Risk factors associated with negative appendicectomy rates: A retrospective cohort study

Risk factors associated with negative appendicectomy rates: A retrospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Risk factors associated with negative appendicectomy rates: A retrospective cohort study Neil Donald, Laura Halliday, Gillian Smith, Shwetal Dighe This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4320667/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Acute appendicitis (AA) is the most common emergency general surgical condition worldwide. Diagnosis is challenging and incorporates clinical, biochemical and radiological investigations. Our aim was to provide data from routine practice investigating widely utilised diagnostic methods from a single centre within the United Kingdom. Methods We conducted a retrospective observational cohort study of patients who underwent a laparoscopic appendicectomy for AA between April 2022–March 2023. AA was defined as the presence of transmural polymorphonuclear leukocytes on histology. Subgroup analysis was performed on paediatric patients. Factors associated with AA were investigated and the diagnostic utility of biochemical and radiological investigations was examined. Results 330 appendicectomies were analysed. We found an overall negative appendicectomy rate (NAR) of 38% and 48% in paediatric patients. Independent factors associated with AA on multivariate analysis included elevated neutrophil counts (> 7 × 10 9 /L) (OR 4.04), elevated CRP (> 5mg/L) (OR 3.04) and a radiological diagnosis (OR 8.0). Computerised tomography (CT) and ultrasound had sensitivity/specificity of 98%/47% and 35%/86% respectively. The positive-predictive values were 85% for CT and 50% for ultrasound and negative-predictive values were 86% for CT and 77% for ultrasound. Conclusion Our study has highlighted the importance of utilising a combination of factors to improve the diagnostic certainty of AA. However, our routine practice data has shown different sensitivities and specificities of imaging in comparison to existing literature, resulting in a high NAR. Further real world data is needed to understand whether these differences from the existing data are seen in other clinical settings. Appendicitis Negative Appendicectomy rate (NAR) Computed tomography (CT) Ultrasound (US) Preoperative imaging Background Acute appendicitis (AA) is the most common abdominal surgical condition in the world, with over 300,000 operations performed annually in the United States and 50,000 in the United Kingdom. 1,2 A systematic review in 2017 of 120 studies found that the pooled incidence of appendicitis range was 100 per 100,000 person years in Northern America to 151 in Western Europe. 3 Further reports by the World Society of Emergency Surgery in 2020 and The European Association of Endoscopic Surgery (EAES) have suggested rates of 5.7–50 per 100,000 and 5.7–57 per 100,000 inhabitants respectively. 4 5 It has further been suggested there is a geographical difference in lifetime risk of developing AA of 9% in the USA, 8% in Europe and 2% in Africa. 6 The diagnosis of AA is often challenging and numerous scoring systems have been created to aid in the diagnosis. The most frequently used are the Alvarado, Appendicitis Inflammatory Response and Adult Appendicitis scores; each system has its own unique advantages and disadvantages and there is as yet no consensus on the most appropriate. 4, 7 . Many of these scoring systems include biomarkers but their role remains controversial, as highlighted by the EAES consensus statement in 2015. More recently, in 2020 the WSES concluded that whilst biomarkers represented a promising and reliable diagnostic tool, further evidence was still required. 4, 5 It has been suggested that in the paediatric cohort white blood cell (WBC), absolute neutrophil count and C-reactive protein (CRP) are useful in predicting the presence of AA. Whilst there is on-going debate surrounding biomarker use, a systematic review of 58 studies suggested AA can be ruled out if WCC, CRP and polymorphonuclear leucocyte levels are all normal. 8 However, individual markers alone lack the accuracy to predict AA. 8, 9 Due to the uncertainty with clinical and biochemical indicators, imaging methods are commonly deployed to help to reduce diagnostic ambiguity. A Cochrane review in 2019 found that computerised tomography (CT) has a high sensitivity and specificity, both within the 90th percentile, for diagnosing AA and these findings were mirrored in a further meta-analysis of 37 studies in 2022. 10, 11 Ultrasound is another commonly used investigation, especially in paediatric patients and young women. However, the sensitivity and specificity are both lower than CT and the investigation is operator dependent. 11, 12 There are risks associated with a late diagnosis of AA and perforated appendicitis has a significant morbidity. 13 However, negative appendicectomies can also lead to complications, and surgical complications have been reported to be similar in patients undergoing a laparoscopic appendicectomy whether or not they have AA. 14, 15 Negative appendicectomy rates (NAR) vary widely. A systematic review and meta-analysis of 76 thousand patients reported a wide variability of 0–46%, with a 13% NAR on meta-analysis. 16 There has been a trend of declining negative appendicectomy rates potentially due to better diagnostics and rates of negative appendicectomies are widely reported to be under 10% with the use of diagnostic imaging and biochemical markers. 17–20 Mandatory imaging has led to reported rates of 2–3%. 21, 22 The aim of our study was to evaluate diagnostic methods that are widely accessible and utilised in clinical practice within a District General Hospital to determine their effectiveness individually and in combination to enhance the diagnosis of AA. Methods We conducted a retrospective observational analysis of all patients undergoing a laparoscopic appendicectomy for AA over a one-year period from April 2022 to March 2023 at a District General Hospital in the UK. Appendicectomies performed as part of other abdominal surgery, elective or interval appendicectomies and appendicectomies performed for any reason other than AA were excluded. We recorded data regarding operative details, length of stay, biochemical markers, pathology results and imaging results from hospital electronic medical records. Paediatric patients were defined as those patients under the age of 16 years old at the time of presentation. The definition of AA was standardised and defined as the presence of transmural polymorphonuclear leukocytes on histology. The decision to whether to perform any imaging, and the selection of imaging modality, was made clinically by the