Journal of Gastrointestinal Surgery (2019) 23:297–303 https://doi.org/10.1007/s11605-018-4021-5

ORIGINAL ARTICLE

Percutaneous Cholecystostomy Versus Conservative Treatment for Acute Cholecystitis: a Cohort Study

Stine Ydegaard Turiño 1 & Daniel Mønsted Shabanzadeh1 & Nethe Malik Eichen1 & Stine Lundgaard Jørgensen1 & Lars Tue Sørensen1 & Lars Nannestad Jørgensen1

Received: 2 July 2018 /Accepted: 18 October 2018 /Published online: 2 November 2018 # 2018 The Society for Surgery of the Alimentary Tract

Abstract Background Percutaneous cholecystostomy is frequently used as a treatment option for acute calculous cholecystitis in patients unfit for surgery. There is sparse evidence on the long-term impact of cholecystostomy on gallstone-related morbidity and mortality in patients with acute calculous cholecystitis. This study describes the long-term outcome of acute calculous chole- cystitis following percutaneous cholecystostomy compared to conservative treatment. Methods This was a cohort study of patients admitted at our institution from 2006 to 2015 with acute calculous cholecystitis without early or delayed cholecystectomy. Endpoints were gallstone-related readmissions, recurrent cholecystitis, and overall mortality. Results The investigation included 201 patients of whom 97 (48.2%) underwent percutaneous cholecystostomy. Patients in the cholecystostomy group had significantly higher age, comorbidity level, and inflammatory response at admission. The median duration of catheter placement in the cholecystostomy group was 6 days. The complication rate of cholecystostomy was 3.1% and the mortality during the index admission was 3.5%. The median follow-up was 1.6 years. The rate of gallstone-related readmissions was 38.6%, and 25.3% had recurrence of cholecystitis. Cox regression analyses revealed no significant differences in gallstone-related readmissions, recurrence of acute calculous cholecystitis, and overall mortality in the two groups. Conclusions Percutaneous cholecystostomy in the treatment of acute calculous cholecystitis was neither associated with long- term benefits nor complications. Based on the high gallstone-related readmission rates of this study population and todays perioperative improvements, we suggest rethinking the indications for non-operative management including percutaneous cholecystostomy in acute calculous cholecystitis.

