Sex-based Analysis of Laparoscopic Cholecystectomy Outcomes: A Prospective Cohort Study

Sex-based Analysis of Laparoscopic Cholecystectomy Outcomes: A Prospective 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 Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Sex-based Analysis of Laparoscopic Cholecystectomy Outcomes: A Prospective Cohort Study Waleed Mohammed Gilan, Yasser Abdurabo Obadiel, Nezar Mohammed Mahyoub, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7055064/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 Sex-based differences in laparoscopic cholecystectomy (LC) outcomes remain poorly understood, with conflicting evidence regarding the effects of patient sex on surgical complexity and complications. This study aimed to comprehensively evaluate sex-based differences in laparoscopic cholecystectomy outcomes using rigorous statistical analysis. Methods This prospective cohort study was conducted at Al-Kuwait University Hospital, Yemen, between January 2023 and June 2024. After applying strict exclusion criteria, 218 patients were included: 175 females (80.3%) and 43 males (19.7%). Bivariate analysis, multivariate logistic regression, and enhanced analyses were used to examine the demographic characteristics, preoperative profiles, intraoperative findings, and postoperative outcomes. Results Males were significantly older (46.0 ± 15.3 vs 40.9 ± 11.8 years, p = 0.034) with a higher prevalence of diabetes (27.9% vs 8.6%, p = 0.001) and chronic liver disease (7.0% vs 0.6%, p = 0.025). Males more frequently presented with acute cholecystitis (55.8% vs. 35.4%, p = 0.005). The incidence of intraoperative complications, particularly gallbladder perforation (41.9% vs. 21.1%, p = 0.009), was significantly higher in men than in women (16.3% vs. 5.7%, p = 0.046). Males had longer hospital stays (2.7 ± 1.7 vs 2.4 ± 2.1 days, p = 0.021). Multivariate analysis identified acute cholecystitis as the strongest predictor of conversion to open surgery (OR 3.90, 95% CI: 1.95–7.80, p = 0.001). Conclusions This study demonstrated significant sex-based differences in the LC outcomes. Males present with more complex disease patterns, experience higher rates of intraoperative complications, and require longer hospital stays. These findings necessitate sex-specific considerations in preoperative counseling, surgical planning, and postoperative care protocols. Laparoscopic cholecystectomy Sex differences Surgical outcomes Multivariate analysis Risk factors Gallbladder perforation Acute cholecystitis Figures Figure 1 Figure 2 Figure 3 Background Since its introduction in the late 1980s, laparoscopic cholecystectomy (LC) has been established as the gold standard for the surgical treatment of gallbladder diseases since its introduction in the late 1980s[ 1 ]. The minimally invasive approach offers significant advantages over open cholecystectomy, including reduced postoperative pain, shorter hospital stay, and faster recovery times[ 2 ]. Despite these well-documented benefits, emerging evidence suggests that patient outcomes may be influenced by a complex interplay of demographic, clinical, and anatomical factors, which warrants systematic investigation. Sex-based differences in surgical outcomes have been documented across various procedures, with gallbladder disease presenting unique considerations that extend beyond simple epidemiological patterns. The pathophysiology of gallbladder disease demonstrates clear sex-related variations influenced by hormonal factors, particularly estrogen, which affect bile composition and gallbladder motility through complex mechanisms involving cholecystokinin and gallbladder smooth muscle function[ 3 ]. These physiological differences manifest clinically, with females experiencing a higher overall incidence of gallstone disease, whereas males tend to present with more severe and complicated forms of the disease[ 4 ]. The contemporary literature on sex differences in LC outcomes reveals a complex and sometimes contradictory landscape. A systematic review and meta-analysis by Magnano San Lio et al. (2022) demonstrated that male sex significantly increased the probability of conversion from laparoscopic to open cholecystectomy (OR = 1.907; 95% CI = 1.254–2.901), establishing it as an independent preoperative risk factor[ 5 ]. This finding is supported by multiple large-scale studies that have consistently reported higher conversion rates in male patients [ 6 ]. However, the mechanisms underlying these differences remain unclear. Recent high-quality studies have provided additional insights into sex-based variations in LC outcome. Nikfarjam et al. (2013) demonstrated that male patients with acute cholecystitis were older (66 vs. 57 years; p < 0.001), had higher comorbidity burdens, including diabetes (21% vs. 9%; p = 0.001) and ischemic heart disease (24% vs. 8%; p < 0.001), and were more likely to present gangrenous pathology (45% vs. 23%; p < 0.001)[ 7 ]. Similarly, AlKhalifah et al. (2023) found that male sex was independently associated with both intraoperative (p = 0.005) and postoperative complications (p = 0.045) after multivariate adjustment[ 8 ]. The anatomical and physiological basis of these sex differences has been elucidated through detailed surgical studies. Akcakaya et al. (2015) demonstrated that male patients exhibited significantly longer operative times (71 ± 33 min vs. 58 ± 27 min; p < 0.001), higher anatomical difficulty scores (p < 0.0001), and an increased frequency of adhesions between the gallbladder and surrounding structures[ 6 ]. These findings suggest that the increased surgical complexity in males may be attributable to more severe inflammatory changes, denser adhesions, and anatomical variations that complicate laparoscopic dissection. Several well-designed studies have reported conflicting results. Despite significantly longer operative times in males, Bazoua and Tilston (2014) found no significant differences in conversion rates (7.5% vs. 2.9%; p = 0.142) or perioperative morbidity (12.1% vs. 10.2%; p = 0.66) between male and female patients undergoing elective LC, despite significantly longer operative times in males[ 9 ]. This discrepancy may be attributable to differences in case selection, with elective procedures potentially excluding the most complex presentations more commonly observed in male patients. Healthcare utilization patterns also contributed to the observed sex-related differences. Dua et al. (2013) analyzed a large national database and found that women undergo cholecystectomy earlier (1.6 vs. 1.9 days; p < 0.05) and more frequently by laparoscopy (86% vs. 76%), resulting in lower mortality (0.6% vs. 1.1%), fewer complications (16.9% vs. 24.1%), and shorter hospital stays (4.2 vs. 5.4 days). These findings suggest that delayed presentation and treatment in males may contribute to worse outcomes through disease progression and increased inflammation[ 4 ]. The inconsistency in findings across studies can be attributed to several methodological limitations that have hampered definitive conclusions. Many previous studies have been limited by small sample sizes, particularly for male patients who comprise only 20–30% of cholecystectomy cases, inadequate statistical power for subgroup analyses, and a lack of comprehensive multivariate analysis to control for confounding factors such as age, comorbidities, and disease severity. Few studies have employed rigorous statistical protocols, including detailed bivariate comparisons and enhanced analytical approaches, to isolate the independent effects of sex on the related variables. Recent advances in surgical techniques and technologies have influenced sex-based outcomes. Blohm et al. (2023) examined surgeon sex effects and found that female surgeons achieved significantly better patient outcomes with fewer complications and bile duct injuries despite longer operative times, suggesting that surgical techniques and approaches may modify sex-based differences in outcomes[ 10 ]. This prospective cohort study aimed to address these methodological limitations by systematically evaluating sex differences in a comprehensive range of outcomes following LC, using a robust analytical framework. This study sought to provide definitive evidence regarding sex-based differences in laparoscopic cholecystectomy outcomes by employing advanced statistical methodologies including bivariate analysis, multivariate logistic regression, and enhanced analytical approaches. This study will specifically examine whether male sex is an independent risk factor for adverse outcomes or whether other clinical variables such as age, comorbidities, and disease severity mediate the observed differences. The findings of this study will inform evidence-based clinical decision-making and contribute to the development of sex-specific surgical protocols and risk-stratification models. Methods Study Design and Setting This prospective cohort study was conducted at the Al-Kuwait University Hospital, Sana'a, Yemen, between January 2023 and June 2024. This study was designed to use comprehensive statistical analysis to investigate sex-based differences in LC outcomes of laparoscopic cholecystectomy. Ethical approval was obtained from the Institutional Review Board of the Al-Kuwait University Hospital, and written informed consent was obtained from all participants. Participants The initial study cohort included 238 patients who had undergone LCC. The inclusion criteria were as follows: (1) male and female patients aged ≥ 18 years; (2) diagnosed with gallstone disease, including symptomatic gallstones, acute cholecystitis, or chronic cholecystitis; and (3) undergoing elective or emergency laparoscopic cholecystectomy, including those requiring conversion to open surgery. Strict exclusion criteria were applied to ensure a homogeneous study population: (1) previous abdominal surgery (n = 19), (2) choledocholithiasis (n = 1), or (3) porcelain gallbladder (n = 1). After exclusion, 218 patients were included in the final analysis: 175 females (80.3%) and 43 males (19.7%) (Fig. 1 ). Data Collection Data were collected prospectively using a standardized data collection form designed to capture the variables necessary for comprehensive statistical analysis. Demographic characteristics included age, sex, body mass index (BMI), and American Society of Anesthesiologists (ASA) classification. The recorded comorbidities included diabetes mellitus, hypertension, heart disease, chronic liver disease, and chronic lung disease. Preoperative clinical data included the presenting symptoms (biliary colic, jaundice, and fever) and surgical indications (symptomatic gallbladder stones, acute cholecystitis, and chronic cholecystitis). Intraoperative variables included operative time, surgical approach, surgeon experience level, inflammation severity, dissection difficulty graded according to established criteria, and intraoperative complications, including bleeding, bile duct injury, bile or stone spillage, and gallbladder perforation. The postoperative outcomes included specific complications (wound infection, abdominal abscess/peritonitis, and bile leak), reoperation, readmission, length of hospital stay, and mortality. All patients were followed-up until discharge or 30 days after surgery, whichever was longer. Statistical Analysis A comprehensive statistical analysis protocol was employed to ensure accuracy of the results. Descriptive statistics were calculated for all variables, with continuous variables presented as mean ± standard deviation and categorical variables as frequencies and percentages. Bivariate analysis was used to compare male and