Retrospective Analysis of Non-Surgical Treatment of Acute Cholecystitis

Abstract

Background:

Worldwide, acute cholecystitis is a common disease. The current standard of treatment is according to the Tokyo Guidelines established in 2018. Conservative management with various combinations of analgesics, anti-inflammatory drugs, and percutaneous drainage are sometimes used to avoid or delay surgery, especially in frail patients, but little is known about the efficacy and safety of these strategies. Therefore, we evaluated the effect of antibiotic agents, with or without gallbladder drainage, or symptomatic treatment alone in patients with acute cholecystitis who were considered unfit for acute surgery.

Patients and Methods:

All patients whose initial treatment for cholecystitis was conservative who were admitted between 2014 and 2016 were included in this study. Patients were divided into three groups: those treated with antibiotic agents, those who received antibiotic agents in combination with percutaneous gallbladder drainage and those whose treatment was only symptomatic. Demographic characteristics, comorbidities, Tokyo Severity Classification, length of stay, re-admission rates, secondary treatment (delayed drainage or surgery), and complication rates were retrieved from their medical records.

Results:

Initially 33 were treated with conservative methods in this period. Fifteen patients were treated initially with antibiotic agents, 12 patients with antibiotic agents in combination with percutaneous drainage, and 6 patients received symptomatic treatment only. One patient had mild cholecystitis (Tokyo Severity Classification grade I) and the other 32 patients had moderate to severe (grade II or III) cholecystitis. Eventually, 25 patients (76%) underwent cholecystectomy, 2 of whom (8%) were emergency operations because of disease progression. Twelve patients (36%) were re-admitted, of whom the majority (83%) was re-admitted before cholecystectomy.

Conclusion:

Treatment of cholecystitis with antibiotic agents, drainage, or analgesic agents is feasible. However, it should be regarded as a bridge to surgery rather than a definitive solution because of frequent recurrence. Occasionally, an emergency operation could not be avoided as a result of disease progression under conservative treatment.

Worldwide, acute cholecystitis is a common disease and its incidence is increasing [1 –4]. Traditionally, the treatment consisted of a cholecystectomy that was either performed within three days of the onset of symptoms or six weeks after the resolution of symptoms. Presently, the treatment strategy preferably follows the Tokyo Guidelines that were established in 2018 [5,6]. Negative predictive factors, such as a high American Society of Anaesthesiologists (ASA) classification, Charlson comorbidity index, and organ system failure are used to determine the use of percutaneous gallbladder drainage or operation. In high-risk patients, the management of acute cholecystitis remains controversial. Moreover, it is not uncommon that the medical information, required to apply the Tokyo Guidelines, is incomplete and not available in the acute setting. Therefore, some perform percutaneous gallbladder drainage in combination with antibiotic agents to control the inflammation and then perform a delayed cholecystectomy. There is limited evidence to support conservative management as a safe alternative to surgery in patients with uncomplicated acute cholecystitis [7 –9]. Therefore, we evaluated the effect of antibiotic agents with or without drainage, or symptomatic treatment only, of acute cholecystitis, in patients who were referred to our tertiary referral center and in whom immediate surgery was believed to be ill advised.

Patients and Methods

A retrospective cohort study of consecutive patients who underwent non-operative treatment for cholecystitis between 2014 and 2016 in the Radboud Medical Centre, a university hospital in The Netherlands, was performed. The study has been carried out in accordance with the applicable rules regarding the review of research ethics committees and has been reported in line with the STROCSS criteria.

All adult patients with a cholecystitis whose initial treatment was conservative were identified. All patients who met all three criteria of the Tokyo Guideline Classifications 2018, i.e., local signs of inflammation, systemic signs of inflammation, and imaging findings were enrolled in the study. These patients were subdivided into three groups. The first group was treated with antibiotic agents alone, the second group with percutaneous gallbladder drainage (within 72 hours) as well as antibiotic agents. The third group comprised patients who were treated symptomatically with analgesics.

Demographic characteristics, comorbidities, ASA classification, Tokyo Severity Classification, length of hospitalization, re-admission rates, subsequent treatment (delayed drainage or surgery), and complication rates were retrieved from their medical records. The reasons to avoid acute cholecystectomy were noted. Data were extracted independently and cross-checked by three authors (E.R.I.J., T.H., T.N.). Statistical analysis was performed using the SPSS statistical software package (version 24, SPSS Inc., Chicago, IL).

