Original Paper Received: December 8, 2013 Accepted: March 25, 2014 Published online: September 4, 2014
Digestion 2014;90:75–80 DOI: 10.1159/000362444
Risk Factors and Therapeutic Outcomes of Acute Acalculous Cholecystitis Min Geun Gu Tae Nyeun Kim Jay Song Yoon Jeong Nam Jae Young Lee Jun Suk Park Yeungnam University College of Medicine, Daegu, Korea
Abstract Objective: Acute acalculous cholecystitis (AAC) is traditionally known to occur in critically ill patients and to have a poor prognosis. Although cholecystectomy is usually recommended for treating AAC, nonsurgical management may be a good alternative. The objective of this study was to review the incidence, risk factors, treatment modality, and therapeutic outcomes of AAC compared to acute calculous cholecystitis (ACC). Material and Methods: Data from 69 patients with AAC and 415 patients with ACC between January 2007 and August 2011 were collected. Analysis and comparison of clinicopathological features and therapeutic outcomes between patients with AAC and those with ACC was performed. Results: The number of patients over 50 years of age was significantly higher in the AAC group compared with the ACC group (92.8 vs. 81.7%, p = 0.023). Cerebrovascular accidents were significantly more frequent in patients with AAC than in those with ACC (15.9 vs. 6.7%, p = 0.016). A higher incidence of gangrenous cholecystitis was observed in the AAC group (31.2 vs. 5.6%, p = 0.001). The overall therapeutic outcomes for patients did not differ statistically between the AAC and ACC groups, irrespective of treatment modalities. The recurrence rate after nonsurgical treatment
© 2014 S. Karger AG, Basel 0012–2823/14/0902–0075$39.50/0 E-Mail [email protected] www.karger.com/dig
was significantly lower in the AAC group than in the ACC group (2.7 vs. 23.2%, p = 0.005). Conclusions: The risk of AAC increases in patients with advanced age and cerebrovascular accidents. Incidence of gangrenous cholecystitis was higher in AAC compared to ACC. Nonsurgical treatments such as antibiotics alone or percutaneous cholecystostomy might be effective in selected patients. © 2014 S. Karger AG, Basel
Introduction
Acute acalculous cholecystitis (AAC) denotes inflammation of the gallbladder with no evidence of gallstones in the gallbladder, and includes 2–15% of acute cholecystitis [1, 2]. The pathophysiology of AAC is not completely clear. Several predisposing factors including gallbladder epithelial ischemia and reperfusion injury, positive pressure ventilation, parenteral nutrition, and opioid use have been implicated [3–6]. Compared with acute calculous cholecystitis (ACC), AAC tends to have a more fulminant course and is frequently associated with gangrene, perforation, and empyema, as well as significantly higher morbidity and mortality [2, 7]. Recent reports have documented the development of AAC at home without evidence of acute illness or trauma in 77–90% of the patients [8, 9], and, if diagnosed and treated early, the prognosis was good [10]. Although choTae Nyeun Kim Division of Gastroenterology and Hepatology, Department of Internal Medicine Yeungnam University College of Medicine 317-1 Daemyung 5-dong, Nam-gu, Daegu 705-717 (Korea) E-Mail tnkim @ yu.ac.kr
Downloaded by: Freie Universität Berlin 130.133.8.114 - 5/12/2015 12:17:14 PM
Key Words Acalculous cholecystitis · Cholecystectomy · Cerebrovascular Disorders · Outcomes
Methods We retrospectively reviewed the medical records of 69 patients with AAC and 415 patients with ACC treated at Yeungnam University Hospital between January 2007 and August 2011. The diagnostic criteria for acute cholecystitis were based on clinical history, physical examination, and characteristic image findings on abdominal ultrasonography or CT scan that were compatible with acute cholecystitis. Findings suggesting acute cholecystitis on physical examination included right upper quadrant pain and tenderness, a palpable gallbladder with localized tenderness, and sonographic Murphy’s sign. Imaging findings suggesting acute cholecystitis included gallbladder distention, pericholecystic fluid, and a thickened gallbladder wall. AAC was defined when no stones or sludge were observed in the gallbladder on imaging studies. The exclusion criteria included patients with hepatobiliary malignancy, concomitant acute cholangitis or common duct stones, chronic cholecystitis, and nonspecific gallbladder wall thickening associated with acute pancreatitis, hepatitis, pyelonephritis, peritonitis, ascites, hypoalbuminemia, congestive heart failure, or chronic renal failure. Diagnostic criteria of chronic cholecystitis were based on clinical history of recurrent episodes of biliary pain in the right upper abdomen, impaired gallbladder emptying and thickening of the gallbladder wall, and presence of gallstones on abdominal ultrasonography or CT scan [11]. We included all patients compatible with AAC at the time of diagnosis irrespective of underlying chronic cholecystitis because AAC and AAC on chronic cholecystitis could not be distinguished exactly. As a treatment for AAC, antibiotics were given to all patients. Emergency or urgent cholecystectomy was performed if symptoms did not improve or progression to gallbladder empyema was suspected. In cases with a high risk of surgery due to poor general condition or comorbidities, percutaneous cholecystostomy was performed, and delayed cholecystectomy was performed if possible. Demographic characteristics, clinicopathological features, and therapeutic modality and outcomes between AAC and ACC were analyzed and compared. The study protocol was approved by the institutional review board of our center. SPSS version 20.0 (SPSS Inc., Chicago, Ill., USA) was used for statistical analysis and all data were presented as means ± SD. Pearson’s χ2 test and Fisher’s exact test were used as statistical techniques. p < 0.05 was considered statistically significant.
