{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:01:30Z","timestamp":1790845290107,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Difficult laparoscopic cholecystectomy (DLC) in patients with acute cholecystitis (AC) is associated with greater operative complexity and increased perioperative morbidity, yet reliable preoperative risk stratification remains limited. This study aimed to develop and internally validate a preoperative prediction model for DLC and to compare its predictive performance with that of an alternative C-reactive protein\u2013albumin\u2013lymphocyte (CALLY)-based model. Materials and Methods: We retrospectively analyzed consecutive adult patients who underwent laparoscopic cholecystectomy (LC) for AC at a single center between 1 January 2022 and 31 December 2025. DLC was defined as operative time &gt;90 min, conversion to open surgery, subtotal cholecystectomy or a Nassar grade \u22654. Preoperative clinical, laboratory and ultrasonographic variables were evaluated using multivariable logistic regression. Model performance was assessed by discrimination, calibration, Brier score, decision curve analysis and bootstrap internal validation. Results: Among 8530 screened patients, 7736 met the inclusion criteria and 1736 (22.4%) experienced DLC. In the primary multivariable model, Tokyo Guidelines 2018 (TG18) grade II, TG18 grade III and preoperative C-reactive protein (CRP) were independently associated with DLC. The model demonstrated modest discrimination (area under curve (AUC), 0.617; optimism-corrected AUC, 0.612) with a Brier score of 0.167. In the alternative model, TG18 grade III and a lower CALLY index remained independent predictors; however, predictive performance did not improve (AUC, 0.580; Brier score, 0.171). In the sensitivity analysis excluding operative time, severe DLC occurred in 378 patients (4.9%) and none of the candidate predictors remained independently associated with this endpoint. Conclusions: TG18 severity grade and preoperative CRP were independently associated with the composite DLC endpoint, which was predominantly driven by prolonged operative time. Discrimination was limited and no independent associations were identified for severe DLC when operative time was excluded. The alternative CALLY-based model showed lower discrimination than the conventional model. These findings do not support using the model to guide clinical decisions regarding severe operative difficulty.<\/jats:p>","DOI":"10.3390\/diagnostics16193191","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:19:08Z","timestamp":1790842748000},"page":"3191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development and Internal Validation of a Preoperative Risk Stratification Model for Difficult Laparoscopic Cholecystectomy in Acute Cholecystitis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5794-1547","authenticated-orcid":false,"given":"Sinan","family":"Aslan","sequence":"first","affiliation":[{"name":"Department of General Surgery, Mersin City Training and Research Hospital, 33240 Mersin, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8344-3509","authenticated-orcid":false,"given":"\u015eebnem","family":"\u00c7imen","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Akyurt State Hospital, 06750 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1007\/s00535-023-02014-6","article-title":"Evidence-based Clinical Practice Guidelines for Cholelithiasis 2021","volume":"58","author":"Fujita","year":"2023","journal-title":"J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Abdallah, H.S., Sedky, M.H., and Sedky, Z.H. (2025). The Difficult Laparoscopic Cholecystectomy: A Narrative Review. BMC Surg., 25.","DOI":"10.1186\/s12893-025-02847-3"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/jhbp.517","article-title":"Tokyo Guidelines 2018: Surgical Management of Acute Cholecystitis: Safe Steps in Laparoscopic Cholecystectomy for Acute Cholecystitis (with Videos)","volume":"25","author":"Wakabayashi","year":"2018","journal-title":"J. Hepatobiliary Pancreat. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/s00423-004-0509-4","article-title":"Laparoscopic Cholecystectomy in Acute Cholecystitis: Indication, Technique, Risk and Outcome","volume":"390","author":"Giger","year":"2005","journal-title":"Langenbeck\u2019s Arch. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/j.amjsurg.2016.09.024","article-title":"The Difficult Gall Bladder: Outcomes Following Laparoscopic Cholecystectomy and the Need for Open Conversion","volume":"212","author":"Ashfaq","year":"2016","journal-title":"Am. J. Surg."},{"key":"ref_6","first-page":"363","article-title":"Conversion from Laparoscopic to Open Cholecystectomy: Risk Factor Analysis Based on Clinical, Laboratory, and Ultrasound Parameters","volume":"86","author":"Santes","year":"2021","journal-title":"Rev. Gastroenterol. Mex."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.70749\/ijbr.v3i7.2323","article-title":"Frequency of Intraoperative Complications in Patients Undergoing Laparoscopic Cholecystectomy","volume":"3","author":"Zaman","year":"2025","journal-title":"Indus J. Biosci. