Optimal Timing of Laparoscopic Cholecystectomy After Conservative Therapy for Acute Cholecystitis
1Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
2Department of Gastrointestinal and General Surgery, Showa University, School of Medicine, Tokyo, Japan
Cholecystitis is one of the more common diseases. Laparoscopic cholecystectomy (LC) is a common treatment for benign gallbladder disease. Laparoscopic cholecystectomy was first performed in 1987 (1) and has become widely used worldwide (2). At the time, it was generally considered that conservative treatment would be administrated first for acute cholecystitis to prevent complications associated with inflammation, and then LC would be performed 6-8 weeks after the onset (3). However, recent meta-analyses have reported that early LC for acute cholecystitis results in shorter hospital stays and no significant difference in complications compared to delayed LC (4-6)
More than 38,000 cholecystectomy procedures are performed annually in Japan (7). According to Tokyo Guidelines 2018 (8), early surgery (within three days) is recommended for acute cholecystitis, even if the inflammation is severe. However, depending on the patient’s complications or the condition of the facility, it may be necessary to carry out selective LC for four days or more. In addition, many patients come to the hospital for LC after undergoing conservative treatment at another hospital. There are very few reports on the optimal time of LC for patients undergoing conservative treatment without percutaneous transhepatic gallbladder drainage (PTGBD), although there are some reports on the optimal time for elective surgery for acute cholecystitis after PTGBD (9-13).
This study retrospectively examined the cases in which surgery was performed four days or more after the conservative treatment for acute cholecystitis.
Patients and Methods
This is retrospective study of patients who underwent LC at Showa University Northern Yokohama Hospital from January 2019 to December 2020. We began to conduct this study February 24th 2022. A total of 345 LCs were performed. Thirty-seven patients underwent urgent LC within three days due to acute cholecystitis, and 83 cases who underwent LC four days or more days after conservative treatment were included. The elective LC cases were divided into two groups: the Early group (4-90 days after onset, n=36) and the Delayed group [91+ days (13+ weeks) after onset, n=31] (
The rationale for surgery, in this study of two groups of patients, was the presence or history of acute cholecystitis. The standard for elective LC was surgery after four days or more of acute cholecystitis onset during or after conservative therapy. There was no difference in postoperative management.
Due to the nature of our hospital, the majority of both groups were referrals. These patients received conservative treatment at another hospital and were referred after discharge. PTGBD cases (n=16) were excluded (
Patient characteristics included sex, age, height, body weight, and body mass index (BMI). Preoperative data included laboratory data, American society of anesthetists-physical status (ASA), and previous abdominal surgery. Operative factors included total operative time and estimated amount of blood loss. Operative outcomes, including conversion rate, postoperative hospital stay, and postoperative complications were compared between the two groups retrospectively. For standardization purposes, complications were classified according to the Clavien-Dindo classification system (14,15). Postoperative complications were identified by reviewing patient charts retrospectively, and Clavien-Dindo Grade 3 or higher patients were deemed to have a complication. All LCs were performed for symptomatic gallstone disease or cholecystitis. We excluded LCs for suspicious malignant diseases or operations with PTGBD.
All LCs were performed using the conventional 4-port technique in the supine position under general anesthesia and followed the technique previously reported (16). Multiple surgeons performed the procedures. A transumbilical vertical incision was made for the 12mm trocar using the open technique in the umbilicus to achieve carbon dioxide insufflation. Intraoperative cholangiography was not performed routinely.
The data analysis was performed using JMP®Pro 14 (SAS Institute Inc., Cary, NC, USA). For comparisons between the groups, the Fisher’s exact test was used for categorical variables, and the Student’s
The study was conducted in accordance with the Declaration of Helsinki. Moreover, the Committee on Ethics of Showa University Medical School and IRB (Institutional Review Board) reviewed and approved the study protocols (The approval code: No. 19H064). As a retrospective cohort study, the Committee on Ethics of Showa University Medical School and IRB directed that the opt-out method to obtain patient consent was utilized and waived the need for informed consent.
The elective LC cases were divided into two groups: the Early group (LC performed within 4-90 days after onset, n=36) and the Delayed group [91+ days (13+ weeks), n=31]. No significant differences in the patient characteristics, including sex, age, height, body weight and BMI were found between the two groups. The median and inter-quartile range between diagnosis (onset) and surgery for Early and Delayed groups were 38.5 days (19.5-72.25) and 110 days (96-143), respectively (Table I). The preoperative data showed a significant increase in white blood cell count (
Moreover, blood loss was less in the Delayed group, although this did not reach significance (6.4 g,
No postoperative complications were observed in the Delayed group, however, in the Early group, three patients exhibited complications such as intestinal injury, ileus, bleeding, and bile leakage. A patient with postoperative ileus had a long tube inserted, and another patient with postoperative bleeding was managed by surgical hemostasis. Moreover, bleeding and bile leakage were seen in the same patient (
Next, univariate and the multivariate analyzes were performed for the rate of conversion and the incidence of postoperative complications using WBC, CRP, operative time, and postoperative hospital stay, as those four factors were significantly different between the Early and Delayed groups. The cut-off values were obtained by constructing receiver operating characteristic curves for each factor.