Keywords Cholecystostomy . Acute . Cholecystitis . Elderly

Introduction time- and resource-demanding compared to sole antibiotic treatment. It impairs patient mobilization and requires a ded- Cholecystectomy is the recommended treatment for acute cal- icated radiologist for the procedure, a follow-up antegrade culous cholecystitis (ACC).1 However, in elderly and comor- cholangiography, and multiple daily flushing of the catheter. bid patients, many clinicians esteem that this group of patients PC was recommended in the Tokyo Guideline of 2007 and is better off with conservative treatment with or without per- 2013 though with limited evidence in patients with severe cutaneous cholecystostomy (PC), due to assumed increased acute cholecystitis, organ failure, and need for intensive care, perioperative morbidity and mortality. Meanwhile, PC is In addition, PC has been suggested as a treatment option in moderate cholecystitis as bridge to surgery.2,3 According to the latest Tokyo guideline of 2018, the recommended treat- This study was delivered as an oral presentation at the Annual Meeting of ment of severe ACC is early laparoscopic cholecystectomy. In the Danish Surgical Society, 10 November 2017, Copenhagen. lack of an experienced surgeon or if the patient is unfit for surgery, the recommendation still is urgent biliary drainage * Stine Ydegaard Turiño followed by laparoscopic cholecystectomy, once the patient [email protected] condition has improved.1 PC is considered a safe procedure with complication rates at 0–16%.4–9 As the main cause of 1 Digestive Disease Center, Bispebjerg Hospital, University of ACC is obstruction of the cystic duct by gallstones, it may Copenhagen, Bispebjerg Bakke 23, DK-2400 Copenhagen, NV, Denmark seem more efficient to catheter the gallbladder empyema, 298 J Gastrointest Surg (2019) 23:297–303 compared to exclusive antibiotic treatment. However, the lit- hospital stay. Definitions of exposure variables at baseline erature is sparse with only one published randomized clinical are reported in Table 1. trial, allocating 123 high-risk patients to either conservative Patients were followed until gallstone-related readmission, treatment with antibiotics or antibiotics in combination with death, or loss to follow-up. Gallstone-related readmissions PC. No difference was found in morbidity or mortality be- were defined as admissions due to biliary colics, acute chole- tween the two groups after a 12-month follow-up.10 A cystitis, choledocholithiasis with or without pancreatitis, or matched comparative study found that patients undergoing gallstone ileus occurring later than 30 days after the index PC were more comorbid and had higher associated mortality admission. Readmissions were recorded only for the Capital than patients treated with cholecystectomy.9 Region of Denmark. At follow-up, we checked the national At our surgical department, we frequently use PC for the central registration office, and if the patient had moved out of conservative treatment of ACC due to the tradition and easy the region, the follow-up period ended at that time, and the access, thus giving us the opportunity to investigate if PC patient was considered lost to follow-up concerning compared with non-operative management for ACC influ- readmissions. Date of death was recorded from the national ences the long-term risk of gallstone-related morbidity and central registration office. mortality. The main explorative variable was PC versus no-PC. Endpoints were defined as readmissions related to gallstones, readmissions due to recurrence of ACC, and overall mortality. Materials and Methods Diagnosis and Treatment Algorithm This was a retrospective cohort study of long-term outcomes in patients with ACC without early or delayed cholecystecto- The diagnosis of ACC was based on the presence of abdominal my during first admission and treated with or without PC at pain in the right upper quadrant and a positive Murphy’ssign the Digestive Disease Center, Bispebjerg Hospital, University with systemic signs of inflammation and possibly radiologic of Copenhagen from 1st of January 2006 to 31st of December findings according to the Tokyo Guideline 2013 criteria.11 2015. The minimal follow-up period was 12 months after the According to the local guideline, all patients with onset of index admission. The study was approved by the Danish Data symptoms ≤ 5 days were offered emergency cholecystectomy. Protection Agency (ref. j.nr. 2012-58-0004). The remaining patients were treated with- or without PC. The indication for PC was at the discretion of the surgeon. PC was Study Population performed under ultrasound guidance and local anesthesia. In all cases, the radiologist placed a transperitoneal 5.7-Fr pigtail All medical charts from patients discharged with a diagnosis catheter (TCD Single Step, Argon Medical Devices, Inc., code for acute cholecystitis (DK80/DK81) according to the Texas, USA) into the gallbladder. The catheter was fixed to International Classification for Diseases (WHO-ICD10) were the skin and flushed with saline 3–6 times a day. No catheters reviewed. Patients who did not meet the diagnostic criteria were placed through the liver. Following PC, an antegrade were excluded, as were patients with pancreatic-biliary malig- cholangiography through the catheter was routinely performed nancies or acalculous cholecystitis. In this study, we compared after 4–6 days. The catheter was removed if there was passage the clinical course after treatment with- or without PC. In of contrast to the duodenum. order to have a long follow-up of patients with gallbladders The standard regimen of antimicrobial therapy was a combi- in situ treated for ACC, we excluded those patients who nation of intravenous metronidazole and cephalosporin or piper- underwent early cholecystectomy or went uneventfully to de- acillin/tazobactam. When patient condition improved, metroni- layed cholecystectomy 3 months after their first presentation dazole and a fluorquinolone were orally administered. Antibiotic of ACC during the study period. treatment was not administered in patients with mild ACC.12 Data collected for each patient included baseline patient Only younger (< 80 years of age) patients fit for surgery were demographics and comorbidity as reflected by the American offered cholecystectomy 3 months after the index admission. Society of Anesthesiology classification system (ASA) and the Charlson Comorbidity Index (CCI). We also assessed de- Statistical Analysis tails from index admission including vital signs, systemic in- flammatory markers (leucocytes and C-reactive protein), du- Medians with interquartile ranges (IQR) and numbers with ration of cholecystitis symptoms, length of stay, duration of percentages were reported for continuous and categorical var- cholecystostomy catheter placement and antibiotic treatment, iables, respectively. Wilcoxon signed-rank test and Chi square catheter-associated complications within 30 days, and medical test were used for descriptive purposes to identify differences complications. Medical complications were defined as any in baseline variables between the PC and no-PC groups with adverse event requiring additional treatment or prolonging level of significance defined as a p value less than 0.05. J Gastrointest Surg (2019) 23:297–303 299

