Introduction

One of the major common reasons for acute abdominal pain is acute appendicitis (1). Acute appendicitis is referred to as inflammatory process of the vermiform inner lining of the appendix, which then may spread to other parts of the organ and or the surrounding areas (2). The most likely cause of appendicitis appears to be obstruction of the appendiceal lumen caused by a variety of factors which starts the inflammatory response (3). The most frequent causes of luminal blockage are fecaliths and lymphoid hyperplasia (2).

In the United States, men and women have roughly a 1 in 12 and 1 in 15 lifetime risks of developing appendicitis, respectively (4,5). At both extremes of age, it is less common, but it is more prevalent in twenties and thirties (6). The prevalence of acute appendicitis has increased in developing countries as a result of the adoption of a low-fiber diet (7). Appendicitis is primarily diagnosed clinically, while the mainstay treatment is appendectomy which can be done either by open surgery or a laparoscopic (minimally invasive) technique (8,9). As clinical examination has a limited ability to effectively diagnose appendicitis, a number of imaging modalities, including computed tomography (CT), ultrasonography (US), and magnetic resonance imaging (MRI), are frequently used (10). With the use of preoperative CT scan, the frequency of negative appendectomy has decreased, particularly among women where other gynecological emergency diseases were usually misdiagnosed (11).

Granulomatous diseases, endometriosis, neurofibroma, diverticulitis, infectious diseases, and appendiceal cancer have all shown similar clinical manifestations to acute appendicitis (2,12,13). Appendicitis consequences such a perforated appendix, peritonitis, sepsis, and increased morbidity and death could result from a delayed diagnosis (14).

Although all resected specimens can be definitively diagnosed through histopathological analysis of appendectomy specimens (15), various hospitals have different protocols. The rarity of accidental diseases that may affect treatment as well as the financial costs of routine histological evaluations are arguments against the practice (15-17). However, not only in cases of acute appendicitis, but also in situations when unexpected results are present, the pathology report is essential (18). In the center under the study, a secondary care hospital in Saudi Arabia, appendix specimens after appendectomy are routinely histologically examined. The study aimed to identify the results of the routine histopathological examinations of appendectomy specimens and to correlate them with the preoperative imaging tools [ultrasonography (US), and computed tomography (CT)].

Subjects and Methods

Study design and study setting

A retrospective cohort study was carried out in a single-center secondary health care hospital in Qassim region, Saudi Arabia in a period of 3 years; from April 2020 to April 2023. All electronic patients’ records who underwent appendectomy for acute appendicitis was our sample size. The results of their resected appendectomy specimens, which were sent for routine histopathological analysis, were retrieved.

Sampling technique

A convenient non-probability sampling technique was used for data collection from the medical database. The eligibility criteria will be any patient operated with appendectomy after being diagnosed as acute appendicitis. The study excluded patients who underwent an accidental appendectomy while undergoing other procedures.

Data collection methods

Demographic characteristics (age in years and gender), white blood cell count (WBCs) (10⁹/L), preoperative imaging results (US and CT), surgery approach (open or laparoscopic), and histopathology results of all resected specimens for each patient were the data to be obtained. All histopathology records were retrieved, and all results were identified. For preoperative ultrasound imaging, the results were considered as one of the following: appendix can’t be visualized, acute appendicitis, no sonographic evidence of acute appendicitis. Preoperative CT findings were acute appendicitis, or no evidence of acute appendicitis. According to the histopathologic findings, if the appendectomy specimens showed acute appendicitis features, they were classified as positive. A post-operative appendix specimen for suspected appendicitis showed normal histopathologic findings with no signs of inflammation, tumors, or parasitic infestation is defined as “negative appendectomy” (5,19-20).

Pilot study

A pilot study was conducted over 20 patients’ computer records, where their results were excluded from the study.

Data management and analysis plan

The data were coded and analyzed using the standard computer program Statistical Package of Social Sciences (SPSS) version 25.0. Quantitative data appeared as mean and standard deviation (Mean±SD) where Mann-Whiteny-test was used for comparison between two groups of non-normally distributed data. Qualitative data were expressed in the form of number and percentage (n & %) and Chi-square (χ²) test was used. Differences were considered significant at P-value <0.05.

