Histopathological examination of cases with acute appendicitis, A retrospective study at King Abdulaziz University Hospital, Jeddah, Saudi Arabia

1. Name of the registry: ClinicalTrials.gov . 2. Unique Identifying number or registration ID: NCT05391269 . 3. Hyperlink to your specific registration (must be publicly accessible and will be checked): https://www.clinicaltrials.gov/ct2/show/NCT05391269?term=NCT05391269&draw=2&rank=1 .

Conception and design of the study, Mai Kadi, Abdulaziz Saleem; Data acquisition, Rothana Alnahari, Afnan Alhawi, Romaysaa Alyamani; Analysis and interpretation of the data, Mai Kadi; Drafting of the manuscript, Mai Kadi, Ali Nasr, Alaa Shabkah, Abdulaziz Saleem .

The need for informed consent from all patients included in this study was waived because of the retrospective design. The Research Committee at the Unit of Biomedical Ethics at King Abdulaziz University hospital (HA-02-J-008) approved this study with reference number (250-22).

The Research Committee at the Unit of Biomedical Ethics at King Abdulaziz University hospital (HA-02-J-008) approved this study with reference number (250-22).

The STROCSS requirements were followed when reporting our paper [ 13 ]. The study was registered at ClinicalTrials.gov with a unique identifying number ( NCT05391269 ) [ 14 ]. Not involved. A retrospective cohort review was conducted in which 940 appendectomy were analyzed over a period of 8 years (2010–2017) at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. All patient electronic files underwent appendectomy were retrieved using the codes of “open appendectomy”, “laparoscopic appendectomy” and “other appendectomy". For each patient, we obtained demographics data, findings of preoperative imaging, the surgical approach and the histopathological reports of all resected specimens. All specimens were submitted for routine histopathological evaluation. The fixation of the samples was done in 10% buffered formalin and the standard protocols were followed for tissue processing and paraffin embedding. Sections with 3-μm thickness were cut and stained with hematoxylin and eosin stain. The use of special stains, such as periodic acid Schiff and Ziehl Neelsen, was done wherever necessary. Our primary outcome is to describe the histopathological findings of all appendectomy specimens. Our secondary outcomes are to estimate the disease incidence in relation to age, and gender as well as to evaluate the accuracy of imaging tools (CT scan and US) in the preoperative diagnosis of appendicitis. Descriptive statistics were applied using counts, proportions (%) for categorical variables, mean, and standard deviation for continuous variables. For comparisons, the Mann Whitney U test and Chi-square test for non-parametric variables were performed. Data deviates from the normal distribution using the Shapiro-Wilk test (p < 0.05). To demonstrate statistical significance, a p-value of 0.05 (two-sided) was utilized. All data analyses were conducted with the aid of the statistical package for social sciences, version 21. (SPSS, Chicago, IL, USA).

