Delayed Cholecystectomy for Acute Cholecystitis in Elderly Patients Treated Primarily with Antibiotics or Percutaneous Drainage of the Gallbladder

Abstract

Background:

In high-risk patients with acute cholecystitis, antibiotics with or without percutaneous drainage of the gallbladder followed by delayed cholecystectomy (DC) can be performed. This study aimed to review our current management of elderly patients with acute cholecystitis treated with DC.

Methods:

All consecutive patients older than 70 with acute cholecystitis treated primarily with antibiotics with or without percutaneous drainage followed by DC between 2006 and 2015 were retrospectively reviewed.

Results:

Overall 105 elderly patients had acute cholecystitis with planned DC. Ninety-three patients had antibiotherapy alone at first. Twenty-eight patients needed percutaneous drainage either in intention to treat (n = 12) or due to failure of antibiotic treatment (n = 16). Nine (32%) versus 11 patients (12%) required an emergency cholecystectomy (EC) due to failure of percutaneous drainage or antibiotic treatment, respectively. Eighteen patients (64%) underwent DC after percutaneous drainage. Postoperative morbidity was 39% (7/18) after DC in the percutaneous drainage group, and 1 patient died. Compared to DC after antibiotherapy (n = 53), elderly patients who underwent DC after percutaneous drainage (n = 18) had longer median hospital stay (10 days versus 3 days, P = .001) and higher postoperative complications (7/18 versus 6/53, P = .015).

Conclusion:

In elderly patients with acute cholecystitis, DC can be a good alternative to EC. However, after percutaneous drainage DC is associated with high complication rate and long hospital stay.

Introduction

The management of acute cholecystitis is still debated in the high-risk elderly patients with potential increased risk of morbidity after emergency cholecystectomy (EC).^1–3 Laparoscopic cholecystectomy is now recognized as the gold standard to treat acute cholecystitis, with proven lower morbidity and mortality rates than with open approach.^4,5 Several recent studies even concluded that laparoscopic cholecystectomy should be offered to everyone with acute cholecystitis regardless of age, unless the surgical risk is deemed too high.^2,6

Percutaneous drainage has been proposed as alternative to EC in high-risk population with acute cholecystitis, as it allows controlling the infection source without the risk of an operative procedure under general anesthesia.^7,8 Success rates to treat ongoing sepsis despite antibiotics have been shown to be more than 75% with complication rate generally lower than 10%.^8–12 Definitive treatment with cholecystectomy is still necessary after the acute episode to avoid recurrence, especially in case of acute calculous cholecystitis.¹³ Several studies compared the outcome of EC to the outcome of percutaneous drainage.^8,14 However, data assessing the outcome after delayed cholecystectomy (DC) in elderly patients who underwent percutaneous drainage to treat the initial episode of acute cholecystitis are scarce.

The aim of this study was to review our current practice of DC after antibiotics with or without percutaneous drainage in high-risk elderly patients with acute cholecystitis.

Material and Methods

Patients

All consecutive patients older than 70 years treated for acute calculous or acalculous cholecystitis and planned for DC between January 2006 and December 2015 were retrospectively analyzed. Patients with additional pancreatitis or cholangitis were excluded. Medical charts, radiological, surgical, and pathological data were reviewed to analyze pre-/intraoperative and postoperative outcomes before and after DC. The Charlson comorbidity index was calculated for each patient.¹⁵

Success of initial treatment (antibiotherapy or percutaneous drainage) was defined as improvement in clinical (reduction of abdominal tenderness, pain, and fever) and biological signs (reduction of leukocytosis and C-reactive protein of at least 25%) 24 hours after the initial treatment. Recurrence of acute cholecystitis was defined as reappearance of symptoms and signs of acute cholecystitis after initial treatment success. In case of recurrence, EC was performed.

Diagnosis of acute cholecystitis

Acute cholecystitis diagnosis was based on patient's history, clinical signs (i.e., positive Murphy's sign, fever >38°C, and pain in the right upper quadrant), laboratory findings (C-reactive protein >10 mg/L and leukocytes >10 g/L), and positive imaging (computed tomography or ultrasound). Acute cholecystitis was defined on imaging as a 10 cm enlargement of the anteroposterior gallbladder axis and a gallbladder wall thickening >3 mm.