Results

Between 2014 and 2016, 102 records were marked as acute cholecystitis in the hospital database. Immediate cholecystectomy was performed in 69 patients. Thirty-three patients were treated non-operatively and used for the present study: 15 patients (45%) received initial treatment with antibiotic agents alone, 12 patients (36%) with antibiotic agents and percutaneous drainage, and six patients (18%) received symptomatic treatment. The characteristics of these groups are presented in Table 1.

Table 1.

Patient Characteristics

	Antibiotic agents	Antibiotic agents + drainage	Symptomatic	Total
	(n = 15)	(n = 12)	(n = 6)	(n = 33)
Age (y)	70 ± 10	70 ± 9	50 ± 16	68 ± 13
Sex
Male	10 (67)	10 (83)	4 (67)	24 (73)
Female	5 (33)	2 (17)	2 (33)	9 (27)
Tokyo Severity Classification
Mild (grade I)			1 (17)	1 (3)
Moderate (grade II)	10 (67)	4 (33)	5 (83)	19 (58)
Severe (grade III)	5 (33)	8 (67)		13 (39)
Comorbidities
Cardiac/pulmonary	10 (67)	10 (83)	4 (67)	24 (73)
Cancer	7 (47)	5 (42)	1 (17)	13 (39)
Diabetes	2 (13)	1 (8)	1 (17)	4 (12)
Obesity	9 (60)	7 (58)	4 (67)	20 (61)
ASA classification
2	3 (20)	6 (50)	3 (50)	12 (36)
3	8 (53)	5 (42)	1 (17)	14 (42)
4	1 (7)	1 (8)		2 (6)
Not determined	3 (20)		2 (33)	5 (15)

Values are numbers (percentages) unless stated otherwise.

The average age was 68 years. There were 24 males and nine females. Comorbidity of the cardiac or pulmonary system was present in 24 patients (73%), cancer (previous or current) in 13 patients (39%), diabetes in four patients (12%), and obesity in 20 patients (61%). Patients were marked as having mild, moderate, or severe acute cholecystitis according to the Tokyo Severity Classification. One patient had a mild cholecystitis. In the absence of pain and fever on presentation, symptomatic treatment with delayed surgery was chosen. The remaining 32 patients had a moderate or severe cholecystitis. The reasons not to perform an acute cholecystectomy in these patients are shown in Table 2. In 13 patients, comorbidity led to the determination that their surgical risk was elevated to such extent that surgery was to be avoided, at least in the acute setting. Twelve patients had their symptoms of acute cholecystitis for at least 72 hours. Four patients (12%) had recent cardiac surgery or interventions and three patients (9%) recent endoscopic retrograde cholangiopancreatography (ERCP) rendered acute cholecystectomy contraindicated.

Table 2.

Reasons Not To Perform Acute Cholecystectomy

	Antibiotic agents	Antibiotic agents + drainage	Symptomatic	Total
	(n = 15)	(n = 12)	(n = 6)	(n = 33)
Symptoms >72 h	4 (27)	4 (33)	4 (67)	12 (36)
Comorbidity/previous medical history	5 (33)	7 (58)	1 (17)	13 (39)
Local inflammation	3 (20)	1 (8)		4 (12)
Hematologic comorbidity	2 (13)			2 (6)
Age	1 (7)			1 (3)
No symptoms on presentation and grade I Tokyo Severity Classification			1 (17)	1 (3)

Values are numbers (percentages) unless stated otherwise.

Twenty-five of 33 patients (76%) still underwent a cholecystectomy despite the initial choice for some kind of conservative treatment. In 23 cases an urgent or emergency cholecystectomy was avoided, and the operation could be performed in an elective setting after suitable further analysis and preparation. Two patients, both treated with antibiotic agents only, still needed emergency surgery because of disease progression.

Twelve patients were re-admitted after discharge from the hospital. Ten patients (83%) were re-admitted before an elective cholecystectomy was performed. Two patients were re-admitted after surgery, one because of bile leakage and another with an abdominal abscess.

