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Chen Y, Scholten A, Chomsky-Higgins K, et al. Risk Factors Associated With Perioperative Complications and Prolonged Length of Stay After Laparoscopic Adrenalectomy. JAMA Surg. 2018;153(11):1036–1041. doi:10.1001/jamasurg.2018.2648
What factors are associated with perioperative complications after laparoscopic adrenalectomy?
In this single-center cohort study of 653 laparoscopic adrenalectomy procedures in 640 patients, 76 complications occurred in 55 patients (8.4%). Independent risk factors for complications included patients with more comorbidities, pheochromocytoma, a tumor size of 6 cm or larger, and conversion to an open or hand-assisted surgical procedure.
Per these results, laparoscopic transabdominal adrenalectomy is a safe procedure, but selection of surgical candidates should be based on both patient and tumor factors, and surgery on high-risk patients should be performed at a specialized center.
Laparoscopic adrenalectomy is the gold standard for most adrenal disorders and its frequency in the United States is increasing. While national and administrative databases can adjust for patient factors, comorbidities, and institutional variations, granular disease-specific data that may significantly influence the incidence of perioperative complications and length of stay (LOS) are lacking.
To investigate factors associated with perioperative complications and LOS after laparoscopic adrenalectomy.
Design, Setting, and Participants
This cohort study was carried out at a single academic medical center, with all patients who underwent laparoscopic adrenalectomy between 1993 and 2017 by the endocrine surgery department. Multivariable linear and logistic regression were used to obtain adjusted odds ratios (ORs).
Main Outcomes and Measures
The primary outcome was perioperative complications with a Dindo-Clavien grade of 2 or more. The secondary outcome was prolonged length of stay, defined as a stay longer than the 75th percentile of the overall cohort.
We identified 640 patients who underwent 653 laparoscopic adrenalectomies, of whom 370 (56.7%) were female. The median age was 51 (range, 5-88) years. A total of 76 complications with a Dindo-Clavien grade of 2 or more occurred in 55 patients (8.4%), with postoperative mortality in 2 patients (0.3%). The median hospital length of stay was 1 day (range, 0-32 days). Factors independently associated with increased complications were American Society of Anesthesiologists class 3 or 4 (OR, 2.78 [95% CI, 1.39-5.55]; P < .01), diabetes (OR, 2.39 [95% CI, 1.14-5.01]; P = .02), conversion to hand-assisted or open surgery (OR, 5.32 [95% CI, 1.84-15.41]; P < .01), a diagnosis of pheochromocytoma (OR, 4.31 [95% CI, 1.43-13.05]; P = .01), and a tumor size of 6 cm or greater (OR, 2.47 [95% CI, 1.05-5.78]; P = .04). Prolonged length of stay was associated with age 65 years or older (OR, 2.44 [95% CI, 1.31-4.57]; P = .01), an American Society of Anesthesiologists class 3 or 4 (OR, 3.48 [95% CI, 1.88-6.41]; P < .01), any procedural conversion (OR, 63.28 [95% CI, 12.53-319.59]; P < .01), and a tumor size of 4 cm or larger (4-6 cm: OR, 2.38 [95% CI, 1.21-4.67]; P = .01; ≥6 cm: OR, 2.46 [95% CI, 1.12-5.40]; P = .03).
Conclusions and Relevance
Laparoscopic adrenalectomy remains safe for most adrenal disorders. Patient comorbidities, adrenal pathology, and tumor size are associated with the risk of complications and length of stay and should all be considered in selecting and preparing patients for surgery.
Laparoscopic adrenalectomy has become the gold standard for most adrenal disorders. It was first described by Gagner et al1 in 1992 for hypercortisolism and pheochromocytoma, but since then its indication has expanded to include larger benign tumors as well as malignant lesions.