Results
During the 5-year study period, 484 patients were diagnosed with acute cholecystitis (table 1). Of these, 69 patients (14.3%) fulfilled the criteria for the diagnosis of 76
Digestion 2014;90:75–80 DOI: 10.1159/000362444
Table 1. Baseline characteristics of the patients (n = 484)
Gender (M:F) Age, years (mean ± SD) Age ≥50 Fever (>37.7°C) Abdominal pain Leukocytes >10 K/μl Total bilirubin >1 mg/dl Albumin 35 IU/l ALT >40 IU/l Associated diseases Diabetes Hypertension CVA IHD Location of symptom onset Home Hospital
AAC (n = 69)
ACC (n = 415)
p
47:22 66.9±12.1 64 (92.8) 34 (49.3) 68 (98.6) 34 (49.3) 36 (52.2) 8 (11.6) 34 (49.3) 22 (31.9)
256:159 63.1±15.8 339 (81.7) 222 (53.5) 386 (93.0) 212 (51.1) 244 (58.8) 67 (16.1) 195 (47.0) 145 (34.9)
0.348 0.055 0.023 0.603 0.103 0.796 0.357 0.375 0.795 0.683
16 (23.2) 23 (33.3) 11 (15.9) 7 (10.1)
74 (17.8) 135 (32.5) 28 (6.7) 25 (6.0)
0.316 0.890 0.016 0.292 0.135
61 (88.4) 8 (11.6)
388 (93.5) 27 (6.5)
Values represent n (%) unless otherwise indicated. AST = Aspartate aminotransferase; ALT = alanine aminotransferase; CVA = cerebrovascular accidents; IHD = ischemic heart disease.
AAC. Male predominance was observed in both the AAC group and the ACC group. The male:female ratio was 2.1:1 in the AAC group and 1.6:1 in the ACC group (p = 0.348). The mean age was 66.9 ± 12.1 years in the AAC group and 63.1 ± 15.8 years in the ACC group (p = 0.055). When we analyzed age in the characteristics of patient with ACC and AAC, a significant difference was found at the cutoff value of 50 years of age. The proportion of patients over 50 years of age was significantly higher in the AAC group than in the ACC group (92.8 vs. 81.7%, p = 0.023, OR = 5.297, 95% CI: 1.117–7.372; fig. 1). AAC was a frequent occurrence in patients over 50 years of age and those with cardiovascular or cerebrovascular diseases. Occurrence of cerebrovascular accidents was significantly more frequent in patients with AAC than in those with ACC (15.9 vs. 6.7%, p = 0.016, OR = 2.621, 95% CI: 1.238– 5.550). No significant difference in the clinical features and interval from hospital visit to symptom onset was observed between the AAC group and the ACC group. The percentage of patients who visited the hospital within 3 days after symptom onset was 73.9% for patients with AAC and 74.0% for patients with ACC (p = 1.000). Of the Gu/Kim/Song/Nam/Lee/Park
Downloaded by: Freie Universität Berlin 130.133.8.114 - 5/12/2015 12:17:14 PM
lecystectomy is usually recommended for the treatment of AAC, nonsurgical management may be a good alternative treatment, especially for high-risk patients. The objective of this study was to review the incidence, risk factors, treatment modality, and therapeutic outcomes of AAC compared to ACC.
