Timing of cholecystectomy after percutaneous cholecystostomy for acute cholecystitis- A systematic review and meta-analysis

The study was conducted according to the Preferred Reporting Systematic Reviews and Meta-Analyses (PRISMA) statement and MOOSE guidelines. Heterogeneity was measured using Q tests and I2 statistics. The random-effects model was used. We evaluated cholecystectomy performed at different periods after percutaneous cholecystostomy within 72 hours or later, within or after one week or percutaneous cholecystostomy, within 10 days or after 10 days, less than 2 weeks or more than 2 weeks, less than 4 weeks or more than 4 weeks, less than 8 weeks or more than 8 weeks as per literature. Six studies including 18640 patients were included in the final analysis. There was no difference in overall complications within or after 72 hours cholecystectomy group, but mortality and biliary complications were significantly high in the less than 72 hours group (p=0.05 and 0.0002 respectively). There was no difference in mortality, overall complication, biliary tract complications in less than 1 week versus more than 1 week and less than 10 days versus more than 10 days group. Overall complications were significantly less in the less than 2 weeks group compared to the more than 2 weeks group. There was no difference in mortality and biliary tract complications between less than 2 weeks and more than 2 weeks group. Overall complication rate (risk ratio 0.67, p <0.0001), postoperative mortality (risk ratio 0.46, p=0.003), bile duct injury (risk ratio 0.62, p=0.01) was significantly less in earlier than 4-week group. Hospital stay was not significantly different between less than 4 weeks versus more than 4 weeks group. (Mean difference= -2.74, p=0.12). Ove all complication rates were significantly more in less than 8 weeks group. (Risk ratio 1.07, p=0.01). Hospital stay was significantly less in less than 8 weeks group. (Mean difference 0.87, p=0.01).

cholecystectomy should be offered, but now early cholecystectomy preferably within 72 hours of presentation is preferred over interval cholecystectomy. [1,2,3] Percutaneous cholecystostomy is now emerging as a bridge to surgery to control sepsis when a patient is too sick for surgery or when a patient is unfit for surgery or has a high risk of postoperative mortality. [4] In the case of acute calculous cholecystitis, cholecystectomy is needed after a patient is stabilized with percutaneous cholecystostomy. However, the timing of subsequent cholecystectomy remains controversial, and very little data is available regarding that.

Aim:
This systematic review and meta-analysis aimed to evaluate outcomes of early versus late cholecystectomy after percutaneous cholecystectomy.

Methods:
The study was conducted according to the PRISMA 2020 statement and MOOSE guidelines. [5,6].

Study selection:
We conducted a literature search as described by Gossen et al. [7] PubMed, Cochrane Library, Embase, Google Scholar, Web of Science with keywords and "MESH" terms like "percutaneous cholecystostomy", "Cholecystectomy", "Timing of cholecystectomy", "early versus late cholecystostomy", "cholecystectomy AND cholecystostomy", "cholecystectomy after cholecystostomy". Two independent authors extracted the data (B.V. and H.P.) Discussions and mutual understanding resolved any disagreements.
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Statistical analysis:
The meta-analysis was conducted using Review Manager 5.4. Heterogeneity was measured using Q tests and I2, and P < .10 was determined as significant, the random-effects model was used. The odds ratio (OR) was calculated for dichotomous data, and weighted mean differences (WMD) were used for continuous variables. Both differences were presented with 95% CI. For continuous variables, if data were presented with medians and ranges, then we calculated the means and standard deviations according to Hozo et al. [8]. If the study presented the median and interquartile range, the median was treated as the mean, and the interquartile ranges were calculated using 1.35 SDs, as described in the Cochrane handbook. [9] Risk of bias assessment: Cohort studies were assessed for bias using the Newcastle -Ottawa Scale. [10]. It was decided to assess randomized trials based on the Cochrane Handbook. [9]. However, in the final analysis, we could not find any randomized clinical trials fulfilling our inclusion criteria so the Newcastle -Ottawa Scale was used. We evaluated publication bias by funnel plots. We defined mortality as postoperative 90 days mortality. We evaluated various periods of cholecystectomy after percutaneous cholecystectomy like within 72 hours, within 7 days, within 10 days, within two weeks, within 4 weeks, or within or after 8 weeks.

Inclusion criteria:
• Studies that evaluated early vs late cholecystectomy after percutaneous cholecystostomy.
• Conference abstracts that contain adequate information.

Exclusion criteria:
. CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 12, 2021. • Articles where full texts were not available.
• Conference abstracts without adequate details.
Characteristics of the included studies are described in table 1. The risk of bias summary is shown in figure 2.

Cholecystectomy within 72 hours of percutaneous cholecystostomy: [Figure 3]
Two studies consisting of 9323 patients evaluated cholecystectomy within or after 72 hours of initial percutaneous cholecystostomy. [11,12]. There was no difference in overall complications

Cholecystectomy within 1 week of percutaneous cholecystostomy: [Figure 4]
One study consisting of 9256 patients [12] compared cholecystectomy earlier than one week after percutaneous cholecystostomy to cholecystectomy after one week. There was no significant . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Heterogeneity was not significant in the majority of analysis as shown in forest plots, in some of the heterogeneity analysis was not possible as very few studies were there. Publication bias was not significant.

Discussion:
Percutaneous cholecystostomy is increasingly being used for definitive treatment of acalculous cholecystitis and as a bridge to surgery in case of calculous cholecystitis in a patient with a high risk of surgery due to comorbidities or sometimes ongoing septic shock. [16][17][18][19][20]. There is ongoing controversy about the optimal time of cholecystectomy after percutaneous cholecystostomy in the case of calculous cholecystectomy.
In this systematic review and meta-analysis, we tried to evaluate the optimal timing of cholecystectomy after percutaneous cholecystostomy in the case of calculous cholecystitis.. We  is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not certified by peer review)
The copyright holder for this preprint this version posted June 12, 2021. ; https://doi.org/10.1101/2021.06.06.21258426 doi: medRxiv preprint After a systematic search described in methodology and removing duplicates, we found six articles [11][12][13][14][15][16][17] In studies comparing cholecystectomy within or after 8 weeks of percutaneous cholecystostomy [15,16], overall complications and hospital stay were significantly more in cholecystectomy in . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not certified by peer review)
The copyright holder for this preprint this version posted June 12, 2021. ; less than 8 weeks compared to cholecystectomy in more than 8 weeks. There was no difference in conversion to open, 90-day mortality and need for subtotal cholecystectomy between the groups.
Based, on these findings, it seems that less than 4 weeks is the ideal time for cholecystectomy after percutaneous cholecystostomy for calculus cholecystitis. In conclusion, early cholecystectomy preferably within 4 weeks after cholecystostomy is safe and probably beneficial to the patients. However, further studies are still needed to confirm the findings of this meta-analysis.

References:
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(which was not certified by peer review)
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(which was not certified by peer review)
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Identification of studies via databases and registers
Id en tifi ca tio n . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.  . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not certified by peer review)
The copyright holder for this preprint this version posted June 12, 2021.         . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not certified by peer review)
The copyright holder for this preprint this version posted June 12, 2021.   . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not certified by peer review)
The copyright holder for this preprint this version posted June 12, 2021.     . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

(which was not certified by peer review)
The copyright holder for this preprint this version posted June 12, 2021.       . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 12, 2021. ; https://doi.org/10.1101/2021.06.06.21258426 doi: medRxiv preprint     . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 12, 2021. ; https://doi.org/10.1101/2021.06.06.21258426 doi: medRxiv preprint . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 12, 2021. ; https://doi.org/10.1101/2021.06.06.21258426 doi: medRxiv preprint