doctor treating the patient. The definition of positive imaging was one where the report gave a diagnosis of appendicitis. If imaging results were indeterminate, the appendix was not visualised or not commented upon, this was recorded as a negative scan result. Three patients within our cohort underwent an MRI scan, which was too small for analysis and therefore excluded from imaging results. Statistical analysis was performed using SPSS version 28 (IBM, New York, USA). Normality of data was assessed visually and using the Kolmogorov–Smirnov (with Lilliefors correction) and Shapiro–Wilk nor mality tests. Depending on their distribution, continuous variables are presented as either mean ± standard deviation or median [interquartile range, IQR]. Comparison of continuous variables between those with AA and those with a negative appendicectomy was performed using the Independent-Samples T test or Mann–Whitney U test, respectively. Categorical variables were compared using the chi-squared or Fisher’s exact tests. Binary logistic regression was used to determine the factors associated with AA. Two-tailed tests were used throughout with a significance level of P < 0.05. Results A total of 330 patients were included in the analysis; full data sets were available for all 330 participants. A full breakdown of demographics and admission biochemistry is shown in Table 1 . A histological diagnosis of AA, defined as the presence of transmural polymorphonuclear leukocytes, was found in 204 patients. There was no histological diagnosis of AA in 126 patients, giving an overall NAR of 38%. As shown in Table 1 , patients with AA had a higher median age (32 years vs 23 years). AA patients had higher WBC, neutrophil count, CRP and total bilirubin levels. Patients with no histological diagnosis tended to have higher lymphocyte counts. Females accounted for 71% of all negative appendicectomies. Table 1 Demographic breakdown and admission biochemistry. Results are displayed as medians (IQR) unless otherwise stated. Histological diagnosis of appendicitis n = 204 No evidence of acute appendicitis n = 126 p-value Age 32 (18–47) 23 (14–34) < 0.001 Gender, male n (%) ASA 1 2 3 4 93 (46%) 81 110 13 0 36 (29%) 53 64 7 2 0.003 0.71 WBC (× 10 9 /L) 12.6 (10.1–15.7) 8.4 (6.9–11.8) < 0.001 Neutrophils (× 10 9 /L) 10.1 (7.1–12.7) 5.6 (3.7–8.2) < 0.001 Lymphocytes (× 10 9 /L) 1.4 (1.0–2.0) 1.9 (1.4–2.4) < 0.001 CRP (mg/L) 39.2 (11.7-121.9) 8.1 (1.8–51.8) < 0.001 Bilirubin (umol/L) 14.1 (10.0–20.0) 9.0 (7.0–12.0) < 0.001 ALT (U/L) 17.0 (12.0-24.5) 16.0 (12.5–25.5) 0.862 Radiological investigations A total of 204 patients underwent an imaging modality (62%). Of these 124 (38% of study population) underwent a CT scan, and 82 (25% of study population) underwent an ultrasound scan (USS), the breakdown of these are shown in Table 2 . With all imaging modalities combined together the sensitivity was 86% with a specificity of 71%. The positive predictive value (PPV) and negative predictive value (NPV) were 80% and 78% respectively. There were, however, differences within imaging modalities. In this study, CT had a sensitivity of 98% and a specificity of 47%, whilst USS had a sensitivity of 35% and specificity of 86%. PPV values were 85% and 50% for CT and USS respectively. NPV values were 86% for CT and 77% for USS. Table 2 Radiological breakdown of patients with and without acute appendicitis. Histological diagnosis of appendicitis No evidence of acute appendicitis p-value All imaging modalities < 0.001 Appendicitis 102 (86%) 25 (29%) No diagnosis of appendicitis 17 (14%) 60 (71%) Ultrasound 0.029 Appendicitis 8 (35%) 8 (14%) No diagnosis of appendicitis 15 (65%) 51 (86%) CT scan < 0.001 Appendicitis 92 (98%) 16 (53%) No diagnosis of appendicitis 2 (2%) 14 (47%) Factors predicting diagnosis of AA On multivariate analysis, patients with AA were four times more likely to have an elevated neutrophil count above 7× 10 9 /L on admission and three times more likely to have an elevated CRP above 5mg/L on admission compared to patients who did not have appendicitis (Table 3 ). A radiological diagnosis of AA by either modality had an odds radio of 8.0 for a histological diagnosis of AA (P 11 × 10 9 /L, neutrophil count > 7× 10 9 /L, evidence of left shift (> 75% neutrophils:lymphocytes) and a CRP > 5mg/L was significant for a diagnosis of appendicitis (P < 0.001) with a specificity of 88% for the diagnosis of AA, with a positive predictive value of 80%. Table 3 Multivariate analysis of admission blood test parameters and imaging and their associations with acute appendicitis. Variable Odds ratio (95% CI) SE p value WCC > 11 × 10 9 /L 0.96 (0.25 to 3.61) 0.68 0.943 Neutrophil > 7 × 10 9 /L 4.04 (1.11 to 14.73) 0.66 0.035 Lymphocyte > 4 × 10 9 /L 0.95 (0.07 to 13.72) 1.36 0.968 CRP > 5mg/L 3.04 (1.19 to 7.78) 0.48 0.020 Bilirubin > 21 umol/L 2.87 (0.70 to 11.71) 0.72 0.142 ALT > 50 U/L 0.86 (0.18 to 4.16) 0.80 0.853 Radiological diagnosis of appendicitis 8.0 (3.74 to 16.90) 0.39 < 0.001 Paediatric patients 87 paediatric patients were identified; 45 patients in this cohort had histological evidence of AA, leading to a NAR of 48%. On subgroup analysis there were significant differences in the total WBC, neutrophil count, CRP and total bilirubin (Table 4 ). There was also a significant difference in the alanine transaminase though the difference was minimal at 2.5 U/L. 40 patients underwent USS. In this population, USS could not significantly predict the presence or absence of AA (p = 0.439). Both sensitivity and PPV were 36%, and specificity and NPV were 76%. A full breakdown is found in Supplementary Table 1. Table 4 Breakdown of demographic and admission biochemistry in paediatric patients. Results are displayed as median (IQR) unless otherwise stated. Histological diagnosis of appendicitis n = 45 No evidence of acute appendicitis n = 42 p-value Age 12 ( 8 – 14 ) 13 ( 11 – 14 ) 0.065 Gender, male n 17 (38%) 24 (57%) 0.071 WBC (× 10 9 /L) 13.9 (9.5–16.1) 8.0 (6.7–10.3) < 0.001 Neutrophils (× 10 9 /L) 11.5 (6.7–13.5) 4.9 (3.3-7.0) < 0.001 Lymphocytes (× 10 9 /L) 1.2 (0.9–2.2) 2.1 (1.4–2.4) 0.001 CRP (mg/L) 21.6 (7.4-118.7) 3.5 (0.5–25.5) < 0.001 Bilirubin (umol/L) 12.0 (9.0–14.0) 8.0 (6.8–12.0) 0.002 ALT (U/L) 12.0 (10.0–16.0) 14.5 (12.0-18.8) 0.025 Discussion In this single centre study within the United Kingdom we determined a negative appendicectomy rate of 38% based on strict histological criteria, which is slightly higher than reported literature in the field. 8,16–20 Our results though should be interpreted in the context of requiring strict histological criteria of transmural polymorphonuclear leukocyte infiltration, rather than any inflammation. In our cohort we found females were more at risk of undergoing a negative appendicectomy. This may arise due to other gynaecological conditions that may present with similar signs and symptoms, and is in keeping with the known literature at similar rates. 