Initial treatment with antibiotic agents

Fifteen patients were initially treated with antibiotic agents. Of these, five patients (33%) received additional treatment with percutaneous gallbladder drainage after an average of 17 days because their symptoms did not resolve sufficiently. The duration of drainage varied between nine and 176 days. A cholecystectomy was performed in 13 patients (87%) including all patients who received percutaneous drainage. All operations could be performed in an elective setting. The average time from drainage to surgery was 87 days. In two patients no cholecystectomy was performed: one patient was inoperable, even in the elective setting, because of comorbidity. In one other patient further treatment was omitted after common bile duct clearance was obtained by ERCP. All re-admissions in this group were for sequelae of gallstones, either recurrent cholecystitis (5 patients) or colics (1 patient; Table 3).

Table 3.

Outcomes Grouped by Initial Treatment

Intention to treat	Antibiotic agents	Antibiotic agents + drainage	Symptomatic	Total	P
Intention to treat	(n = 15)	(n = 12)	(n = 6)	(n = 33)	P
Length of stay (d)	7 (3–12)	9 (4–26)	1 (0–3)	7 (0–26)	0.003
Drain	5 (33%)	12 (100%)	0 (0%)	17 (52)	<0.001
Days from presentation at emergency department to drainage (mean)	17 (3–41)	1 (0–2)		6 (0–41)	0.002
Days of drainage (mean)	73 (9–176)	55 (9–125)		60 (9–176)	NS
Surgery
Elective	11 (73%)	8 (67%)	4 (67 %)	23 (69%)
Emergency^a	2 (13%)	—	—	2 (6%)
Total operated	13 (87%)	8 (67%)	4 (67%)	25 (76%)	NS
Managed conservatively	2 (13%)	4 (33%)	2 (33%)	8 (24%)
Type of cholecystectomy
Laparoscopic	10 (77%)	6 (75%)	2 (50%)	18 (75%)
Converted to open surgery	3 (23%)	1 (8%)	2 (50%)	6 (18%)
Open surgery	—	1 (8%)	—	1 (4%)
Complications
Biloma	1 (6%)	1 (8%)	1 (17%)	3 (9%)
Bleeding	2 (13%)			2 (6%)
Days from initial presentation to surgery	86 (2–217)	102 (56–147)	68 (50–102)	88 (2–217)	NS
Days from drainage to surgery	87 (41–176)	99 (54–147)		94 (41–176)	NS
Reasons for readmission
Abscess		2 (17%)		2 (6%)
Recurrent cholecystitis	5 (33%)	1 (8%)		6 (18%)
Symptomatic gallstones	1 (7%)			1 (3%)
Biloma			1 (17%)	1 (3%)
Other drain related issues		3 (25%)		3 (9%)
Pneumonia		1 (8%)		1 (3%)
Total	6 (40%)	5 (42%)^b	1 (17%)	12 (36%)	NS

Because of disease progression.

Two patients were re-admitted because of fever or abscess in combination with drain-related issues.

NS = not significant.

Initial treatment with antibiotic agents and percutaneous drainage

Twelve patients began antibiotic agents on admission and received percutaneous gallbladder drainage within 72 hours after presentation. The time during which the drain was kept in varied from nine to 125 days, with an average of 55 days. Sixty-seven percent in this group were scheduled for elective cholecystectomy. In two patients only duct clearance by ERCP was obtained and further surgery avoided. Another two patients were found unfit for elective surgery because of comorbidity and one patient was not eligible surgery because of disseminated malignant disease. In this group, re-admission was necessary in five patients (42%), three of whom had drain-related issues (Table 3).

Symptomatic treatment

In this group of six patients, no additional treatment with antibiotic agents, gallbladder drainage, or ERCP was necessary during the further course. All patients were advised to undergo a delayed cholecystectomy. One patient declined the elective operation and has remained symptom-free for four years; one patient was lost to follow-up before a cholecystectomy could be performed. In four of six patients, a laparoscopic cholecystectomy was performed of which two procedures were converted to open surgery. One patient was re-admitted with epigastric pain and fever three days after surgery because of a symptomatic biloma that resolved spontaneously (Table 3).