female patients across four domains: demographics, preoperative profile, intraoperative findings, and postoperative outcomes. The Mann–Whitney U test was used to analyze continuous variables for non-parametric distributions, whereas categorical variables were analyzed using the chi-square test or Fisher’s exact test for small expected frequencies. Statistical significance was set at p < 0.05. Multivariate logistic regression analysis was performed to identify independent predictors of key outcomes: conversion to open surgery, intraoperative complications, and postoperative complications. The models included the relevant demographic, clinical, and surgical variables to control for confounding factors. Results are reported as odds ratios (OR) with 95% confidence intervals (CI) and p-values. Enhanced analyses included subgroup analysis of interaction effects and predictors of prolonged hospital stay. All analyses were performed using SPSS version 26.0 (IBM Corporation, Armonk, NY, USA) with robust standard error calculations. Results Characteristics of the Study Population Of the 238 patients initially identified, 218 completed the study protocol and were included in the final analysis. The cohort comprised 175 females (80.3%) and 43 males (19.7%), with complete follow-up data available for all participants (Fig. 1 ). Demographic and Baseline Characteristics Males were significantly older than females (46.0 ± 15.3 vs 40.9 ± 11.8 years, p = 0.034). BMI distribution showed significant differences between sexes (p < 0.001), with males demonstrating higher obesity rates (27.9% vs. 13.1%) but lower overweight rates (7.0% vs. 34.3%) than females. The ASA classification distribution showed a trend toward a higher ASA III classification in males (16.3% vs. 6.3%, p = 0.068). The comorbidity analysis revealed a significantly higher prevalence of diabetes (27.9% vs. 8.6%, p = 0.001) and chronic liver disease (7.0% vs. 0.6%, p = 0.025) in men. No significant differences were observed in the prevalence of hypertension or heart disease between sexes (Table 1 ). Table 1 Demographic and baseline characteristics of the participants by sex Variable Female (n = 175) Male (n = 43) p-value Age (mean ± SD), years 40.9 ± 11.8 46.0 ± 15.3 0.034 BMI categories, n (%) < 0.001 Normal 92 (52.6) 28 (65.1) Overweight 60 (34.3) 3 (7.0) Obese 23 (13.1) 12 (27.9) ASA classification, n (%) 0.068 ASA I 87 (49.7) 16 (37.2) ASA II 77 (44.0) 20 (46.5) ASA III 11 (6.3) 7 (16.3) Comorbidities, n (%) Diabetes mellitus 15 (8.6) 12 (27.9) 0.001 Hypertension 32 (18.3) 11 (25.6) 0.388 Heart disease 6 (3.4) 4 (9.3) 0.111 Chronic liver disease (CLD) 1 (0.6) 3 (7.0) 0.025 Preoperative Clinical Profile Analysis of the presenting symptoms revealed no significant sex-based differences in biliary colic (81.4% vs. 73.7%, p = 0.396), jaundice (11.6% vs. 6.3%, p = 0.380), or fever (44.2% vs. 35.4%, p = 0.374). However, the diagnosis distribution was significantly different (p = 0.005), with males more frequently presenting with acute cholecystitis (55.8% vs. 35.4%) and chronic cholecystitis (11.6% vs. 4.0%), whereas females more commonly presented with symptomatic gallbladder stones (57.7% vs. 32.6%) (Table 2 , Fig. 2 ). Table 2 Preoperative clinical characteristics according to the sex Variable Female (n = 175) Male (n = 43) p-value Presenting symptoms, n (%) Biliary colic 129 (73.7) 35 (81.4) 0.396 Jaundice 11 (6.3) 5 (11.6) 0.380 Fever 62 (35.4) 19 (44.2) 0.374 Diagnosis, n (%) 0.005 Symptomatic gallbladder stones 101 (57.7) 14 (32.6) Acute cholecystitis 62 (35.4) 24 (55.8) Chronic cholecystitis 7 (4.0) 5 (11.6) Panel A shows the age distribution of older males. Panel B illustrates the significant differences in BMI distribution. Panel C highlights the higher prevalence of key comorbidities among male patients. Panel D shows a significantly different distribution of surgical indications between sexes. Intraoperative Findings Operative times were similar between sexes (87.0 ± 32.8 vs 78.1 ± 22.1 minutes, p = 0.264). The conversion rates to open surgery were comparable between groups (13.1% vs. 14.0%, p = 1.000). Inflammation severity and dissection difficulty grades showed no significant differences between sexes. However, males experienced significantly higher rates of intraoperative complications (41.9% vs. 21.1%, p = 0.009). Gallbladder perforation was significantly more frequent in males (16.3% vs. 5.7%, p = 0.046), representing a nearly three-fold increase. Other complications, including bile/stone spillage and bleeding, were higher in males but did not reach statistical significance (Table 3 ). Table 3 Intraoperative characteristics and complications according to the sex Variable Female (n = 175) Male (n = 43) p-value Operative time (mean ± SD), min 87.0 ± 32.8 78.1 ± 22.1 0.264 Conversion to open surgery, n (%) 23 (13.1) 6 (14.0) 1.000 Inflammation severity, n (%) 0.112 Mild 89 (50.9) 16 (37.2) Moderate 80 (45.7) 23 (53.5) Severe 6 (3.4) 4 (9.3) Intraoperative complications, n (%) Intraoperative complications 37 (21.1) 18 (41.9) 0.009 Gallbladder perforation 10 (5.7) 7 (16.3) 0.046 Bile/stone spillage 16 (9.1) 6 (14.0) 0.512 Bleeding 8 (4.6) 4 (9.3) 0.259 Postoperative Outcomes The overall postoperative complication rates were similar between sexes (13.1% vs. 14.0%, p = 1.000). Individual complications, including wound infection, abdominal abscess/peritonitis, bile leak, reoperation, and readmission, were not significantly different, although males tended to have higher rates of wound infection and abdominal complications. Males had significantly longer hospital stays (2.7 ± 1.7 vs 2.4 ± 2.1 days, p = 0.021). One case of mortality occurred in the male group (2.3% vs. 0%, p = 0.197); however, this difference was not statistically significant because of the low overall event rate (Table 4 , Fig. 3 ). Table 4 Postoperative outcomes according to the sex Variable Female (n = 175) Male (n = 43) p-value Any postoperative complication, n (%) 23 (13.1) 6 (14.0) 1.000 Specific complications, n (%) Wound infection 9 (5.1) 5 (11.6) 0.227 Abdominal abscess/peritonitis 1 (0.6) 2 (4.7) 0.100 Bile leak 14 (8.0) 2 (4.7) 0.744 Reoperation 4 (2.3) 2 (4.7) 0.338 Readmission 4 (2.3) 2 (4.7) 0.338 Length of stay (mean ± SD), days 2.4 ± 2.1 2.7 ± 1.7 0.021 Mortality, n (%) 0 (0.0) 1 (2.3) 0.197 Panel A displays similar operative time distributions between sexes. Panel B shows a significantly higher rate of intraoperative complications in male patients than in women. Panel C illustrates a nearly three-fold higher incidence of gallbladder perforation in males. Panel D shows a significantly longer length of hospital stay among the male patients. Multivariate Analysis Three multivariate logistic regression models were constructed to identify independent predictors of key outcomes (Table 5 ). Model 1: Conversion to Open Surgery : Acute cholecystitis emerged as the strongest predictor of conversion (OR 3.90, 95% CI: 1.95–7.80, p = 0.001). Male sex was not independently associated with conversion risk (OR 0.75, 95% CI: 0.37–1.50, p = 0.412). Model 2: Intraoperative Complications: Dissection difficulty was the most powerful predictor, with Grade III difficulty associated with significantly increased odds of complications (OR 10.27, 95% CI: 5.14–20.55, p < 0.001) compared with Grade I. Male sex showed a trend toward increased risk (OR 1.84, 95% CI: 0.92–3.69, p = 0.084). Model 3-Postoperative Complications : Conversion to open surgery was the strongest predictor of postoperative complications (OR 5.24, 95% CI: 1.96–13.99, p < 0.001). Male sex was not independently associated with postoperative complications (OR 0.81, 95% CI: 0.25–2.60, p = 0.722). Table 5 Multivariate analysis results Model/Variable Odds Ratio (95% CI) p-value Model 1: Conversion to Open Surgery Male sex 0.75 (0.37–1.50) 0.412 Age (per year) 1.03 (0.52–2.06) 0.934 Acute cholecystitis 3.90 (1.95–7.80) 0.001 Model 2: Intraoperative Complications Male sex 1.84 (0.92–3.69) 0.084 Dissection difficulty Grade II 3.67 (1.83–7.33) < 0.001 Dissection difficulty Grade III 10.27 (5.14–20.55) < 0.001 Model 3: Postoperative Complications Male sex 0.81 (0.25–2.60) 0.722 Conversion to open surgery (OS) 5.24 (1.96–13.99) < 0.001 Age (per year) 1.02 (1.00-1.05) 0.070 Discussion This comprehensive prospective study provides robust evidence for significant sex-based differences in laparoscopic cholecystectomy outcomes, contributing to the growing body of literature examining demographic influences on surgical outcomes. Our findings demonstrate that males present with more complex clinical profiles, which are characterized by advanced age, higher comorbidity burden, and increased prevalence of acute inflammatory conditions. These factors contribute to significantly higher intraoperative complication rates and longer hospital stays, even when operative times and conversion rates remain comparable between sexes. The five-year age difference between males and females in our cohort (46.0 ± 15.3 vs 40.9 ± 11.8 years) aligns with established epidemiological patterns and reflects fundamental differences in disease natural history between sexes. This finding is consistent with that of Nikfarjam et al. (2013), who reported a nine-year age difference (66 vs. 57 years) in patients with acute cholecystitis and may reflect differential healthcare-seeking behaviors, hormonal influences on disease progression, or delayed symptom development in males[ 7 ]. The significantly higher prevalence of diabetes in males (27.9% vs. 8.6%) represents a particularly important finding with substantial clinical implications. This threefold difference exceeds the general population disparities and may reflect both the underlying metabolic differences and the association between metabolic syndrome and gallbladder disease severity. Nikfarjam et al. (2013) reported similar findings (21% vs. 9% prevalence of diabetes), establishing a consistent pattern across different populations. Diabetes is a well-established risk factor for surgical complications, delayed wound healing, and increased risk of infection, which may explain the increased morbidity observed in male patients[ 7 ]. The increased prevalence of chronic liver disease in males, although affecting small absolute numbers, suggests a pattern of more complex underlying health conditions that may contribute to increased surgical risk. This finding, combined with the higher prevalence of diabetes, indicates that males presenting with LC have a higher baseline risk profile that extends beyond the gallbladder pathology itself. Severity of Disease and Inflammatory Patterns One of the most clinically significant findings was the markedly higher prevalence of acute cholecystitis in males (55.8% vs. 35.4%), representing a 58% increase in the likelihood of inflammatory presentation. This finding is consistent with multiple large-scale studies, including that of Dua et al. (2013), who demonstrated that males are less likely to undergo elective surgery and are more likely to present with complicated diseases requiring emergency intervention[ 4 ]. A systematic review by Magnano San Lio et al. (2022) identified acute cholecystitis as the strongest predictor of conversion to open surgery (OR = 5.475; 95% CI = 2.959–10.130), which aligns with our multivariate analysis that confirmed acute cholecystitis as the strongest predictor of conversion (OR = 3.90, p = 0.001)[ 5 ]. The higher prevalence of acute inflammatory conditions in males may be attributable to several factors. First, hormonal influences may provide protective effects in premenopausal women, as estrogen affects bile composition and gallbladder motility [ 3 ]. Second, differences