measured from blood samples collected into 10 ml serum-separating tubes using C-reactive protein assays. At the hospital of Liestal blood-cell counters from the CellDyn® range (Abbott AG, Diagnostics Division, Baar, Switzerland) were used and at the hospital of Tafers the blood-cell counter Sysmex XT 1800i (Sysmex Digitana AG, Horgen, Switzerland) was used. At both hospitals C-reactive protein assay equipment from the COBAS Integra® range (Roche Diagnostics AG, Rotkreuz, Switzerland) were used.

Results

Out of 1073 patients included in the study, nine patients (0.8%) were identified to have a diverticulum of the vermiform appendix by the pathologist; none of these patients had been diagnosed with diverticulitis of the vermiform appendix prior to or during surgery. Age, site of inflammation, presence of neoplasia, presence of perforation and levels of inflammatory markers (C-reactive protein and circulating leucocytes) in patients with a diverticulum of the vermiform appendix were assessed (Table 1). This group was further subdivided into patients with acute appendicitis in the presence of a noninflamed diverticulum (n = 4), and patients with diverticulitis of the vermiform appendix, with or without consecutive localized appendicitis (n = 5, Table 2). Acute appendicitis without diverticular disease was identified in 935 patients (Table 2). 129 patients had negative appendectomies with no single diverticulum of the vermiform appendix identified. Perforation rate was 21% (196/935) in patients with acute appendicitis without presence of a diverticulum of the vermiform appendix, 20% (one of five) in patients with diverticulitis of the vermiform appendix, and 0% (none of four) in patients with acute appendicitis in the presence of a noninflamed diverticulum. A representative histology section from a patient with diverticulosis of the vermiform appendix is shown in Figure 1.

Figure 1.

Representative photomicrograph showing a transverse section of a vermiform appendix with a noninflamed diverticulum, from a patient who underwent appendectomy for suspected acute appendicitis.

Table 1.

Clinical, pathological and laboratory data from patients with diverticular disease of the vermiform appendix who underwent appendectomy for suspected acute appendicitis.

Patient number	Age, years	Appendicitis with a noninflamed diverticulum	Diverticulitis with consecutive localized appendicitis	Diverticulitis without appendicitis	Neuroendocrine carcinoid	Perityphlitic abscess	CRP mg/l	Leucocytes per nl
1	17	+	−	−	−	−	191	12.1
2	21	+	−	−	−	−	13	13.6
3	40	+	−	−	+	−	28	10.2
4	30	+	−	−	−	−	2	12.8
5	49	−	+	−	−	−	51	5.9
9	19	−	+	−	−	−	46	8.8
7	77	−	+	−	−	−	29	10
8	24	−	−	+	−	+	14	12.8
9	23	−	−	+	+	−	76	10.3

CRP, C-reactive protein.

Table 2.

Comparison of median age and laboratory values of patients who underwent appendectomy for acute appendicitis without diverticulosis, acute appendicitis in the presence of a noninflamed diverticulum, and diverticulitis of the vermiform appendix with or without consecutive localized appendicitis.

Characteristic	Acute appendicitis without diverticulosis, n = 935	Acute appendicitis in the presence of a noninflamed diverticulum, n = 4	Diverticulitis of the vermiform appendix with or without consecutive localized appendicitis, n = 5
Age, years	30 (5–92)	26 (17–40)	24 (19–77)
CRP, mg/l	25 (0–471)	21 (2–191)	46 (14–76)
Leucocytes per nl	13.2 (1.3–30.3)	11.2 (10.2–13.6)	10 (5.9–12.8)
Bilirubin, µmol/l	16.5 (3–118)	13.8 (12.0–50.4)	12.5 (4.9–27.1)

Data presented as median (range).

CRP, C-reactive protein.

Discussion

As was found in the present study, appendiceal diverticulosis occurs in ∼1% of all examined cases of patients undergoing appendectomy. ⁴

Some studies have indicated that diverticulitis of the vermiform appendix tends to occur in older patients (mean age, 60 years) compared with normal appendicitis,^4,5 however, this was not shown in the present study.