Ethical considerations

IRB approval was obtained from the institutional Regional Review Board (Number: 607/44/8271). Approval of the hospital manager was, also, asked prior to entering the hospital. All data were kept confidential and were used only for research purposes.

Results

Patients’ Characteristics

A total of 350 appendectomies was performed throughout the study period. The recorded mean age was 27.84±10.05 (ranged from 5-62). Of the study population, patients below 12-year-old represented 1.6%, adults between 12-50 were 95.3% while people over 50 accounted 3%. One third of the patients were females (32.1%) and the rest were males (67.9%). Laparoscopic approach was performed for more than three-fifths of the group (77%). Half of the patients were diagnosed with leukocytosis (WBC count > 11*10⁹/L) (51.2%) where normal WBC count was observed between 48.8% of them. The mean WBC count was 11.69±4.18 (Table 1).

Imaging

Preoperative US was done for 258 patients (70.7%), of them, two-thirds identified AA (65.5%), one-fourth (24%) with no sonographic evidence of appendicitis and 9.6% the appendix was not visualized. CT scan was performed preoperatively for 194 patients (53.2%) where AA was confirmed between 191 of them (98.5%) and failed to diagnose AA in three patients (1.5%).

Histopathological findings

Out of the 365 postoperative appendix specimens, 352 were consistent with AA (96.4%) while the negative appendectomy rate was 3.6% (13 specimens) (Table 1). Acute appendicitis represented 50.7% of all cases, followed by acute suppurative appendicitis (41.6%), then acute gangrenous appendicitis (2.5%), and acute perforated appendicitis (1.6%). Microscopically, six cases appeared as having lymphoid hyperplasia (1.6%), two cases with fibrous obliteration of the appendix (0.6%), while neoplasms were reported in two cases (one case with low grade appendiceal mucenous neoplasm with focal extra appendicular extension, and the other case was well differentiated neuroendocrine tumor, grade 2, 0.3% each). Finally, one case was appearing for each of the following: periappendicitis, lymphoid hyperplasia with periappendicitis and mucocele with fibrous obliteration of the lumen (0.3% each) (Table 2).

Relationship between histopathological findings and patients’ characteristics

It was obvious that the mean value of WBC count was significantly higher among those with positive histopathological results than others (P-value=0.001). Although younger age, male gender, laparoscopic approach, performing preoperative US and CT scan were linked to confirmed AA histopathologically, but all didn’t reach a significant level (P-value=0.5, 0.6, 0.49, 0.91 and 0.24; respectively) (Table 3).

Accuracy of radiological imaging in acute appendicitis detection vs histopathological findings:

In the current study, before having the appendectomy operation, 258 patients had US and 194 received CT scan. The sensitivity as well as the accuracy of US in diagnosing AA was 66.7%, while the sensitivity of CT was 100% and its accuracy was 96.9%. (Table 4).

Discussion

The most frequent emergency surgical presentation is acute appendicitis, and the most common surgery performed globally is an emergency appendectomy (6,21-22). Even with the use of advanced diagnostic investigations, no single tool can provide a definite diagnosis (22-23). As a result, a substantial percentage of misdiagnosis leads in a negative appendectomy (24). Therefore, it is still a clinical dilemma (25).

In the current study, acute appendicitis is more prone among males then females. This is in agreement with other studies (26,29)

Elevated level of WBC count was used as a basic diagnostic laboratory test to diagnose suspected appendicitis. A significantly higher mean value of WBCs was linked to positive appendicitis group in our studied patients. This finding agrees with the results obtained from other studies (30).

In this study, 70.7% and 53.2% of the patients received preoperative imaging in the form of US and CT; respectively. However, US showed a sensitivity 66.7% of and accuracy of 66.7% in acute appendicitis correct diagnosis. Those values are non-concordant with the literature that US sensitivity ranged from 74.2-76% with an accuracy rate of 83-92%. This is most likely due to US restrictions and the fact that it depends on the operator. Obviously, CT is superior to US in diagnosing suspected appendicitis. The sensitivity of CT in this study was reported as 100 and its accuracy was 96.9% in the diagnosis of suspected AA. This is consistent with other studies(20,26,29). This finding may support the low NAR observed in our study.

