The Prevalence of Malignant Tumors of the Appendix in Patients with a History of Appendectomy and its Association with Demographic and Laboratory Variables

INTRODUCTION

The appendix is an essential organ of the gut-associated lymphoid tissue system, whose physiological function is mostly unknown.¹ Some hypotheses suggest that the appendix plays a vital role in training, developing, and maturing the immune system.² When the appendix suffers infection and inflammation, appendicitis occurs, which is one of the most common acute abdominal diseases requiring surgery.³ The risk of mortality in acute appendicitis has been reported 7–8%.⁴ In the United States, around 77,000 people develop appendicitis every year, incurring 680 million dollars to the government.⁵ The incidence of appendicitis throughout the lifetime is 8.6% and 6.7% for men and women, respectively.⁶ The prevalence of appendicitis differs across various populations, regions, and ages.⁷ Although lymphoid hyperplasia and fecalith are the most common factors underlying acute appendicitis, other factors have also been identified, including pinworms and tumors as the etiological factors.⁸ Despite antibiotic treatment, laparoscopy appendectomy is established as a standard treatment for acute appendicitis.^9,10

Appendix cancer is very rare,^11,12 yet less than 1% of those experiencing appendectomy have the chance of developing appendix cancer on average.¹³ Pathologically, appendix tumors are diverse, and it seems that the risk of developing various neoplasms of the appendix (except for malignant carcinoid, which involves women three times more than men) is the same for both males and females.¹⁴ Carcinoid is the most common appendix tumor, while adenocarcinoma, lymphosarcoma, paraganglioma, and granular-cellular tumors account for only 10–20% of appendix tumors.¹⁵ Most carcinoid tumors are asymptomatic, and on average, it usually takes 9 years to diagnose the tumor from the time of early symptoms.¹⁶ When the tumor is located on the appendix base, it blocks the hole, whereby the patients manifest symptoms similar to those of appendicitis.¹⁷ The present study aims to examine the prevalence of malignant tumors of the appendix and determine its association with demographic and laboratory variables in 4940 patients who have undergone appendectomy in Imam Reza Hospital in Kermanshah, Iran.

MATERIALS AND METHODS

The present study is descriptive cross-sectional, with the study population consisting of all patients who had undergone appendectomy in 2011–2018 in Imam Reza Hospital in Kermanshah, Iran. The exclusion criteria included lack of pathology tests in the file, incomplete information, suffering cancers before appendectomy, metastasis to appendix before appendectomy, taking chemotherapeutic and corticosteroid drugs, radiotherapy, and use of other immunosuppressive drugs in patients with acquired immune deficiency syndrome (AIDS). From 6086 medical files of patients undergoing an appendectomy, 1146 were excluded, and eventually, 4940 files were examined. The required information, including age, gender, type of tumor, and laboratory information, was collected from these files.

RESULTS

The results indicated that most patients who had undergone appendectomy in the mentioned hospital were male (n = 3017, 61%), and the rest were female (n = 1923, 39%). The mean age of the studied patients was 25.50 ± 15.16 years. The youngest patient was a one-day-old neonate, while the oldest patient had 94 years of age. Out of all patients undergoing an appendectomy, 41 (0.8%) showed positive pathology regarding tumor in the appendix; out of them, 26 (0.5%) had malignant, while 15 (0.3%) showed benign types. Among the malignant tumors, 9 (34.61%) were adenocarcinoma mucinous, 6 (23.07%) were carcinoid, 5 (19.23%) were adenocarcinoma, 5 (19.23%) were malignant mucocele, and 1 (3.84%) was cystadenoma. Among the benign tumors, 9 (60%) were follicular hyperplasia, 3 (20%) were lymphoid hyperplasia, 1 (6.6%) was mucinous cystadenoma, 1 (6.6%) was sinus histiocytosis, and 1 (6.6%) was follicular lymphoid hyperplasia. The frequency distribution of different types of malignant and benign tumors of the appendix is presented in Table 1.