8,22–25 Also in keeping with other literature we found advancing age to be negatively associated with a negative appendicectomy. 8, 17, 19, 22–23 This may be due to older patients being more likely to undergo cross-sectional radiological imaging to exclude other diagnosis that can mimic AA or identify any underlying pathology that may cause AA in older patients. 4 The findings in this study cohort have suggested USS is of no discernible benefit in paediatric patients. However, less than half of the paediatric patients in this study underwent ultrasound and the sample size may be too small to detect a significant differences. Further research is needed to examine the local practices around the decision to request pre-operative imaging in children in this study population. The sensitivity of USS in this study was very low, with only 35% of AA patients who had a USS having a positive finding of AA on scanning, indicating it is of little use in excluding AA. In addition the PPV value of 50% gives little value in confirming a histological diagnosis of AA. In contrast, CT imaging had a 98% sensitivity and was very good in successfully excluding AA. This clear advantage of CT imaging in the diagnosis of AA has to be weighed against the associated radiation exposure and a low specificity in this study, with 53% of cases reported as acute appendicitis resulting in a negative appendicectomy. However, as previously discussed, other studies have shown higher specificities and sensitivities for pre-operative imaging and therefore further research is needed to understand the reasons behind the lower specificities and sensitivities in this study population. 10–12, 14 Whilst we did find a significant difference in total WBC between those who did and did not have AA, we did not find on multivariate analysis a WBC > 11,000 independently increasing the odds of an AA diagnosis. Though this is in contrast to some of the existing literature. 8, 19, 24, 25 , other studies have suggested WBC is not a predictor of AA. 26 Furthermore it has been suggested that WBC is a poor predictor of AA due to an unreliable specificity and sensitivity and there is no consensus for a reliable cut off value. 28 We did however find that patients with AA were four times more likely to have an elevated neutrophil count at admission in comparison to those with a negative appendicectomy, which is in keeping with other literature. 27,28 With increasing use of imaging as a key diagnostic tool, this study highlights important limitations in its use for the diagnosis of AA and the need to continue pursuing a combination approach that includes clinical scoring systems, multiple biomarkers and the use of radiological imaging. Further research is needed to implement a new scoring system taking into account a combination approach of clinical signs and symptoms together with biomarkers in patients who may be unable to undergo imaging modalities and where there is diagnostic uncertainty. We also suggest further research from various centres using real time practice data to further investigate the utility of imaging to either exclude or confirm the diagnosis of AA and its role influencing local NAR. Limitations A limitation of our study was that despite the high number of patients, it is a single centre study. There is furthermore the potential for inter-operator variability in interpreting imaging, which may affect results. Data was not reliably recorded on clinical perimeters, such as heart rate and temperature, and therefore could not be included in these analyses. Conclusion We have demonstrated in our cohort that an elevated neutrophil and CRP count are independent risk factors for a diagnosis of AA. Our findings have also demonstrated that the use of several biochemical markers in combination can increase the confidence with which a diagnosis can be made. The usefulness of CT imaging to reduce the likelihood of missed AA has been highlighted. However we found a low specificity and therefore it may be of limited use in reducing a high NAR in clinical practice. USS was of less diagnostic utility, even in paediatric groups. Within our routine practice there was discordance with radiological sensitivity and specificity values compared with that described in prior studies. Declarations Funding: This research received no external funding Conflicts of interest: The authors declare no conflict of interest. Author Contributions: ND and SD contributed to study conceptualisation and design. ND, LH and GS contributed to data collections. LH conducted statistical analysis and interpretations of results. ND and LH contributed to draft manuscript production. All authors contributed to final manuscript review and editing. Ethics approval: Ethics guidance was not required for this study, which was defined as a clinical audit, in accordance with NHS Health Research Authority guidance. All information within this study was collected and approved following approval and governance checks by the Dartford and Gravesham NHS Trust clinical audit department. Consent for publication: Not applicable. Availability of data and materials: Further data available upon request. Acknowledgements: No further acknowledgements. References Wu JX, Dawes AJ, Sacks GD, Brunicardi FC, Keeler EB. Cost effectiveness of nonoperative management versus laparoscopic appendectomy for acute uncomplicated appendicitis. Surgery. 2015;158(3):712–21. 10.1016/j.surg.2015.06.021 . Baird DL, Simillis C, Kontovounisios C, Rasheed S, Tekkis PP. Acute appendicitis. BMJ. 2017. 10.1136/bmj.j1703 . Ferris M, Quan S, Kaplan BS, Molodecky N, Ball CG, Chernoff GW, et al. The global incidence of appendicitis. Ann Surg. 2017;266(2):237–41. 10.1097/sla.0000000000002188 . Di Saverio S, Podda M, De Simone B, Ceresoli M, Augustin G, Gori A, et al. Diagnosis and treatment of acute appendicitis: 2020 update of the WSES jerusalem guidelines. World J Emerg Surg. 2020;15(1). 10.1186/s13017-020-00306-3 . Gorter RR, Eker HH, Gorter-Stam MA, Abis GS, Acharya A, Ankersmit M et al. Diagnosis and management of acute appendicitis. EAES Consensus Development Conference 2015. Surgical Endoscopy. 2016;30(11):4668–90. 10.1007/s00464-016-5245-7 . 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. 10.1016/s0140-6736(15)00275-5 . Bhangu A. Evaluation of appendicitis risk prediction models in adults with suspected appendicitis. Br J Surg. 2019;107(1):73–86. 10.1002/bjs.11440 . Kabir SA, Kabir SI, Sun R, Jafferbhoy S, Karim A. How to diagnose an acutely inflamed appendix; a systematic review of the latest evidence. Int J Surg. 2017;40:155–62. 