in healthcare-seeking behavior may result in males presenting later in the disease course, allowing progression to more severe inflammatory states. Third, anatomical differences in the body habitus and fat distribution may influence the inflammatory response and adhesion formation patterns. Surgical Complexity and Intraoperative Outcomes Despite comparable operative times and conversion rates, males experienced significantly higher intraoperative complication rates (41.9% vs. 21.1%), with gallbladder perforation being nearly three times more frequent. This finding is consistent with that of AlKhalifah et al. (2023), who reported that males were more likely to experience intraoperative complications (24.4% vs. 6.5%; p < 0.001) and that male sex was independently associated with intraoperative complications after multivariate adjustment (p = 0.005)[ 8 ]. The mechanistic basis for increased surgical complexity in males has been elucidated through detailed intraoperative assessment. According to Akcakaya et al. (2015), male patients exhibited significantly higher anatomical difficulty scores (p < 0.0001), an increased frequency of omental adhesions (p = 0.003), and more severe inflammatory findings in histological specimens[ 6 ]. These findings suggest that the increased complication rates in males are attributable to more challenging surgical conditions than to inherent differences in surgical techniques or surgeon experience. The finding of comparable operative times between sexes, despite higher complication rates in males, may reflect several factors. First, surgeons may adopt more conservative approaches in male patients and spend additional time on careful dissection to minimize complications. Second, the use of intraoperative techniques such as subtotal cholecystectomy or fundus-first approaches may maintain operative efficiency while managing difficult anatomies. Third, our exclusion criteria may have selected cases in which surgical expertise was adequate to manage complex anatomy within a reasonable timeframe. Conversion Patterns and Risk Stratification The comparable conversion rates between sexes (despite higher complication rates in males) contrasts with some published series but aligns with recent high-quality studies. Bazoua and Tilston (2014) [ 9 ]reported similar conversion rates (7.5% vs. 2.9%; p = 0.142) in elective cases, whereas Warchałowski et al. (2020) found that the male sex was associated with conversion in univariate analysis but not in multivariate models[ 11 ]. However, a meta-analysis by Magnano San Lio et al. (2022) demonstrated that the male sex increased the conversion probability (OR = 1.907; 95% CI = 1.254–2.901) across multiple studies[ 5 ]. Our multivariate analysis revealed that acute cholecystitis was the most powerful predictor of conversion (OR 3.90, p = 0.001), which aligns with the systematic review finding that acute cholecystitis carries the highest conversion risk (OR, 5.475). The fact that males have higher rates of acute cholecystitis but comparable conversion rates suggests that other factors may be protective or that surgical management has evolved to better manage inflammatory cases. Postoperative outcomes and utilization of healthcare resources The significantly longer hospital stays in males (2.7 ± 1.7 vs 2.4 ± 2.1 days) represent a clinically meaningful difference with important implications for healthcare resource utilization and cost-effectiveness. This finding is consistent with that of Dua et al. (2013), who reported longer stays in males (5.4 vs 4.2 d) and higher costs ( $ 13,201 vs $ 10,556)[ 4 ]. Prolonged hospitalization in males may reflect higher complication rates, slower recovery due to comorbidities, or more conservative discharge practices in higher-risk patients. Interestingly, while males had higher intraoperative complication rates, overall postoperative complication rates were similar between the sexes. This paradox may reflect several factors: first, intraoperative complications (particularly gallbladder perforation) may be managed effectively during surgery without subsequent clinical impact; second, more intensive perioperative monitoring and management may offset the higher comorbidity burden in males; third, the effectiveness of modern perioperative care protocols in managing high-risk patients may reflect comparable postoperative outcomes. Independent Risk Factors and Multivariate Analysis The identification of conversion to open surgery as the strongest predictor of postoperative complications (OR 5.24, p < 0.001) underscores the cascade effect of intraoperative complexity on postoperative outcomes. This finding emphasizes the importance of case selection, surgical planning, and maintenance of the laparoscopic approach, when it is safe and feasible. Multivariate analysis confirmed that dissection difficulty was the most powerful predictor of intraoperative complications, with Grade III difficulty associated with more than ten times the odds of complications, highlighting the importance of surgical technique and case complexity assessment. Our multivariate analysis demonstrated that male sex was not an independent predictor of conversion or major complications, after adjusting for confounding variables. This finding aligns with those of several recent studies, including Bazoua and Tilston (2014) and Coelho et al. (2019), who concluded that male sex is not an independent risk factor for adverse outcomes after controlling for confounders[ 9 , 12 ]. This suggests that the observed sex differences in outcomes are mediated by other clinical variables such as age, comorbidities, and disease severity, rather than representing an inherent biological disadvantage. Clinical Implications and Future Directions These findings have several important clinical implications for surgical practice. First, male patients should receive enhanced preoperative counseling regarding the increased likelihood of intraoperative complications and prolonged hospital stays. Second, risk stratification models should incorporate sex-specific factors such as a higher prevalence of OC and comorbidities in males. Third, increased complexity in male patients should be anticipated in surgical planning, with consideration of senior surgeon involvement and allocation of adequate operative time. The implications of the healthcare system are equally significant. Longer hospital stays and higher complication rates in males translate into increased healthcare costs and resource utilization. Dua et al. (2013) estimated a $ 2,645 cost difference between male and female patients, suggesting that sex-based differences have substantial economic implications at the population level[ 4 ]. Future research should focus on several key areas: first, prospective multicenter studies with larger sample sizes to validate these findings across different populations and healthcare systems; second, investigation of the underlying biological mechanisms driving sex differences, including hormonal influences, anatomical variations, and inflammatory response patterns; third, development and validation of sex-specific risk prediction models to guide clinical decision-making; and fourth, evaluation of targeted interventions to reduce sex-based disparities in outcomes. Study Strengths and Limitations The strengths of this study include its prospective design with standardized data collection protocols, comprehensive statistical methodology with multivariate analysis, detailed analysis of multiple outcome measures, and focus on sex-specific differences using rigorous analytical approaches. The inclusion of both elective and emergency cases provides a comprehensive view of sex differences across the severity spectrum of gallbladder disease. However, this study has several limitations. First, the relatively small sample size of male patients (consistent with the general epidemiology of gallbladder disease) may limit the statistical power of some subgroup analyses. Second, the single-center design may limit the generalizability to other healthcare systems and populations. Third, the lack of long-term follow-up data prevents the assessment of chronic complications or quality of life outcomes. Fourth, unmeasured confounders, such as surgeon experience, case complexity beyond our measured variables, and patient-specific factors, may have influenced the outcomes. Conclusions This prospective study provides robust evidence that males undergoing laparoscopic cholecystectomy present with more complex clinical profiles, including older age, higher comorbidity burden, and increased prevalence of acute inflammatory conditions. These factors contribute to significantly higher rates of intraoperative complications and longer hospital stays, representing clinically meaningful differences that impact patient outcomes and utilization of healthcare resources. However, after controlling for confounding variables, the male sex itself did not appear to be an independent risk factor for adverse outcomes, suggesting that other clinical variables mediate the observed differences. The findings of this study support the implementation of sex-specific approaches to perioperative care, including enhanced preoperative counseling, risk stratification, and surgical planning for male patients. Healthcare systems should recognize and account for sex-based differences in resource allocation and quality improvement initiatives. Future research should focus on validating these findings in larger multicenter cohorts and investigating targeted interventions to reduce sex-based disparities in surgical outcomes. Declarations Ethics Approval and Consent to Participate This study was conducted in accordance with the ethical standards of the Declaration of Helsinki and was approved by the Institutional Review Board of Al-Kuwait University Hospital, Yemen (IRB approval number: KUH-2023-001). All participants provided written informed consent prior to enrollment. Consent for Publication Not applicable. No individual patient data or images have been presented in this manuscript. Availability of Data and Materials The datasets used and analyzed in this study are available from the corresponding author upon reasonable request. Competing Interests The authors declare that they have no conflicts of interest. Funding This study did not receive any grants from public, commercial, or not-for-profit funding agencies. Authors' Contributions WMG conceived and designed the study, collected and analyzed the data, and wrote the manuscript. YAO and NMM contributed to study design, supervised the statistical analyses, and revised the manuscript. HMJ participated in data collection and interpretation, supervised the overall research process, and provided critical revisions to the manuscript. All authors have read and approved the final version of the manuscript. Acknowledgments The authors would like to thank the medical staff of the Al-Kuwait University Hospital, Yemen, for their support and assistance with data collection. We acknowledge the contributions of our colleagues, who provided insights and expertise that facilitated this research. References Ahmed HO. Gender Difference in Elective Laparoscopic Cholecystectomy for Chronic Cholecystitis. Basrah J Surg. 2012;18:75–9. https://doi.org/10.33762/bsurg.2012.55552 . Kim J, You Y, Hong T, Lee S, Park J, Yoon Y, et al. Single-port laparoscopic cholecystectomy: A comparative study in 106 initial cases. Asian J Endosc Surg. 2010;3:127–32. https://doi.org/10.1111/j.1758-5910.2010.00038.x . Cirillo DJ, Wallace RB, Rodabough RJ, Greenland P, LaCroix AZ, Limacher MC, et al. Effect of Estrogen Therapy on Gallbladder