Authors: Nelimar Cruz-Centeno, Gerardo Jovet-Toledo, Carlos Ramirez-Tanchez
Categories: Research Article, Cholecystitis, Cholecystostomy tube, Cholecystectomy, Biliary
Source: Surgery in Practice and Science
Authors: Nelimar Cruz-Centeno, Gerardo Jovet-Toledo, Carlos Ramirez-Tanchez
•PCT can be a temporary treatment for acute calculous cholecystitis.•High incidence of biliary complications after PCT placement calls for timely cholecystectomy.•Interval cholecystectomy is recommended after PCT for calculous cholecystitis.
Acute cholecystitis is a surgical diagnosis affecting approximately 25% of patients who have a diagnosis of cholelithiasis [1]. The gold standard treatment is laparoscopic cholecystectomy when feasible [2,3]. As per the latest Tokyo guidelines (2018) regarding management of high-risk patients with acute cholecystitis, percutaneous gallbladder drainage should be considered the first alternative to surgical intervention [4]. PCT placement is a minimally invasive and low-risk procedure that has been shown to be successful in the management of acute cholecystitis [5]. However, this is only a temporizing measure and does not represent the final treatment option for the management of acute calculous cholecystitis.
Most patients with a history of PCT have plenty of comorbidities, low functional status, intensive care unit admission, or advanced age. These factors drastically increase the risks of surgery. A study conducted by Pavurala et al [2] demonstrated that 62.2% of patients who had a PCT did not undergo interval cholecystectomy due to older age and multiple comorbidities. Surgery can represent high morbidity and mortality for patients with low functional status and comorbidities who were not deemed fit for surgery at the time of diagnosis. However, non-surgical management can result in an array of complications including recurrence of cholecystitis, gallstone pancreatitis, ascending cholangitis, gallstone ileus, or choledocholithiasis. These complications related to cholelithiasis also pose a mortality risk [3]. The decision to perform surgery on high-risk patients continues to be individualized and represents a challenge to the surgeon. In this retrospective study, we compare the outcomes of performing an interval cholecystectomy vs. conservative management after PCT placement for ACC and evaluate the mortality rate of both treatment options. We hypothesize that surgeons are more likely to avoid surgery in elderly patients due to comorbidities that increase surgical risks.
We performed a retrospective single-center study at the VA Caribbean Healthcare System (VACHS) after approval by the VACHS Institutional Review Board, which waived the requirement for consent. Data was collected from the electronic medical record system of all cases of acute calculous cholecystitis (ACC) that underwent PCT placement by Interventional Radiology from October 2010-March 2015.
Inclusion criteria for this study age ≥ 21 years old, and diagnosis of ACC confirmed by imaging studies with PCT placement at the time of diagnosis. Patients who were admitted for other medical conditions and developed ACC during their hospital stay requiring PCT placement were also included. Patients with acalculous cholecystitis, PCT placement for obstructive jaundice, or a history of hepatobiliary malignancy were excluded from this study. Patients selected had an exclusive diagnosis of ACC without clinical or laboratory evidence of pancreatitis, cholangitis, or choledocholithiasis at the time of PCT placement. Therefore, biliary complications included in the statistical analysis were documented in the medical record as an additional admission or emergency room visit occurring after discharge for PCT placement.
Biliary complications gallstone pancreatitis, cholangitis, choledocholithiasis, recurrence of cholecystitis, and worsening of biliary colic symptoms. Recurrence of cholecystitis was confirmed by abdominal CT or US performed at the time of re-admission and patient symptoms; the presence of choledocholithiasis was confirmed by magnetic resonance cholangiopancreatography (MRCP) or follow-up cholangiogram showing common bile duct (CBD) stones or filling defect. Worsening of symptoms was defined as biliary colic symptoms documented on follow-up notes to be progressing over time. These symptoms right upper quadrant abdominal pain, nausea, and vomiting. Gallstone pancreatitis was diagnosed based on imaging showing cholelithiasis, patient symptoms, and laboratory results showing serum lipase levels greater than three times the upper limit of normal. Cholangitis diagnosis was done based on the Tokyo guidelines 2018 criteria for definitive diagnosis [4].