Antibiotherapy

All patients diagnosed with acute cholecystitis were given intravenous antibiotherapy according to the institutional guidelines based on local bacterial epidemiology and germ sensitivity. First-choice antibiotic was amoxicillin–clavulanic acid. The antibiotherapy was tailored according to the severity of the infection and the risk of resistant pathogen. The therapy was administered for at least 5 days and then reevaluated according to the evolution of the clinical status and biological parameters (C-reactive protein and white blood cell count). Patients who failed antibiotic treatment underwent either EC or percutaneous drainage.

Percutaneous drainage

Indications for percutaneous drainage were failure to control cholecystitis sepsis despite the use of antibiotherapy or high-risk patients for general anesthesia with severe sepsis. High-risk patients were defined as patients with advanced cardiomyopathy, pneumopathy, or other severe comorbidities contraindicating general anesthesia.

Percutaneous drainage was performed under local anesthesia by an experimented and board certified radiologist. After percutaneous transhepatic puncture of the gallbladder under US or CT guidance, an 8-French Autolock catheter (Boston Scientific, Natick, MA) was inserted using the standard Seldinger technique. Percutaneous drainage was always associated with antibiotherapy. The catheter was removed after resolution of the cholecystitis sepsis and after cholecystography to exclude cystic duct obstruction. In case of cystic duct obstruction, the drain was left in place until cholecystectomy. In case of percutaneous drainage failure, EC was performed.

Cholecystectomy

DC was performed at least 6 weeks after acute cholecystitis to allow resolution of the inflammation. While open cholecystectomy was performed using a subcostal incision, a three-trocar technique was the standard approach for laparoscopic cholecystectomy. In all cases, the gallbladder was removed in toto, i.e., no subtotal cholecystectomy was performed. Intraoperative cholangiography was only selectively performed in case of suspicion of common bile duct obstruction or biliary anatomical variations. Specimens were sent for routine pathological examination.

Postoperative complications were graded according to Dindo-Clavien classification.¹⁶ Major complications were classified as grade III-IV, while minor complications as grade I-II.¹⁶ Mortality (grade V) was defined as any death occurring during the hospital stay and up to 90 days after the operative day.¹⁶ The comprehensive complication index (CCI) was also used to assess the overall surgical complications of single patients.¹⁷

Statistical analyses

For continuous variables, a Mann–Whitney U test or Student's t-test was used depending on the normality of the distribution and homogeneity of the variances. For discrete variables, a Fisher's exact test was performed. A P value <.05 was considered statistically significant. All statistical analyses were performed using GraphPad Prism^© 5.0 for Mac OS X.

The study was approved by the internal institutional review board (ID number 437/15).

Results

Patients

A total of 105 elderly patients had acute cholecystitis with planned DC during the study period. Among them, 12 had percutaneous drainage in intention to treat at the time of admission for acute cholecystitis, and 93 had antibiotherapy alone. Overall, 19% of patients (20/105) required an EC due to conservative treatment failure. Among the 93 patients with antibiotherapy, 27 had treatment failure: 16 underwent percutaneous drainage and 11 underwent EC. The flowchart of the included patients is summarized in Figure 1.

FIG. 1.

Flowchart of the study patients.

Outcome of percutaneous drainage

Demographic data of patients with percutaneous drainage and percutaneous drainage outcome are summarized in Table 1. Twelve patients (43%) presented with acalculous cholecystitis, and 6 patients (21%) were admitted in the intensive care unit. Median initial length of stay was 26 days (interquartile range [IQR] 15–48). Complications after percutaneous drainage occurred in 8 patients (29%). Median drainage time after percutaneous drainage was 14 days (IQR 8–20). In the 28 patients who had percutaneous drainage, 9 patients (32%) had failure of the percutaneous drainage and underwent EC. Nineteen patients had successful percutaneous drainage. Among them, 1 had recurrent symptoms and needed EC, while the other 18 patients underwent DC.

Table 1.