Disease. JAMA. 2005;293:330–9. https://doi.org/10.1001/JAMA.293.3.330 . Dua A, Dua A, Desai SS, Kuy S, Sharma R, Jechow SE, et al. Gender based differences in management and outcomes of cholecystitis. Am J Surg. 2013;206:641–6. https://doi.org/10.1016/j.amjsurg.2013.07.011 . Magnano San Lio R, Barchitta M, Maugeri A, Quartarone S, Basile G, Agodi A. Preoperative Risk Factors for Conversion from Laparoscopic to Open Cholecystectomy: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2023;20. https://doi.org/10.3390/IJERPH20010408 . Akcakaya A, Okan I, Bas G, Sahin G, Sahin M. Does the Difficulty of Laparoscopic Cholecystectomy Differ Between Genders? Indian J Surg. 2015;77:452–6. https://doi.org/10.1007/s12262-013-0872-x . Nikfarjam M, Harnaen E, Tufail F, Muralidharan V, Fink MA, Starkey G, et al. Sex Differences and Outcomes of Management of Acute Cholecystitis. Surg Laparosc Endosc Percutan Tech. 2013;23:61–5. https://doi.org/10.1097/SLE.0b013e3182773e52 . AlKhalifah Z, Alzahrani A, Abdu S, Kabbarah A, Kamal O, Althoubaity F. Assessing incidence and risk factors of laparoscopic cholecystectomy complications in Jeddah: a retrospective study. Annals Med Surg. 2023;85:2749–55. https://doi.org/10.1097/MS9.0000000000000720 . Bazoua G, Tilston MP. Male gender impact on the outcome of laparoscopic cholecystectomy. J Soc Laparoendoscopic Surg. 2014;18:50–4. https://doi.org/10.4293/108680813X13693422518830 . Blohm M, Sandblom G, Enochsson L, Österberg J. Differences in Cholecystectomy Outcomes and Operating Time Between Male and Female Surgeons in Sweden. JAMA Surg. 2023;158:1168. https://doi.org/10.1001/jamasurg.2023.3736 . Warchałowski Ł, Łuszczki E, Bartosiewicz A, Dereń K, Warchałowska M, Oleksy Ł, et al. The Analysis of Risk Factors in the Conversion from Laparoscopic to Open Cholecystectomy. Int J Environ Res Public Health. 2020;17:7571. https://doi.org/10.3390/IJERPH17207571 . Coelho JCU, Dalledone GO, Schiel W, Berbardin J, de Claus P, Matias CMP, DOES MALE GENDER INCREASE THE RISK OF LAPAROSCOPIC CHOLECYSTECTOMY?. Arq Bras Cir Dig. 2019;32:e1438. https://doi.org/10.1590/0102-672020190001e1438 . Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board 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-7055064","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":491568713,"identity":"ae49f8ca-c36d-4bad-978e-8a7d0c588924","order_by":0,"name":"Waleed Mohammed Gilan","email":"","orcid":"","institution":"Sana'a University","correspondingAuthor":false,"prefix":"","firstName":"Waleed","middleName":"Mohammed","lastName":"Gilan","suffix":""},{"id":491568715,"identity":"d4918aa5-ee72-416d-817a-1b1fa428ca64","order_by":1,"name":"Yasser Abdurabo Obadiel","email":"","orcid":"","institution":"Sana'a University","correspondingAuthor":false,"prefix":"","firstName":"Yasser","middleName":"Abdurabo","lastName":"Obadiel","suffix":""},{"id":491568718,"identity":"9efd1d5b-7db7-4312-94a9-23ec39675d9b","order_by":2,"name":"Nezar Mohammed Mahyoub","email":"","orcid":"","institution":"Al-Kuwait University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Nezar","middleName":"Mohammed","lastName":"Mahyoub","suffix":""},{"id":491568721,"identity":"24ddedd4-cb53-4d31-9834-0c1db0481d0d","order_by":3,"name":"Haitham Mohammed Jowah","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYBACAwaGBCB1QA7M4yFFizFJWkDgQGID0VrMGRgePuapuZM+f0YC44O3bQyJ/YS0WDYwJBvzHHuWu+FGArPhXKCWmQ2EHHaAIU06h+1w7gaJBDZpXqCWDQeI0vLvcLr8jAT23yAt+4nSktt2OIHhRgIbM9gWQn4xOAz0y9++w4YbzjxslpxzTsJ4BkFbjvckPpzx7bC8fHvywQ9vymxk+xsIWcPMkwBlMYLUSjgS1MHAwI7qEHvCOkbBKBgFo2CkAQCEAUMIrb03fgAAAABJRU5ErkJggg==","orcid":"","institution":"Sana'a University","correspondingAuthor":true,"prefix":"","firstName":"Haitham","middleName":"Mohammed","lastName":"Jowah","suffix":""}],"badges":[],"createdAt":"2025-07-05 22:23:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7055064/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7055064/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87800226,"identity":"7aaa0c29-bd5e-40b2-9972-81e469e46417","added_by":"auto","created_at":"2025-07-29 07:47:27","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":84596,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow diagram of patients.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7055064/v1/120891f108dc9e948bef6848.png"},{"id":87800230,"identity":"be97da44-9e3e-49d3-8315-7f2ee3f9035e","added_by":"auto","created_at":"2025-07-29 07:47:27","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":119084,"visible":true,"origin":"","legend":"\u003cp\u003ePanel A shows the age distribution of older males. Panel B illustrates the significant differences in BMI distribution. Panel C highlights the higher prevalence of key comorbidities among male patients. Panel D shows a significantly different distribution of surgical indications between sexes.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7055064/v1/395b106e8b44e514a139967a.png"},{"id":87800229,"identity":"9e01f012-fbc3-4ee3-a742-5cdb9bbc717d","added_by":"auto","created_at":"2025-07-29 07:47:27","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":97119,"visible":true,"origin":"","legend":"\u003cp\u003ePanel A displays similar operative time distributions between sexes. Panel B shows a significantly higher rate of intraoperative complications in male patients than in women. Panel C illustrates a nearly three-fold higher incidence of gallbladder perforation in males. Panel D shows a significantly longer length of hospital stay among the male patients.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7055064/v1/5a0e8550010a6ece5d9e290b.png"},{"id":88428644,"identity":"a98657a5-1acd-4874-9821-b7289df263e5","added_by":"auto","created_at":"2025-08-06 10:17:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1366358,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7055064/v1/16ccde7c-b94e-4c88-8ea4-f102913ca0f6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sex-based Analysis of Laparoscopic Cholecystectomy Outcomes: A Prospective Cohort Study","fulltext":[{"header":"Background","content":"\u003cp\u003eSince its introduction in the late 1980s, laparoscopic cholecystectomy (LC) has been established as the gold standard for the surgical treatment of gallbladder diseases since its introduction in the late 1980s[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The minimally invasive approach offers significant advantages over open cholecystectomy, including reduced postoperative pain, shorter hospital stay, and faster recovery times[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Despite these well-documented benefits, emerging evidence suggests that patient outcomes may be influenced by a complex interplay of demographic, clinical, and anatomical factors, which warrants systematic investigation.\u003c/p\u003e\u003cp\u003eSex-based differences in surgical outcomes have been documented across various procedures, with gallbladder disease presenting unique considerations that extend beyond simple epidemiological patterns. The pathophysiology of gallbladder disease demonstrates clear sex-related variations influenced by hormonal factors, particularly estrogen, which affect bile composition and gallbladder motility through complex mechanisms involving cholecystokinin and gallbladder smooth muscle function[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. These physiological differences manifest clinically, with females experiencing a higher overall incidence of gallstone disease, whereas males tend to present with more severe and complicated forms of the disease[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe contemporary literature on sex differences in LC outcomes reveals a complex and sometimes contradictory landscape. A systematic review and meta-analysis by Magnano San Lio et al. (2022) demonstrated that male sex significantly increased the probability of conversion from laparoscopic to open cholecystectomy (OR\u0026thinsp;=\u0026thinsp;1.907; 95% CI\u0026thinsp;=\u0026thinsp;1.254\u0026ndash;2.901), establishing it as an independent preoperative risk factor[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. This finding is supported by multiple large-scale studies that have consistently reported higher conversion rates in male patients [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, the mechanisms underlying these differences remain unclear.\u003c/p\u003e\u003cp\u003eRecent high-quality studies have provided additional insights into sex-based variations in LC outcome. Nikfarjam et al. (2013) demonstrated that male patients with acute cholecystitis were older (66 vs. 57 years; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), had higher comorbidity burdens, including diabetes (21% vs. 9%; p\u0026thinsp;=\u0026thinsp;0.001) and ischemic heart disease (24% vs. 8%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and were more likely to present gangrenous pathology (45% vs. 23%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001)[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Similarly, AlKhalifah et al. (2023) found that male sex was independently associated with both intraoperative (p\u0026thinsp;=\u0026thinsp;0.005) and postoperative complications (p\u0026thinsp;=\u0026thinsp;0.045) after multivariate adjustment[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe anatomical and physiological basis of these sex differences has been elucidated through detailed surgical studies. Akcakaya et al. (2015) demonstrated that male patients exhibited significantly longer operative times (71\u0026thinsp;\u0026plusmn;\u0026thinsp;33 min vs. 58\u0026thinsp;\u0026plusmn;\u0026thinsp;27 min; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), higher anatomical difficulty scores (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), and an increased frequency of adhesions between the gallbladder and surrounding structures[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. These findings suggest that the increased surgical complexity in males may be attributable to more severe inflammatory changes, denser adhesions, and anatomical variations that complicate laparoscopic dissection.\u003c/p\u003e\u003cp\u003eSeveral well-designed studies have reported conflicting results. Despite significantly longer operative times in males, Bazoua and Tilston (2014) found no significant differences in conversion rates (7.5% vs. 2.9%; p\u0026thinsp;=\u0026thinsp;0.142) or perioperative morbidity (12.1% vs. 10.2%; p\u0026thinsp;=\u0026thinsp;0.66) between male and female patients undergoing elective LC, despite significantly longer operative times in males[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. This discrepancy may be attributable to differences in case selection, with elective procedures potentially excluding the most complex presentations more commonly observed in male patients.\u003c/p\u003e\u003cp\u003eHealthcare utilization patterns also contributed to the observed sex-related differences. Dua et al. (2013) analyzed a large national database and found that women undergo cholecystectomy earlier (1.6 vs. 1.9 days; p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and more frequently by laparoscopy (86% vs. 76%), resulting in lower mortality (0.6% vs. 1.1%), fewer complications (16.9% vs. 24.1%), and shorter hospital stays (4.2 vs. 5.4 days). These findings suggest that delayed presentation and treatment in males may contribute to worse outcomes through disease progression and increased inflammation[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe inconsistency in findings across studies can be attributed to several methodological limitations that have hampered definitive conclusions. Many previous studies have been limited by small sample sizes, particularly for male patients who comprise only 20\u0026ndash;30% of cholecystectomy cases, inadequate statistical power for subgroup analyses, and a lack of comprehensive multivariate analysis to control for confounding factors such as age, comorbidities, and disease severity. Few studies have employed rigorous statistical protocols, including detailed bivariate comparisons and enhanced analytical approaches, to isolate the independent effects of sex on the related variables.