This study represents one of the largest patient cohorts addressing the correlation between the time elapsed from hospital admission for AC and definitive surgery and the risk for intra- and postoperative AE. We found that the optimal time slot for surgery was within the first 2 days after hospital admission. Cholecystectomy on admission day was performed in close to 12 % of the AC patients, and the risk of intraoperatively detected bile duct injuries was lowest when the cholecystectomy was done on the day of admission with a thereafter day-by-day stepwise increase. These findings support the findings in the literature of the beneficial effect of early surgery on AC.5,8,19 This information is clinically relevant since the majority of minor bile duct lesions are detected intraoperatively and repair is usually attempted at the index procedure with satisfactory results,25 an observation which is not entirely consistent with the international experiences.20,21 However, in the multivariate analysis, we observed a significantly lower risk for AE when the operation was done on the first or second day after admission. These differences in morbidity were also translated into 30-day mortality risk, which were significantly lower when the cholecystectomy was completed during the first day after admission. Even the 90-day mortality risk was significantly reduced for those operated within 3 days of admission. Although operation on admission day in most of our assessments has a significantly better outcome than in those being operated 5 days or more after admission, the frequency of adverse events was somewhat higher compared to an operation performed 1 or 2 days thereafter. The reason for these findings may be found in the fact that some patients arrive at the emergency unit in a bad general condition where time is required for resuscitation and stabilization of the patient, before embarking on definitive surgery. Furthermore, if the patient with acute cholecystitis arrives at the hospital during non-office hours and is immediately scheduled for cholecystectomy, the issue of not being able to offer the highest level of laparoscopic surgical expertise may have a bearing on the outcome. Nevertheless, these issues did not translate into an enhanced risk for BDI.

In a similar analysis of 4113 prospective cholecystectomies performed on patients with acute cholecystitis as reported from the Swiss Association of Laparoscopic and Thoracoscopic Surgery (SALTS) database, the authors concluded that immediate surgery (surgery on the day of admission or at the latest within 24 h of admission) significantly reduced the risk of conversion from laparoscopic to open surgery, which can be used as a proxy variable for the safety and accuracy of the respective operations.12 This is to some extent in line with our study, where the conversion rate, when operation occurred on admission day, was 16.6 % and then increased in a linear fashion to 27.8 % in patients operated on 4 days later. However, whereas the technical conditions for surgery may be optimal on admission day, due to less extent of the inflammation, the findings in our study of a better outcome when patients are operated on the first or second day after admission may indicate that other factors, like the general condition of the patient, mandate attention in order to optimize the outcome.

Studies on the management of patients with AC in routine surgical practice have revealed that basically, no major changes have occurred over recent years.14,26,27 This illustrates the problems and challenges in the implementation of evidence-based guidelines for the treatment of AC. To some extent, this may be explained by a larger proportion of elderly patients with high comorbidity; however, one cannot rule out a widespread conservative attitude with resistance to new evidence-based approaches.26 The slow adaptation to new guidelines could have several other explanations such as local logistic problems and lack of resources for acute surgery. There may also be a proportion of patients with a long duration of symptoms before seeking medical attention, resulting in reluctance to an emergency operation.

The strengths of the current analyses are represented by the magnitude of the database, extracted from the national Swedish Registry of Gallstone Surgery and ERCP (GallRiks), which describes the outcome of cholecystectomies performed at nearly all hospitals in Sweden in routine clinical practice. Thus, regional differences, as well as differences in catchment areas and profiles of the hospitals, can be compensated for. An additional strength of the study is that the data are registered prospectively by the respective surgeons, online, at the time of completion of the operation.

We also recognize that there are some obvious limitations of the study. GallRiks is a national quality register for gallstone surgery and ERCP, and accordingly, the quality and relevance of some clinical data can rightfully be questioned since these are not entered into the registry as a part of a randomized controlled trial protocol with the specific, dedicated aim of addressing specific questions. A further limitation of the register relates to the definition of the variable postoperative adverse event. Although AEs are defined in the Web protocol, these can be interpreted differently by the local coordinators at the participating hospitals. In order to minimize this risk, a list of the most common postoperative adverse events like pancreatitis, cholangitis, bile leakage, and deep venous thrombosis, just to mention a few, will from August 2016 and onwards be visible as predefined options to the local coordinator as an aid to minimize the interobserver variability. However, for the data presented in this study, the coordinator had to decide first whether a postoperative adverse event prevailed before the respective alternatives were chosen. Another possible limitation of these data is a possible risk of selection bias where the reporting surgeon may avoid reporting on negative adverse events related to the surgical intervention. To avoid this, special attention has been directed towards corresponding issues, in order to minimize loss of data quality. An independent coordinator at each participating hospital reviews each individual intervention and reports on imbalances at a compulsory 30-day follow-up. The GallRiks board also undertakes regular validation visits to all the participating hospitals, in order to ensure the accuracy and validity of the registered data. In order to adjust for the possible skewness of data and other confounding factors such as gender, age, comorbidity (American Society of Anesthesiologists classification scale), emergent or scheduled surgery, indication for and type of surgery, as well as a history of previous acute cholecystitis, these were managed through the multivariate analysis. It needs to be pointed out that the time elapsed from admission to the operation was only possible to calculate according to the final date of surgery by the date of admission. Accordingly, the exact time in hours between operation and surgery could not be captured. Likewise, the exact time from onset of symptoms of acute cholecystitis to admission is not registered in GallRiks. Finally, it must be emphasized that GallRiks is designed with the Swedish Health Care System in mind and that the findings in this study must be interpreted cautiously from an international perspective. Accordingly some aspects on the current problem related to the management of AC can, due to methodological limitations, only be addressed by indirect measures.