A total of 940 patients who underwent appendectomy were enrolled in this study. Demographic data for the patients are shown in Table 1 . The patients' mean age was 23.4 years (±12.2), with a 3:2 male to female proportion. The percentage of patients who had US was 30.9%, and 41.3% of them had acute appendicitis. The percentage of patients who got CT scans, on the other hand, was 29%, with an acute appendicitis detection rate of up to 85.7% ( Table 2 ). Table 1 Baseline characteristics of patients who underwent appendectomy from 2010 to 2017, King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia (n = 940). Table 1 Study variables N (%) Age, years (mean ± SD) 23.4 ± 12.2 Gender ● Male 558 (59.4%) ● Female 382 (40.6%) Ultrasound ● Yes 288 (30.9%) ● No 652 (69.4%) Ultrasound findings (n = 288) a ● The appendix is not visualized 103 (35.8%) ● Acute appendicitis 119 (41.3%) ● Others 24 (08.3%) ● No appendicitis 42 (14.6%) CT Scan (n = 940) ● Yes 273 (29.0%) ● No 667 (71.0%) CT scan findings (n = 273) a ● No evidence of appendicitis 14 (5.1%) ● Acute appendicitis 234 (85.7%) ● Other 25 (9.2%) Approach ● Laparoscopic appendectomy 671 (71.4%) ● Open appendectomy 269 (28.6%) Histopathology Results ● Acute appendicitis 805 (85.6%) ● Negative appendicitis 135 (14.4%) White blood cells, 10 9 per L (mean ± SD) 13.5 ± 5.28 a The number of patients who received diagnostic imaging differs from the total number included in the analysis. Table 2 Relationship between acute appendicitis and baseline characteristics of the patients (n = 940). Table 2 Variable Acute Appendicitis P-value Positive N (%) (n = 805) Negative N (%) (n = 135) Gender ● Male 506 (62.9%) 52 (38.5%) <  0.001 ● Female 299 (37.1%) 83 (61.5%) Ultrasound ● Yes 227 (28.2%) 61 (45.2%) <  0.00 ● No 578 (71.8%) 74 (54.8%) CT Scan ● Yes 238 (29.6%) 35 (25.9%) 0.389 ● No 567 (70.4%) 100 (74.1%) Approach ● Laparoscopic appendectomy 574 (71.3%) 97 (71.9%) <  0.001 ● Open appendectomy 231 (28.7%) 38 (28.1%) Age, years mean ± SD 23.2 ± 12.4 24.2 ± 10.9 0.119 White blood cells 10 9 per L mean ± SD 13.9 ± 5.11 10.5 ± 5.29 <  0.001 Baseline characteristics of patients who underwent appendectomy from 2010 to 2017, King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia (n = 940). Male Female Yes No The appendix is not visualized Acute appendicitis Others No appendicitis Yes No No evidence of appendicitis Acute appendicitis Other Laparoscopic appendectomy Open appendectomy Acute appendicitis Negative appendicitis The number of patients who received diagnostic imaging differs from the total number included in the analysis. Relationship between acute appendicitis and baseline characteristics of the patients (n = 940). Male Female Yes No Yes No Laparoscopic appendectomy Open appendectomy The majority of appendectomies were performed laparoscopically 71.4%. Of all the appendectomy specimens, 85.6% were consistent with acute appendicitis. The mean white blood cell count preoperatively was 13.5 × 10 9 per L (±5.28). The histopathological findings of the appendectomy specimens of our cohort are demonstrated in Fig. 1 . Our data showed that most of the positive appendicitis cases 85.6% were reported as acute suppurative appendicitis in the final histopathology report 62%, followed by perforated appendicitis 16.2% and acute hemorrhagic appendicitis 0.53%. In this cohort, the normal appendectomy rate was 14.4%. Other unexpected findings in the appendectomy specimen 3.93% included fecolith, granulomas, mucocele, endometriosis, food/fecal impaction, and schistosomiasis. Fig. 1 Frequencies of histological findings of the appendectomy specimens (n = 940). Fig. 1 Frequencies of histological findings of the appendectomy specimens (n = 940). The Chi-square test was used to determine the relationship between the diagnosis of acute appendicitis and the baseline characteristics of the patients, as shown in Table 3 . Being male (p < 0.001), undergoing preoperative ultrasound (p < 0.001), having elevated white blood cells count (p < 0.001) was significantly associated with accurate diagnosis of acute appendicitis confirmed by histopathology. Table 3 Histopathological findings of patients who received radiographic diagnostic imaging. Table 3 US (N = 288) Appendicitis positive histopathology (n = 230) Appendicitis negative histopathology (n = 58) +ve appendicitis (n = 119) 106 13 -ve appendicitis (n = 169) 124 45 CT (N  =  273) Appendicitis positive histopathology (n  =  255) Appendicitis negative histopathology (n  =  18) + ve appendicitis (n = 234) 230 4 -ve appendicitis (n = 39) 25 14 CT: Computed tomography US: Ultrasonography Histopathological findings of patients who received radiographic diagnostic imaging. In our study, 288 patients received ultrasound and 273 had CT scan before having an appendectomy. CT sensitivity as a technique to diagnose acute appendicitis is 90.2%, and its accuracy is 89.4%, while the US sensitivity is 46% and its accuracy is 52.4% ( Table 3 ).