Data from all eligible participants was collected by the research team and summarized using descriptive statistics. Data collected age, past medical history, ASA score, surgical history, procedure notes, date of PCT placement and removal, surgery clinic notes, surgery consult notes, admission/discharge notes, date, and cause of death (if applicable). We divided our study population into two patients who were treated with interval cholecystectomy and those who were treated conservatively. Afterward, we compared both groups in terms of demographics, BMI, comorbidities, biliary complications, hospital re-admissions, mortality rate, PCT indwelling time (defined as the number of days from PCT placement to removal), and length of hospital stay.
Median and interquartile range (IQR) were reported since there was significant variation in the continuous variables. Cross tabulation methods were employed to assess morbidity and mortality based on categorical variables. When the required assumptions were met, chi-square tests were used to test associations between morbidity, mortality, and interval cholecystectomy; if not met, Fisher's exact test was used. For continuous variables, the non-parametric Mann-Whitney test was used. Logistic regression analysis was performed using interval cholecystectomy as a dependent variable. Variables that resulted in statistical significance in the bivariate analysis (p<0.05) were included in the regression model as independent variables. Mechanical ventilation and vasopressors were excluded from the analysis based on the low frequency of the outcome in the interval cholecystectomy group. All analyses were performed using the Stata v.17 software and a significance level of α=0.05.
A total of 121 patients underwent PCT placement at VACHS between October 2010-March 2015. After exclusion criteria, we had a total of 95 male patients in our study group. The median age was 79 years, with a median body mass index (BMI) of 26 and an American Society of Anesthesiology (ASA) physical status classification of 3. Comorbidities in our study group included hypertension (93.7%), diabetes (71.6%), chronic obstructive pulmonary disease (COPD) (23.2%), dementia (36.8%) and coronary artery disease (CAD) (64.2%). There was no difference in terms of comorbidities between the surgical and non-surgical groups (Table 1).Table 1Patient's demographic characteristics and median values of each categorical variable between surgical and non-surgical groups.Table Interval CholecystectomyTotal(N = 95)Yes(n = 25; 26.3%)No(n = 70; 73.7%)MedianIQR1MedianIQRMedianIQRpAge7915721481.5140.023BMI267.727.77257.90.439LoHS^2^10169911200.119PCT days^3^5559817547.5530.118ASA score3030300.805n%n%n%pMale95100.025100.070100.0–Hypertension8993.72496.06592.90.999Diabetes6871.62080.04868.60.277COPD2223.2832.01420.00.222Dementia3536.8624.02941.40.121CAD6164.21664.04564.30.980ICU admission4143.2520.03651.40.006Mechanical ventilation1920.014.01825.70.020Vasopressors2122.114.02028.60.011Worsening of symptoms2728.7936.01826.10.348Cholecystitis recurrence2122.1520.01622.90.768Pancreatitis1010.5312.0710.00.720Cholangitis1111.6416.0710.00.472Choledocholithiasis2627.41144.01521.40.03030-days post-op complications1456.01456.0–––Readmission due to biliary disease3133.01040.02130.40.383Mortality22.100.022.91.01Interquartile range; ^2^LoHS: Length of hospital stay after initial ACC diagnosis requiring PCT placement; ^3^PCT Days from PCT placement to removal.
Only 25 patients (26.3%) underwent interval cholecystectomy after PCT placement. The median time from ACC diagnosis to surgery was 107 days (IQR 57,129). There was a difference in age between the surgical and non-surgical groups, with the non-surgical group being older with a median age of 81.5 years vs. 72.0 years (p = 0.023). There was no difference between groups in terms of BMI or ASA score. Patients who were managed non-surgically after PCT were more likely to have had intensive care unit admission (ICU) (51.4% vs. 20%; p = 0.006), respiratory failure on mechanical ventilation (25.7% vs. 4%; p = 0.020) and need for vasopressor therapy at the time of diagnosis of ACC (28.6% vs. 4%; p = 0.011) (Table 1). The ICU admission was not necessarily secondary to the ACC diagnosis since there were patients who were admitted to the ICU for another diagnosis and developed ACC requiring PCT due to their critical condition.
