Safety and cost analysis of selective histopathological examination following appendicectomy and cholecystectomy (FANCY study): protocol and statistical analysis plan of a prospective observational multicentre study

Abstract

IntroductionRoutine histopathological examination following appendicectomy and cholecystectomy has significant financial implications and comprises a substantial portion of the pathologists’ workload, while the incidence of unexpected pathology is low. The aim of the selective histopathological examination Following AppeNdicectomy and CholecystectomY (FANCY) study is to investigate the oncological safety and potential cost savings of selective histopathological examination based on macroscopic assessment performed by the surgeon.Methods and analysisThis is a Dutch multicentre prospective observational study, in which removed appendices and gallbladders will be systematically assessed by the operating surgeon for macroscopic abnormalities suspicious for malignant neoplasms. After visual inspection and digital palpation of the removed specimen, the operating surgeon will report whether macroscopic abnormalities suspicious for a malignant neoplasm are present, and if he or she believes additional microscopic examination by the pathologist is indicated. Regardless of the surgeon’s assessment, all specimens will be sent for histopathological examination. In this way, routine histopathological examination can be compared with a hypothetical situation in which specimens are routinely examined by surgeons and only sent to the pathologist on indication. The two main outcomes are oncological safety and potential cost savings of a selective policy. Oncological safety of selective histopathological examination will be assessed by calculating the number of patients in whom a histopathological diagnosis of an appendiceal neoplasm or gallbladder cancer with clinical consequences benefitting the patient would have been missed. A cost analysis will be performed to quantify the potential cost savings.Ethics and disseminationThe study protocol was reviewed by the Institutional Review Board of the Amsterdam UMC, location AMC, which decided that the Dutch Medical Research Involving Human Subjects Act is not applicable. In all participating centres, approval for execution of the FANCY study has been obtained from the local Institutional Review Board before the start of inclusion of patients. The study results will be disseminated through peer-reviewed publications and conference presentations. Guidelines will be revised according to the findings of the study.Trial registration numberNCT03510923.

Safe, selective histopathological examination of gallbladder specimens: a systematic review

“…To gain more evidence on safety and potential cost savings of selective histopathological examination, a large prospective cohort of patients is required. The FANCY study 97 (NCT03510923) was designed for this reason.…”

Spectrum of Histologic Findings in Orchiectomy Specimens of Patients Seeking Male to Female Physical Adaptation

“…Some groups have studied benign specimens such as sleeve gastrectomies, gallbladders, appendices, and hernia sacs and have come up with recommendations to accurately document the histologic findings in a costeffective manner. [23][24][25][26] Some of these groups have even suggested a "gross-only" approach in which no tissue sections are submitted for microscopic examination if no lesions are grossly identified. The gross-only approach may not be the best way to go in the orchiectomy specimens just yet, as this filed is constantly and rapidly evolving.…”

Oncological Safety and Potential Cost Savings of Routine vs Selective Histopathological Examination After Appendectomy

“… 15 The study protocol and statistical analysis plan were published before. 16 This study was conducted in accord with the ethical standards of the Helsinki Declaration of 1975.…”

“…Secondary outcomes were described in detail in the previously published study protocol 16 , and included (1) the clinical outcomes of patients with an appendiceal neoplasm, both in terms of benefit and harm, (2) the ability of the surgeon to detect an appendiceal neoplasm during macroscopic examination, and (3) the incidence of other histo-pathological diagnoses after appendectomy. In a posthoc analysis, the different reasons for histopathological examination described by the surgeons were evaluated and allocated into categories.…”

“…Details concerning the group size calculation are reported in the statistical analysis plan. 16 In short, it was assumed that (1) less than 1 out of 1000 examined specimens will contain an appendiceal neoplasm with clinical consequences benefiting the patient that is not recognized by the surgeon, and (2) selective histopathological examination is considered safe if the upper limit of the two-sided 95% confidence interval (CI) of the proportion of missed appendiceal neoplasms with clinical consequences benefiting the patient is below 3 per 1000 examined specimens, within the group of specimens that would have been refrained from histopathological examination. A sample size of 4462 specimens was needed to achieve 84% power to detect a difference of 0.002 using a one-sided binominal test at a target significance level of 0.025, assuming a baseline and actual proportion of 0.001, and a noninferiority limit of 0.00299.…”