\u003c/p\u003e\u003cp\u003eRecent advances in surgical techniques and technologies have influenced sex-based outcomes. Blohm et al. (2023) examined surgeon sex effects and found that female surgeons achieved significantly better patient outcomes with fewer complications and bile duct injuries despite longer operative times, suggesting that surgical techniques and approaches may modify sex-based differences in outcomes[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThis prospective cohort study aimed to address these methodological limitations by systematically evaluating sex differences in a comprehensive range of outcomes following LC, using a robust analytical framework. This study sought to provide definitive evidence regarding sex-based differences in laparoscopic cholecystectomy outcomes by employing advanced statistical methodologies including bivariate analysis, multivariate logistic regression, and enhanced analytical approaches. This study will specifically examine whether male sex is an independent risk factor for adverse outcomes or whether other clinical variables such as age, comorbidities, and disease severity mediate the observed differences. The findings of this study will inform evidence-based clinical decision-making and contribute to the development of sex-specific surgical protocols and risk-stratification models.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cb\u003eStudy Design and Setting\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis prospective cohort study was conducted at the Al-Kuwait University Hospital, Sana'a, Yemen, between January 2023 and June 2024. This study was designed to use comprehensive statistical analysis to investigate sex-based differences in LC outcomes of laparoscopic cholecystectomy. Ethical approval was obtained from the Institutional Review Board of the Al-Kuwait University Hospital, and written informed consent was obtained from all participants.\u003c/p\u003e\u003cp\u003e\u003cb\u003eParticipants\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe initial study cohort included 238 patients who had undergone LCC. The inclusion criteria were as follows: (1) male and female patients aged\u0026thinsp;\u0026ge;\u0026thinsp;18 years; (2) diagnosed with gallstone disease, including symptomatic gallstones, acute cholecystitis, or chronic cholecystitis; and (3) undergoing elective or emergency laparoscopic cholecystectomy, including those requiring conversion to open surgery.\u003c/p\u003e\u003cp\u003eStrict exclusion criteria were applied to ensure a homogeneous study population: (1) previous abdominal surgery (n\u0026thinsp;=\u0026thinsp;19), (2) choledocholithiasis (n\u0026thinsp;=\u0026thinsp;1), or (3) porcelain gallbladder (n\u0026thinsp;=\u0026thinsp;1). After exclusion, 218 patients were included in the final analysis: 175 females (80.3%) and 43 males (19.7%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cb\u003eData Collection\u003c/b\u003e\u003c/p\u003e\u003cp\u003eData were collected prospectively using a standardized data collection form designed to capture the variables necessary for comprehensive statistical analysis. Demographic characteristics included age, sex, body mass index (BMI), and American Society of Anesthesiologists (ASA) classification. The recorded comorbidities included diabetes mellitus, hypertension, heart disease, chronic liver disease, and chronic lung disease.\u003c/p\u003e\u003cp\u003ePreoperative clinical data included the presenting symptoms (biliary colic, jaundice, and fever) and surgical indications (symptomatic gallbladder stones, acute cholecystitis, and chronic cholecystitis). Intraoperative variables included operative time, surgical approach, surgeon experience level, inflammation severity, dissection difficulty graded according to established criteria, and intraoperative complications, including bleeding, bile duct injury, bile or stone spillage, and gallbladder perforation.\u003c/p\u003e\u003cp\u003eThe postoperative outcomes included specific complications (wound infection, abdominal abscess/peritonitis, and bile leak), reoperation, readmission, length of hospital stay, and mortality. All patients were followed-up until discharge or 30 days after surgery, whichever was longer.\u003c/p\u003e\u003cdiv id=\"Sec2\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eA comprehensive statistical analysis protocol was employed to ensure accuracy of the results. Descriptive statistics were calculated for all variables, with continuous variables presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and categorical variables as frequencies and percentages.\u003c/p\u003e\u003cp\u003eBivariate analysis was used to compare male and female patients across four domains: demographics, preoperative profile, intraoperative findings, and postoperative outcomes. The Mann\u0026ndash;Whitney U test was used to analyze continuous variables for non-parametric distributions, whereas categorical variables were analyzed using the chi-square test or Fisher\u0026rsquo;s exact test for small expected frequencies. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003cp\u003eMultivariate logistic regression analysis was performed to identify independent predictors of key outcomes: conversion to open surgery, intraoperative complications, and postoperative complications. The models included the relevant demographic, clinical, and surgical variables to control for confounding factors. Results are reported as odds ratios (OR) with 95% confidence intervals (CI) and p-values. Enhanced analyses included subgroup analysis of interaction effects and predictors of prolonged hospital stay. All analyses were performed using SPSS version 26.0 (IBM Corporation, Armonk, NY, USA) with robust standard error calculations.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003eCharacteristics of the Study Population\u003c/b\u003e\u003c/p\u003e\u003cp\u003eOf the 238 patients initially identified, 218 completed the study protocol and were included in the final analysis. The cohort comprised 175 females (80.3%) and 43 males (19.7%), with complete follow-up data available for all participants (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cb\u003eDemographic and Baseline Characteristics\u003c/b\u003e\u003c/p\u003e\u003cp\u003eMales were significantly older than females (46.0\u0026thinsp;\u0026plusmn;\u0026thinsp;15.3 vs 40.9\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8 years, p\u0026thinsp;=\u0026thinsp;0.034). BMI distribution showed significant differences between sexes (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with males demonstrating higher obesity rates (27.9% vs. 13.1%) but lower overweight rates (7.0% vs. 34.3%) than females. The ASA classification distribution showed a trend toward a higher ASA III classification in males (16.3% vs. 6.3%, p\u0026thinsp;=\u0026thinsp;0.068).\u003c/p\u003e\u003cp\u003eThe comorbidity analysis revealed a significantly higher prevalence of diabetes (27.9% vs. 8.6%, p\u0026thinsp;=\u0026thinsp;0.001) and chronic liver disease (7.0% vs. 0.6%, p\u0026thinsp;=\u0026thinsp;0.025) in men. No significant differences were observed in the prevalence of hypertension or heart disease between sexes (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\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 and baseline characteristics of the participants by sex\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\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale (n\u0026thinsp;=\u0026thinsp;175)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMale (n\u0026thinsp;=\u0026thinsp;43)\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 (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD), years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e40.9\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e46.0\u0026thinsp;\u0026plusmn;\u0026thinsp;15.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.034\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBMI categories, n (%)\u003c/b\u003e\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\u003eNormal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e92 (52.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28 (65.1)\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\u003eOverweight\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60 (34.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (7.0)\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\u003eObese\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23 (13.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (27.9)\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\u003e\u003cb\u003eASA classification, n (%)\u003c/b\u003e\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\u003e0.068\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eASA I\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e87 (49.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (37.2)\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\u003eASA II\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e77 (44.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (46.5)\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\u003eASA III\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (6.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (16.3)\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\u003e\u003cb\u003eComorbidities, n (%)\u003c/b\u003e\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=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes mellitus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (8.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (27.9)\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\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32 (18.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (25.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.388\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeart disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (3.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (9.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.111\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChronic liver disease (CLD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (0.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (7.0)\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\u003cp\u003e\u003cb\u003ePreoperative Clinical Profile\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAnalysis of the presenting symptoms revealed no significant sex-based differences in biliary colic (81.4% vs. 73.7%, p\u0026thinsp;=\u0026thinsp;0.396), jaundice (11.6% vs. 6.3%, p\u0026thinsp;=\u0026thinsp;0.380), or fever (44.2% vs. 35.4%, p\u0026thinsp;=\u0026thinsp;0.374). However, the diagnosis distribution was significantly different (p\u0026thinsp;=\u0026thinsp;0.005), with males more frequently presenting with acute cholecystitis (55.8% vs. 35.4%) and chronic cholecystitis (11.6% vs. 4.0%), whereas females more commonly presented with symptomatic gallbladder stones (57.7% vs. 32.6%) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\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\u003ePreoperative clinical characteristics according to the sex\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=\"char\" char=\".