10.1016/j.ijsu.2017.03.013 . Snyder MJ, Guthrie M, Cagle S. Acute Appendicitis: Efficient Diagnosis and Management. Am Fam Physician. 2018;98(1):25–33. Rud B, Vejborg TS, Rappeport ED, Reitsma JB, Wille-Jørgensen P. Computed tomography for diagnosis of acute appendicitis in adults. Cochrane Database Syst Reviews. 2019;2019(11). 10.1002/14651858.cd009977.pub2 . Arruzza E, Milanese S, Li LSK, Dizon J. Diagnostic accuracy of computed tomography and ultrasound for the diagnosis of acute appendicitis: A systematic review and meta-analysis. Radiography. 2022;28(4):1127–41. 10.1016/j.radi.2022.08.012 . Giljaca V, Nadarevic T, Poropat G, Nadarevic VS, Stimac D. Diagnostic accuracy of abdominal ultrasound for diagnosis of acute appendicitis: Systematic Review and meta-analysis. World J Surg. 2016;41(3):693–700. 10.1007/s00268-016-3792-7 . Potey K, Kandi A, Jadhav S, Gowda V. Study of outcomes of perforated appendicitis in adults: A prospective cohort study. Annals Med Surg. 2023;85(4):694–700. 10.1097/ms9.0000000000000277 . Bhangu A. Multicentre observational study of performance variation in provision and outcome of emergency appendicectomy. Br J Surg. 2013;100(9):1240–52. 10.1002/bjs.9201 . Allaway MG, Eslick GD, Cox MR. The unacceptable morbidity of negative laparoscopic appendicectomy. World J Surg. 2018;43(2):405–14. 10.1007/s00268-018-4784-6 . Henriksen SR, Christophersen C, Rosenberg J, Fonnes S. Varying negative appendectomy rates after laparoscopic appendectomy: A systematic review and meta-analysis. Langenbeck’s Archives Surg. 2023;408(1). 10.1007/s00423-023-02935-z . Seetahal SA, Bolorunduro OB, Sookdeo TC, Oyetunji TA, Greene WR, Frederick W, et al. Negative appendectomy: A 10-year review of a nationally representative sample. Am J Surg. 2011;201(4):433–7. 10.1016/j.amjsurg.2010.10.009 . Krajewski S. Impact of computed tomography of the abdomen on clinical outcomes in patients with acute right lower quadrant pain: A meta-analysis. Can J Surg. 2011;54(1):43–53. 10.1503/cjs.023509 . Chaochankit W, Boocha A, Samphao S. Negative appendectomy rate in patients diagnosed with acute appendicitis. BMC Surg. 2022;22(1). 10.1186/s12893-022-01852-0 . Mariadason J, Wang W, Wallack M, Belmonte A, Matari H. Negative appendicectomy rate as a quality metric in the management of appendicitis: Impact of computed tomography, Alvarado score and the definition of negative appendicectomy. Ann R Coll Surg Engl. 2012;94(6):395–401. 10.1308/003588412x13171221592131 . D’Souza N, Hicks G, Beable R, Higginson A, Rud B. Magnetic Resonance Imaging (MRI) for diagnosis of acute appendicitis. Cochrane Database Syst Reviews. 2021;2021(12). 10.1002/14651858.cd012028.pub2 . Alhamdani Y, Rizk H, Algethami M, Algarawi A, Albadawi R, Faqih S, et al. Negative appendectomy rate and risk factors that influence improper diagnosis at King Abdulaziz University Hospital. Materia Socio Med. 2018;30(2):215. 10.5455/msm.2018.30.215-220 . Noureldin K, Hatim Ali AA, Issa M, Shah H, Ayantunde B, Ayantunde A. Negative appendicectomy rate: Incidence and predictors. Cureus. 2022. 10.7759/cureus.21489 . Saaiq M, Niaz-Ud-Din, Jalil A, Zubair M, Shah SA. Diagnostic accuracy of leukocytosis in prediction of acute appendicitis. J Coll Physicians Surg Pak. 2014;24(1):67–9. Mackay TG, Dissanayake B, Yuide PJ, Burstow MJ, Gundara JS, Chua TC. Cohort Study of 1241 patients to identify predictors of negative appendicectomy. ANZ J Surg. 2020;90(10):1984–90. 10.1111/ans.16203 . Yokoyama S, Takifuji K, Hotta T, Matsuda K, Nasu T, Nakamori M, et al. C-reactive protein is an independent surgical indication marker for appendicitis: A retrospective study. World J Emerg Surg. 2009;4(1). 10.1186/1749-7922-4-36 . Al-gaithy ZK. Clinical value of total white blood cells and neutrophil counts in patients with suspected appendicitis: Retrospective Study. World J Emerg Surg. 2012;7(1):32. 10.1186/1749-7922-7-32 . Fatima SR, Zaheer F, Moosa FA, Arqam SM, Mussab RM, Choudhry MS. Combined diagnostic accuracy of total leukocyte count, neutrophil count, and ultrasonography for the diagnosis of acute appendicitis. Cureus. 2021. 10.7759/cureus.13086 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4320667","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":297169760,"identity":"680e0409-9a38-45d3-855b-174b0d9522b4","order_by":0,"name":"Neil Donald","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7klEQVRIiWNgGAWjYHACAyC2YOxnSEARTcCmFFmLBOPMBqCiAyRp2XCAWC3mDMwbHxfUSMhuPp588POHinv2DOy9j18wtqXh1GLZwFZsPOOYhPG2M8+SJQ6cKU5s4DluZsHYloPbVQd4zKR52CQSt93IMWM42JaQwCCRxmbA2FZBQMs/icTNMyBa7InTwtsmkbhBAqKFsUEijfkBXocdBvqFt0/CeAbIL2fOJCS28RxjY0g4h9v7BsebNz7m+WYj29+efPBDRUWCPT97G/OHD2XJOLUwMKMLsAGRRAJuDTiM+UCqjlEwCkbBKBjWAADtzFAK3D5lxgAAAABJRU5ErkJggg==","orcid":"","institution":"Dartford and Gravesham NHS Trust","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Neil","middleName":"","lastName":"Donald","suffix":""},{"id":297169762,"identity":"3921e4b7-48df-4564-960c-4482a433abae","order_by":1,"name":"Laura Halliday","email":"","orcid":"","institution":"Dartford and Gravesham NHS Trust","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Laura","middleName":"","lastName":"Halliday","suffix":""},{"id":297169764,"identity":"6d21e8fa-ea89-44e3-b5d7-e56c581921ba","order_by":2,"name":"Gillian Smith","email":"","orcid":"","institution":"Dartford and Gravesham NHS Trust","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Gillian","middleName":"","lastName":"Smith","suffix":""},{"id":297169765,"identity":"84ef6b84-529c-4292-a8d7-f81ec160f20c","order_by":3,"name":"Shwetal Dighe","email":"","orcid":"","institution":"Dartford and Gravesham NHS Trust","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shwetal","middleName":"","lastName":"Dighe","suffix":""}],"badges":[],"createdAt":"2024-04-25 00:39:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4320667/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4320667/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":56161179,"identity":"2e704224-5b4c-4f8a-84c1-05173ce6cd8a","added_by":"auto","created_at":"2024-05-09 09:31:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":477817,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4320667/v1/2d351dd5-eb8a-4820-9f41-51f584a55484.