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4549","DOI":"10.1007\/s00464-019-07244-5","article-title":"Predicting the Difficult Laparoscopic Cholecystectomy: Development and Validation of a Pre-Operative Risk Score Using an Objective Operative Difficulty Grading System","volume":"34","author":"Nassar","year":"2020","journal-title":"Surg. Endosc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.amjsurg.2017.07.029","article-title":"Risk Factors for Conversion of Laparoscopic Cholecystectomy to Open Surgery: A Systematic Literature Review of 30 Studies","volume":"214","author":"Hu","year":"2017","journal-title":"Am. J. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2559","DOI":"10.1038\/s41598-021-81938-6","article-title":"Difficult Laparoscopic Cholecystectomy and Preoperative Predictive Factors","volume":"11","author":"Buono","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"375","DOI":"10.47717\/turkjsurg.2022.5816","article-title":"Preoperative Scoring System Validation and Analysis of Associated Risk Factors in Predicting Difficult Laparoscopic Cholecystectomy in Patients with Acute Calculous Cholecystitis: A Prospective Observational Study","volume":"38","author":"Paul","year":"2022","journal-title":"Turk. J. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Stoica, P.L., Serban, D., Bratu, D.G., Serboiu, C.S., Costea, D.O., Tribus, L.C., Alius, C., Dumitrescu, D., Dascalu, A.M., and Tudor, C. (2024). Predictive Factors for Difficult Laparoscopic Cholecystectomies in Acute Cholecystitis. Diagnostics, 14.","DOI":"10.3390\/diagnostics14030346"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2827","DOI":"10.1007\/s00464-020-07568-7","article-title":"Safe Cholecystectomy Multi-Society Practice Guideline and State-of-the-Art Consensus Conference on Prevention of Bile Duct Injury During Cholecystectomy","volume":"34","author":"Brunt","year":"2020","journal-title":"Surg. Endosc."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lio, R.M.S., Barchitta, M., Maugeri, A., Quartarone, S., Basile, G., and Agodi, A. (2023). Preoperative Risk Factors for Conversion from Laparoscopic to Open Cholecystectomy: A Systematic Review and Meta-Analysis. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20010408"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1159\/000445505","article-title":"Preoperative Risk Factors for Conversion of Laparoscopic Cholecystectomy to Open Surgery: A Systematic Review and Meta-Analysis of Observational Studies","volume":"33","author":"Rothman","year":"2016","journal-title":"Dig. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1001\/jama.2022.2350","article-title":"Acute Cholecystitis: A Review","volume":"327","author":"Gallaher","year":"2022","journal-title":"JAMA"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Korayem, I.M., and Bessa, S.S. (2024). Preoperative Predictors of Difficult Early Laparoscopic Cholecystectomy among Patients with Acute Calculous Cholecystitis in Egypt. BMC Surg., 24.","DOI":"10.1186\/s12893-024-02532-x"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1089\/lap.2020.0151","article-title":"Risk Prediction in Acute Calculous Cholecystitis: A Systematic Review and Meta-Analysis of Prognostic Factors and Predictive Models","volume":"31","author":"Tufo","year":"2021","journal-title":"J. Laparoendosc. Adv. Surg. Tech. A"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.surge.2020.06.010","article-title":"Accuracy of Pre-Operative Parameters in Predicting Severe Cholecystitis: A Systematic Review","volume":"19","author":"Khan","year":"2021","journal-title":"Surgeon"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Sar\u0131da\u015f, A., and \u00c7etinkaya, R. (2025). The Prognostic Value of the CALLY Index in Sepsis: A Composite Biomarker Reflecting Inflammation, Nutrition, and Immunity. Diagnostics, 15.","DOI":"10.3390\/diagnostics15081026"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.hpb.2021.06.414","article-title":"Superiority of CRP-Albumin-Lymphocyte Index (CALLY Index) as a Non-Invasive Prognostic Biomarker after Hepatectomy for Hepatocellular Carcinoma","volume":"24","author":"Iida","year":"2022","journal-title":"HPB"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.hpb.2023.12.002","article-title":"Combining Preoperative C-Reactive Protein Values with the Tokyo Guidelines 2018 Grading Criteria Can Enhance the Prediction of Surgical Difficulty in Early Laparoscopic Cholecystectomy for Acute Cholecystitis","volume":"26","author":"Mishima","year":"2024","journal-title":"HPB"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1002\/bjs5.50189","article-title":"C-Reactive Protein Level as a Predictor of Difficult Emergency Laparoscopic Cholecystectomy","volume":"3","author":"Ng","year":"2019","journal-title":"BJS Open"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e2016.00065","DOI":"10.4293\/JSLS.2016.00065","article-title":"Risk Factors for Difficult Laparoscopic Cholecystectomy in Acute Cholecystitis","volume":"20","author":"Hayama","year":"2016","journal-title":"JSLS"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Amezcua-Castillo, E., Gonz\u00e1lez-Pacheco, H., Mart\u00edn, A.S.