Postoperative outcomes with cholecystectomy in lung transplant recipients

Postoperative outcomes with cholecystectomy in lung transplant recipients Sharven Taghavi, MD, MPH,a Vishnu Ambur, MD,a Senthil N. Jayarajan, MD, MS,a John Gaughan, PhD,b Yoshiya Toyoda, MD, PhD,c Elizabeth Dauer, MD,a Lars Ola Sjoholm, MD,a Abhijit Pathak, MD,a Thomas Santora, MD,a Amy J. Goldberg, MD,a and Joseph Rappold, MD,a Philadelphia, PA

Introduction. There is a paucity of data on outcomes for lung transplant (LT) recipients requiring general surgery procedures. This study examined outcomes after cholecystectomy in LT recipients using a large database. Methods. The National Inpatient Sample Database (2005–2010) was queried for all LT patients requiring laparoscopic cholecystectomy (LC) and open cholecystectomy (OC). Results. There were a total of 377 cholecystectomies performed in LT patients. The majority were done for acute cholecystitis (n = 218; 57%) and were done urgently/emergently (n = 258; 68%). There were a total of 304 (81%) laparoscopic cholecystectomies and 73 (19%) OC. There was no difference in age when comparing the laparoscopic and open groups (53.6 vs 55.5 years; P = .39). In addition, the Charlson Comorbidity Index was similar in the 2 groups (P = .07). Patients undergoing OC were more likely to have perioperative myocardial infarction, pulmonary embolus, or any complication compared with the laparoscopic group. Total hospital charges ($59,137.00 vs $106,329.80; P = .03) and median duration of stay (4.0 vs 8.0 days; P = .02) were both greater with open compared with LC. Conclusion. Cholecystectomy can be performed safely in the LT population with minimal morbidity and mortality. (Surgery 2015;158:373-8.) From the Department of Surgery,a Biostatistics Consulting Center,b and Department of Cardiac Surgery,c Temple University School of Medicine, Philadelphia, PA

LUNG TRANSPLANTATION (LT) remains the treatment of choice for select patients with end-stage pulmonary disease.1,2 As survival after LTcontinues to improve,3,4 the number of patients who have undergone LT presenting with surgical pathology will increase. Although the management of gallstone disease in the general population is well-studied and accepted,5,6 the optimal approach in LTrecipients remains controversial. LT recipients require immunosuppression, which can impair wound healing and affect postoperative outcomes.7 Currently, there is a paucity of data on outcomes for LT recipients with The authors have no disclosures to report. Presented at the 10th Annual Academic Surgical Congress in Las Vegas, Nevada, February 3–5, 2015. Accepted for publication February 28, 2015. Reprint requests: Sharven Taghavi, MD, MPH, Temple University Hospital, 3401 N. Broad Street, Parkinson Pavilion, Suite 400, Philadelphia, PA 19140. E-mail: Sharven.Taghavi@tuhs. temple.edu. 0039-6060/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.surg.2015.02.021

biliary disease, and few guidelines exist for the management of these patients. The goal of this study was to evaluate the outcomes after cholecystectomy in LT recipients using a large, national database. METHODS Database. The National Inpatient Sample (NIS) Database was utilized for this study. The NIS database was developed by the Healthcare Cost and Utilization Project and contains data from approximately 8 million hospital stays each year. The database represents a stratified sample of 20% of non-federal hospitals in the United States. The NIS database is the largest publicly available, all-payer, inpatient health care database in the United States.8 A self-weighting design decreases the margin of error for estimates and delivers population-based estimates. All of our statistical analysis was based on this weighting design as established in previous studies.9 The NIS is a publically available, deidentified database and was therefore, granted exempt status from our institutional review board. Study population. Adult recipients of LT who underwent open cholecystectomy (OC) or SURGERY 373

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Table I. Patient diagnoses Diagnosis Acute cholecystitis Chronic cholecystitis Gallstone pancreatitis Choledocholithiasis Cholelithiasis without cholecystitis Other diagnoses