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Risk factors associated with negative appendicectomy rates: A retrospective cohort study","fulltext":[{"header":"Background","content":"\u003cp\u003eAcute appendicitis (AA) is the most common abdominal surgical condition in the world, with over 300,000 operations performed annually in the United States and 50,000 in the United Kingdom. \u003csup\u003e1,2\u003c/sup\u003e A systematic review in 2017 of 120 studies found that the pooled incidence of appendicitis range was 100 per 100,000 person years in Northern America to 151 in Western Europe. \u003csup\u003e3\u003c/sup\u003e Further reports by the World Society of Emergency Surgery in 2020 and The European Association of Endoscopic Surgery (EAES) have suggested rates of 5.7\u0026ndash;50 per 100,000 and 5.7\u0026ndash;57 per 100,000 inhabitants respectively. \u003csup\u003e4 5\u003c/sup\u003e It has further been suggested there is a geographical difference in lifetime risk of developing AA of 9% in the USA, 8% in Europe and 2% in Africa. \u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe diagnosis of AA is often challenging and numerous scoring systems have been created to aid in the diagnosis. The most frequently used are the Alvarado, Appendicitis Inflammatory Response and Adult Appendicitis scores; each system has its own unique advantages and disadvantages and there is as yet no consensus on the most appropriate. \u003csup\u003e4, 7\u003c/sup\u003e. Many of these scoring systems include biomarkers but their role remains controversial, as highlighted by the EAES consensus statement in 2015. More recently, in 2020 the WSES concluded that whilst biomarkers represented a promising and reliable diagnostic tool, further evidence was still required. \u003csup\u003e4, 5\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIt has been suggested that in the paediatric cohort white blood cell (WBC), absolute neutrophil count and C-reactive protein (CRP) are useful in predicting the presence of AA. Whilst there is on-going debate surrounding biomarker use, a systematic review of 58 studies suggested AA can be ruled out if WCC, CRP and polymorphonuclear leucocyte levels are all normal. \u003csup\u003e8\u003c/sup\u003e However, individual markers alone lack the accuracy to predict AA. \u003csup\u003e8, 9\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eDue to the uncertainty with clinical and biochemical indicators, imaging methods are commonly deployed to help to reduce diagnostic ambiguity. A Cochrane review in 2019 found that computerised tomography (CT) has a high sensitivity and specificity, both within the 90th percentile, for diagnosing AA and these findings were mirrored in a further meta-analysis of 37 studies in 2022. \u003csup\u003e10, 11\u003c/sup\u003e Ultrasound is another commonly used investigation, especially in paediatric patients and young women. However, the sensitivity and specificity are both lower than CT and the investigation is operator dependent. \u003csup\u003e11, 12\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThere are risks associated with a late diagnosis of AA and perforated appendicitis has a significant morbidity. \u003csup\u003e13\u003c/sup\u003e However, negative appendicectomies can also lead to complications, and surgical complications have been reported to be similar in patients undergoing a laparoscopic appendicectomy whether or not they have AA. \u003csup\u003e14, 15\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eNegative appendicectomy rates (NAR) vary widely. A systematic review and meta-analysis of 76 thousand patients reported a wide variability of 0\u0026ndash;46%, with a 13% NAR on meta-analysis. \u003csup\u003e16\u003c/sup\u003e There has been a trend of declining negative appendicectomy rates potentially due to better diagnostics and rates of negative appendicectomies are widely reported to be under 10% with the use of diagnostic imaging and biochemical markers. \u003csup\u003e17\u0026ndash;20\u003c/sup\u003e Mandatory imaging has led to reported rates of 2\u0026ndash;3%. \u003csup\u003e21, 22\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe aim of our study was to evaluate diagnostic methods that are widely accessible and utilised in clinical practice within a District General Hospital to determine their effectiveness individually and in combination to enhance the diagnosis of AA.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eWe conducted a retrospective observational analysis of all patients undergoing a laparoscopic appendicectomy for AA over a one-year period from April 2022 to March 2023 at a District General Hospital in the UK. Appendicectomies performed as part of other abdominal surgery, elective or interval appendicectomies and appendicectomies performed for any reason other than AA were excluded. We recorded data regarding operative details, length of stay, biochemical markers, pathology results and imaging results from hospital electronic medical records. Paediatric patients were defined as those patients under the age of 16 years old at the time of presentation.\u003c/p\u003e \u003cp\u003eThe definition of AA was standardised and defined as the presence of transmural polymorphonuclear leukocytes on histology.\u003c/p\u003e \u003cp\u003eThe decision to whether to perform any imaging, and the selection of imaging modality, was made clinically by the doctor treating the patient. The definition of positive imaging was one where the report gave a diagnosis of appendicitis. If imaging results were indeterminate, the appendix was not visualised or not commented upon, this was recorded as a negative scan result. Three patients within our cohort underwent an MRI scan, which was too small for analysis and therefore excluded from imaging results.\u003c/p\u003e \u003cp\u003eStatistical analysis was performed using SPSS version 28 (IBM, New York, USA). Normality of data was assessed visually and using the Kolmogorov\u0026ndash;Smirnov (with Lilliefors correction) and Shapiro\u0026ndash;Wilk nor mality tests. Depending on their distribution, continuous variables are presented as either mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median [interquartile range, IQR]. Comparison of continuous variables between those with AA and those with a negative appendicectomy was performed using the Independent-Samples T test or Mann\u0026ndash;Whitney U test, respectively. Categorical variables were compared using the chi-squared or Fisher\u0026rsquo;s exact tests. Binary logistic regression was used to determine the factors associated with AA. Two-tailed tests were used throughout with a significance level of P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 330 patients were included in the analysis; full data sets were available for all 330 participants. A full breakdown of demographics and admission biochemistry is shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eA histological diagnosis of AA, defined as the presence of transmural polymorphonuclear leukocytes, was found in 204 patients. There was no histological diagnosis of AA in 126 patients, giving an overall NAR of 38%.