No funding was obtained for this study.

The Guarantor are Mai Kadi and Abdulaziz Saleem.

Routine review of all histopathological specimen after appendectomy is essential to avoid missing uncommon pathology in the appendix. Surgeons should be aware of the uncommon histopathology findings as some disorders call for additional management beyond appendectomy. The clinical details, radiological investigations including CT scan and histopathological diagnoses are required for better management in cases of appendicular lesions.

Acute appendicitis is by far the most prevalent surgical emergency for several decades [ 6 ]. Although doctors regard this as a simple diagnosis, a significant proportion of misdiagnosis frequently results in a negative appendectomy [ 15 ]. As a result, it continues to be a clinical entity and a diagnostic dilemma [ 16 ]. The incidence of appendicitis is more common in men than females [ [17] , [18] , [19] , [20] ]. In the current study, the incidence in males and females was 59.4% and 40.6%, respectively. Our study emphasizes the need of doing basic laboratory tests and using imaging modalities to diagnose acute appendicitis. An elevated total leukocyte count with a left shift has been linked to the diagnosis of acute appendicitis [ 21 , 22 ]. Leukocytosis was found in both positive and negative appendicitis patients in our population. However, positive acute appendicitis patients had a considerably higher mean leukocytic count. In the previous literature, CT scan showed specificity ranges from 89% to 98%, sensitivity ranges of 96%–97%, with a negative predicted value of 95%–98.8%, a positive predicted value of 90%–96% and accuracy of 94%–97.6% [ 23 , 24 ] and these estimated diagnostic values are concordant with our study. In contrast, the previous studies showed that ultrasonography has a specificity of 91%–97%, sensitivity of 74.2%–76%, negative predicted value of 76%–93%, positive predicted value of 88%–95% and accuracy of 83%–92% [ 23 , 25 ] and these values are non-concordant with our findings, which is likely to be related to the US limitations and the fact that it is operator dependent. It has been noted that even when acute appendicitis was not proven by histopathology, patients' symptoms typically improve after surgery [ 26 ]. In this case, the underlying reason could be an early subclinical appendicitis at the microcellular level. As a result, macroscopic examination cannot provide an appropriate diagnosis of appendiceal inflammation, highlighting the importance of histological investigation [ 27 ]. The majority of patients in our analysis had an appendicitis histological diagnosis verified, 85.6%, and the remaining 14.4% were negative for appendicitis. This finding was consistent with many studies [ [28] , [29] , [30] ]. The negative appendectomy rate in our population was 14.4%, which is higher than in the literature, where it is reported to be around 6%. This could be attributed to the less frequent use of diagnostic imaging modalities at our institute [ 5 , 31 , 32 ]. Delays in identifying appendicitis can result in consequences including perforation, gangrene, and septic shock. The incidence of perforation in appendicitis was noted to be 12.6% in our study, as shown in ( Fig. 1 ). Korner H. et al. [ 33 ] observed that perforated appendicitis occurred in 12%, with higher rates in children and the elderly, regardless of gender [ 33 ]. Gofrit O. et al. reported that the incidence of perforation in appendicitis was 8.7% [ 34 ]. The rate of gangrenous appendicitis was 2.55% in our study. A study by Kulkarni M. et al. [ 35 ] and Nabipour [ 36 ] reported the incidence of gangrenous appendicitis are 1.53% and 8% of all cases of appendicitis, respectively. Previous studies have shown that most positive appendicitis cases were reported as acute suppurative appendicitis, gangrenous appendicitis, and perforated appendicitis, confirmed by the final histopathology [ 5 , 31 , 32 ]. These findings are consistent with our data which showed that most of the positive appendicitis cases 85.6% were reported as acute suppurative appendicitis in the final histopathology report 62%, followed by perforated appendicitis 16.2% and the lowest percentage for the acute hemorrhagic appendicitis 0.53%. In contrast the negative appendicitis has a wide range of unusual histopathological findings including carcinoid tumor, mucocele, mucinous neoplasms, adenocarcinoma, tuberculosis, actinomycosis , Enterobius vermicularis parasite infection, granulomatous inflammation, appendiceal endometriosis, eosinophilic infiltration, and appendicular diverticulitis [ 5 , 31 , 32 ]. In our study, negative appendicitis, which represents 14.4% of cases were reported mainly as normal appendix with no inflammatory changes 7.44%, followed by other miscellaneous (faecolith, granulomas, mucocele, endometriosis, food/stool impaction, schistosomiasis), which represented 3.93% of the negative appendicitis cases. Numerous studies have found that females experience more negative appendectomies than males [ 6 , 16 , 18 , [35] , [36] , [37] , [38] , [39] , [40] ]. Seetahal et al. [ 41 ] reported that 11.83% of 475,651 appendectomy cases were negative appendectomies, with women accounting for 71.6% of negative appendectomies. Gynecological disorders affecting the ovary are the most frequently mistaken for appendicitis [ 41 ]. This is consistent with the observations of this study, in which women represented about 61.5% of the negative appendectomies. This observation might be due to gynecological illnesses that resemble the clinical appearance of acute appendicitis. Benign and malignant ovarian neoplasms, ovarian cysts, leiomyomas, endometriosis and pelvic adhesions have purportedly been misinterpreted in women as acute appendicitis [ 41 ]. It is obvious from the preceding discussion that sending all appendectomy specimens for histological evaluation is both obligatory and beneficial. When the expense of the operation is weighed against the potential advantages, it is discovered that the benefit much surpasses the cost in this instance. Early detection and management of an appendicular lesion might save the patient from incurring further fees if the disease progresses to other organs. Our main strengths of this study were the large number of patients included in the study. Moreover, this topic is understudied in our geographical region (Gulf countries). Our major limitation of this study was that it is done in single tertiary center. As the study is in a retrospective design, the possibility of unintentional patient selection bias cannot be excluded. Hence, results should be interpreted with caution.