Demographics, Etiology, Length of Primary Stay, and Postdrainage Complications of the 28 Patients Who Underwent Percutaneous Drainage (12 in Intention to Treat and 16 After Antibiotic Failure)

	Percutaneous drainage
	n = 28
Gender, men/women	14/14
Age, years [median (IQR)]	77 (73–87)
Cardiomyopathy	1
Renal failure	14
Diabetes	8
Obesity	3
COPD	10
Hypertension	17
Charlson comorbidity index [median (IQR)]	4 (3–5)
Acalculous cholecystitis	12
Patients admitted in ICU	6
Length of hospital stay, days [median (IQR)]	26 (15–48)
Complications	8
Failure	9

Complications of the percutaneous drainage encompassed drain malposition/displacement (3), bleeding (3), biliary leak (1), and ileus (1).

COPD, chronic obstructive pulmonary disease; ICU, intensive care unit; IQR, interquartile range.

Outcome of DC after percutaneous drainage

Median time from percutaneous drainage to DC was 91 days (IQR 20–112). Preoperative characteristics, intraoperative data, and postoperative outcomes of the 18 patients who underwent DC after percutaneous drainage compared to the 53 patients who underwent DC after initial antibiotherapy are shown in Table 2. Patients with DC after percutaneous drainage had more renal failures (9/18 versus 11/53, P = .031), more chronic obstructive pulmonary diseases (5/18 versus 1/53, P = .003), more acalculous cholecystitis (7/18 versus 1/53, P < .001), and were more often admitted in the intensive care unit (5/18 versus 0/53, P < .001).

Table 2.

Preoperative Characteristics and Intra- and Postoperative Outcomes of Patients Who Underwent Delayed Cholecystectomy After Percutaneous Drainage (n = 18) Compared to Patients Who Underwent Delayed Cholecystectomy After Initial Antibiotherapy (n = 53)

	Percutaneous drainage	Antibiotics
	n = 18	n = 53	P
Gender, men/women	10/8	32/21	.785
Age, years [median (IQR)]	74 (73–84)	79 (73–81)	.407
Cardiomyopathy	1	0	.254
Renal failure	9	11	.031
Diabetes	6	13	.542
Obesity	1	6	.669
COPD	5	1	.003
Hypertension	11	26	.424
Charlson comorbidity index [median (IQR)]	4 (3–6)	4 (3–5)	.492
Acalculous cholecystitis	7	1	<.001
Patients admitted in ICU	5	0	<.001
Length of initial hospital stay, days [median (IQR)]	27 (16–46)	6 (3–10)	<.001
Length of second hospital stay, days [median (IQR)]	10 (3–29)	3 (2–4)	.001
Operative time, minutes [median (IQR)]	103 (77–165)	97 (72–136)	.273
Open/laparoscopy	4/14	0/53	.003
Conversion to laparotomy	2	0	.041
Morbidity rate	7	6	.015
Minor complications	4	5	.218
Major complications	3	1	.048
Mortality	1	0	.254
CCI (mean ± standard deviation)	14.0 ± 26.7	1.8 ± 5.6	.006

Significant p-values appear in bold.

CCI, comprehensive complication index; COPD, chronic obstructive pulmonary disease; ICU, intensive care unit; IQR, interquartile range.

The initial and second lengths of stay were both longer in the percutaneous drainage group. Laparoscopy was performed more often in the antibiotic group (14/18 versus 53/53, P = .003). The two conversions from laparoscopy to laparotomy in the percutaneous drainage group were due to adhesions secondary to previous abdominal surgery. The morbidity rate was higher in the percutaneous drainage group (7/18 versus 6/53, P = .015) with more major complications (3/18 versus 1/53, P = .048, percutaneous drainage group: 1 bilioma, 2 respiratory failures, antibiotic group: 1 pleural effusion). Mean CCI was 14.0 ± 26.7 in the percutaneous drainage group and 1.8 ± 5.6 in the antibiotic group (P = .006). The death in the percutaneous drainage group was due to multiple organ failure.

Outcome of EC

Table 3 summarizes the preoperative and intraoperative data and postoperative outcomes of patients who had EC after antibiotherapy (n = 24) or percutaneous drainage (n = 10) in case of initial treatment failure or recurrence of symptoms. Patients in the percutaneous drainage group had more renal failures (5/10 versus 3/24, P = .031) and a longer median total hospital stay (26 days versus 15 days, P = .028). Complication rates were similar between both groups.