\u003c/p\u003e \u003cp\u003eAs shown in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, patients with AA had a higher median age (32 years vs 23 years). AA patients had higher WBC, neutrophil count, CRP and total bilirubin levels. Patients with no histological diagnosis tended to have higher lymphocyte counts. Females accounted for 71% of all negative appendicectomies.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic breakdown and admission biochemistry. Results are displayed as medians (IQR) unless otherwise stated.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHistological diagnosis of appendicitis\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;204\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo evidence of acute appendicitis\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;126\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (18\u0026ndash;47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (14\u0026ndash;34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender, male\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003cp\u003eASA 1\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93 (46%)\u003c/p\u003e \u003cp\u003e81\u003c/p\u003e \u003cp\u003e110\u003c/p\u003e \u003cp\u003e13\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (29%)\u003c/p\u003e \u003cp\u003e53\u003c/p\u003e \u003cp\u003e64\u003c/p\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003cp\u003e0.71\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC (\u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.6 (10.1\u0026ndash;15.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.4 (6.9\u0026ndash;11.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophils (\u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.1 (7.1\u0026ndash;12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.6 (3.7\u0026ndash;8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocytes (\u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.4 (1.0\u0026ndash;2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.9 (1.4\u0026ndash;2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39.2 (11.7-121.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.1 (1.8\u0026ndash;51.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilirubin (umol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.1 (10.0\u0026ndash;20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.0 (7.0\u0026ndash;12.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.0 (12.0-24.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.0 (12.5\u0026ndash;25.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.862\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eRadiological investigations\u003c/h2\u003e \u003cp\u003eA total of 204 patients underwent an imaging modality (62%). Of these 124 (38% of study population) underwent a CT scan, and 82 (25% of study population) underwent an ultrasound scan (USS), the breakdown of these are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eWith all imaging modalities combined together the sensitivity was 86% with a specificity of 71%. The positive predictive value (PPV) and negative predictive value (NPV) were 80% and 78% respectively.\u003c/p\u003e \u003cp\u003eThere were, however, differences within imaging modalities. In this study, CT had a sensitivity of 98% and a specificity of 47%, whilst USS had a sensitivity of 35% and specificity of 86%. PPV values were 85% and 50% for CT and USS respectively. NPV values were 86% for CT and 77% for USS.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRadiological breakdown of patients with and without acute appendicitis.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHistological diagnosis of appendicitis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo evidence of acute appendicitis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll imaging modalities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAppendicitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e102 (86%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo diagnosis of appendicitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60 (71%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUltrasound\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAppendicitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo diagnosis of appendicitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (65%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51 (86%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCT scan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAppendicitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92 (98%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (53%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo diagnosis of appendicitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (47%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003eFactors predicting diagnosis of AA\u003c/h2\u003e \u003cp\u003eOn multivariate analysis, patients with AA were four times more likely to have an elevated neutrophil count above 7\u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L on admission and three times more likely to have an elevated CRP above 5mg/L on admission compared to patients who did not have appendicitis (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). A radiological diagnosis of AA by either modality had an odds radio of 8.0 for a histological diagnosis of AA (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eA combination of WCC\u0026thinsp;\u0026gt;\u0026thinsp;11 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L, neutrophil count\u0026thinsp;\u0026gt;\u0026thinsp;7\u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L, evidence of left shift (\u0026gt;\u0026thinsp;75% neutrophils:lymphocytes) and a CRP\u0026thinsp;\u0026gt;\u0026thinsp;5mg/L was significant for a diagnosis of appendicitis (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) with a specificity of 88% for the diagnosis of AA, with a positive predictive value of 80%.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate analysis of admission blood test parameters and imaging and their associations with acute appendicitis.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOdds ratio (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWCC\u0026thinsp;\u0026gt;\u0026thinsp;11 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.96 (0.25 to 3.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.943\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophil\u0026thinsp;\u0026gt;\u0026thinsp;7 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.04 (1.11 to 14.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocyte\u0026thinsp;\u0026gt;\u0026thinsp;4 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.95 (0.07 to 13.