Oncological Safety and Potential Cost Savings of Routine vs Selective Histopathological Examination After Appendectomy: Results of the Multicenter, Prospective, Cross-Sectional FANCY Study.

OBJECTIVE: To investigate the oncological safety and potential cost savings of selective histopathological examination after appendectomy. BACKGROUND: The necessity of routine histopathological examination after appendectomy has been questioned, but prospective studies investigating the safety of a selective policy are lacking. METHODS: In this multicenter, prospective, cross-sectional study, inspection and palpation of the (meso)appendix was performed by the surgeon in patients with suspected appendicitis. The surgeon's opinion on additional value of histopathological examination was reported before sending all specimens to the pathologist. Main outcomes were the number of hypothetically missed appendiceal neoplasms with clinical consequences benefiting the patient (upper limit two-sided 95% confidence interval below 3:1000 considered oncologically safe) and potential cost savings after selective histopathological examination. RESULTS: Seven thousand three hundred thirty-nine patients were included. After a selective policy, 4966/7339 (67.7%) specimens would have been refrained from histopathological examination. Appendiceal neoplasms with clinical consequences would have been missed in 22/4966 patients. In 5/22, residual disease was completely resected during additional surgery. Hence, an appendiceal neoplasm with clinical consequences benefiting the patient would have been missed in 1.01:1000 patients (upper limit 95% confidence interval 1.61:1000). In contrast, twice as many patients (10/22) would not have been exposed to potential harm due to re-resections without clear benefit, whereas consequences were neither beneficial nor harmful in the remaining seven. Estimated cost savings established by replacing routine for selective histopathological examination were €725,400 per 10,000 patients. CONCLUSIONS: Selective histopathological examination after appendectomy for suspected appendicitis is oncologically safe and will likely result in a reduction of pathologists' workload, less costs, and fewer re-resections without clear benefit.

Daytime versus Nighttime in Acute Appendicitis.

BACKGROUND: Little is known about patients with appendicitis presenting at nighttime. It is hypothesized that patients presented at night more frequently have a complicated (gangrenous or perforated) appendicitis and therefore develop more postoperative complications. METHODS: In this study data were used from the nationwide, prospective SNAPSHOT study appendicitis, including 1975 patients undergoing surgery for suspected appendicitis. This study included only adults. Two primary outcomes were defined: (A) The proportion of patients with complicated appendicitis and (B) the proportion of patients with a complication postoperatively presenting during daytime versus nighttime period. Analysis for both complicated and uncomplicated appendicitis was performed, and a multivariate model was used to correct for baseline characteristics and time to surgery. RESULTS: In total, 1361 adult patients with appendicitis were analyzed. Both at nighttime and at daytime, 34% had complicated appendicitis. In patients presenting in the daytime, 12.1% developed a postoperative complication versus 18.6% for presentation at night (p = 0.008). In a multivariate analysis, the risk for a postoperative complication when presenting at night was significantly increased (adjusted OR 1.74; 95% CI 1.14-2.66, p = 0.01). Surgery within eight hours after presentation does not lower this risk (adjusted OR 1.37; 95% CI 0.97-1.95, p = 0.078). CONCLUSION: Complicated appendicitis is seen as frequently during the day as at nighttime. For patients who present at nighttime with acute appendicitis, the risk of a postoperative complication is higher compared with a presentation at daytime. In multivariate analysis, nighttime presentation but not surgery within 8 h after presentation is independently associated with postoperative complication risk.

Safety and economic analysis of selective histopathology following cholecystectomy: multicentre, prospective, cross-sectional FANCY study.