In the present study, AA was proven by microscopic histopathology examination in 96.4% of the cases. Many study results are concordant with ours (29,31). In our study, negative appendectomy rate was 3.6% which is less than in the literature, around 6%. This could be attributed to the widespread use of diagnostic radiological tools, especially preoperative CT, in the hospital under the study. Indeed, NAR has gained acceptance as a quality indicator in the treatment of acute appendicitis (24). Worldwide, the reported NAR ranged from 6%-40%(4,32). However, the suggested acceptance rate is 20% (6,22,23). NAR was reported as 14.4%, 9.7%, 4.7%, 6% and 11.3%; respectively in Saudi Arabia(29), Oman (33), Jordan (34), Turkey (35) and United Kingdom(26). To avoid the possible consequences of appendicitis like perforation, peritonitis, gangrene, abscess formation and septic shock; it was fine to accept high NAR (36). Based on the use of the modern diagnostic procedures as CT, a notable decline in the NAR was observed (20,36).

In addition, the incidence of acute perforated appendicitis in this study was 1.6%. This result was lower than the reported values of a recent study (29) which indicates non-delay in appendicitis identification. Gangrenous appendicitis rate was 2.5% in our study which is in line with the literature (29,37). In the current study, the most frequently reported positive cases confirmed in the histopathology reports was acute appendicitis, acute suppurative appendicitis, gangrenous appendicitis and perforated appendicitis. These results are consistent with data from other studies (35,38).

In the current study, the incidence of negative appendicitis representing 3.6% (13 specimens) were mainly included unusual pathology (11 specimens), and 2 neoplasms. The findings in the literature go in line with our results (2,26,33,35).

Histopathological examination of the resected appendectomy specimen is of great importance in appropriate diagnosis of appendiceal inflammation, it is mandatory and advantageous. Relying solely on the intraoperative diagnosis is highly variable and insufficient in recognizing the uncommon disease.

Limitation of the study: Although the number of the studied group is not small, but large sample size will give more precision. Cautiously, we can deal with the results as studying only single secondary health care hospital is a limitation. Also, being a retrospective cohort study can’t protect against the liability of unintentional selection bias.

Conclusion

Histopathological examination of the resected appendectomy specimen is mandatory and advantageous in appropriate diagnosis of appendiceal inflammation. Relying solely on the intraoperative diagnosis is highly variable and insufficient in ruling out the uncommon disease. Preoperative utilization of CT in the diagnosis of cases with AA symptoms is beneficial in reducing the NAR.

Funding: No funding or financial support.

Ethical approval: Approval of the study was obtained from the Regional Research Ethics Committee in Qassim region (No 607-43-8271). The aim of the study was explained to the Head manager of the studied hospital to get his approval before conducting the study. All data was kept confidential and were used only for research purposes.

Conflict of Interest: The author has no conflict of interest to declare.

Acknowledgments: Author is thankful all people in the selected hospital who facilitate this research, Mr. Hamad and Miss Samar in medical records room, Miss Amnah in the radiology department and Dr. Eman in the histopathology lab.

