The laparoscopic technique is by far the treatment of choice for the performance of cholecystectomy, and with growing experience, more patients have been treated by laparoscopy [1]. These authors concluded that this has resulted in lower morbidity rates, shorter hospital stays, and quicker returns to work [2]. The cosmetic result also is important for most patients. However, conversion to open surgery is sometimes necessary. This was the case for 7.7% of Danish patients in 2007 [3]. The conversion rate corresponds well with results from Switzerland in a study of 22,953 patients (conversion, rate 8.5%) [4]. Mortality rates seem to be higher when primary laparoscopic operations are converted to open surgery [5]. Identification of risk factors for conversion to open surgery will make the surgeon more capable to inform and prepare patients for the operation and the expected outcome.

This article aims to document the relationship of gender to conversion rate and length of postoperative hospital stay after laparoscopic cholecystectomy in the Danish population.

Methods

Patient data from the year 2007 was pulled from the national Danish Cholecystectomy Database [6], which comprises two sets of data, as described earlier [7]: (1) clinical data registered immediately after the operation by the surgeon through a secure Web site to the database and (2) administrative data from the National Patient Registry (Box 1). Several indicators can be derived from these data and used to monitor the quality of surgery [7, 8].

Box 1 The two sets of data used in the Danish cholecystectomy database
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Length of postoperative hospital stay (LOS) was defined with operation day as day 0 [8]. The American Society of Anesthesiology (ASA) score was determined according to the standard of that organization. The diagnosis of “previous acute cholecystitis” required finding of a thick-walled fibrotic gallbladder with or without adhesions. “Previous pancreatitis” required that the patient had been hospitalized due to acute pancreatitis within the 3 months before the cholecystectomy.

The Danish Cholecystectomy Database was created in 2004 and made mandatory nationwide in 2006. A report is made each year, and statistics are sent to the respective departments to provide the most complete data set possible. The database has been validated with data from 2004 to 2005, and these data were found to be a valid tool for monitoring the quality of the database (97.1–100% agreement between journals and administrative data; kappa, 0.73–1.00) [7].

In 2007, 7,011 cholecystectomies were performed (Table 1). Of the patients involved, 828 were excluded due to data-recording errors, and 232 patients were excluded because they had primary open operations. A total of 5,951 patients with intended laparoscopic operations were analyzed. Of these patients, 1,500 (25.2%) were men.

Table 1 Patient flowchart
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Statistical analyses were conducted using SAS 9.1 (SAS Institute Inc., Cary, NC, USA). The normality of the scale variables was tested with the Kolmogorov–Smirnov test. Variables without normal distribution are given as median and range. Categorical variables are given as numbers and percentages. The Student t-test and chi-square test were used to analyse for potential associations with the patient’s sex, whereas the Mann–Whitney test (rank-sum) was used to rank scale variables. The results are considered to be statistically significant at a p value of 0.05 or less. Multiple logistic regression analyses were performed in several models.

Results

The men were significantly older than the women (p = 0.0002). The mean age was 47 years (range, 11–101 years) for the women and 53 years (range, 15–93 years) for the men. There was a minor but significant difference in body mass index (BMI) between the men (27.5 kg/cm2; 95% confidence interval [CI], 27.3–27.7) and the women (27.9 kg/cm2; 95% CI, 27.8–28.1). The average ASA score of 1.38 for the women was significantly lower than 1.43 for the men (p = 0.021), with a total of 5,727 patients (96.2%) scoring 1 or 2.

The distribution of the risk factors is shown in Table 2. There was a higher percentage of acute cholecystitis among the men than among the women. The men had sequelae more frequently after previous cholecystitis and previous pancreatitis, such as dense adhesions or a fibrous gallbladder wall found during the operation. The frequency of previous upper abdominal surgery was not significantly different between the sexes.

Table 2 Risk factors for men and women
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The primary outcomes are shown in Table 3. The findings show that significantly more of the operations were converted from laparoscopic to open surgery among the men than among the women (odds ratio [OR], 2.48; 95% CI, 2.04–3.01). Thus, 259 (5.8%) of 4,451 operations for the women were converted to laparotomy compared with 199 (13.3%) of 1,500 operations for the men. Altogether, 7.7% of the operations were converted to laparotomy.

Table 3 Odds ratio for primary outcomes
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The findings also showed a significant difference in the postoperative LOS, because men were more often admitted longer than 1 day (OR, 1.5; 95% CI, 1.33–1.70), and had a higher risk of an LOS longer than 3 days and of a readmittance (OR, 1.48; 95% CI, 1.28–1.71). The total number of hospitalization days at the primary hospitalization after surgery averaged 1.3 days for the women and 1.9 days for the men (p < 0.001), with a maximum of 73 days for the women and 78 days for the men. There were no differences in the proportion of biliary tract injuries or in mortality.