BACKGROUND: There is ongoing debate concerning the necessity of routine histopathological examination following cholecystectomy. In order to reduce the pathology workload and save costs, a selective approach has been suggested, but evidence regarding its oncological safety is lacking. METHODS: In this multicentre, prospective, cross-sectional study, all gallbladders removed for gallstone disease or cholecystitis were systematically examined by the surgeon for macroscopic abnormalities indicative of malignancy. Before sending all specimens to the pathologist, the surgeon judged whether histopathological examination was indicated. The main outcomes were the number of patients with hypothetically missed malignancy with clinical consequences (upper limit two-sided 95 per cent c.i. below 3:1000 considered oncologically safe) and potential cost savings of selective histopathological examination. RESULTS: Twenty-two (2.19:1000) of 10 041 specimens exhibited malignancy with clinical consequences. In case of a selective policy, surgeons would have held back 7846 of 10041 (78.1 per cent) gallbladders from histopathological examination. Malignancy with clinical consequences would have been missed in seven of 7846 patients (0.89:1000, upper limit 95% c.i. 1.40:1000). No patient benefitted from the clinical consequences, while two were harmed (futile additional surgery). Of 15 patients in whom malignancy with clinical consequences would have been diagnosed, one benefitted (residual disease radically removed), two potentially benefitted (palliative systemic therapy), and four experienced harm (futile additional surgery). Estimated cost savings established by replacing routine for selective histopathological examination were €703 500 per 10 000 patients. CONCLUSION: Selective histopathological examination following cholecystectomy is oncologically safe and could reduce pathology workload, costs, and futile re-resections.

Discrepancies between Intraoperative and Histological Evaluation of the Appendix in Acute Appendicitis.

PURPOSE: To identify discrepancies between intraoperative and histological evaluations of the appendix in acute appendicitis and to evaluate the effect on surgical outcome. METHODS: Data was used from our previous multicentre, prospective, cohort study of patients with suspected acute appendicitis. Appendices were scored during intraoperative and histological evaluation as uncomplicated or complicated appendicitis. Primary outcome was percentage of concordance between intraoperative and histological evaluation. Secondary outcomes were (infectious) postoperative complications, length of hospital stay, hospital re-admission and re-intervention rate, all within 30 days of surgery. RESULTS: A total of 1850 patients were included. In 65.7% (1215/1850) of the appendices, the intraoperative evaluation was uncomplicated and in 34.3% (635/1850), complicated appendicitis. Patients with uncomplicated appendicitis had a postoperative course with significantly less postoperative complications (7.2% vs 24.3%), a shorter length of hospital stay (2 vs 5 days) and a lower re-admission (4.2% vs 9.6%) and re-intervention rate (1.1% vs 4.3%) than intraoperative complicated appendicitis (p < 0.001). In 93.5% (1136/1215) of the intraoperative uncomplicated patients and in 46.6% (296/635) of the intraoperative complicated patients, there was an agreement with pathology (Kappa 0.45). In 23.9% (81/339) of patients with intraoperative complicated and histological uncomplicated appendicitis, a postoperative complication was observed, which was similar to the postoperative complication rate of complicated appendicitis both on intraoperative and histological evaluation (24.7% (73/296)). CONCLUSIONS: There is a moderate agreement between a surgeon and pathologist in diagnosing patients with complicated appendicitis. However, the intraoperative diagnosis of complicated appendicitis was significantly associated with postoperative complications. Routine histological evaluation should be preserved for excluding malignancies in suspect appendices.

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.

INTRODUCTION: Routine 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 ANALYSIS: This 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 DISSEMINATION: The 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 NUMBER: NCT03510923.

Postoperative Outcomes of Patients With Nonperforated Gangrenous Appendicitis: A National Multicenter Prospective Cohort Analysis.