Table 1 Baseline characteristics

Percutaneous cholecystostomy, No percutaneous cholecystostomy, Missing, P value1 (n =97) (n =104) n

N (%)/median[IQR] Sex 0.857 Male 60 (61.9) 60 (61.9) Age (years) 84.0 [75.0–89.0] 68.0 [53.8–82.0] < 0.0001 Charlson comorbidity index (1–9) 1.0 [1.0–2.0] 1.0 [0.0–2.0] 1 0.002 American Society of Anesthesiologists’ score 3[2–3] 2 [2–3] 0.0003 (1–4) Heart rate (beats/min) 86.0 [77–98] 77.0 [68–89] 19 0.0008 Body temperature (°C) 37.0 [36.7–37.7] 37.2 [36.8–37.7] 19 0.348 Blood leucocytes (cells *109/L) 16.5 [11.5–20.3] 12.4 [10.5–16.0] 12 0.0001 C-reactive protein (mg/L) 203.0 [100.0–294.5] 100.0 [38.5–195.5] 11 < 0.0001 Indication for non-operative management: 0.0001 - co-morbidity 87 (89.7) 62 (59.6) - patient preference 7 (7.2) 26 (25.0) - scheduled surgery never performed 3 (3.1) 16 (15.4) Antibiotic treatment 90 (93.8) 87 (83.7) 1 0.044 Duration of symptoms (days) 3.0 [2–4] 2 [2–3] 0.0003

1 Derived from Chi square test or Wilcoxon signed-rank test

Unadjusted cumulative incidence proportions were reported comprised 201 patients (Fig. 1) who were admitted with with death as the competing outcome and patients alive or lost ACC and did not undergo emergent or delayed cholecystec- to follow-up censored on last date available. Cox regression tomy. One hundred forty-one patients (74.1%) were included was used for inferential statistical analyses. Hazard ratios because of comorbidity and 33 patients (16.4%) would not (HR) with 95% confidence intervals (CI) were reported, and consent to emergent cholecystectomy in spite of young age significant associations were defined by a confidence interval and low perioperative risk. Four patients (2%) were lost to not including one. Analysis of endpoints was performed with follow-up for readmission of which three were tourists and PC as a binary variable (PC/no-PC) where the no-PC group one had moved from the region. The follow-up time for was considered reference. Statistical estimates were reported readmissions was median 1.61 years (IQR 0.24–3.29). as multiple adjusted models to adjust for confounding. Possible confounding variables at baseline were identified in Discharged with the diagnosis the descriptive statistical analyses. A minimum of ten outcome acute cholecyss, n = 1170 events per parameter was required in the multiple adjusted models. Scaled Schoenfeld residuals were used to test good- Fault diagnosis,n = 125 ness of fit in the most adjusted models. The assumption of proportional hazards was not violated in any of the analyses. Acalculous cholecyss, n = 22 All statistical analyses were performed with the BR Studio^ software (RStudio Inc., Boston, MA) with the Bsurvival^ and Early cholecystectomy, n = 586 Bcmprsk^ packages. The study is reported according to the STROBE guideline for observational studies.13 Delayed cholecystectomy, n = 230

Early cholecystectomy due to Results abscess/perforaon, n = 3

Pancreato-biliary cancer, n = 3 A total of 1170 patients were discharged with a diagnosis of acute cholecystitis during the study period. One hundred and twenty-five patients did not meet the diagnostic criteria, 22 had acalculous cholecystitis, 819 underwent early or delayed Paents included in the study, n = 201 cholecystectomy, and three were excluded because of pancreato-biliary malignancy. The final study population Fig. 1 Study population consort diagram 300 J Gastrointest Surg (2019) 23:297–303