The median time from ACC diagnosis to complication due to biliary disease was 85 days (IQR 32.2,203.5). Recurrence of cholecystitis was higher in the non-surgical group (22.9% vs. 20%; p = 0.768). In contrast, the worsening of symptoms of biliary colic was higher in the surgical group (36.0% vs. 26.1%; p = 0.348). The occurrence of gallstone pancreatitis, cholangitis, and choledocholithiasis was higher in the surgical group; choledocholithiasis being the only statistically significant variable (44% vs. 21.4%; p = 0.030). There was only one case of choledocholithiasis due to a retained common bile duct stone occurring after surgical intervention, the others were diagnosed before cholecystectomy, after having a diagnosis of ACC that was managed with PCT placement.
Table 2 shows the results of the logistic regression performed using interval cholecystectomy as a dependent variable. Both, increasing age (OR 0.94, 95% CI 0.89-0.98, p = 0.007) and ICU admission (OR 0.21, 95% CI 0.07-0.66, p = 0.008) were associated with a lower likelihood of undergoing interval cholecystectomy after PCT placement. Occurrence of choledocholithiasis (OR 2.45, 95% CI 0.82-7.29, p = 0.108) as a complication after initial ACC diagnosis was associated with a higher likelihood of undergoing definitive surgery. As shown in Fig. 1, the predicted probability of performing interval cholecystectomy decreased with age and ICU admission.Table 2Logistic regression analysis of interval cholecystectomy.Table OR****95% CIp-valueAge0.940.89–0.980.007ICU admission0.210.07–0.660.008Choledocholithiasis2.450.82–7.290.108Fig. 1Probability of interval cholecystectomy by age and ICU stay. Older age and ICU admission was associated with less likelihood of undergoing interval cholecystectomy after PCT placement.Fig
Of the 25 patients that had an interval cholecystectomy, 56% (14/25) had a complication in the first 30 days after surgery (Table 3). Only 9/25 cholecystectomies (36%) were performed with a completely laparoscopic technique. Six (24%) were laparoscopic converted to open due to inability to obtain the critical view of safety secondary to adhesions or bleeding and 10/25 (40%) were done in an open fashion due to surgeon preference. Table 3 shows complications arising after surgery and their frequency as documented on the medical record. The two most common complications were surgical site infections and cystic duct leak. Most complications occurred when surgery was performed in an open or converted to open technique (11/14=78.6%) vs. laparoscopic (3/14=21.4%). The median time from ACC diagnosis to death related to gallbladder sepsis in the non-surgical group was 32.5 days (IQR 27.8,37.8). Although not statistically significant, the mortality rate within 6 weeks of ACC diagnosis was higher in the non-surgical group when compared to the surgical group (2.9% vs. 0%; p = 1)Table 3Complications in the first 30 days after interval cholecystectomy.Table Post-operative complication****Number of casesSurgical site infection4 (28.6%)Cystic duct leak4 (28.6 %)Ileus2 (14.3%)Gastroduodenal artery bleeding + non-ST elevation myocardial infarction1 (7.1%)Urinary tract infection1 (7.1%)Retained common bile duct stone1 (7.1%)Surgical site hematoma1 (7.1%)
The median indwelling PCT time for the study population (defined as the time from PCT placement to removal) was 55 days, with surgically treated patients having the PCT for a longer period than the non-surgical group (81 days vs. 47.5 days; p = 0.118). Of the 25 patients who had cholecystectomy performed, the PCT tube was removed before surgery in 8 cases while in the remaining 17 cases the tube was removed at the time of surgical intervention. The decision to remove the PCT was done after performing a follow-up cholangiogram by Interventional Radiology documenting on the medical record adequate cystic duct drainage into the CBD without filling defects or biliary obstruction. The average length of hospital stays (LoHS) for the initial admission, (where ACC was diagnosed and the PCT was placed) was 10 days. There was no difference between groups in terms of LoHS.
All patients were followed up at Interventional Radiology Clinics after discharge with PCT for ACC until the PCT was removed or the patient underwent cholecystectomy. Patients were also given an appointment at surgery clinics if they were seen by the surgery team during admission. However, 37.9% (n = 36) of patients were lost to follow up at the surgery clinics.