Diverticula of the vermiform appendix can be classified as acquired false diverticula or true congenital diverticula, however the latter are very rare. ⁶ Diverticula have to be distinguished from a partial duplicature of the vermiform appendix which is the vestige of a secondary transient vermiform appendix: this atrophies when the embryo reaches a length of 20 mm. ⁷ False diverticula are often diagnosed in the presence of an obstruction. ⁸ Thus, the aetiology is thought to be increased intraluminal pressure, resulting in mucosal herniation through a defect or a weak spot in the muscularis propria, often at the site of a penetrating artery. ⁸ This hypothesis is underlined by the fact that patients with cystic fibrosis have a far higher prevalence of acquired diverticula of the vermiform appendix, compared with other people. ⁹ In the present study, two patients with diverticula of the vermiform appendix were found to have a neuroendocrine carcinoid, which possibly led to an increase in intraluminal pressure, resulting in diverticular formation. In the remaining patients, no obstruction could be identified. If, indeed, formation of false diverticula is triggered by a high wall tension, then according to the law of Laplace, very high pressures must occasionally be present in the vermiform appendix. It can be speculated that the wall of the vermiform appendix (with its circular inner and outer muscular layer) is adapted to these high pressures.

Diverticulitis of the vermiform appendix is very rarely diagnosed preoperatively, and since treatment is appendectomy (as in the case of proper appendicitis) the clinical importance of this entity might at first be assumed to be low. However, ruptured diverticula of the vermiform appendix, resulting in serosal mucin deposits, can be misdiagnosed as low-grade appendiceal mucinous neoplasms, although it has been shown that ruptured diverticula are not a precursor lesion of pseudomyxoma peritonei. ¹⁰ In true appendiceal mucinous neoplasms, the risk of pseudomyxoma peritonei syndrome is approximately 4–8% in the case of deposition of extra-appendiceal acellular mucin, rising to 33–75% if localized extra-appendiceal cellular mucin is present.^11,12 Because these deposits might not be on the resected vermiform appendix, the surgeon must be aware of this issue.

The clinical evolution of diverticulitis of the vermiform appendix seems to be less acute than the evolution of normal appendicitis. ⁴ In the present study, the lower levels of inflammatory markers in the group with diverticulitis of the vermiform appendix (compared with the group with normal appendicitis) support this. However, due to the low number of patients with diverticula of the vermiform appendix, statistical analyses could not be performed.

In the case of inflammation of the vermiform appendix, perforation is thought to occur earlier in the presence of a diverticulum than in absence of a diverticulum.^4,5 In the present study, there was no difference in the perforation rate between patients with diverticulitis (20%) and patients with acute appendicitis (21%). Limited conclusions can be drawn from our results, due to the low number of patients analysed in our study, and the possible misdiagnosis of a perforated diverticulitis of the appendix as a perforated localized appendicitis, which cannot be excluded in this retrospective study. Despite these limitations, the appendiceal diverticulitis perforation rate of 20% in the present study was similar to the perforation rate of ∼33% observed in studies of sigmoid diverticulitis.^13,14

Out of nine patients with diverticulosis of the vermiform appendix, five had a localized inflammation of the diverticulum. The diverticulitis rate of 56% in patients with diverticulosis of the vermiform appendix was high, compared with a diverticulitis rate of ∼25%, in patients with sigmoid diverticulosis. ¹⁴ However, a selection bias cannot be excluded, as only patients with suspected appendicitis were included in the present study. Nevertheless, if a diverticulum of the vermiform appendix is diagnosed incidentally in a noninflamed vermiform appendix during abdominal surgery for other reasons, incidental appendectomy is recommended.

In conclusion, diverticula of the vermiform appendix are rare. If inflamed, diverticula of the vermiform appendix mimic acute appendicitis and are treated by appendectomy. If not inflamed, and if diagnosed intraoperatively, incidental appendectomy is recommended, to prevent inflammation with possible perforation and to exclude a neoplasm.