40 35
AAC ACC
Incidence (%)
30 25 20 15 10 5 0
0–9
10–19
20–29
30–39
40–49
50–59
60–69
70–79
80–89
Age * p = 0.023 100
Age 50
60 40
Fig. 1. Comparison of incidence of acute
20
cholecystitis according to age. The proportion of patients over 50 years of age was significantly higher in the AAC group than in the ACC group.
0
AAC
ACC
69 AAC patients, development of AAC occurred at home in 61 patients (88.4%) and at the hospital in 8 patients (11.6%). Of the 415 patients with ACC, development of ACC occurred at home in 388 patients (93.5%) and at the hospital in 27 patients (6.5%). No significant differences regarding the location of disease development was observed between the two groups (p = 0.135). The histopathological findings of 32 patients with AAC who underwent cholecystectomy revealed gangrenous cholecystitis in 10 patients (31.2%), gallbladder empyema in 10 patients (31.2%), and acute cholecystitis in 12 patients (37.5%). The incidence of gangrenous cholecystitis was significantly higher in the AAC group than in the ACC group (31.2 vs. 5.6%, p = 0.001, OR = 7.647, 95% CI: 3.130–18.685). On the other hand, the histopathological findings of 303 patients with ACC who underwent
cholecystectomy revealed gallbladder empyema in 173 patients (57.0%), acute cholecystitis in 107 patients (35.3%), gangrenous cholecystitis in 17 patients (5.6%), and xanthogranulomatous cholecystitis in 6 patients (1.9%). A higher incidence of gallbladder empyema was observed in the ACC group compared to the AAC group (57.0 vs. 31.2%, p = 0.008, OR = 2.928, 95% CI: 1.340– 6.395; table 2). As a treatment modality, cholecystectomy was performed in a significantly lower proportion in the AAC group as compared to the ACC group (46.4 vs. 73.0%, p = 0.001). The proportion of patients treated by percutaneous cholecystostomy did not differ significantly between the two groups (17.4 vs. 9.9%, p = 0.092). The proportion of patients who were treated with antibiotics only was significantly higher in the AAC group, compared to the
Therapeutic Outcomes of AAC
Digestion 2014;90:75–80 DOI: 10.1159/000362444
77
Downloaded by: Freie Universität Berlin 130.133.8.114 - 5/12/2015 12:17:14 PM
Incidence (%)
80
Age
Digestion 2014;90:75–80 DOI: 10.1159/000362444
Risk Factors and Therapeutic Outcomes of Acute Acalculous Cholecystitis Min Geun Gu Tae Nyeun Kim Jay Song Yoon Jeong Nam Jae Young Lee Jun Suk Park Yeungnam University College of Medicine, Daegu, Korea
Abstract Objective: Acute acalculous cholecystitis (AAC) is traditionally known to occur in critically ill patients and to have a poor prognosis. Although cholecystectomy is usually recommended for treating AAC, nonsurgical management may be a good alternative. The objective of this study was to review the incidence, risk factors, treatment modality, and therapeutic outcomes of AAC compared to acute calculous cholecystitis (ACC). Material and Methods: Data from 69 patients with AAC and 415 patients with ACC between January 2007 and August 2011 were collected. Analysis and comparison of clinicopathological features and therapeutic outcomes between patients with AAC and those with ACC was performed. Results: The number of patients over 50 years of age was significantly higher in the AAC group compared with the ACC group (92.8 vs. 81.7%, p = 0.023). Cerebrovascular accidents were significantly more frequent in patients with AAC than in those with ACC (15.9 vs. 6.7%, p = 0.016). A higher incidence of gangrenous cholecystitis was observed in the AAC group (31.2 vs. 5.6%, p = 0.001). The overall therapeutic outcomes for patients did not differ statistically between the AAC and ACC groups, irrespective of treatment modalities. The recurrence rate after nonsurgical treatment
© 2014 S. Karger AG, Basel 0012–2823/14/0902–0075$39.50/0 E-Mail [email protected] www.karger.com/dig
was significantly lower in the AAC group than in the ACC group (2.7 vs. 23.2%, p = 0.005). Conclusions: The risk of AAC increases in patients with advanced age and cerebrovascular accidents. Incidence of gangrenous cholecystitis was higher in AAC compared to ACC. Nonsurgical treatments such as antibiotics alone or percutaneous cholecystostomy might be effective in selected patients. © 2014 S. Karger AG, Basel
Introduction