-S., M\u00e9ndez-Ocampo, P., Gutierrez-Moctezuma, I., Mass\u00f3, F., Sierra-Lara, D., Springall, R., Rodr\u00edguez, E., and Arias-Mendoza, A. (2023). C-Reactive Protein: The Quintessential Marker of Systemic Inflammation in Coronary Artery Disease\u2014Advancing toward Precision Medicine. Biomedicines, 11.","DOI":"10.3390\/biomedicines11092444"},{"key":"ref_26","first-page":"e4573","article-title":"C-Reactive Protein Is an Independent Predictor of Difficult Emergency Cholecystectomy","volume":"11","author":"Gregory","year":"2019","journal-title":"Cureus"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1097\/SLE.0b013e318220f1b1","article-title":"Difficult Laparoscopic Cholecystectomy: Current Evidence and Strategies of Management","volume":"21","author":"Hussain","year":"2011","journal-title":"Surg. Laparosc. Endosc. Percutan. Tech."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.hpb.2016.07.015","article-title":"Preoperative Risk Factors for Conversion from Laparoscopic to Open Cholecystectomy: A Validated Risk Score Derived from a Prospective U.K. Database of 8820 Patients","volume":"18","author":"Sutcliffe","year":"2016","journal-title":"HPB"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1089\/lap.2022.0407","article-title":"The Modification of a Preoperative Scoring System to Predict Difficult Elective Laparoscopic Cholecystectomy","volume":"33","author":"Tongyoo","year":"2023","journal-title":"J. Laparoendosc. Adv. Surg. Tech. A"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1177\/10926429251379864","article-title":"The Prediction of Difficult Laparoscopic Cholecystectomy for Acute Cholecystitis from Preoperative Clinical Factors and Radiological Findings","volume":"35","author":"Chung","year":"2025","journal-title":"J. Laparoendosc. Adv. Surg. Tech. A"},{"key":"ref_31","first-page":"e35767","article-title":"Intraoperative Scoring System to Assess the Difficult Laparoscopic Cholecystectomy: A Prospective Study from a Tertiary Care Centre","volume":"15","author":"Pal","year":"2023","journal-title":"Cureus"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e13309","DOI":"10.1111\/ases.13309","article-title":"Preoperative Difficulty Factors in Delayed Laparoscopic Cholecystectomy: Tokyo Guidelines 2018 Surgical Difficulty Score Analysis","volume":"17","author":"Naito","year":"2024","journal-title":"Asian J. Endosc. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"M\u00fcller, L., Hahn, F., M\u00e4hringer-Kunz, A., Stoehr, F., Gairing, S.J., Michel, M., Foerster, F., Weinmann, A., Galle, P.R., and Mittler, J. (2021). Immunonutritive Scoring for Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization: Evaluation of the CALLY Index. Cancers, 13.","DOI":"10.3390\/cancers13195018"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zhang, J., Lin, Y., Zeng, J., Luo, G., Liao, P., Chen, Q., Zhong, H., Liang, S., Zhou, C., and Yang, B. (2025). The C-Reactive Protein (CRP)-Albumin-Lymphocyte (CALLY) Index Exhibits an L-Shaped Association with All-Cause Mortality in Rheumatoid Arthritis Patients: A Retrospective Cohort Study. BMC Rheumatol., 9.","DOI":"10.1186\/s41927-025-00499-7"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Li, H., Mo, Z., and Tong, G. (2025). Value of CRP, Albumin, and Lymphocyte Index in Predicting Survival of Patients with Gastrointestinal Malignancies: A Systematic Review and Meta-Analysis. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1592794"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/jhbp.440","article-title":"An Opportunity in Difficulty: Japan\u2013Korea\u2013Taiwan Expert Delphi Consensus on Surgical Difficulty during Laparoscopic Cholecystectomy","volume":"24","author":"Iwashita","year":"2017","journal-title":"J. Hepatobiliary Pancreat. Sci."},{"key":"ref_37","first-page":"e47774","article-title":"Preoperative and Intraoperative Risk Factors for Conversion of Laparoscopic Cholecystectomy to Open Cholecystectomy: A Systematic Review of 30 Studies","volume":"15","author":"Chin","year":"2023","journal-title":"Cureus"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1007\/s00464-018-6281-2","article-title":"Utilisation of an Operative Difficulty Grading Scale for Laparoscopic Cholecystectomy","volume":"33","author":"Griffiths","year":"2019","journal-title":"Surg. Endosc."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/19\/3191\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:36:19Z","timestamp":1790843779000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/19\/3191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":38,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["diagnostics16193191"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16193191","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]}}}