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.968\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP\u0026thinsp;\u0026gt;\u0026thinsp;5mg/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.04 (1.19 to 7.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilirubin\u0026thinsp;\u0026gt;\u0026thinsp;21 umol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.87 (0.70 to 11.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.142\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT\u0026thinsp;\u0026gt;\u0026thinsp;50 U/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.86 (0.18 to 4.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.853\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiological diagnosis of appendicitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.0 (3.74 to 16.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003ePaediatric patients\u003c/h2\u003e \u003cp\u003e87 paediatric patients were identified; 45 patients in this cohort had histological evidence of AA, leading to a NAR of 48%.\u003c/p\u003e \u003cp\u003eOn subgroup analysis there were significant differences in the total WBC, neutrophil count, CRP and total bilirubin (Table \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). There was also a significant difference in the alanine transaminase though the difference was minimal at 2.5 U/L.\u003c/p\u003e \u003cp\u003e40 patients underwent USS. In this population, USS could not significantly predict the presence or absence of AA (p\u0026thinsp;=\u0026thinsp;0.439). Both sensitivity and PPV were 36%, and specificity and NPV were 76%. A full breakdown is found in Supplementary Table\u0026nbsp;1.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBreakdown of demographic and admission biochemistry in paediatric patients. Results are displayed as median (IQR) unless otherwise stated.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHistological diagnosis of appendicitis\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;45\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo evidence of acute appendicitis\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;42\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (\u003cspan additionalcitationids=\"CR9 CR10 CR11 CR12 CR13\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.065\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender, male\u003c/p\u003e \u003cp\u003en\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (38%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.071\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC (\u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.9 (9.5\u0026ndash;16.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.0 (6.7\u0026ndash;10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophils (\u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.5 (6.7\u0026ndash;13.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.9 (3.3-7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocytes (\u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.2 (0.9\u0026ndash;2.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.1 (1.4\u0026ndash;2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.6 (7.4-118.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.5 (0.5\u0026ndash;25.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilirubin (umol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.0 (9.0\u0026ndash;14.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.0 (6.8\u0026ndash;12.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.0 (10.0\u0026ndash;16.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.5 (12.0-18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this single centre study within the United Kingdom we determined a negative appendicectomy rate of 38% based on strict histological criteria, which is slightly higher than reported literature in the field.\u003csup\u003e8,16\u0026ndash;20\u003c/sup\u003e Our results though should be interpreted in the context of requiring strict histological criteria of transmural polymorphonuclear leukocyte infiltration, rather than any inflammation.\u003c/p\u003e \u003cp\u003eIn our cohort we found females were more at risk of undergoing a negative appendicectomy. This may arise due to other gynaecological conditions that may present with similar signs and symptoms, and is in keeping with the known literature at similar rates. \u003csup\u003e8,22\u0026ndash;25\u003c/sup\u003e Also in keeping with other literature we found advancing age to be negatively associated with a negative appendicectomy. \u003csup\u003e8, 17, 19, 22\u0026ndash;23\u003c/sup\u003e This may be due to older patients being more likely to undergo cross-sectional radiological imaging to exclude other diagnosis that can mimic AA or identify any underlying pathology that may cause AA in older patients. \u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe findings in this study cohort have suggested USS is of no discernible benefit in paediatric patients. However, less than half of the paediatric patients in this study underwent ultrasound and the sample size may be too small to detect a significant differences. Further research is needed to examine the local practices around the decision to request pre-operative imaging in children in this study population.\u003c/p\u003e \u003cp\u003eThe sensitivity of USS in this study was very low, with only 35% of AA patients who had a USS having a positive finding of AA on scanning, indicating it is of little use in excluding AA. In addition the PPV value of 50% gives little value in confirming a histological diagnosis of AA. In contrast, CT imaging had a 98% sensitivity and was very good in successfully excluding AA. This clear advantage of CT imaging in the diagnosis of AA has to be weighed against the associated radiation exposure and a low specificity in this study, with 53% of cases reported as acute appendicitis resulting in a negative appendicectomy.\u003c/p\u003e \u003cp\u003eHowever, as previously discussed, other studies have shown higher specificities and sensitivities for pre-operative imaging and therefore further research is needed to understand the reasons behind the lower specificities and sensitivities in this study population. \u003csup\u003e10\u0026ndash;12, 14\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWhilst we did find a significant difference in total WBC between those who did and did not have AA, we did not find on multivariate analysis a WBC\u0026thinsp;\u0026gt;\u0026thinsp;11,000 independently increasing the odds of an AA diagnosis. Though this is in contrast to some of the existing literature. \u003csup\u003e8, 19, 24, 25\u003c/sup\u003e, other studies have suggested WBC is not a predictor of AA.