Table 3.

Preoperative Characteristics and Intra- and Postoperative Outcomes of Patients Who Underwent Emergency Cholecystectomy After Percutaneous Drainage (n = 10) Compared to Patients Who Underwent Emergency Cholecystectomy After Antibiotherapy (n = 24)

	Percutaneous drainage	Antibiotics
	n = 10	n = 24	P
Gender, men/women	4/6	10/14	1
Age, years [median (IQR)]	83 (73–90)	78 (72–86)	.609
Cardiomyopathy	0	0	1
Renal failure	5	3	. 031
Diabetes	2	2	.564
Obesity	2	1	.201
COPD	4	4	.195
Hypertension	6	9	.276
Charlson comorbidity index [median (IQR)]	4 (3–4)	4 (3–5)	.937
Acalculous cholecystitis	5	4	.085
Patients admitted in ICU	1	0	.294
Length of total hospital stay, days [median (IQR)]	26 (18–54)	15 (7–27)	.028
Operative time, minutes [median (IQR)]	97 (81–112)	96 (64–122)	1
Open/laparoscopy	4/6	2/22	.048
Conversion to laparotomy	2	4	.581
Morbidity rate	6	13	1
Minor complications	2	6	1
Major complications	4	7	1
Mortality	1	1	.508
CCI (mean ± standard deviation)	30.6 ± 34.7	17.1 ± 23.5	.383

Significant p-values appear in bold.

Discussion

The results of the present study showed that DC can be a good alternative to EC in elderly patients. However, 19% of patients may need an EC due to treatment failure. In addition, after percutaneous drainage, DC is associated with substantial morbidity and long hospital stay.

In patients who had percutaneous drainage followed by DC, postoperative complications developed in 39% of the cases compared to 11% in the antibiotic group. CCI after DC was also significantly higher in the percutaneous drainage group. Postoperative minor complications were similar, but major complications were higher in the percutaneous drainage group (3/18 versus 1/53, P = .048), mainly related to bilioma (bile leak from vesicular bed that spontaneously resolved after radiological drainage) and respiratory failures, whereas in the antibiotic group only one pleural effusion was observed. Only few data analyzing the outcome of DC after percutaneous drainage in critically ill or old patients have been published.

Morse et al. retrospectively collected 50 critically ill patients who had DC after percutaneous drainage.¹⁸ Inclusion criteria were admission to the intensive care unit for acute cholecystitis, patients judged unfit for general anesthesia at admission, and placement of a cholecystostomy tube. The mean age was 72 ± 11 years. Out of these 50 patients, 25 died during the first 30 days. Among the remaining 25 patients, only 11 underwent DC. After DC, 2 major complications (2/11) appeared (bile leakage and common bile duct injury), corroborating our findings.

Another study by Kim et al. reported that postoperative morbidity was only 5% in patients undergoing DC after percutaneous drainage.¹⁹ Conversion from laparoscopic to open cholecystectomy was 3%.¹⁹ These low morbidity and conversion rates are in contrast with the findings of the present study. However, in the latter study, the cholecystostomy tube was left in place until surgery for most of the patients, compared to the present study where median time of percutaneous drainage removal was 14 days.¹⁹ Of note, our protocol includes a cholecystography through the cholecystostomy tube before removal of the drain. This imaging aims to exclude any occlusion of the cystic duct, which would contraindicate the removal of the drainage. This is an important issue in the management of patients with percutaneous drainage to prevent recurrent symptoms and/or complications.

Despite a longer hospital stay related to patients' comorbidities, EC after percutaneous drainage failure was associated with similar postoperative complications (13/24 = 54% versus 6/10 = 60%, P = 1.000) compared to EC after antibiotic treatment failure. Karakayali et al. showed that EC after antibiotherapy failure had a mean postoperative hospital stay of 5.3 ± 3.3 days and a postoperative morbidity of 35% (17/48).²⁰ Of note, all patients in the latter study were ASA I or II compared to the present study cohort of relatively ill patients (median Charlson comorbidity index of 4), which can explain the difference in postoperative complication rates. In the present study, percutaneous drainage failed to treat sepsis in 32% (9/28) of patients, and all underwent successful EC.