In the univariate analysis of the rate of conversion, WBC (
Moreover, the univariate and multivariate analyzes of postoperative complications were performed, but none of these four factors were extracted as significant risk factors.
Regarding the optimal timing of cholecystectomy, there have been some reports about patients after percutaneous transhepatic gallbladder drainage (PTGBD) (9-13), but there are very few reports on the optimal timing of surgery for cases after hospitalization and conservative treatment. However, this study does not deny the benefit of conducting urgent cholecystectomy within 72 hours for acute cholecystitis. Instead, we examined the second-best timing of cholecystectomy for patients who had missed the best opportunity for surgery due to preoperative condition, complications, or re-hospitalization from other hospitals.
As for a comparison between within three days and four days or more after onset, Ota
Hence, we conducted our study simply in two groups, 4-90 days and 91+ days (13+ weeks), focusing on the timing of surgery after conservative treatment. The results of this study showed significant reductions in operative times and postoperative hospital stays in the Delayed group (91+ days). In addition, the amount of blood loss, conversion rate, and incidence of postoperative complications were also lower in the Delayed group (91+ days), although the differences were not significant.
There were no significant differences in patient age, sex, height, body weight, or BMI, but preoperative data showed that the WBC and the value of CRP were significantly higher in the Early group (4-90 days), and the inflammatory response remained when the laparoscopic cholecystectomy was performed. Whereas there were no significant differences in total bilirubin, AST, ALT, PT, or preoperative liver function. Moreover, there were no significant differences in preoperative conditions or complications.
However, regarding surgical factors, our data showed that the operative time was significantly longer in the Early group. Furthermore, there was no significant difference in the amount of bleeding, but it tended to be higher in the Early group. These seemed to indicate the difficulty of surgery in early cases where inflammation remained. The same tendency was observed in the literature of cases in which PTGBD was inserted (12,18). Furthermore, the conversion rate, length of postoperative hospital stay, and postoperative complications, tended to be more in the early group, especially the length of postoperative hospital stay was significantly longer. Similarly, these also seemed to indicate the difficulty of surgery in early cases where inflammation remains. In addition, as the structure of the inner and outer layers in the gallbladder wall disappeared due to progressive fibrosis, it could make LC more difficult after severe cholecystitis (19).
Several previous reports indicated that early surgery for acute cholecystitis shortened the length of hospital stay (20-22). However, our data revealed a significant reduction in hospital stay length in the Delayed group, specifically “postoperative” hospital stays. Our data indicates that most patients were readmitted, including from other hospitals. Therefore, the calculation of postoperative hospital stay was the same as for the first hospitalization, and the inflammation was sufficiently relieved.
For postoperative complications, multivariate analysis did not extract independent risk factors. However, its analysis revealed high levels of CRP as independent risk factors for conversion. This fact could indicate that in early cases where the inflammatory reaction persists or prolongs, the difficulty of adhesion detachment and the risk of bleeding increases, resulting in a conversion.
In patients with cholecystitis who had undergone conservative treatment and missed the opportunity for cholecystectomy within three days, it is recommended that laparoscopic cholecystectomy is performed after 91 days (13+ weeks) or more.
The limitations of our study are sample size, single institution, and the retrospective design. Further analysis and more patients are needed to confirm our conclusion.
When the conservative treatment for acute cholecystitis precedes and precludes urgent/early LC within 3 days, delaying LC for at least 91 days (13+ weeks) after onset could reduce operative time and postoperative hospital stay, moreover, there would not be complications after LC, and the rates of conversion may be kept low during LC.
Conflicts of Interest
All Authors have no conflicts of interest to declare in relation to this study.
Y.E. contributed to the writing of the article and preparing of the figure and tables. Y.E., K.T., T.H., H.S., K.S., S.N., Y.T., J.S., S.S., K.N., Y.T., and S.M. contributed to the surgeries and the analysis of the data. T.A., N.S., F.I., and S.K. contributed to the design and implementation of this study. All Authors have read and approved the article.
We are pleased to inform our readers that a portion of this article has been posted as a preprint on Research Square (https://www.researchsquare.com/article/rs-1615264/v1).