\" 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\u003eFemale (n\u0026thinsp;=\u0026thinsp;175)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMale (n\u0026thinsp;=\u0026thinsp;43)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePresenting symptoms, n (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBiliary colic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e129 (73.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e35 (81.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.396\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eJaundice\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11 (6.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5 (11.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.380\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFever\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e62 (35.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e19 (44.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.374\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDiagnosis, n (%)\u003c/b\u003e\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\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSymptomatic gallbladder stones\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e101 (57.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14 (32.6)\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\u003eAcute cholecystitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e62 (35.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e24 (55.8)\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\u003eChronic cholecystitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7 (4.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5 (11.6)\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\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003ePanel A shows the age distribution of older males. Panel B illustrates the significant differences in BMI distribution. Panel C highlights the higher prevalence of key comorbidities among male patients. Panel D shows a significantly different distribution of surgical indications between sexes.\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eIntraoperative Findings\u003c/b\u003e\u003c/p\u003e\u003cp\u003eOperative times were similar between sexes (87.0\u0026thinsp;\u0026plusmn;\u0026thinsp;32.8 vs 78.1\u0026thinsp;\u0026plusmn;\u0026thinsp;22.1 minutes, p\u0026thinsp;=\u0026thinsp;0.264). The conversion rates to open surgery were comparable between groups (13.1% vs. 14.0%, p\u0026thinsp;=\u0026thinsp;1.000). Inflammation severity and dissection difficulty grades showed no significant differences between sexes.\u003c/p\u003e\u003cp\u003eHowever, males experienced significantly higher rates of intraoperative complications (41.9% vs. 21.1%, p\u0026thinsp;=\u0026thinsp;0.009). Gallbladder perforation was significantly more frequent in males (16.3% vs. 5.7%, p\u0026thinsp;=\u0026thinsp;0.046), representing a nearly three-fold increase. Other complications, including bile/stone spillage and bleeding, were higher in males but did not reach statistical significance (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\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\u003eIntraoperative characteristics and complications according to the sex\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\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale (n\u0026thinsp;=\u0026thinsp;175)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMale (n\u0026thinsp;=\u0026thinsp;43)\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\u003eOperative time (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD), min\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e87.0\u0026thinsp;\u0026plusmn;\u0026thinsp;32.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e78.1\u0026thinsp;\u0026plusmn;\u0026thinsp;22.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.264\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConversion to open surgery, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23 (13.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (14.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInflammation severity, n (%)\u003c/b\u003e\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\u003e0.112\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMild\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e89 (50.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (37.2)\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\u003eModerate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e80 (45.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23 (53.5)\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\u003eSevere\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (3.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (9.3)\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\u003e\u003cb\u003eIntraoperative complications, n (%)\u003c/b\u003e\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=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntraoperative complications\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37 (21.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18 (41.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.009\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGallbladder perforation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (5.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (16.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.046\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBile/stone spillage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (9.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (14.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.512\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBleeding\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (4.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (9.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.259\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cb\u003ePostoperative Outcomes\u003c/b\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe overall postoperative complication rates were similar between sexes (13.1% vs. 14.0%, p\u0026thinsp;=\u0026thinsp;1.000). Individual complications, including wound infection, abdominal abscess/peritonitis, bile leak, reoperation, and readmission, were not significantly different, although males tended to have higher rates of wound infection and abdominal complications.\u003c/p\u003e\u003cp\u003eMales had significantly longer hospital stays (2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7 vs 2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1 days, p\u0026thinsp;=\u0026thinsp;0.021). One case of mortality occurred in the male group (2.3% vs. 0%, p\u0026thinsp;=\u0026thinsp;0.197); however, this difference was not statistically significant because of the low overall event rate (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\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\u003ePostoperative outcomes according to the sex\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=\"char\" char=\".\" 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\u003eFemale (n\u0026thinsp;=\u0026thinsp;175)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMale (n\u0026thinsp;=\u0026thinsp;43)\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\u003eAny postoperative complication, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e23 (13.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6 (14.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSpecific complications, n (%)\u003c/b\u003e\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=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWound infection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9 (5.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5 (11.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.227\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbdominal abscess/peritonitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1 (0.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (4.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.100\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBile leak\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e14 (8.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (4.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.744\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReoperation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4 (2.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (4.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.338\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReadmission\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4 (2.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (4.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.338\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLength of stay (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD), days\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.021\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMortality, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (2.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.197\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003ePanel A displays similar operative time distributions between sexes. Panel B shows a significantly higher rate of intraoperative complications in male patients than in women. Panel C illustrates a nearly three-fold higher incidence of gallbladder perforation in males. Panel D shows a significantly longer length of hospital stay among the male patients.\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eMultivariate Analysis\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThree multivariate logistic regression models were constructed to identify independent predictors of key outcomes (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cb\u003eModel 1: Conversion to Open Surgery\u003c/b\u003e: Acute cholecystitis emerged as the strongest predictor of conversion (OR 3.90, 95% CI: 1.95\u0026ndash;7.80, p\u0026thinsp;=\u0026thinsp;0.001). Male sex was not independently associated with conversion risk (OR 0.75, 95% CI: 0.37\u0026ndash;1.50, p\u0026thinsp;=\u0026thinsp;0.412).\u003c/p\u003e\u003cp\u003e\u003cb\u003eModel 2: Intraoperative\u003c/b\u003e Complications: Dissection difficulty was the most powerful predictor, with Grade III difficulty associated with significantly increased odds of complications (OR 10.27, 95% CI: 5.14\u0026ndash;20.55, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared with Grade I. Male sex showed a trend toward increased risk (OR 1.84, 95% CI: 0.92\u0026ndash;3.69, p\u0026thinsp;=\u0026thinsp;0.084).\u003c/p\u003e\u003cp\u003e\u003cb\u003eModel 3-Postoperative Complications\u003c/b\u003e: Conversion to open surgery was the strongest predictor of postoperative complications (OR 5.24, 95% CI: 1.96\u0026ndash;13.99, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Male sex was not independently associated with postoperative complications (OR 0.81, 95% CI: 0.25\u0026ndash;2.60, p\u0026thinsp;=\u0026thinsp;0.722).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMultivariate analysis results\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eModel/Variable\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\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u003cp\u003eModel 1: Conversion to Open Surgery\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale sex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.75 (0.37\u0026ndash;1.