Ninety-seven (48.3%) patients were treated with PC and were group was readmitted at 11 months of follow-up with recur- significantly older and more comorbid than the 104 patients in rent cholecystitis and had an emergency laparoscopic chole- the no-PC group. Moreover, they revealed an increased inflam- cystectomy due to perforated cholecystitis. matory response at admission as compared with the no-PC group Significant differences in age, ASA score, heart rate, CRP, (Table 1). In the PC group, 93.8% were treated with antibiotics as and antibiotic treatment were identified between the PC and compared with 83.7% in the no-PC group (p = 0.044). In both no-PC groups at baseline and were therefore adjusted for in groups, the median duration of symptoms of ACC prior to ad- Cox regression multiple models. In both age- and multiple- mission were about 3.0 days. The PC catheters were placed adjusted models, we found no significant differences for median 1 day (IQR 1.0–2.0) after hospital admission. The me- readmissions between the two groups (Table 4). dian duration of PC was 6.0 days. There were no significant There was a cumulative incidence proportion of 25.3% for differences in rates of medical complications or mortality during recurrence of ACC. No significant differences between the PC the index admission between the two groups (Table 2). Seven and the no-PC groups were found in age- and multiple- patients (3.5%) died during the index admission. An 87-year old adjusted models (Table 4). man died of grade 3 cholecystitis with a liver abscess. The re- The overall mortality during follow-up was 71.6%. Two maining six patients died from myocardial infarction, stroke, patients died during the readmission due to choledocholithiasis respiratory insufficiency due to pneumonia, congestive heart fail- with cholangitis and respiratory insufficiency following emer- ure, hepatocellular carcinoma, and end-stage myelodysplastic gency cholecystectomy on the indication of ACC (Table 3). syndrome in combination with ACC, respectively. The PC group The disease-specific mortality during readmission was 2.9%. had a longer hospital stay than the no-PC group (median 9.0 days Age- and multiple-adjusted models revealed no significant dif- (IQR 7.0–12.0) versus 4.0 days (IQR 2.0–6.0), p < 0.0001). We ferences in overall mortality between the two groups (Table 4). found multiple catheter dislocations, but placement of a new PC was only indicated in three cases (7.2%). There were only three (3.1%) severe complications to PC (bile leak, n = 1 and abscess, Discussion n = 2). There were no complications in the patients where the catheter was dislocated and taken out before time. This retrospective cohort study was conducted to investigate if During long-term follow-up, 70 patients (34.8%) were PC as compared with no-PC for the treatment of patients with readmitted with gallstone-related symptoms (Table 3). The ACC and without indication for surgery was associated with a majority of readmissions occurred within the first 3 years, more favorable clinical long-term outcome. We found no dif- and the cumulative incidence for all readmissions was ference in the long-term risk of gallstone-related readmission, 38.6% (Fig. 2). Five patients (5.2%) were readmitted with recurrence of ACC, or overall mortality between these two complications to PC; three with abscess and two with a treatment algorithms. Surprisingly, we found a high rate of cholecystocutaneous fistula. Another patient from the PC gallstone-related readmissions in both groups. In resemblance

Table 2 Course of treatment during admission

Percutaneous cholecystostomy No percutaneous cholecystostomy P value1 n =97 n =104 n (%)/median [IQR]

Duration of percutaneous cholecystostomy catheter treatment (days) 6 [5; 9] – Complications related to catheter - Dislocation (leading to new catheter) 7 (7.2) – - Intraabdominal abscess 2 (2.1) – - Bile leak 1 (1.0) – Medical complications 18 (18.6) 12 (11.5) 0.163 - cardiovascular 4 6 - infection 8 5 - gastroenteritis 3 1 -delirium 2 0 - loss of function/dependency 1 0 Duration of hospital stay (days) 9 [7–12] 4 [2–6] < 0.0001 Death during admission 6 (6.2) 1 (1.0) 0.102