Laparoscopic cholecystectomy (n = 304), n (%) 159 19 15 35 24 51

**laparoscopic cholecystectomy (LC) between 2005 and 2010 were initially identified by the International Classification of Disease, Ninth Revision (ICD-9) diagnosis and procedure code as established in prior studies.9 Patients who had undergone LT on a prior admission were initially selected based on diagnosis code for LT (V42.6) and then identified using the procedure codes for OC (51.21, 51.22) and LC (51.23, 51.24). Individuals with a concurrent diagnosis of benign or malignant neoplasm involving the biliary tree, liver, intrahepatic bile ducts, gallbladder, extrahepatic bile ducts, or ampulla of Vater, or who had a cyst or pseudocyst of the pancreas identified by ICD-9 diagnosis codes 211.5, 197.7, 155, 155.0, 155.1, 155.2, 230.8, 156, 156.0, 156.1, 156.2, 156.8, 156.9, or 577.2 were excluded from the analysis. The other diagnoses category in Table I included obstruction of the gallbladder, hydrops of the gallbladder, perforation of gallbladder, fistula of gallbladder, cholesterolosis of gallbladder, and other specified disorders of the gallbladder. Data and statistical analysis. The primary outcome was inpatient mortality after cholecystectomy. Secondary outcomes included in-hospital complications, duration of stay, and cost. Common postoperative complications were identified by ICD-9 codes as established in previous studies.9 Continuous and categorical variables were compared with Student’s t test and Chi-square analysis. All continuous variables are presented as mean values ± standard deviation. Weighted frequencies and weighted multiple variable logistic regression analysis using clinically relevant variables were used to examine postoperative complications. In our multiple variable logistic regression analysis, we corrected for disease severity index. Disease severity index is determined by the NIS database using the 3M All Patient Refined Diagnosis Related Groups, which estimates the severity of illness and risk of mortality. Patients are assigned to severity and mortality subclasses according to a

(52) (6) (5) (12) (8) (17)

Open cholecystectomy (n = 73), n (%)

P value

59 (81) 0 4 (6) 5 (7) 5 (7) 0

<.001 .02 .77 .30 .99 <.001

sophisticated clinical logic that evaluates comorbidities, age, procedure, and clinical diagnosis. Disease severity index is widely used throughout the United States for adjusting data for severity of illness and risk of mortality in patients undergoing surgery8 Odds ratios with 95% CIs were presented for each covariate. Data was analyzed using SAS 9.2 software (SAS Institute, Cary, NC). RESULTS There were a total of 377 cholecystectomies performed in LT recipients during the study period. Of these, 304 (81%) were LC and 73 (19%) were OC. Baseline patient characteristics. A comparison of baseline patient characteristics is shown in Table II. The 2 groups were not different with respect to age (53.6 vs 55.5 years; P = .39) or Charlson Comorbidity Index (2.69 vs 3.49; P = .07). The LC group was more likely to have an elective admission compared with the OC group (38% vs 21%; P = .002). The LC group was less likely to be male (44% vs 67%; P <.001), less likely to be white (66% vs 86%; P < .001) or black (0% vs 14%; P <.001), and more likely to be Hispanic (17% vs 0%; P <.001). The LC group was less likely to have private insurance (33% vs 49%; P = .049) or Medicare (59% vs 59%; P = .049) and more likely to have Medicaid (8% vs 0%; P = .049). The number of LC done at hospitals with a large bed capacity was not different from the OC group (70% vs 64%; P = .40). A summary of patient diagnoses is shown in Table I. Although acute cholecystitis was the most common primary diagnosis in both groups, the OC group was more likely to carry this diagnosis (52% vs 81%; P < .001). The LC group was more likely to have a primary diagnosis of chronic cholecystitis (6% vs 0%; P = .03) or some other diagnoses (17% vs 0%; P < .001). There was no difference in patients with a diagnosis of choledocolithiasis (12% vs 7%; P = .29), cholelithiasis without cholecystitis (8% vs 7%; P = .99), or gallstone pancreatitis (5% vs 6%; P = .77).

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Table II. Baseline patient characteristics Characteristic

Laparoscopic cholecystectomy (n = 304)

Age (y) Charlson Comorbidity Index Elective admission (%) Male (%) White (%) Black (%) Hispanic (%) Other race (%) Larger hospital bed size Private insurance (%) Medicare (%) Medicaid (%) Other insurance (%)

53.6 ± 33.4 2.69 ± 3.51 114 (37.5) 134 (44.1) 200 (65.8) 0 63 (16.7) 0 212 (69.7) 100 (32.9) 178 (58.6) 25 (8.2) 4 (1.3)

Open cholecystectomy (n = 73) 55.5 3.49 15 49 63 10 5 47 36 43

± 30.1 ± 2.78 (21) (67) (86) (14) 0 (7) (64) (49) (59) 0 0

P value .39 .07 .002 <.001 <.001 <.001 <.001 <.001 .40 .049 .049 .049 .049

Table III. Postoperative complications and outcomes Complication

Laparoscopic cholecystectomy (n = 304)