Acute acalculous cholecystitis (AAC) denotes inflammation of the gallbladder with no evidence of gallstones in the gallbladder, and includes 2–15% of acute cholecystitis [1, 2]. The pathophysiology of AAC is not completely clear. Several predisposing factors including gallbladder epithelial ischemia and reperfusion injury, positive pressure ventilation, parenteral nutrition, and opioid use have been implicated [3–6]. Compared with acute calculous cholecystitis (ACC), AAC tends to have a more fulminant course and is frequently associated with gangrene, perforation, and empyema, as well as significantly higher morbidity and mortality [2, 7]. Recent reports have documented the development of AAC at home without evidence of acute illness or trauma in 77–90% of the patients [8, 9], and, if diagnosed and treated early, the prognosis was good [10]. Although choTae Nyeun Kim Division of Gastroenterology and Hepatology, Department of Internal Medicine Yeungnam University College of Medicine 317-1 Daemyung 5-dong, Nam-gu, Daegu 705-717 (Korea) E-Mail tnkim @ yu.ac.kr
Downloaded by: Freie Universität Berlin 130.133.8.114 - 5/12/2015 12:17:14 PM
Key Words Acalculous cholecystitis · Cholecystectomy · Cerebrovascular Disorders · Outcomes
Methods We retrospectively reviewed the medical records of 69 patients with AAC and 415 patients with ACC treated at Yeungnam University Hospital between January 2007 and August 2011. The diagnostic criteria for acute cholecystitis were based on clinical history, physical examination, and characteristic image findings on abdominal ultrasonography or CT scan that were compatible with acute cholecystitis. Findings suggesting acute cholecystitis on physical examination included right upper quadrant pain and tenderness, a palpable gallbladder with localized tenderness, and sonographic Murphy’s sign. Imaging findings suggesting acute cholecystitis included gallbladder distention, pericholecystic fluid, and a thickened gallbladder wall. AAC was defined when no stones or sludge were observed in the gallbladder on imaging studies. The exclusion criteria included patients with hepatobiliary malignancy, concomitant acute cholangitis or common duct stones, chronic cholecystitis, and nonspecific gallbladder wall thickening associated with acute pancreatitis, hepatitis, pyelonephritis, peritonitis, ascites, hypoalbuminemia, congestive heart failure, or chronic renal failure. Diagnostic criteria of chronic cholecystitis were based on clinical history of recurrent episodes of biliary pain in the right upper abdomen, impaired gallbladder emptying and thickening of the gallbladder wall, and presence of gallstones on abdominal ultrasonography or CT scan [11]. We included all patients compatible with AAC at the time of diagnosis irrespective of underlying chronic cholecystitis because AAC and AAC on chronic cholecystitis could not be distinguished exactly. As a treatment for AAC, antibiotics were given to all patients. Emergency or urgent cholecystectomy was performed if symptoms did not improve or progression to gallbladder empyema was suspected. In cases with a high risk of surgery due to poor general condition or comorbidities, percutaneous cholecystostomy was performed, and delayed cholecystectomy was performed if possible. Demographic characteristics, clinicopathological features, and therapeutic modality and outcomes between AAC and ACC were analyzed and compared. The study protocol was approved by the institutional review board of our center. SPSS version 20.0 (SPSS Inc., Chicago, Ill., USA) was used for statistical analysis and all data were presented as means ± SD. Pearson’s χ2 test and Fisher’s exact test were used as statistical techniques. p < 0.05 was considered statistically significant.
Results
During the 5-year study period, 484 patients were diagnosed with acute cholecystitis (table 1). Of these, 69 patients (14.3%) fulfilled the criteria for the diagnosis of 76
Digestion 2014;90:75–80 DOI: 10.1159/000362444
Table 1. Baseline characteristics of the patients (n = 484)
Gender (M:F) Age, years (mean ± SD) Age ≥50 Fever (>37.7°C) Abdominal pain Leukocytes >10 K/μl Total bilirubin >1 mg/dl Albumin 35 IU/l ALT >40 IU/l Associated diseases Diabetes Hypertension CVA IHD Location of symptom onset Home Hospital
AAC (n = 69)
ACC (n = 415)
p
47:22 66.9±12.1 64 (92.8) 34 (49.3) 68 (98.6) 34 (49.3) 36 (52.2) 8 (11.6) 34 (49.3) 22 (31.9)
256:159 63.1±15.8 339 (81.7) 222 (53.5) 386 (93.0) 212 (51.1) 244 (58.8) 67 (16.1) 195 (47.0) 145 (34.9)
0.348 0.055 0.023 0.603 0.103 0.796 0.357 0.375 0.795 0.683
16 (23.2) 23 (33.3) 11 (15.9) 7 (10.1)
74 (17.8) 135 (32.5) 28 (6.7) 25 (6.0)
0.316 0.890 0.016 0.292 0.135
61 (88.4) 8 (11.6)
388 (93.5) 27 (6.5)
Values represent n (%) unless otherwise indicated. AST = Aspartate aminotransferase; ALT = alanine aminotransferase; CVA = cerebrovascular accidents; IHD = ischemic heart disease.