Not commissioned, externally peer reviewed.

One of the most frequent abdominal emergencies globally is acute appendicitis [ 1 ]. It is less frequent at both extremes of age, but more common in the twenties and thirties [ 2 ] with a 6.7% lifetime risk in women and 8.6% in men [ 3 ]. Adoption of a low-fiber diet in developing nations has resulted in a rise in the incidence of acute appendicitis [ 4 ]. It is characterized by an inflammation of the vermiform inner layer of the appendix [ 5 ]. The most prevalent pathophysiological mechanisms of acute appendicitis are lymphoid hyperplasia and fecolith. Other conditions have shared a similar clinical presentation of acute appendicitis, such as endometriosis, infectious diseases, granulomatous diseases, neurofibroma, diverticulitis, and appendiceal malignancies [ [6] , [7] , [8] ]. The ability of clinical evaluation to accurately diagnose appendicitis is limited [ 9 ]. As a result, several imaging modalities such as magnetic resonance imaging (MRI), ultrasonography (US), and computed tomography (CT) are commonly employed to further investigate individuals suspected of having acute appendicitis [ 9 ]. The incidence of negative appendectomy has been reduced with the use of preoperative CT scan, especially in women, where it is frequently misdiagnosed as other gynecological emergency disorders [ 10 ]. Histopathological examination of appendectomy specimens provides the definitive diagnosis for all resected specimens [ 11 ]. The pathology report is crucial not just in situations of acute appendicitis, but also in cases with unexpected findings [ 12 ]. Our aims are three folds. First, is to describe the histopathological findings of all appendectomy specimens. And second, is to estimate the disease incidence in relation to age, and gender. Third, the accuracy of imaging tools (CT scan and US) in the preoperative diagnosis of appendicitis will be evaluated.

The authors declare that there are no conflicts of interests.