\u003csup\u003e26\u003c/sup\u003e Furthermore it has been suggested that WBC is a poor predictor of AA due to an unreliable specificity and sensitivity and there is no consensus for a reliable cut off value. \u003csup\u003e28\u003c/sup\u003e We did however find that patients with AA were four times more likely to have an elevated neutrophil count at admission in comparison to those with a negative appendicectomy, which is in keeping with other literature.\u003csup\u003e27,28\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWith increasing use of imaging as a key diagnostic tool, this study highlights important limitations in its use for the diagnosis of AA and the need to continue pursuing a combination approach that includes clinical scoring systems, multiple biomarkers and the use of radiological imaging. Further research is needed to implement a new scoring system taking into account a combination approach of clinical signs and symptoms together with biomarkers in patients who may be unable to undergo imaging modalities and where there is diagnostic uncertainty. We also suggest further research from various centres using real time practice data to further investigate the utility of imaging to either exclude or confirm the diagnosis of AA and its role influencing local NAR.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eA limitation of our study was that despite the high number of patients, it is a single centre study. There is furthermore the potential for inter-operator variability in interpreting imaging, which may affect results. Data was not reliably recorded on clinical perimeters, such as heart rate and temperature, and therefore could not be included in these analyses.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe have demonstrated in our cohort that an elevated neutrophil and CRP count are independent risk factors for a diagnosis of AA. Our findings have also demonstrated that the use of several biochemical markers in combination can increase the confidence with which a diagnosis can be made. The usefulness of CT imaging to reduce the likelihood of missed AA has been highlighted. However we found a low specificity and therefore it may be of limited use in reducing a high NAR in clinical practice. USS was of less diagnostic utility, even in paediatric groups. Within our routine practice there was discordance with radiological sensitivity and specificity values compared with that described in prior studies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This research received no external funding\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest:\u0026nbsp;\u003c/strong\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e ND and SD contributed to study conceptualisation and design. ND, LH and GS contributed to data collections. LH conducted statistical analysis and interpretations of results. ND and LH contributed to draft manuscript production. All authors contributed to final manuscript review and editing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u003c/strong\u003e Ethics guidance was not required for this study, which was defined as a clinical audit, in accordance with NHS Health Research Authority guidance. All information within this study was collected and approved following approval and governance checks by the Dartford and Gravesham NHS Trust clinical audit department.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e Further data available upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e No further acknowledgements.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWu JX, Dawes AJ, Sacks GD, Brunicardi FC, Keeler EB. 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Cureus. 2021. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7759/cureus.13086\u003c/span\u003e\u003cspan address=\"10.7759/cureus.13086\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Appendicitis, Negative Appendicectomy rate (NAR), Computed tomography (CT), Ultrasound (US), Preoperative imaging","lastPublishedDoi":"10.21203/rs.3.rs-4320667/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4320667/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAcute appendicitis (AA) is the most common emergency general surgical condition worldwide. Diagnosis is challenging and incorporates clinical, biochemical and radiological investigations. Our aim was to provide data from routine practice investigating widely utilised diagnostic methods from a single centre within the United Kingdom.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective observational cohort study of patients who underwent a laparoscopic appendicectomy for AA between April 2022\u0026ndash;March 2023. AA was defined as the presence of transmural polymorphonuclear leukocytes on histology. Subgroup analysis was performed on paediatric patients. Factors associated with AA were investigated and the diagnostic utility of biochemical and radiological investigations was examined.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e330 appendicectomies were analysed. We found an overall negative appendicectomy rate (NAR) of 38% and 48% in paediatric patients. Independent factors associated with AA on multivariate analysis included elevated neutrophil counts (\u0026gt;\u0026thinsp;7 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L) (OR 4.04), elevated CRP (\u0026gt;\u0026thinsp;5mg/L) (OR 3.04) and a radiological diagnosis (OR 8.0). Computerised tomography (CT) and ultrasound had sensitivity/specificity of 98%/47% and 35%/86% respectively. The positive-predictive values were 85% for CT and 50% for ultrasound and negative-predictive values were 86% for CT and 77% for ultrasound.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOur study has highlighted the importance of utilising a combination of factors to improve the diagnostic certainty of AA. However, our routine practice data has shown different sensitivities and specificities of imaging in comparison to existing literature, resulting in a high NAR. Further real world data is needed to understand whether these differences from the existing data are seen in other clinical settings.\u003c/p\u003e","manuscriptTitle":"Risk factors associated with negative appendicectomy rates: A retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-03 20:04:15","doi":"10.21203/rs.3.rs-4320667/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dce3fbbb-bc57-453a-989a-5fd8c6ad340d","owner":[],"postedDate":"May 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-09T09:23:22+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-03 20:04:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4320667","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4320667","identity":"rs-4320667","version":["v1"]},"buildId":"cTy_lsJlmDsVRNrSptgXS","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}