AAC. Male predominance was observed in both the AAC group and the ACC group. The male:female ratio was 2.1:1 in the AAC group and 1.6:1 in the ACC group (p = 0.348). The mean age was 66.9 ± 12.1 years in the AAC group and 63.1 ± 15.8 years in the ACC group (p = 0.055). When we analyzed age in the characteristics of patient with ACC and AAC, a significant difference was found at the cutoff value of 50 years of age. The proportion of patients over 50 years of age was significantly higher in the AAC group than in the ACC group (92.8 vs. 81.7%, p = 0.023, OR = 5.297, 95% CI: 1.117–7.372; fig. 1). AAC was a frequent occurrence in patients over 50 years of age and those with cardiovascular or cerebrovascular diseases. Occurrence of cerebrovascular accidents was significantly more frequent in patients with AAC than in those with ACC (15.9 vs. 6.7%, p = 0.016, OR = 2.621, 95% CI: 1.238– 5.550). No significant difference in the clinical features and interval from hospital visit to symptom onset was observed between the AAC group and the ACC group. The percentage of patients who visited the hospital within 3 days after symptom onset was 73.9% for patients with AAC and 74.0% for patients with ACC (p = 1.000). Of the Gu/Kim/Song/Nam/Lee/Park
Downloaded by: Freie Universität Berlin 130.133.8.114 - 5/12/2015 12:17:14 PM
lecystectomy is usually recommended for the treatment of AAC, nonsurgical management may be a good alternative treatment, especially for high-risk patients. The objective of this study was to review the incidence, risk factors, treatment modality, and therapeutic outcomes of AAC compared to ACC.
40 35
AAC ACC
Incidence (%)
30 25 20 15 10 5 0
0–9
10–19
20–29
30–39
40–49
50–59
60–69
70–79
80–89
Age * p = 0.023 100
Age 50
60 40
Fig. 1. Comparison of incidence of acute
20
cholecystitis according to age. The proportion of patients over 50 years of age was significantly higher in the AAC group than in the ACC group.
0
AAC
ACC
69 AAC patients, development of AAC occurred at home in 61 patients (88.4%) and at the hospital in 8 patients (11.6%). Of the 415 patients with ACC, development of ACC occurred at home in 388 patients (93.5%) and at the hospital in 27 patients (6.5%). No significant differences regarding the location of disease development was observed between the two groups (p = 0.135). The histopathological findings of 32 patients with AAC who underwent cholecystectomy revealed gangrenous cholecystitis in 10 patients (31.2%), gallbladder empyema in 10 patients (31.2%), and acute cholecystitis in 12 patients (37.5%). The incidence of gangrenous cholecystitis was significantly higher in the AAC group than in the ACC group (31.2 vs. 5.6%, p = 0.001, OR = 7.647, 95% CI: 3.130–18.685). On the other hand, the histopathological findings of 303 patients with ACC who underwent
cholecystectomy revealed gallbladder empyema in 173 patients (57.0%), acute cholecystitis in 107 patients (35.3%), gangrenous cholecystitis in 17 patients (5.6%), and xanthogranulomatous cholecystitis in 6 patients (1.9%). A higher incidence of gallbladder empyema was observed in the ACC group compared to the AAC group (57.0 vs. 31.2%, p = 0.008, OR = 2.928, 95% CI: 1.340– 6.395; table 2). As a treatment modality, cholecystectomy was performed in a significantly lower proportion in the AAC group as compared to the ACC group (46.4 vs. 73.0%, p = 0.001). The proportion of patients treated by percutaneous cholecystostomy did not differ significantly between the two groups (17.4 vs. 9.9%, p = 0.092). The proportion of patients who were treated with antibiotics only was significantly higher in the AAC group, compared to the
Therapeutic Outcomes of AAC
Digestion 2014;90:75–80 DOI: 10.1159/000362444
77
Downloaded by: Freie Universität Berlin 130.133.8.114 - 5/12/2015 12:17:14 PM
Incidence (%)
80
Age