1 Derived from Chi square test or Wilcoxon signed-rank test J Gastrointest Surg (2019) 23:297–303 301

Table 3 Gallstone-related re- admissions during long-term Cause of re-admission Percutaneous No percutaneous follow-up cholecystostomy, cholecystostomy n = 36/97 (37.1%) n = 34/104 (32.7%)

Catheter complications 5 (5.2) 0 (0) Non-operative treatment of acute cholecystitis 20 (20.6) 13 (12.5) Biliary colic 4 (4.1) 9 (8.7) Emergent surgery due to cholecystitis 5 (5.2)1 6 (5.8) Choledocholithiasis 1 (1.0) 4 (3.8)2 Pancreatitis 1 (1.0) 1 (1.0) Gallstone ileus 0 (0) 1 (1.0)

1 One patient died of respiratory insufficiency 6 days after emergency cholecystectomy 2 One patient died of cholangitis with other series, there were few short-term complications were performed due to the retrospective study design but since related to the PC, but the PC group had longer hospital stay. the confidence intervals in the regression analyses were close Two patients were readmitted with secretion from a to one, the risk of type 2 error is considered very low. Based on cholecystocutaneous fistula. Their preceding cholangiography the differences in baseline characteristics, we may suspect a had demonstrated an open cystic duct, and the PC catheter had selection bias in choosing PC to the patients with more ad- been removed on days 3 and 5, respectively. vanced levels of ACC, comorbidity, and age. The significant We could not investigate if there was an immediate benefit difference in initiating antibiotic treatment in the two groups of PC on pain as well as prevention of gallbladder necrosis, (PC 93.8% and no-PC 83.7%) supports the difference in se- perforation, or abscess formation. Several studies report a dra- verity of ACC. This limitation was addressed through adjust- matic response in pain relief and decrease of CRP within 2– ment in multiple models. However, a risk of residual con- 3 days after PC,7,14,15 but the only randomized study compar- founding may still be present. Randomized controlled trials ing PC to antibiotic treatment reports comparable levels of should be performed to fully address these limitations. symptoms in both groups at 72 h.10 After patients had recovered from their first attack of ACC, The strengths of this study include an almost complete more than one out of three were readmitted with gallstone- long-term follow-up of the population based on register data related morbidity and one out of four developed recurrent including the entire Capital Region of Denmark. Such com- ACC. To our surprise, the assumption that the elderly and prehensive follow-up is rarely seen in studies performed in comorbid patients will die before experiencing further gall- other countries. Some limitations need to be addressed. First, stone events requiring hospitalization, was wrong in more it is a single-center study. Second, due to the retrospective and than one third of cases. This emphasizes cholecystectomy as non-randomized study design, the decision to perform PC or the only curative treatment for ACC, and our findings also antibiotic treatment only instead of cholecystectomy was at indicate that there has been—at least in our department—a the discretion of the surgeon. No sample size calculations tendency to treat too many patients with PC. Several reviews also support early laparoscopic cholecystectomy in the elderly and/or comorbid patients.16,17 A recent meta-analysis includ- ing 337, 500 critically ill patients with ACC treated either with cholecystectomy or PC showed a significant difference in fa- vor of cholecystectomy regarding length of hospital stay, readmissions for biliary complaints, and mortality.17 However, there was no difference in complications or re- interventions in the two groups in the meta-analysis.16 Recent advances in laparoscopic techniques and perioperative care have changed the indication for surgery in the elderly patients in general. These findings are reflected by a decline in mortality rates after cholecystectomy in the elderly from 12% before 1995 to 4% after 1995.16 In a large retrospective study of 703 patients with ACC treated with early cholecys- tectomy, no statistically significant difference in 30-day mor- Fig. 2 Readmissions during long-term follow-up tality in two age groups (3% (≥ 75 years) versus 1% (< 302 J Gastrointest Surg (2019) 23:297–303

Table 4 Cox regression analyses of long-term outcomes following acute calculous cholecystitis treated with percutaneous cholecystostomy (PC) or without percutaneous cholecystostomy (no-PC)