The duration of drainage and timing of DC to avoid recurrence is not well established.²¹ In a previous study, the cholecystostomy tube was left in place until the time of surgery, which was performed usually 3 weeks after percutaneous drainage (median of 19 days), with acceptable postoperative morbidity (5%).¹⁹ A study by Han et al. compared early cholecystectomy versus DC after percutaneous drainage.²² Early cholecystectomy performed at an average of 1.7 days after percutaneous drainage had a trend toward longer operative time and significantly higher complications, but total hospital stay was shorter compared to DC.²² In the present study, only planned DC was performed after percutaneous drainage with a median time to DC of 91 days.

We can assume that percutaneous drainage, probably depending on the drainage duration, induces an inflammatory reaction in the gallbladder bed and the Calot triangle with potential of adhesion creation, making DC more challenging and therefore more at risk of postoperative complications. The precise timing for DC and percutaneous drainage duration is not well established yet. Some studies have advocated the only use of gallbladder aspiration without drainage to reduce the risks of a long-standing drainage tube.²³ This method has been shown to be safe and efficient.²³

The present study has two limitations. First, this is a retrospective study with its inherent risks of bias (data collection in patients' charts, missing data, and loss of follow-up). Second, the percutaneous drainage group included patients who had percutaneous drainage in intention to treat and patients who failed antibiotherapy, but this reflects the current practice.

To conclude, DC can be a good alternative to EC in elderly patients with severe comorbidities. However, one fifth of patients may require an EC due to conservative treatment failure. In addition, after percutaneous drainage DC may induce high morbidity and long length of hospital stay.

Footnotes

Acknowledgments

This study did not receive any particular funding.

Ethical Approval

The subjects have given their informed consent, and the study protocol has been approved by the local ethics committee.

Authors' Contributions

G.R.J.: analysis and interpretation of the data, drafting of the article, final approval of the last article version, and agreement to be accountable for all aspects of the work.

G.L.: design of the study, acquisition and analysis of the data, drafting of the article, final approval of the last article version, and agreement to be accountable for all aspects of the work.

C.D.: acquisition of the data, critical revision of the article, final approval of the last article version, and agreement to be accountable for all aspects of the work.

A.D.: design of the study, critical revision of the article, final approval of the last article version, and agreement to be accountable for all aspects of the work.

N.D.: design of the study, critical revision and editing of the article, final approval of the last article version, and agreement to be accountable for all aspects of the work.

E.M.: design of the study, analysis and interpretation of data, critical revision and editing of the article, final approval of the last article version, and agreement to be accountable for all aspects of the work.

Disclosure Statement

No competing financial interests exist.

References

Riall

, Zhang

, Townsend

, Kuo

Y-F

, Goodwin

. Failure to perform cholecystectomy for acute cholecystitis in elderly patients is associated with increased morbidity, mortality, and cost. J Am Coll Surg, 2010; 210:668–679.

García-Alonso

, de Lucas Gallego

, Bonillo Cambrodón

, Algaba

, de la Poza

, Martín-Mateos

, et al. Gallstone-related disease in the elderly: Is there room for improvement?. Dig Dis Sci, 2015; 60:1770–1777.

Gurusamy

, Rossi

, Davidson

. Percutaneous cholecystostomy for high-risk surgical patients with acute calculous cholecystitis. Cochrane Database Syst Rev, 2013; 12:CD007088.

Bingener

, Richards

, Schwesinger

, Strodel

, Sirinek

. Laparoscopic cholecystectomy for elderly patients: Gold standard for golden years?. Arch Surg, 2003; 138:531–535.

N-J

, Han

H-S

, Min

S-K

. The safety of a laparoscopic cholecystectomy in acute cholecystitis in high-risk patients older than sixty with stratification based on ASA score. Minim Invasive Ther Allied Technol, 2006; 15:159–164.

Winbladh

, Gullstrand

, Svanvik

, Sandström

. Systematic review of cholecystostomy as a treatment option in acute cholecystitis. HPB (Oxford), 2009; 11:183–193.