Open cholecystectomy (n = 73)

P value

Any complication, n (%) Acute renal failure, n (%) Pneumonia, n (%) Myocardial infarction, n (%) Deep vein thrombosis, n (%) Pulmonary embolus, n (%) Postoperative hemorrhage, n (%) Surgical site infection, n (%) Total hospital stay (d) Total hospital charges ($)

14 (4.6) 0 0 0 5 (1.6) 0 5 (1.6) 5 (1.6) 4.0 ± 3.0 59,137 ± 6,387

14 (19) 0 0 5 (7) 0 9 (12) 0 0 8.0 ± 3.0 106,329 ± 5,120

<.001 .99 .99 <.001 .49 <.001 .53 .49 .02 .03

Postoperative outcomes. There were no inpatient deaths for any patients undergoing LC or OC (Table III). The OC group was more likely to develop any complication (5% vs 19%; P < .001). The OC group was more likely to experience postoperative myocardial infarction (0% vs 7%; P < .001) or pulmonary embolus (0% vs 12%; P < .001) compared with the LC cohort. All patients with complications were treated at hospitals with a large bed capacity. Multiple variable analysis was carried out to determine which variables were associated with mortality (Table IV). Disease severity index was most associated with the development of any complication (hazard ratio [HR], 38.29; 95% CI, 8.12–180.44; P < .001). Requirement of an OC (HR, 27.52; 95% CI, 4.15–182.41; P = .001) and female sex (HR, 14.21; 95% CI, 2.18–92.78; P = .01) were also associated with the development of complications. Duration of stay was greater (8.0 vs 4.0 days; P = .02) and total hospital charges were greater ($106,329 vs $59,137; P = .03) with OC compared with the laparoscopic procedure.

Table IV. Logistic regression examining variables associated with any complication Covariate

Odds ratio

95% CI

P value

Open cholecystectomy Disease Severity Index White race Female gender

27.52 38.29 0.85 14.21

4.15–182.41 8.12–180.44 0.25–2.83 2.18–92.78

.001 <.001 .78 .01

Elective versus urgent/emergent procedures. Of the 387 cholecystectomies, 218 (68.2%) were done urgently/emergently (Table V). Patients having an urgent/emergent admission were more likely to develop any complication (9% vs 4%; P = .05) postoperatively. In addition, they were more likely to suffer pulmonary embolus (4% vs 0%; P = .03). Patients admitted electively were more likely to develop surgical site infection than those admitted urgently/emergently (0% vs 4%; P = .003). Duration of stay (6.0 vs 3.0 days, P = .19) and total hospital charges ($123,706 vs $121,134, P = .33) were not different when

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Table V. Postoperative complications in elective versus nonelective admissions Complication

Elective (n = 129), n (%)

Urgent/Emergent (n = 258), n (%)

P value

Any complication Renal failure Pneumonia Myocardial infarction Deep vein thrombosis Pulmonary embolus Postoperative hemorrhage Surgical site infection

5 (3.9) 0 0 0 0 0 0 5 (3.9)

24 (9.3) 0 0 5 (1.9) 5 (1.9) 9 (3.5) 5 (1.9) 0

.05 .99 .99 .11 .11 .03 .11 .003

comparing urgent/emergent admissions with elective admissions. DISCUSSION Although many studies have focused on increasing the pool of lung donors3,10-12 and maximizing survival in recipients of a LT,4,13,14 few studies have examined how to manage general surgery problems in this transplant patient population. Although cholecystectomy is among the more common operations undertaken by general surgeons,15 few studies exist that examine the optimal treatment of biliary disease in LT recipients. The goal of this study was to examine outcomes in LT recipients undergoing lap and OC for benign gallbladder disease. Currently, there is no clear consensus on the treatment of biliary disease in LT patients. Previous studies have documented the high risk for intraabdominal complications in LT patients because of their immunosuppression. However, these case series have focused on intestinal complications and generally contain of a very small number of cholecystectomies.16-19 One study recommended prophylactic cholecystectomy before LT in patients with gallstones, citing a high mortality when cholecystectomy is carried out posttransplantation. This study, however, consisted of only 14 patients who underwent cholecystectomy after heart transplantation or LT.20 In addition, this study was performed before the institution of the lung allocation score, which changed the way donor lungs are distributed and improved survival in the LT population.21,22 In our study, there were no inpatient deaths after LC or OC. Previous research has shown that inpatient mortality is very low in patients undergoing LC and OC.6 Our study demonstrates that cholecystectomy can be performed in the LT population with low inpatient mortality; therefore, patients with symptomatic gallstones and otherwise acceptable operative risk should be evaluated for cholecystectomy.