Outcome Follow-up time Cumulative incidence proportion Age adjusted model Multivariable adjusted (person days) at end of follow-up HR [95% CI] model HR [95% CI]

Re-admission1 no-PC 103,633 38.1% Ref. Ref. PC 62,944 39.2% 1.55 [0.90–2.66] 1.47 [0.80–2.71]2 Re-admission due to recurrence of cholecystitis no-PC 103,633 21.5% Ref. Ref. PC 62,944 29.5% 1.71 [0.88–3.35] 1.89 [0.93–3.84]3 Overall mortality4 no-PC 154,273 59.5% Ref. Ref. PC 95,124 84.0% 1.27 [0.84–1.94] 1.42 [0.87–2.32]2

1 Re-admission due to cholecystitis, biliary colic, choledocholithiasis, pancreatitis, drain complications, or gallstone ileus 2 Multivariable model includes age, American Society of Anesthesiologists score (1–4), heart rate, C-reactive protein, and antibiotic treatment 3 Multivariable model includes age, American Society of Anesthesiologists score, and heart rate 4 Overall mortality during follow-up was 71.6%

75 years), p = 0.07) was found.18 Although cholecystectomy Jørgensen: Drafting the work or revising it critically for important intel- in the elderly patients is associated with a higher conversion lectual content. Stine Ydegaard Turiño, Daniel Mønsted Shabanzadeh, Nethe Malik rate (18% vs. 5%) and longer postoperative length of stay Eichen, Stine Lundgaard Jørgensen, Lars Tue Sørensen, Lars Nannestad (5 days vs. 3 days),18 curative surgical treatment for ACC Jørgensen: Final approval of the version to be published. for this patient group is still considered indicated by many. Agreement to be accountable for all aspects of the work in ensur- There are currently two ongoing randomized clinical trials ing that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: Stine Ydegaard addressing acute cholecystectomy versus non-operative man- Turiño, Daniel Mønsted Shabanzadeh, Nethe Malik Eichen, Stine agement. In a Dutch multicenter trial (CHOCOLATE), high- Lundgaard Jørgensen, Lars Tue Sørensen, Lars Nannestad Jørgensen. risk patients with ACC are randomly allocated to laparoscopic cholecystectomy or PC.19 In a Finnish multicenter trial, pa- tients with ACC and above 80 years of age are randomized to cholecystectomy or antibiotic treatment.20 Hopefully, these References studies will clarify the superior treatment for ACC in the el- derly and comorbid patients. 1. Okamoto K, Suzuki K, Takada T, et al. Tokyo Guidelines 2018 flow- chart for the management of acute cholecystitis. J Hepatobiliary Pancreat Sci 2017. https://doi.org/10.1002/jhbp.516. 2. Itoi T, Tsuyuguchi T, Takada T, et al. TG13 indications and tech- Conclusion niques for biliary drainage in acute cholangitis (with videos). J Hepatobiliary Pancreat Sci 2013; 20: 71–80. 3. Yamashita Y, Takada T, Kawarada Y, et al. Surgical treatment of The present study failed to demonstrate a long-term clinical patients with acute cholecystitis: Tokyo guidelines. JHepatobiliary benefit from the use of PC in high-aged comorbid patients Pancreat Surg 2007; 14: 91–7. with ACC. Because gallstone-related readmission rates were 4. Atar E, Bachar GN, Berlin S, et al. Percutaneous cholecystostomy high and perioperative care has been improved, we suggest in critically ill patients with acute cholecystitis: Complications and late outcome. Clin Radiol 2014; 69: e247–52. that PC should not be used routinely in the management of 5. Horn T, Christensen SD, Kirkegård J, Larsen LP, Knudsen AR, ACC. Ongoing and future randomized clinical trials may con- Mortensen F V. Percutaneous cholecystostomy is an effective treat- tribute further to optimized treatment algorithm for ACC. ment option for acute calculous cholecystitis: A 10-year experience. HPB (Oxford) 2015; 17: 326–31. Author Contributions Stine Ydegaard Turiño, Daniel Mønsted 6. Zerem E, Omerović S. Can percutaneous cholecystostomy be a Shabanzadeh, Lars Tue Sørensen, Lars Nannestad Jørgensen: definitive management for acute cholecystitis in high-risk patients?. Conception or design of the work. Surg Laparosc Endosc Percutaneous Tech 2014; 24: 187–91. Stine Ydegaard Turiño, Daniel Mønsted Shabanzadeh, Nethe Malik 7. Granlund A, Karlson BM, Elvin A, Rasmussen I. Ultrasound- Eichen, Stine Lundgaard Jørgensen: Acquisition, analysis of the work. guided percutaneous cholecystostomy in high-risk surgical patients. Stine Ydegaard Turiño, Daniel Mønsted Shabanzadeh, Lars Langenbeck’sArchSurg2001; 386: 212–7. Nannestad Jørgensen: Interpretation of data for the work. 8. Sanjay P, Mittapalli D, Marioud A, White RD, Ram R, Alijani A. Stine Ydegaard Turiño, Daniel Mønsted Shabanzadeh, Nethe Malik Clinical outcomes of a percutaneous cholecystostomy for acute Eichen, Stine Lundgaard Jørgensen, Lars Tue Sørensen, Lars Nannestad cholecystitis: A multicentre analysis. Hpb 2013; 15: 511–6. J Gastrointest Surg (2019) 23:297–303 303