Discussion

The aim of this study was to evaluate the various forms of conservative treatment of cholecystitis: treatment with antibiotic agents alone, antibiotic agents combined with percutaneous drainage, or symptomatic treatment with analgesic agents only. Are these options safe and effective to delay surgery in patients with acute cholecystitis in whom acute cholecystitis is contraindicated, either by the general condition of the patient or extensive local infiltration? This was approximately one-third of the total caseload in the study period, which is explained by the setting being a university hospital that deals almost exclusively with tertiary referrals and patients with severe comorbidity and rarely deals with patients whose cholecystitis is the only medical problem.

In this cohort of 33 patients whose initial treatment was conservative, cholecystectomy was performed in 25 patients (76%), and only two of those patients underwent an acute procedure as a result of disease progression, both in the group with antibiotic treatment only. Fifteen patients were treated initially with antibiotic agents. However, five of 15 patients still underwent percutaneous drainage as a result of disease progression. Thus, antibiotic treatment alone failed in seven (half of the patients). The combination of antibiotic agents and (primary or delayed) gallbladder drainage allowed the avoidance of emergency operations in all 17 patients.

The patient population in this study had many comorbidities. This is reflected by the substantial rate of re-admissions. The duration of admissions was long. The cost of the additional procedures to delay surgery must be outweighed by the anticipated additional morbidity in the case of emergency operations in these vulnerable patients. Although the Dutch Cholecystitis Guideline does not rule out the use of monotherapy with antibiotic agents it does stress the lack of evidence to support such treatment. Moreover, the mechanism of working on the pathophysiologic level is also doubtful as effective concentrations of the antibiotic agents can only be expected in the gallbladder wall, not in the contaminated gallbladder contents nor on the outer surface of the gallbladder when it is layered with a fibrinous exudate [10]. Finally, inflammation, edema, and hemorrhage in the wall are frequently seen microscopically [11]. If the entire gallbladder is edematous, this will also apply to the cystic duct that may lead to complete obstruction and gallbladder empyema. The usual treatment of abscesses and empyema consists of drainage and the additional use of antibiotic agents is disputed, especially in the era of antibiotic stewardship.

Applying this to cholecystitis, we may conclude that, theoretically, it should be treated by removal of the gallbladder or by maintaining adequate drainage. The latter can be achieved by a percutaneous drainage. In cases of sepsis or bacteremia because of acute cholecystitis, the use of antibiotic agents can be expected to contribute to the treatment of the septicemia, not of the underlying cause. In the group in which the initial treatment consisted of antibiotic agents and percutaneous drainage we found results similar to Viste et al. [12]. They concluded that percutaneous gallbladder drainage is a valid alternative for patients with moderate to severe acute cholecystitis. In our study, a cholecystectomy was performed in eight of 12 patients (67%) after initial treatment with antibiotic agents and drainage. All procedures were elective, and none had to be performed because of progression of gallbladder disease. Previous investigators found similar operation rates of 42% and 49% after percutaneous drainage [13,14]. Drain-related complications led to repeated hospitalization of three patients (25%), which is similar to the 23% described by Hjaltadottir et al. [14].

In this study, a total of 12 patients (36%) were re-admitted, which confirms the 35% published by Turino at al. [15]. It was remarkable to note that in the symptomatic treatment group only one patient (17%) was re-admitted, compared with six (40%) and five (42%) re-admissions in the antibiotic treatment group and antibiotic agents combined with percutaneous drainage group, respectivley. Obviously, surgeons did not select the very ill patients to be treated with painkillers alone.

Ten of 12 readmissions happened while patients were waiting for their elective cholecystectomy. This indicates that of the 25 patients who underwent operations, 40% was re-admitted before surgery. Conservative treatment can hardly be regarded as a treatment of cholecystitis: it may be used to avoid acute surgery and elective surgery must not be postponed unduly unless the risk associated with recurrence is believed to be acceptable. Some may argue that cholecystectomy is the gold standard for symptomatic gallstone patients, but expectant management may also represent a valid therapeutic approach [16]. Our results support the accepted view that after cholecystitis the risk of recurrence is substantial although an expectative management may turn out to be successful.

This study is limited by its retrospective character, the small number of patients, an exceptional high prevalence of comorbidity, and, presumably, a substantial bias in the distribution across the various treatment strategies. What is does show is that a combination of antibiotic agents and gallbladder drainage is an effective and safe strategy to avoid emergency surgery for cholecystitis in vulnerable patients.

Footnotes

Funding Information

No funding was received.

Author Disclosure Statement

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this article.

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