References

1. Humes DJ, Simpson J. Acute appendicitis. BMJ. 2006 Sep 9;333(7567):530-4. doi: 10.1136/bmj.38940.664363.AE.
2. Akbulut S, Tas M, Sogutcu N, Arikanoglu Z, Basbug M, Ulku A, Semur H, Yagmur Y. Unusual histopathological findings in appendectomy specimens: a retrospective analysis and literature review. World J Gastroenterol. 2011;21;17(15):1961-70. doi:10.3748/wjg.v17.i15.1961.
3. Jaschinski T, Mosch C, Eikermann M, Neugebauer EAJBg. Laparoscopic versus open appendectomy in patients with suspected appendicitis: a systematic review of meta-analyses of randomised controlled trials. BMC Gastroenterol. 2015;15(1):1–10. doi.org/10.1186/s12876-015-0277-3 .
4. Marudanayagam R, Williams GT, Rees BI. Review of the pathological results of 2660 appendicectomy specimens. J. Gastroenterol. 2006; 41:745–9. doi: 10.1007/s00535-006-1855-5.
5. Charfi S, Sellami A, Affes A, Yaich K, Mzali R, Boudawara T. Histopathological findings in appendectomy specimens: a study of 24,697 cases. Int. J. Colorectal Dis. 2014;29 (8):1009–12. doi: 10.1007/s00384-014-1934-7.
6. Bhangu A, Søreide K, Di Saverio S, Assarsson JH, Drake FT. Acute appendicitis: modern understanding of pathogenesis, diagnosis, and management. Lancet. 2015;386(10000):1278–87. doi.org/10.1016/S0140-6736(15) 00275-5.
7. Arnbjornsson E. Acute appendicitis and dietary fiber. Arch Surg. 1983;118(7):868–70. doi: 10.1001/archsurg.1983.01390070076015.
8. Hale DA, Molloy M, Pearl RH, Schutt DC, Jaques DP. Appendectomy: a contemporary appraisal. Ann Surg. 1997; 225:252-61. doi: 10.1097/00000658-199703000-00003.
9. Dai L, Shuai J. Laparoscopic versus open appendectomy in adults and children: a meta-analysis of randomized controlled trials. United European Gastroenterol J. 2017; 5:542-53. 10.1177/2050640616661931
10. Birnbaum BA, Wilson RS. Appendicitis at the millennium. Radiology. 2000;215(2) 337–48. doi: 10.1148/radiology.215.2.r00ma24337.
11. Wagner PL, Eachempati SR, Soe K, Pieracci FM, Shou J, Barie PS. Defining the Current Negative Appendectomy Rate: for Whom Is Preoperative Computed Tomography Making an Impact?. Surgery. 2008;144 (2):276–82. doi: 10.1016/j.surg.2008.03.040.
12. Yilmaz M, Akbulut S, Kutluturk K, Sahin N, Arabaci E, Ara C, et al. Unusual histopathological findings in appendectomy specimens from patients with suspected acute appendicitis. World J Gastroenterol. 2013;19(25):4015-22. doi: 10.3748/wjg.v19.i25.4015.
13. Shapiro R, Eldar S, Sadot E, Papa MZ, Zippel DB. Appendiceal Carcinoid at a Large Tertiary Center: Pathologic Findings and Long-Term Follow Up Evaluation. Am J Surg. 2011; 201(6):805-8. doi:10.1016/j.amjsurg. 2010.04.016
14. Zoarets I, Poluksht N, Halevy A. Does selective use of computed tomography scan reduce the rate of "white" (negative) appendectomy? Isr Med Assoc J. 2014; 16:335-7.
15. Dafle V, Das A, Jagtap SV et al. Clinico-pathological Study of Appendicectomy Specimens. Indian Journal of Pathology: Research and Practice. 2020;9(1 Part II):221-227. doi: 10.21088/ijprp.2278.148X.9120.34
16. Matthyssens LE, Ziol M, Barrat C, Champault G. Routine Surgical Pathology in General Surgery. Br J Surg. 2006; 93:362-8. doi: 10.1002/bjs.5268
17. Jones AE, Phillips AW, Jarvis JR, Sargen K. The value of routine histopathological examination of appendicectomy specimens. BMC Surg. 2007;10(7):17. doi: 10.1186/1471-2482-7-17.
18. Sinha R, Dey A. A retrospective study of histopathological features of appendectomy specimens–What all can expect. J Med Sci Health. 2016;2(2):6–12. doi: 10.46347/JMSH.2016. v02i02.002
19. SCOAP Collaborative; Cuschieri J, Florence M, Flum DR, Jurkovich GJ, Lin P, Steele SR, et al. Negative appendectomy and imaging accuracy in the Washington State Surgical Care and Outcomes Assessment Program. Ann Surg. 2008 Oct;248(4):557-63. doi: 10.1097/SLA.0b013e318187aeca.
20. Raja AS, Wright C, Sodickson AD, Richard DZ, Gordon DS, Richard H, et al. Negative appendectomy rate in the era of CT: an 18-year perspective. Radiology. 2010;256:460-5. doi: 10.1148/radiol.10091570