Cholecystectomy is considered the gold standard for the treatment of acute cholecystitis. Although this procedure is mastered by most general surgeons, it can result in multiple complications. A retrospective study by Rice et al [6] analyzed complications after cholecystectomy for acute cholecystitis and reported that the most common complications were retained stone (2.5%), wound infection (2.1%), and bile leak (1.9%). The most common complications in our surgical group were cystic duct leak and wound infection, but our complication rate was much higher than that reported in the literature. Complication rates for laparoscopic cholecystectomy have been reported to range between 0.5-6% [7]. In comparison, complication rates for open cholecystectomy have been reported to be approximately 16% with increased risks of developing an incisional hernia, wound infection, and hematoma formation [8,9]. Additionally, studies have shown that in acute cholecystitis, postoperative morbidity, mortality, and hospital stay are reduced by the laparoscopic technique when compared with open surgery [9]. In our cohort, most surgeries were performed in an open fashion instead of the laparoscopic approach.
Mortality from cholecystectomy has been reported to be between 0.1% and 0.7% [10]. Despite the fear of increased risk for elderly patients, studies have shown that cholecystectomy is safe for the elderly population. Kim et al [11] showed that cholecystectomy in elderly patients between 80-90 years old was safe and efficient with a survival rate of more than 95%. When feasible, the laparoscopic technique should be used because elderly patients have improved outcomes after laparoscopic cholecystectomy when compared with open surgery [8]. Post-operative complications in our cohort were non-fatal and conservative management with PCT had a higher mortality rate, however, this was not statistically significant. Schlottham et al [12] described a mortality rate of 4.7% associated with the treatment of cholecystitis with PCT in the elderly population vs. 1.2% for cholecystectomy. Thus, highlighting the fact that conservative management of cholecystitis in the elderly also comes with risks.
Loozen et al [13] reported that recurrent biliary disease was more common in patients treated with PCT alone after a diagnosis of ACC when compared to those managed with cholecystectomy (53% vs 5%). Cases of choledocholithiasis diagnosed before surgery in our cohort required re-admission and additional invasive procedures including endoscopic retrograde cholangiopancreatography and/or biliary stent placement.
The average ASA score was 3 in both groups, meaning that all patients had severe systemic disease with substantial functional limitations. Therefore, the criteria used to determine if a patient was fit for surgery were not equal among different surgeons. The average age of the non-surgically treated group was higher than the surgical group, supporting that the surgeon considered the patient's age as a decisive factor to decide against surgical management. The ASA physical status has been reported to be associated with multiple outcomes, including postoperative morbidity and mortality [14]. There are other operative risk calculators (The Surgical Risk Scale, Surgical Outcome Risk Tool, and the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) surgical risk calculator) that incorporate this classification along with other clinical variables to accurately predict patient outcomes [14]. These comprehensive risk assessment tools can help surgeons decide more clearly which patients would benefit from surgical intervention.
Percutaneous cholecystostomy tubes are usually left in place for 3-6 weeks until the tract matures and the inflammation resolves [2,15]. However, the average duration of PCT placement in our cohort was 7.9 weeks (55 days). A longer duration of PCT drainage has been associated with increased rates of readmission for biliary complications [16]. Additionally, it has been reported that one in four patients with acute calculous cholecystitis may develop recurrent cholecystitis within two to three months of PCT placement [16,17].
Limitations of this study include its retrospective design, selection bias, and small sample size. Our sample only included elderly male patients, therefore, it is not representative of all populations. All patients were male because in this Veteran's Hospital there is a much higher proportion of male patients than females. During the study period, the list of patients who underwent cholecystostomy tube placement for ACC and met inclusion criteria did not include female patients. Additionally, the sample size was small which could cause the study to be underpowered to detect differences in outcomes between groups. Despite limitations, this article emphasizes that conservative management of the elderly is not without risk.
The relatively high incidence of biliary complications in the period between tube placement and cholecystectomy calls for timely cholecystectomy in patients treated with PCT. When feasible, all patients with a history of ACC should undergo interval cholecystectomy. Implementing more comprehensive surgical risk assessment tools that include multiple patient characteristics can help decide if the surgery benefits outweigh the risks.
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
The contents of this publication do not represent the views of the VA Caribbean Healthcare System, the Department of Veterans Affairs, or the United States Government.
The Authors declare that there is no conflict of interest.