Out of the 26 cases with the appendix’s malignant tumors, 14 (53.8%) were male, and 12 (46.2%) were female. The results found no significant relationship between gender and the presence of the appendix’s malignant tumors (p = 0.340). The majority of cancerous cases were observed in those above 50 years of age. In addition, the relationship between age and the existence of malignant tumors was significant (p = 0.025); older individuals were significantly more likely to develop malignant tumors of the appendix compared to younger individuals (Fig. 1). The mean WBC count in those with appendectomy was 12.34 ± 4.184 Tho/µL. White blood cell count equal to and larger than 12 Tho/µL was considered positive (57.2% of cases), and below this value was regarded as negative (42.8% of cases). The relationship between the number of WBC and the appendix’s malignant tumors was significant; the WBC count was significantly lower in those with malignant tumors compared to others (Fig. 2). The mean erythrocyte sedimentation rate (ESR) in the studied population was 25.04 ± 23.98 mm/h. No significant relationship was observed between ESR and the presence of malignant tumors of the appendix. Moreover, the C-reactive protein (CRP) test results showed 40.4% negative and 59.6% positive cases. No significant relationship was observed between CRP level and the presence of the appendix’s malignant tumors (Fig. 3).

DISCUSSION

This study investigated the prevalence of the appendix’s malignant tumors and determined the possible relationship between these tumors and demographic and laboratory variables in 4940 patients with a history of appendectomy in Imam Reza Hospital, Kermanshah. The results showed that the prevalence of the appendix’s malignant tumors in those who had undergone appendectomy was 0.5%. Here, 61% of patients were male. In this regard, other studies have also shown a higher prevalence of appendectomy among men.¹⁸ In the present research, the primary type of malignant tumor was mucinous adenocarcinoma (34.61%), followed by carcinoid tumor (23.07%). The prevalence of carcinoid tumors in this study across the entire population was 0.0012%. This value is slightly lower than the value obtained in the study by Chinifroush et al. in Iran (0.0019%),¹⁹ Vessal et al. in Iran (0.0024%),²⁰ Guraya et al. in Saudi Arabia (0.0058%),²¹ and Tchana-Sato et al. in Belgium (0.0040%).¹³ In a study performed by Ahmadi Nejad et al. in Lorestan province, Iran, the prevalence of the appendix’s carcinoid tumors in those with a history of an appendectomy was reported at 0.17%.²² Although the prevalence of carcinoid tumors in the general population of the United States has been estimated to be 1–2 per 100,000 people,²³ it seems that the actual prevalence might be higher. Note that the incidence of carcinoid tumors is often asymptomatic and can often remain so for years.²⁴ Based on the obtained results, although no significant relationship was found between gender and the presence of malignant tumors of the appendix, the frequency of malignant tumors was higher in men. Unlike the results obtained from the present study, other investigations have shown a higher incidence of the appendix’s malignant tumors in women.^19,23,25 In our study, a significant relationship was observed between presence of malignant tumors of the appendix and age, with older individuals showing larger numbers of malignant tumors. C-reactive protein assessment in the patients showed 40.4% negative and 59.6% positive cases. No significant relationship was found between CRP level and presence of malignant tumors of appendix. C-reactive protein is an acute phase reactant synthesized by the liver in response to infection. The serum levels of this protein begin to rise 6–12 h after initiation of tissue inflammation. C-reactive protein assessment is often done easily and rapidly in laboratories, with studies showing that CRP level can confirm appendicitis with high accuracy.^26,27

CONCLUSION

Since the diagnosis of malignant tumors of the appendix may not be made easily, noting some variables, including advanced age and high WBC count in the laboratory test, can help diagnose malignant tumors. Moreover, given the malignancy as well as local invasion and distant metastasis of some appendix tumors, follow-up of the pathology report by the patient (especially older individuals) as well as physician and during checkup following appendectomy within short and regular intervals and if required follow-up treatment is essential.

ACKNOWLEDGMENTS

The proposal of this research has been approved by the Research Deputy of Kermanshah University of Medical Sciences with the code of 980527. The authors highly appreciate those who cooperated with us in this research, as well as the general surgeons of Imam Reza Hospital in Kermanshah.

ORCID

Mansour Rezaei https://orcid.org/0000-0002-6446-7289

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