21. Bhangu A. RIFT Study Group on behalf of the West Midlands Research Collaborative. Evaluation of appendicitis risk prediction models in adults with suspected appendicitis. Br J Surg. 2020;107(1):73- 86. doi:10.1002/bjs.11440.
22. Poletti P-A, Becker M, Becker CD. Emergency assessment of patients with acute abdominal pain using low-dose CT with iterative reconstruction: A comparative study. Eur Radiol. 2017;27(8):3300-9. doi: 10.1007/s00330-016-4712-9.
23. Chang D, Maluda M, Lee L, Premaratne C, Khamhing S. A 3-Year Study of Predictive Factors for Positive and Negative Appendicectomies. J Invest Surg. 2019;32(5):469-73. doi: 10.1080/08941939.2018.1441341.
24. Flum DR, Koepsell T. The clinical and economic correlates of misdiagnosed appendicitis: nationwide analysis. Arch. Surg. 2002;137(7):799–804. doi.org/10.1001/archsurg.137.7.799.
25. Jat MA, Al-Swailmi FK, Mehmood Y, Alrowaili M, Alanazi S. Histopathological Examination of Appendicectomy Specimens at a District Hospital of Saudi Arabia. Pak J Med Sci. 2015 Jul-Aug;31(4):891-4. doi: 10.12669/pjms.314.7453.
26. Omiyale AO, Adjepong S. Histopathological correlations of appendectomies: a clinical audit of a single center. Ann Transl Med. 2015 Jun;3(9):119. doi: 10.3978/j.issn.2305-5839.2015.05.02.
27. Abd Al-Fatah M. Importance of Histopathological Evaluation of Appendectomy Specimens. Al-Azhar Assiut Med J. 2017;15(2):97-103. doi: 10.4103/AZMJ.AZMJ_19_17
28. Tayfur M, Balci M. Pathological changes in appendectomy specimens including the role of parasites: a retrospective study of 2400 cases of acute appendicitis. Niger. J. Clin. Pract. 2019;22 (2):270–5. doi.org/10.4103/njcp.njcp_ 271_18.
29. Kadi M, Nasr A, Shabkah AA, Alnahari R, Alhawi A, Alyamani R, et al. Histopathological examination of cases with acute appendicitis, A retrospective study at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Ann Med Surg (Lond). 2022 19; 81:104401. doi: 10.1016/j.amsu.2022.104401. eCollection 2022 Sep.
30. Rehman S, Khan AI, Ansari HA et al. Retrospective analysis of appendicectomy specimens: a tertiary care center-based study. Saudi Surg J. 2017; 5(2):71-5. doi: 10.4103/ssj.ssj_16_17
31. Patel MM, Shah RJ. Impact of histopathological examination of appendix in context to clinical management of patients. Annals Pathol. Lab. Med. 2017;4(6): A699–A704. doi.org/10.21276/APALM.1496.
32. Slotboom T, Hamminga JT, Hofker HS, Heineman E, Haveman JW. Apple Study Group Appendicitis and Laparoscopic Evaluation. Intraoperative motive for performing a laparoscopic appendectomy on a postoperative histological proven normal appendix. Scand J Surg. 2014 Dec;103(4):245-8. doi: 10.1177/1457496913519771.
33. Talreja DP, Bai R, Talreja S, Al-Amri HH, Al-Sawafi K, Haque PW, Albatanony A. Incidence of negative appendicectomy: retrospective follow-up of histopathology specimens. Int Surg J. 2022 Sep;9(9):1524-7. doi: https://doi.org/10.18203/2349-2902.isj20222095
34. Al-Balas H, Al-Saffar RS, Al-Balas M et al. Unusual histopathological findings in appendectomy specimens with clinical diagnosis of acute appendicitis: A retrospective cohort analysis. Annals of Medicine and Surgery. 2021;69. doi: 10.1016/j.amsu.2021.102720
35. Emre A, Akbulut S, Bozdag Z, Yilmaz M, Kanlioz M, Emre R, et al. Routine histopathologic examination of appendectomy specimens: retrospective analysis of 1255 patients. Int Surg. 2013 Oct-Dec;98(4):354-62. doi: 10.9738/INTSURG-D-13-00098.1.
36. Webb EM, Nguyen A, Wang ZJ, Stengel JW, Westphalen AC, Coakley FV. The negative appendectomy rate: who benefits from preoperative CT? AJR Am J Roentgenol. 2011 Oct;197(4):861-6. doi: 10.2214/AJR.10.5369.
37. Kulkarni MP, Sulhyan KR, Barodawala SM, Yadav DH. Histopathological study of lesions of the appendix. Int. J. Health Sci. Res. 2017; 7 (4):90-5. ISSN: 2249-9571
38. Unver N, Coban G, Arıcı DS et al. Unusual histopathological findings in appendectomy specimens: a retrospective analysis of 2047 cases. Int. J. Surg. Pathol. 2019;27 (2): 142–6. doi.org/ 10.1177/1066896918784650.