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Introduction
Inflammation of the appendix, called acute appendicitis, is a common intra-abdominal condition requiring immediate surgical intervention 1,2. Despite the advanced modalities appendectomy remains the standard treatment of acute appendicitis H Acute appendicitis is considered to have a high risk of occurrence 5, which remains close to 7 % of individuals, 23.1 % and 12 % in men and women, respectively 6. Removal of the appendix not only decreases the risk of presenting life-threatening complications, including perforation and sepsis, but also allows histopathological analysis, which is the gold standard for the confirmation of the diagnosis of acute appendicitis, independent of the intraoperative findings 6,7 If the pathologist shows transmural inflammation of the appendix or granulocytes in the mucosa or infiltration within the epithelium, the diagnosis of acute appendicitis is made 8. However, open appendectomy has the disadvantage of a high rate of negative appendectomy 5, which refers to an appendectomy based on the clinical diagnosis of acute appendicitis, but in which the histopathological analysis of the appendix is normal 8.
While patients who are found to have simple appendicitis have been shown to be discharged safely on the day of surgery without additional antibiotic management, patients with complex appendicitis have a longer course requiring hospitalization for treatment with intravenous antibiotics. According to Weis et al. 9, appendicitis incurs in significant costs in health care in the United States, with estimated hospital charges of $2.4 billion annually. Therefore, the importance of knowing the relationship between the intraoperative surgical findings and the pathological result in our setting is raised.
Methods
Study design and patient eligibility
We conducted an observational, cross-sectional study to evaluate the agreement between surgical and histopathological findings of patients who underwent an appendectomy as treatment for acute appendicitis at the central military hospital in Bogotá, Colombia. Patients of any age and sex were deemed eligible if they underwent an appendectomy between October 2015 and October 2016. We excluded patients with incomplete data (surgical records, histopathological report or both) or patients who underwent surgery in another institution.
Outcomes
Data was collected from the patient's surgical notes and were classified according to the institutional standards as negative appendix, inflamed, suppurative, gangrenous and perforated. Original histopathological reports were obtained for histological diagnosis, which were classified in the same fashion. False positive results were defined as positive surgical finding for appendicitis and a normal histopathological finding, false negative was occurred when surgeons diagnosed a normal appendix and pathology was positive for appendicitis.
Data Collection and Sample Size
Data was collected and tabulated in a Microsoft® Excel spreadsheet. We estimated a minimum sample size of 329 subjects by employing a power based approach for studies of inter-observer agreement with a multinomial outcome of five levels; alpha was set at 0.05 and a power of 0.8, with an expected kappa of 0.3 from previous studies 10. Expecting a maximum of 20 % of loss to follow-up we included 82 patients for our final sample size of 411 patients.
Statistical analysis
Descriptive statistics were used to summarize differences in demographic characteristics, surgical and histopathological findings among study subjects. For primary analyses inter-rater concordance with five categories of diagnosis was determined using weighted Cohen's Kappa statistics. Data was analyzed using SAS/STAT® university edition Copyright© 2012-2017, SAS Institute Inc., Cary, NC, USA.
Results
Patient results
A total of 4I8 patients we included prospectively of which 71 % (n=297) were male and 29 % (n=121) were female, with a mean age of 31.8 ± 14.72 years (range: 15-86). Data on C-reactive protein was available for 390 patients with a mean value of 6.59 ± 8.70 mg/dL, while leucocyte information was available for 412 patient. Pre-operative abdominal echography and double contrasted CT-scans was performed on 230 and 67 patients, respectively, with suggestive findings for appendicitis in 99 (26.0 %) for abdominal echography and 48 (11.9 %) for abdominal CT-scan. Full patients' demographics and other clinical details are shown in table 1.
Surgical and pathological agreement
Documentation on histopathological finding was not available in eight patients, because appendectomy for these patients was performed in another institution. Of the 410 available records, the pathologist assessed the tissue samples as 17 (4.1 %) negative, 80 (19.5 %) inflamed, 244 (59.5 %) suppurative, 68 (16.6 %) gangrenous and one (0.2 %) perforated. According to intraoperative findings, surgeons determined 32 (7.8 %) appendix as negative, 78 (18.9 %) as inflamed, 110 (26.7 %) as suppurative, 137 (33.2 %) gangrenous and 55 (13.3 %) as perforated. Using the histopathological diagnosis as the gold standard, agreement was the highest in patients with suppurative appendicitis (82/11O; 74.5 %), and the lowest were with perforated appendix O (0 %). The results are shown in table 2. Overall Kappa statistics for interrater reliability using a five diagnostic categories indicated a poor-fair agreement between the pathologist and surgeons (Kappa = 0.2950, 95%CI 0.2384-035.17, p < 0.0001).
Discussion
The ability to diagnose the degree of intraoperative appendicitis is essential as it will ultimately influence postoperative care 11. According to Lamps et al and Rabah et al the diagnostic criteria remain controversial 12,13. Moreover, there is no standard definition for histopathological reports, some authors argue the presence of neutrophils in the mucosa 14, while other require extension to muscularis propia 12. This issue is evident in various studies where it has been that the intraoperative impression of the surgeon at the time of appendectomy does not always allow a correlation with the pathological diagnosis 15. One study compared the microscopic and macroscopic findings in 200 consecutive appendectomies and found that 9% of macroscopically normal appendix were found with inflammation on microscopic analysis 16. Excluding 139 patients with obvious macroscopic disease and 21 female patients with other pathologies, this increased the incidence of false negative appendicitis to 45 %. Other study by Bliss et al over 255 children undergoing appendectomy found that 48 % of patients treated for complicated appendicitis were classified in an inconsistent manner between the surgeon and the pathologist 17. Finally, Roberts et al found that the overall accuracy in the macroscopic evaluation of the appendix during surgery was 87.3 %, with cases of gangrene, perforation or abscess diagnosed at the time of surgery, correlating well with the histopathological findings; the positive predictive value, however, was lower than 91.7 % if only inflammation was evident 18.
Concomitantly, we found that there is a poor correlation between macroscopic surgical findings by the surgeon and the histopathological findings reported by the pathologist in negative appendicitis (K = 0.2, 95%CI 0.191-0.394, p = 0.000), which is similar in other studies 19,20. On the other hand, the inflammatory phase was mostly reported by the surgeon as the gangrenous phase (30.8 %); however, according to pathological findings, the gangrenous phase reached only 14.9 % (30.8 vs. 14.9 %). Contrary to the previous study, where there is greater concordance in the findings of uncomplicated vs. perforated appendicitis, in our study we found that the highest concordance was in early stages of appendicitis or uncomplicated appendicitis both in histopathologic vs. surgical findings.
The main limitation of our study was the lack of standardization of the surgical reports and the participation of eight different surgeons in our study. These factors may have influenced the variability of the reports and influenced the lack of agreement. Nonetheless, we consider that our sample size allows us to draw special attention to the low agreement between the pathological and surgical reports.
Conclusion
Intra-operative findings dictate post-operative treatment strategies for acute appendicitis. Current debate between histological and surgical criteria may influence inter-rater agreement. There is a poor concordance between surgical and pathologic findings in our study, similar to previous published articles. It is therefore essential that surgeons and pathologist revise the clinical working definition of appendicitis as well as the histological criteria to better the agreement. This will ultimately improve the treatment of the patients.