Because our study was limited to inpatient outcomes, further studies are needed to determine long-term mortality for cholecystectomy in LT recipients. Although few studies have examined OC or LC in LT recipients, several studies have documented that other abdominal operations can be carried out when necessary with good outcomes in this patient group. Nissen fundoplication has been studied extensively in the LT population, given that these patients carry a high risk for developing gastroesophageal reflux. Fundoplication has been shown to have low mortality when performed in LT recipients and can result in improved graft survival.23 Postoperative complications were found to have a relatively low incidence in this study, with 5% of patients in the LC group developing an inpatient complication. The total number of complications in the OC group were greater (19%). These complication rates are similar to what is documented in the literature for all patients undergoing cholecystectomy. A recent analysis of the American College of Surgeons National Surgical Quality Improvement Program database showed a 3% morbidity rate for LC and 18% morbidity rate for OC.6 In our study, patients in the OC group were more likely to have a myocardial infarction or pulmonary embolus. A greater number of total complications and specifically cardiopulmonary complications are known sequelae of open surgery when compared with laparoscopic procedures.24 To determine whether outcomes after cholecystectomy are affected by volume, we examined the incidence of complications by hospital bed size capacity. LT volume is not available in the NIS database, but bed size capacity may be a marker of volume. Interestingly, all patients who developed complications were treated at hospitals with a large bed size capacity. The 2 variables most strongly associated with the development of complications were increasing disease severity index and need

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for an open procedure. We also found duration of stay to be greater in the OC group and total hospital charges to be greater. These findings are consistent with previous studies.24 Unfortunately, the number of common bile duct injuries or bile duct leaks could not be determined from the NIS database. These specific complications are identified using Current Procedural Terminology codes and these are not available in the NIS database, which uses ICD-9 diagnosis and procedure codes. The incidence of common bile duct injuries or bile duct leaks in the LT population needs further investigation. However, the lesser number of postoperative complications seen with LC stresses the importance of performing a laparoscopic procedure if technically feasible and safe. We found that patients undergoing elective cholecystectomy developed fewer complications than those undergoing an urgent or emergent operation. There were greater numbers of total complications or pulmonary embolus when the operation was done urgently/emergently. Abdominal operations performed in the urgent or emergent setting are known to result in worse outcomes in the LT population.16,18,19,25 These findings demonstrate the importance of performing cholecystectomy in an elective setting for patients with symptomatic gallstones, before the development of more advanced gallbladder disease that could result in an urgent or emergent operation. This consideration also raises the issue of whether LT recipients with asymptomatic gallstones should undergo prophylactic cholecystectomy before developing advanced disease that requires an open and/or emergent operation. Prior studies have advocated cholecystectomy in heart transplant recipients with asymptomatic gallstones, citing high morbidity and mortality observed in these patients after cholecystectomy.9,20 Further studies are needed to determine the optimal treatment for asymptomatic gallstones in LT recipients. Interestingly, we found that patients undergoing elective cholecystectomy were more likely to develop surgical site infections than those undergoing urgent/ emergent operations. This finding needs further investigation, because patients undergoing urgent/emergent procedures would be expected to develop a greater number of surgical site infections. This study was not without limitations. The NIS database is limited to inpatient outcomes from a single hospital admission. Therefore, we could not examine long-term survival, complications that occur after discharge, readmissions, or need for further procedures. In addition, we could not examine procedure specific complications such

as bile leak, intraabdominal abscess formation, or common bile duct injuries. These complications cannot be identified using ICD-9 codes. In addition, we could not evaluate specific intraoperative variables, such as conversion to open surgery. Finally, the indication for LT could not be ascertained from the database, because the LT occurred on a hospital admission before cholecystectomy. Therefore, we could not determine whether the indication for LT affected postcholecystectomy outcomes. In conclusion, cholecystectomy can be performed in the LT population with minimal inpatient morbidity and mortality. Long-term outcomes in LT recipients undergoing cholecystectomy need further investigation. Patients requiring open surgery and urgent/emergent procedures have worse outcomes. LT recipients with symptomatic gallstone disease should undergo elective LC. Further studies are needed to determine the optimal treatment of LT recipients with asymptomatic gallstones.

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