Suzuki

, Bower

, Cassaro

, Patel

, Karpeh

, Leitman

. Tube cholecystostomy before cholecystectomy for the treatment of acute cholecystitis. JSLS, 2015; 19:e2014.00200.

Melloul

, Denys

, Demartines

, Calmes

J-M

, Schäfer

. Percutaneous drainage versus emergency cholecystectomy for the treatment of acute cholecystitis in critically ill patients: Does it matter?. World J Surg, 2011; 35:826–833.

Jang

, Lim

, Joo

, Cha

, Shin

, Joo

. Outcome of conservative percutaneous cholecystostomy in high-risk patients with acute cholecystitis and risk factors leading to surgery. Surg Endosc, 2015; 29:2359–2364.

10.

Vázquez Tarragón

, Azagra Soria

, Lens

, Manzoni

, Fabiano

, Goergen

. Two staged minimally invasive treatment for acute cholecystitis in high risk patients. Hepatogastroenterology, 2013; 60:466–469.

11.

Koebrugge

, van Leuken

, Ernst

, van Munster

, Bosscha

. Percutaneous cholecystostomy in critically ill patients with a cholecystitis: A safe option. Dig Surg, 2010; 27:417–421.

12.

Kortram

, de Vries Reilingh

, Wiezer

, van Ramshorst

, Boerma

. Percutaneous drainage for acute calculous cholecystitis. Surg Endosc, 2011; 25:3642–3646.

13.

McKay

, Abulfaraj

, Lipschitz

. Short- and long-term outcomes following percutaneous cholecystostomy for acute cholecystitis in high-risk patients. Surg Endosc, 2012; 26:1343–1351.

14.

Rodríguez-Sanjuán

, Arruabarrena

, Sánchez-Moreno

, González-Sánchez

, Herrera

, Gómez-Fleitas

. Acute cholecystitis in high surgical risk patients: Percutaneous cholecystostomy or emergency cholecystectomy?. Am J Surg, 2012; 204:54–59.

15.

Charlson

, Pompei

, Ales

, MacKenzie

. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis, 1987; 40:373–383.

16.

Dindo

, Demartines

, Clavien

P-A

. Classification of surgical complications: A new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg, 2004; 240:205–213.

17.

Slankamenac

, Nederlof

, Pessaux

, de Jonge

, Wijnhoven

, Breitenstein

, et al. The comprehensive complication index: A novel and more sensitive endpoint for assessing outcome and reducing sample size in randomized controlled trials. Ann Surg, 2014; 260:757–762.

18.

Morse

, Smith

, Lawdahl

, Roettger

. Management of acute cholecystitis in critically ill patients: Contemporary role for cholecystostomy and subsequent cholecystectomy. Am Surg, 2010; 76:708–712.

19.

Kim

, Ho Son

, Yoo

, Ho Shin

. Impact of delayed laparoscopic cholecystectomy after percutaneous transhepatic gallbladder drainage for patients with complicated acute cholecystitis. Surg Laparosc Endosc Percutan Tech, 2009; 19:20–24.

20.

Karakayali

, Akdur

, Kirnap

, Harman

, Ekici

, Moray

. Emergency cholecystectomy vs percutaneous cholecystostomy plus delayed cholecystectomy for patients with acute cholecystitis. Hepatobiliary Pancreat Dis Int, 2014; 13:316–322.

21.

Yuval

, Mizrahi

, Mazeh

, Weiss

, Almogy

, Bala

, et al. Delayed laparoscopic cholecystectomy for acute calculous cholecystitis: Is it time for a change?. World J Surg, 2017; 41:1762–1768.

22.

Han

, Jang

J-Y

, Kang

, Lee

, Kim

S-W

. Early versus delayed laparoscopic cholecystectomy after percutaneous transhepatic gallbladder drainage. J Hepato-Biliary-Pancreat Sci, 2012; 19:187–193.

23.

Chung

, Kim

, Tae

, Choi

, Ko

, et al. Clinical usefulness of percutaneous transhepatic gallbladder aspiration in patients with acute calculous cholecystitis. J Clin Gastroenterol, 2013; 47:288–290.