BACKGROUND: Controversy exists regarding the use of postoperative antibiotics for nonperforated gangrenous appendicitis. OBJECTIVE: The aim of this study was to evaluate the rate of postoperative infectious complications and the effect of postoperative antibiotic use among patients with nonperforated gangrenous appendicitis. DESIGN: This was a prospective cohort study conducted during 2 months. SETTINGS: A national multicenter observational study was conducted in 62 Dutch hospitals. PATIENTS: All of the consecutive patients who had surgery for suspected acute appendicitis were included. Patients were excluded if no appendectomy was performed or appendectomy was performed for pathology other than acute appendicitis. MAIN OUTCOMES MEASURES: Type of appendicitis was categorized as phlegmonous, gangrenous, or perforated. The primary end point was the rate of infectious complications (intra-abdominal abscess and surgical site infection) within 30 days after appendectomy. Univariable and multivariable logistic regression analyses were performed to identify predictors of infectious complications. RESULTS: A total of 1863 patients were included: 1321 (70.9%) with phlegmonous appendicitis, 181 (9.7%) with gangrenous appendicitis, and 361 (19.4%) with perforated appendicitis. Infectious complications were more frequent in patients with gangrenous versus phlegmonous appendicitis (7.2% vs 3.8%; p = 0.03). This association was no longer statistically significant in multivariable analysis (OR = 1.09 (95% CI, 0.49-2.44)). There was no significant difference in infectious complications between ≤24 hours (n = 57) of postoperative antibiotics compared with >24 hours (n = 124; 3.6% vs 8.9%; p = 0.35) in patients with gangrenous appendicitis. LIMITATIONS: Possible interobserver variability in the intraoperative classification of appendicitis was a study limitation. CONCLUSIONS: Patients with nonperforated gangrenous appendicitis are at higher risk of infectious complications than patients with phlegmonous appendicitis, yet gangrenous disease is not an independent risk factor. Postoperative antibiotic use over 24 hours was not associated with decreased infectious complications. See Video Abstract at http://links.lww.com/DCR/A1000. RESULTADOS POSTOPERATORIOS DE PACIENTES CON APENDICITIS GANGRENOSA NO PERFORADA: UN ANÁLISIS DE COHORTE PROSPECTIVO MULTICÉNTRICO NACIONAL:: Existe controversia sobre el uso de antibióticos postoperatorios para la apendicitis gangrenosa no perforada.El objetivo de este estudio fue evaluar la tasa de complicaciones infecciosas postoperatorias y el efecto del uso de antibióticos postoperatorios en pacientes con apendicitis gangrenosa no perforada.Estudio de cohorte prospectivo realizado durante dos meses.Estudio observacional multicéntrico nacional en 62 hospitales holandeses.Todos los pacientes consecutivos sometidos a cirugía por sospecha de apendicitis aguda. Los pacientes fueron excluidos si no se realizó una apendicectomía o si se realizó una apendicectomía para otra patología que no fuera la apendicitis aguda.El tipo de apendicitis se clasificó como flegmonosa, gangrenosa o perforada. El criterio de valoración primario fue la tasa de complicaciones infecciosas (absceso intraabdominal e infección en el sitio quirúrgico) dentro de los 30 días posteriores a la apendicectomía. Se realizaron análisis de regresión logística univariables y multivariables para identificar predictores de complicaciones infecciosas.Se incluyeron un total de 1863 pacientes: 1321 (70,9%) con apendicitis flegmonosa, 181 (9,7%) con apendicitis gangrenosa y 361 (19,4%) con apendicitis perforada. Las complicaciones infecciosas fueron más frecuentes en pacientes con apendicitis gangrenosa frente a flegmonosa (7,2% frente a 3,8%, p = 0,03). Esta asociación ya no fue estadísticamente significativa en el análisis multivariable (OR 1,09; IC del 95%: 0,49 a 2,44). No hubo diferencias significativas en las complicaciones infecciosas entre ≤ 24 h (n = 57) de los antibióticos postoperatorios en comparación con> 24 h (n = 124) (3,6% vs. 8,9%, p = 0,35) en pacientes con apendicitis gangrenosa.Posible variabilidad interobservador en la clasificación intraoperatoria de la apendicitis.Los pacientes con apendicitis gangrenosa no perforada tienen un mayor riesgo de complicaciones infecciosas que los pacientes con apendicitis flegmonosa, aunque la enfermedad gangrenosa no es un factor de riesgo independiente. El uso de antibióticos postoperatorios durante 24 horas no se asoció con una disminución de las complicaciones infecciosas. Vea el Resumen del Video en http://links.lww.com/DCR/A1000.

Propensity Score Adjusted Comparison of Pelviperineal Morbidity With and Without Omentoplasty Following Abdominoperineal Resection for Primary Rectal Cancer.