The overall 30-day mortality rate was 0.4%, with no specific relationship to gender (OR, 0.93; 95% CI, 0.34–2.53), and the proportion of biliary tract injuries was 0.5% (n = 27), again, with no relationship to sex (OR, 0.96; 95% CI, 0.39–2.70). Of these injuries, 12 (0.2%) were injuries with transection or ligation of the common bile duct that needed reconstruction, typically with a hepaticojejunostomy [9].

A multivariate model was tested with logistic regression analysis. As shown in Table 4, male gender was a significant factor for conversion (OR, 1.58; 95% CI, 1.27–1.96) as were age, BMI, acute cholecystitis, and sequelae after acute cholecystitis. Two models were set for LOS and readmission but did not show a significant correlation between sex and LOS. A fourth model tested with patients undergoing additional procedures also showed no significant association with sex (OR, 0.86; 95% CI, 0.73–1.01).

Table 4 Multiple logistic regression analysis
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Discussion

The multivariate logistic regression analyses showed a significant sex-dependent difference in the risk for conversion to open surgery. Age, BMI, acute cholecystitis, and sequelae after prior acute cholecystitis also were significant predictors of conversion.

A recent study of 2,000 patients also found that men had a greater risk for conversion (OR, 2.0; 95% CI, 1.3–2.9), but when multivariate analysis was used to control for confounders, the significant difference disappeared [10]. A larger study including 22,953 patients from the years 1995 through 2003 found by multivariate analysis that the perioperative complication rate was higher for men (OR, 1.18; p < 0.02) [4]. Perioperative complications often are a good indication for conversion, and other studies [11–17] have shown an association of perioperative complications with a high risk for conversion, so this association is well in line with the results of the current study.

The differences in risk factors and conversion rates between men and women are hard to explain. Differences in anatomy or physiology such as volume of the abdomen, hormones, or fat distribution may play a role. Alternatively, behavioral differences may contribute (i.e., men may have a longer duration of symptoms before seeking a physician).

One article points to an association between men with great body weight and severity of gallbladder inflammation [4]. Greater body weight led to a greater risk of empyema formation and gallbladder perforation. Thus, 62% of perforations were found in men weighing more than 70 kg. A second study found a significant difference between men and women in the amount of inflammation found during surgery (OR, 1.9; p < 0.001) [10]. A third study reviewed 326 patients with acute cholecystitis and found that male sex was an independent risk factor for more complicated disease (OR, 1.76; p = 0.029) [18]. The findings also showed that the main reason for conversion was anatomic changes around the gallbladder [18].

Several other studies have suggested that anatomic changes due to inflammation and adherences were the main reasons for conversions [13–15, 17, 19–22]. An early study from 1992 to 1994 examined the relationship between the success rate for laparoscopic surgery and the time from onset of acute cholecystitis symptoms to surgery. The success rate dropped significantly after the first 4 days with pain [23]. These results have been confirmed in more recent studies [19, 24].

None of the aforementioned studies have addressed the reason for the apparent increased inflammation and adherence formation in men. One study of 80 patients with symptomatic gallbladder stones showed that men had a significantly higher amount of hydroxyproline (collagen component) in the connective tissues of the gallbladder wall and in the pericholecystic tissues than women [25]. Moreover, they found a significantly higher number of macrophages, mast cells, and eosinophilic granulocytes in tissue samples from the gallbladder wall and pericholecystic tissue of men. The authors point out the difference in hormone levels as an explanatory model, in which a higher testosterone level may lead to increased fibroblast activity and consequently collagen synthesis, fibrosis, and adherences. Further research into inflammatory processes and connective tissue formation in men and women is needed to explain the observed sex differences.

In contrast to the conversion rate, we found no significant association between male gender and LOS or readmissions. This confirms the results from a previous study [10]. Giger et al. [4] found that the risk of postoperative local complications was associated with male sex (OR, 1.26; p < 0.003). The risk of postoperative systemic complications was not associated with sex, whereas age, acute cholecystitis, conversion, ASA score, and duration of surgery were associated. Previous findings have shown LOS to be highly associated with complications, organizational quality, or both [7], meaning that it often is possible to achieve a fast-track optimized regimen in laparoscopic cholecystectomy by a simple reorganization of patient care in the department.

In conclusion, our nationwide data showed that men had a significantly higher risk for conversion of laparoscopic cholecystectomy to open surgery than women. The reason may be that men more frequently had acute cholecystitis or sequelae from previous acute cholecystitis. Whatever the reason for these differences, the increased risk for men should be included in the risk calculation before surgery. Our results can be used to improve preoperative information and give patients a better foundation for their informed consent. In resource management, it also is important to know the risks and be prepared for conversion.