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.412\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (per year)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.03 (0.52\u0026ndash;2.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.934\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAcute cholecystitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.90 (1.95\u0026ndash;7.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eModel 2: Intraoperative Complications\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale sex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.84 (0.92\u0026ndash;3.69)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.084\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDissection difficulty Grade II\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.67 (1.83\u0026ndash;7.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDissection difficulty Grade III\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.27 (5.14\u0026ndash;20.55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eModel 3: Postoperative Complications\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale sex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.81 (0.25\u0026ndash;2.60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.722\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConversion to open surgery (OS)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.24 (1.96\u0026ndash;13.99)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (per year)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.02 (1.00-1.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.070\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis comprehensive prospective study provides robust evidence for significant sex-based differences in laparoscopic cholecystectomy outcomes, contributing to the growing body of literature examining demographic influences on surgical outcomes. Our findings demonstrate that males present with more complex clinical profiles, which are characterized by advanced age, higher comorbidity burden, and increased prevalence of acute inflammatory conditions. These factors contribute to significantly higher intraoperative complication rates and longer hospital stays, even when operative times and conversion rates remain comparable between sexes.\u003c/p\u003e\u003cp\u003eThe five-year age difference between males and females in our cohort (46.0\u0026thinsp;\u0026plusmn;\u0026thinsp;15.3 vs 40.9\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8 years) aligns with established epidemiological patterns and reflects fundamental differences in disease natural history between sexes. This finding is consistent with that of Nikfarjam et al. (2013), who reported a nine-year age difference (66 vs. 57 years) in patients with acute cholecystitis and may reflect differential healthcare-seeking behaviors, hormonal influences on disease progression, or delayed symptom development in males[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe significantly higher prevalence of diabetes in males (27.9% vs. 8.6%) represents a particularly important finding with substantial clinical implications. This threefold difference exceeds the general population disparities and may reflect both the underlying metabolic differences and the association between metabolic syndrome and gallbladder disease severity. Nikfarjam et al. (2013) reported similar findings (21% vs. 9% prevalence of diabetes), establishing a consistent pattern across different populations. Diabetes is a well-established risk factor for surgical complications, delayed wound healing, and increased risk of infection, which may explain the increased morbidity observed in male patients[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe increased prevalence of chronic liver disease in males, although affecting small absolute numbers, suggests a pattern of more complex underlying health conditions that may contribute to increased surgical risk. This finding, combined with the higher prevalence of diabetes, indicates that males presenting with LC have a higher baseline risk profile that extends beyond the gallbladder pathology itself.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSeverity of Disease and Inflammatory Patterns\u003c/b\u003e\u003c/p\u003e\u003cp\u003eOne of the most clinically significant findings was the markedly higher prevalence of acute cholecystitis in males (55.8% vs. 35.4%), representing a 58% increase in the likelihood of inflammatory presentation. This finding is consistent with multiple large-scale studies, including that of Dua et al. (2013), who demonstrated that males are less likely to undergo elective surgery and are more likely to present with complicated diseases requiring emergency intervention[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. A systematic review by Magnano San Lio et al. (2022) identified acute cholecystitis as the strongest predictor of conversion to open surgery (OR\u0026thinsp;=\u0026thinsp;5.475; 95% CI\u0026thinsp;=\u0026thinsp;2.959\u0026ndash;10.130), which aligns with our multivariate analysis that confirmed acute cholecystitis as the strongest predictor of conversion (OR\u0026thinsp;=\u0026thinsp;3.90, p\u0026thinsp;=\u0026thinsp;0.001)[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe higher prevalence of acute inflammatory conditions in males may be attributable to several factors. First, hormonal influences may provide protective effects in premenopausal women, as estrogen affects bile composition and gallbladder motility [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Second, differences in healthcare-seeking behavior may result in males presenting later in the disease course, allowing progression to more severe inflammatory states. Third, anatomical differences in the body habitus and fat distribution may influence the inflammatory response and adhesion formation patterns.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSurgical Complexity and Intraoperative Outcomes\u003c/b\u003e\u003c/p\u003e\u003cp\u003eDespite comparable operative times and conversion rates, males experienced significantly higher intraoperative complication rates (41.9% vs. 21.1%), with gallbladder perforation being nearly three times more frequent. This finding is consistent with that of AlKhalifah et al. (2023), who reported that males were more likely to experience intraoperative complications (24.4% vs. 6.5%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and that male sex was independently associated with intraoperative complications after multivariate adjustment (p\u0026thinsp;=\u0026thinsp;0.005)[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe mechanistic basis for increased surgical complexity in males has been elucidated through detailed intraoperative assessment. According to Akcakaya et al. (2015), male patients exhibited significantly higher anatomical difficulty scores (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), an increased frequency of omental adhesions (p\u0026thinsp;=\u0026thinsp;0.003), and more severe inflammatory findings in histological specimens[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. These findings suggest that the increased complication rates in males are attributable to more challenging surgical conditions than to inherent differences in surgical techniques or surgeon experience.\u003c/p\u003e\u003cp\u003eThe finding of comparable operative times between sexes, despite higher complication rates in males, may reflect several factors. First, surgeons may adopt more conservative approaches in male patients and spend additional time on careful dissection to minimize complications. Second, the use of intraoperative techniques such as subtotal cholecystectomy or fundus-first approaches may maintain operative efficiency while managing difficult anatomies. Third, our exclusion criteria may have selected cases in which surgical expertise was adequate to manage complex anatomy within a reasonable timeframe.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConversion Patterns and Risk Stratification\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe comparable conversion rates between sexes (despite higher complication rates in males) contrasts with some published series but aligns with recent high-quality studies. Bazoua and Tilston (2014) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]reported similar conversion rates (7.5% vs. 2.9%; p\u0026thinsp;=\u0026thinsp;0.142) in elective cases, whereas Warchałowski et al. (2020) found that the male sex was associated with conversion in univariate analysis but not in multivariate models[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, a meta-analysis by Magnano San Lio et al. (2022) demonstrated that the male sex increased the conversion probability (OR\u0026thinsp;=\u0026thinsp;1.907; 95% CI\u0026thinsp;=\u0026thinsp;1.254\u0026ndash;2.901) across multiple studies[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOur multivariate analysis revealed that acute cholecystitis was the most powerful predictor of conversion (OR 3.90, p\u0026thinsp;=\u0026thinsp;0.001), which aligns with the systematic review finding that acute cholecystitis carries the highest conversion risk (OR, 5.475). The fact that males have higher rates of acute cholecystitis but comparable conversion rates suggests that other factors may be protective or that surgical management has evolved to better manage inflammatory cases.\u003c/p\u003e\u003cp\u003e\u003cb\u003ePostoperative outcomes and utilization of healthcare resources\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe significantly longer hospital stays in males (2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7 vs 2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1 days) represent a clinically meaningful difference with important implications for healthcare resource utilization and cost-effectiveness. This finding is consistent with that of Dua et al. (2013), who reported longer stays in males (5.4 vs 4.2 d) and higher costs (\u003cspan\u003e$\u003c/span\u003e13,201 vs \u003cspan\u003e$\u003c/span\u003e10,556)[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Prolonged hospitalization in males may reflect higher complication rates, slower recovery due to comorbidities, or more conservative discharge practices in higher-risk patients.\u003c/p\u003e\u003cp\u003eInterestingly, while males had higher intraoperative complication rates, overall postoperative complication rates were similar between the sexes. This paradox may reflect several factors: first, intraoperative complications (particularly gallbladder perforation) may be managed effectively during surgery without subsequent clinical impact; second, more intensive perioperative monitoring and management may offset the higher comorbidity burden in males; third, the effectiveness of modern perioperative care protocols in managing high-risk patients may reflect comparable postoperative outcomes.\u003c/p\u003e\u003cp\u003e\u003cb\u003eIndependent Risk Factors and Multivariate Analysis\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe identification of conversion to open surgery as the strongest predictor of postoperative complications (OR 5.24, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) underscores the cascade effect of intraoperative complexity on postoperative outcomes. This finding emphasizes the importance of case selection, surgical planning, and maintenance of the laparoscopic approach, when it is safe and feasible. Multivariate analysis confirmed that dissection difficulty was the most powerful predictor of intraoperative complications, with Grade III difficulty associated with more than ten times the odds of complications, highlighting the importance of surgical technique and case complexity assessment.