BACKGROUND: Abdominoperineal resection is associated with a high incidence of perineal complications, and whether this is reduced by an omentoplasty is still unclear. OBJECTIVE: This study aimed to investigate the impact of omentoplasty on pelviperineal morbidity in patients undergoing abdominoperineal resection for rectal cancer. DESIGN: This was a retrospective comparative cohort study using propensity score analyses to reduce potential confounding. SETTING: The study was undertaken in 2 teaching hospitals and 1 university hospital. PATIENTS: Patients who underwent abdominoperineal resection for primary rectal cancer between 2000 and 2017 were included. MAIN OUTCOME MEASURES: The main end points were primary perineal wound healing at 30 days and overall and specific pelviperineal morbidity until the end of the study period. RESULTS: Among 254 included patients, 106 had an omentoplasty. The primary perineal wound healing rate at 30 days was similar for omentoplasty and no omentoplasty (65% vs 60%; p = 0.422), also after adjusting for potential confounding by propensity score analysis (OR, 0.89; 95% CI, 0.45-1.75). Being free from any pelviperineal complication at 6 months (75% vs 79%; p = 0.492), absence of any pelviperineal morbidity until 1 year (54% vs 49%; p = 0.484), and incidence of persistent perineal sinus (6% vs 10%; p = 0.256) were also similar in both groups. The unadjusted higher perineal hernia rate after omentoplasty (18% vs 7%; p = 0.011) did not remain statistically significant after regression analysis including the propensity score (OR, 1.34; 95% CI, 0.46-3.88). Complications related to the omentoplasty itself were observed in 8 patients, of whom 6 required reoperation. LIMITATIONS: This study was limited by the retrospective and nonrandomized design causing some heterogeneity between the 2 cohorts. CONCLUSION: In this multicenter study using propensity score analyses, the use of omentoplasty did not lower the incidence or the duration of pelviperineal morbidity in patients undergoing abdominoperineal resection for rectal cancer, and omentoplasty itself was associated with a risk of reoperation. See Video Abstract at http://links.lww.com/DCR/A918.

Two versus five days of antibiotics after appendectomy for complex acute appendicitis (APPIC): study protocol for a randomized controlled trial.

BACKGROUND: Acute appendicitis is one of the most common indications for emergency surgery. In patients with a complex appendicitis, prolonged antibiotic prophylaxis is recommended after appendectomy. There is no consensus regarding the optimum duration of antibiotics. Guidelines propose 3 to 7 days of treatment, but shorter courses may be as effective in the prevention of infectious complications. At the same time, the global issue of increasing antimicrobial resistance urges for optimization of antibiotic strategies. The aim of this study is to determine whether a short course (48 h) of postoperative antibiotics is non-inferior to current standard practice of 5 days. METHODS: Patients of 8 years and older undergoing appendectomy for acute complex appendicitis - defined as a gangrenous and/or perforated appendicitis or appendicitis in presence of an abscess - are eligible for inclusion. Immunocompromised or pregnant patients are excluded, as well as patients with a contraindication to the study antibiotics. In total, 1066 patients will be randomly allocated in a 1:1 ratio to the experimental treatment arm (48 h of postoperative intravenously administered (IV) antibiotics) or the control arm (5 days of postoperative IV antibiotics). After discharge from the hospital, patients participate in a productivity-cost-questionnaire at 4 weeks and a standardized telephone follow-up at 90 days after appendectomy. The primary outcome is a composite endpoint of infectious complications, including intra-abdominal abscess (IAA) and surgical site infection (SSI), and mortality within 90 days after appendectomy. Secondary outcomes include IAA, SSI, restart of antibiotics, length of hospital stay (LOS), reoperation, percutaneous drainage, readmission rate, and cost-effectiveness. The non-inferiority margin for the difference in the primary endpoint rate is set at 7.5% (one-sided test at ɑ 0.025). Both per-protocol and intention-to-treat analyses will be performed. DISCUSSION: This trial will provide evidence on whether 48 h of postoperative antibiotics is non-inferior to a standard course of 5 days of antibiotics. If non-inferiority is established, longer intravenous administration following appendectomy for complex appendicitis can be abandoned, and guidelines need to be adjusted accordingly. TRIAL REGISTRATION: Dutch Trial Register, NTR6128 . Registered on 20 December 2016.