9. Smith TJ, Manske JG, Mathiason MA, Kallies KJ, Kothari SN. 15. van Overhagen H, Meyers H, Tilanus HW, Jeekel J, Laméris JS. Changing trends and outcomes in the use of percutaneous Percutaneous cholecystectomy for patients with acute cholecys- cholecystostomy tubes for acute cholecystitis. Ann Surg 2013; titis and an increased surgical risk. Cardiovasc Intervent Radiol 257: 1112–5. 1996; 19: 72–6. 10. Hatzidakis AA, Prassopoulos P, Petinarakis I, et al. Acute chole- 16. Winbladh A, Gullstrand P, Svanvik J, Sandström P. Systematic cystitis in high-risk patients: Percutaneous cholecystostomy vs con- review of cholecystostomy as a treatment option in acute cholecys- servative treatment. Eur Radiol 2002; 12: 1778–84. titis. HPB (Oxford) 2009; 11: 183–93. 11. Yokoe M, Takada T, Strasberg SM, et al. TG13 diagnostic criteria 17. Ambe PC, Kaptanis S, Papadakis M, Weber SA, Jansen S, Zirngibl and severity grading of acute cholecystitis (with videos). J H. The treatment of critically Ill patients with acute cholecystitis. Hepatobiliary Pancreat Sci 2013; 20: 35–46. Dtsch Arztebl Int 2016; 113: 545–51. 12. Mazeh H, Mizrahi I, Dior U, et al. Role of antibiotic therapy in mild 18. Loozen CS, Van Ramshorst B, Van Santvoort HC, Boerma D. Early acute calculus cholecystitis: A prospective randomized controlled cholecystectomy for acute cholecystitis in the elderly population: A – trial. World J Surg 2012;36:1750–59. systematic review and meta-analysis. Dig. Surg 2017; 34: 371 9. 13. STROBE statement - Checklist of items that should be included in 19. Kortram K, van Ramshorst B, Bollen TL, et al. Acute cholecystitis reports of observational studies (STROBE Initiative). Int J Public in high risk surgical patients: percutaneous cholecystostomy versus Health 2008; 53: 3–4. laparoscopic cholecystectomy (CHOCOLATE trial): study protocol for a randomized controlled trial. Trials 2012; 13: 7. 14. Boland GW, Lee MJ, Leung J, Mueller PR. Percutaneous 20. Paajanen H. Laparoscopic cholecystectomy or conservative treatment cholecystostomy in critically ill patients: Early response and in the acute cholecystitis of the elderly patients. November 25, 2016. final outcome in 82 patients. Am J Roentgenol 1994; 163: Available at: https://clinicaltrials.gov/ct2/show/NCT02972944? 339–42. term=paajanen&rank=7. Accessed September 07, 2018