\u003c/p\u003e\u003cp\u003eOur multivariate analysis demonstrated that male sex was not an independent predictor of conversion or major complications, after adjusting for confounding variables. This finding aligns with those of several recent studies, including Bazoua and Tilston (2014) and Coelho et al. (2019), who concluded that male sex is not an independent risk factor for adverse outcomes after controlling for confounders[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. This suggests that the observed sex differences in outcomes are mediated by other clinical variables such as age, comorbidities, and disease severity, rather than representing an inherent biological disadvantage.\u003c/p\u003e\u003cp\u003e\u003cb\u003eClinical Implications and Future Directions\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThese findings have several important clinical implications for surgical practice. First, male patients should receive enhanced preoperative counseling regarding the increased likelihood of intraoperative complications and prolonged hospital stays. Second, risk stratification models should incorporate sex-specific factors such as a higher prevalence of OC and comorbidities in males. Third, increased complexity in male patients should be anticipated in surgical planning, with consideration of senior surgeon involvement and allocation of adequate operative time.\u003c/p\u003e\u003cp\u003eThe implications of the healthcare system are equally significant. Longer hospital stays and higher complication rates in males translate into increased healthcare costs and resource utilization. Dua et al. (2013) estimated a \u003cspan\u003e$\u003c/span\u003e2,645 cost difference between male and female patients, suggesting that sex-based differences have substantial economic implications at the population level[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFuture research should focus on several key areas: first, prospective multicenter studies with larger sample sizes to validate these findings across different populations and healthcare systems; second, investigation of the underlying biological mechanisms driving sex differences, including hormonal influences, anatomical variations, and inflammatory response patterns; third, development and validation of sex-specific risk prediction models to guide clinical decision-making; and fourth, evaluation of targeted interventions to reduce sex-based disparities in outcomes.\u003c/p\u003e\u003cp\u003e\u003cb\u003eStudy Strengths and Limitations\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe strengths of this study include its prospective design with standardized data collection protocols, comprehensive statistical methodology with multivariate analysis, detailed analysis of multiple outcome measures, and focus on sex-specific differences using rigorous analytical approaches. The inclusion of both elective and emergency cases provides a comprehensive view of sex differences across the severity spectrum of gallbladder disease.\u003c/p\u003e\u003cp\u003eHowever, this study has several limitations. First, the relatively small sample size of male patients (consistent with the general epidemiology of gallbladder disease) may limit the statistical power of some subgroup analyses. Second, the single-center design may limit the generalizability to other healthcare systems and populations. Third, the lack of long-term follow-up data prevents the assessment of chronic complications or quality of life outcomes. Fourth, unmeasured confounders, such as surgeon experience, case complexity beyond our measured variables, and patient-specific factors, may have influenced the outcomes.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis prospective study provides robust evidence that males undergoing laparoscopic cholecystectomy present with more complex clinical profiles, including older age, higher comorbidity burden, and increased prevalence of acute inflammatory conditions. These factors contribute to significantly higher rates of intraoperative complications and longer hospital stays, representing clinically meaningful differences that impact patient outcomes and utilization of healthcare resources. However, after controlling for confounding variables, the male sex itself did not appear to be an independent risk factor for adverse outcomes, suggesting that other clinical variables mediate the observed differences.\u003c/p\u003e\u003cp\u003eThe findings of this study support the implementation of sex-specific approaches to perioperative care, including enhanced preoperative counseling, risk stratification, and surgical planning for male patients. Healthcare systems should recognize and account for sex-based differences in resource allocation and quality improvement initiatives. Future research should focus on validating these findings in larger multicenter cohorts and investigating targeted interventions to reduce sex-based disparities in surgical outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics\u0026nbsp;Approval\u0026nbsp;and\u0026nbsp;Consent\u0026nbsp;to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the ethical standards of the Declaration of Helsinki and was approved by the Institutional Review Board of Al-Kuwait University Hospital, Yemen (IRB approval number: KUH-2023-001). All participants provided written informed consent prior to enrollment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent\u0026nbsp;for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. No individual patient data or images have been presented in this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability\u0026nbsp;of\u0026nbsp;Data\u0026nbsp;and Materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analyzed in this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study did not receive any grants from public, commercial, or not-for-profit funding agencies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWMG\u0026nbsp;conceived\u0026nbsp;and\u0026nbsp;designed\u0026nbsp;the\u0026nbsp;study,\u0026nbsp;collected\u0026nbsp;and\u0026nbsp;analyzed\u0026nbsp;the\u0026nbsp;data,\u0026nbsp;and\u0026nbsp;wrote\u0026nbsp;the manuscript. YAO and NMM contributed to study design, supervised the statistical analyses, and revised the manuscript. HMJ participated in data collection and interpretation,\u0026nbsp;supervised\u0026nbsp;the\u0026nbsp;overall\u0026nbsp;research\u0026nbsp;process,\u0026nbsp;and\u0026nbsp;provided\u0026nbsp;critical\u0026nbsp;revisions\u0026nbsp;to the manuscript.\u0026nbsp;All authors have read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the medical staff of the Al-Kuwait University Hospital, Yemen, for their support and assistance with data collection. We acknowledge the contributions of our colleagues, who provided insights and expertise that facilitated this research.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAhmed HO. Gender Difference in Elective Laparoscopic Cholecystectomy for Chronic Cholecystitis. Basrah J Surg. 2012;18:75\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.33762/bsurg.2012.55552\u003c/span\u003e\u003cspan address=\"10.33762/bsurg.2012.55552\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKim J, You Y, Hong T, Lee S, Park J, Yoon Y, et al. Single-port laparoscopic cholecystectomy: A comparative study in 106 initial cases. 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Int J Environ Res Public Health. 2020;17:7571. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/IJERPH17207571\u003c/span\u003e\u003cspan address=\"10.3390/IJERPH17207571\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCoelho JCU, Dalledone GO, Schiel W, Berbardin J, de Claus P, Matias CMP, DOES MALE GENDER INCREASE THE RISK OF LAPAROSCOPIC CHOLECYSTECTOMY?. Arq Bras Cir Dig. 2019;32:e1438. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1590/0102-672020190001e1438\u003c/span\u003e\u003cspan address=\"10.1590/0102-672020190001e1438\" 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":"Laparoscopic cholecystectomy, Sex differences, Surgical outcomes, Multivariate analysis, Risk factors, Gallbladder perforation, Acute cholecystitis","lastPublishedDoi":"10.21203/rs.3.rs-7055064/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7055064/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eSex-based differences in laparoscopic cholecystectomy (LC) outcomes remain poorly understood, with conflicting evidence regarding the effects of patient sex on surgical complexity and complications. This study aimed to comprehensively evaluate sex-based differences in laparoscopic cholecystectomy outcomes using rigorous statistical analysis.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis prospective cohort study was conducted at Al-Kuwait University Hospital, Yemen, between January 2023 and June 2024. After applying strict exclusion criteria, 218 patients were included: 175 females (80.3%) and 43 males (19.7%). Bivariate analysis, multivariate logistic regression, and enhanced analyses were used to examine the demographic characteristics, preoperative profiles, intraoperative findings, and postoperative outcomes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eMales were significantly older (46.0\u0026thinsp;\u0026plusmn;\u0026thinsp;15.3 vs 40.9\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8 years, p\u0026thinsp;=\u0026thinsp;0.034) with a higher prevalence of diabetes (27.9% vs 8.6%, p\u0026thinsp;=\u0026thinsp;0.001) and chronic liver disease (7.0% vs 0.6%, p\u0026thinsp;=\u0026thinsp;0.025). Males more frequently presented with acute cholecystitis (55.8% vs. 35.4%, p\u0026thinsp;=\u0026thinsp;0.005). The incidence of intraoperative complications, particularly gallbladder perforation (41.9% vs. 21.1%, p\u0026thinsp;=\u0026thinsp;0.009), was significantly higher in men than in women (16.3% vs. 5.7%, p\u0026thinsp;=\u0026thinsp;0.046). Males had longer hospital stays (2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7 vs 2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1 days, p\u0026thinsp;=\u0026thinsp;0.021). Multivariate analysis identified acute cholecystitis as the strongest predictor of conversion to open surgery (OR 3.90, 95% CI: 1.95\u0026ndash;7.80, p\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThis study demonstrated significant sex-based differences in the LC outcomes. Males present with more complex disease patterns, experience higher rates of intraoperative complications, and require longer hospital stays. These findings necessitate sex-specific considerations in preoperative counseling, surgical planning, and postoperative care protocols.\u003c/p\u003e","manuscriptTitle":"Sex-based Analysis of Laparoscopic Cholecystectomy Outcomes: A Prospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-29 07:47:23","doi":"10.21203/rs.3.rs-7055064/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":"05b1dc45-21cd-4e82-9c5d-7a0ba1efc3b1","owner":[],"postedDate":"July 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-06T10:09:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-29 07:47:23","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7055064","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7055064","identity":"rs-7055064","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}