It has been well established through multiple national database analyses that laparoscopic adrenalectomy has significantly lower perioperative morbidity and shorter length of stay (LOS) than open adrenalectomy.2-4 Alternative minimally invasive approaches with retroperitoneoscopic5 and robotic6 techniques have reported similar results to those of transabdominal lateral laparoscopic adrenalectomy. Regardless of approach, several studies have shown that high-volume adrenal surgeons also produce favorable outcomes compared with low-volume surgeons.7,8
While national and administrative databases can adjust for patient factors, comorbidities, and institutional variations, granular, disease-specific data that may significantly influence the incidence of perioperative complications and LOS are lacking. We hypothesize that both tumor size and diagnosis, including the nature of hormonal hypersecretion, are independently associated with complications and LOS after laparoscopic adrenalectomy.
We performed a retrospective analysis of all patients who underwent laparoscopic transabdominal adrenalectomy performed by surgeons from the endocrine surgery service at a single academic medical center. The period spanned from November 1993, the date of the first laparoscopic adrenalectomy performed at this institution, to August 2017. Patients who underwent retroperitoneoscopic approaches were excluded from the analysis.
Institutional review board approval was obtained from the University of California San Francisco. Patient consent was waived given that this was a retrospective review of medical records.
Data were collected on patient demographics, comorbidities, diagnosis, operative details, pathology, and perioperative outcomes. The primary outcome was overall complications, which were scored using the Dindo-Clavien classification system. Complications with a grade of 2 or greater were included in our analysis.9 Secondary outcomes included prolonged LOS, which was defined as an LOS longer than the 75th percentile of the cohort.
Indications for adrenalectomy and surgical technique were the same, as previously described by our institution.10 All patients underwent a standardized hormonal workup.10 From 2010, all patients who presented with adrenal disease were discussed at a multidisciplinary meeting involving surgeons, endocrinologists, and radiologists before surgical resection. Perioperative management was tailored to the disease process. Electrolytes were monitored for aldosterone-producing lesions. Patients with Cushing syndrome received postoperative steroid therapy with a subsequent taper. Patients with pheochromocytoma were α-blocked preoperatively, typically with phenoxybenzamine. Postoperatively, they were monitored in the postanesthesia care unit for 4 hours and were not routinely admitted to the intensive care unit.
Statistical analysis was performed using Stata version 12.0 (StataCorp LP). The χ2 test was used to compare categorical variables, and the Kruskal-Wallis test was used for continuous variables, assuming nonparametric distributions. A P value of <.05 was considered statistically significant. Clinically relevant variables on univariate analysis with a P < .20 were entered into a multivariate model for logistic regression analysis to obtain adjusted odds ratios (ORs).
We identified 640 patients who underwent 653 laparoscopic adrenal operations over this period. Of these, 370 (56.7%) were female, and the full cohort had a median (range) age of 51 (5-88) years at the time of operation. Median body mass index across the cohort was 27.3 (range, 15.5-50.5). Of the 640 patients, 446 (68.3%) had a preoperative diagnosis of hypertension and 117 (17.9%) had diabetes. Most patients had an American Society of Anesthesiology (ASA) class 1 or 2 (440 [67.4%]) with the remainder class 3 or 4 (213 [32.6%]). One in 4 patients (160 [24.5%]) had a history of previous abdominal or retroperitoneal surgery and 3.8% had previous adrenal surgery.
The most common indication for surgery (Table 1) was primary hyperaldosteronism, accounting for 219 cases (33.5%). This was followed by pheochromocytoma (194 [29.7%]), Cushing syndrome (102 [15.6%]), nonfunctioning adenomas (53 [8.1%]), metastasis (48 [7.4%]), virilizing tumor (3 [0.5%]), adrenocortical carcinoma (3 [0.5%]), and other lesions (31 [4.8%]). Median overall tumor size was 2.7 cm (range, 0.1-12 cm). Of the 640 patients, 449 (68.8%) had a tumor size less than 4 cm, 127 (19.4%) a tumor 4 to 5.9 cm, and 77 (11.8%) had a tumor of 6 cm or greater. The largest tumor removed laparoscopically was 15 cm.
All operations were performed with a lateral transabdominal approach. There were 324 patients (49.6%) whose operation was on the left side, 280 patients (42.9%) whose operation was on the right side, and 49 patients (7.5%) who had bilateral adrenalectomies. The overall median operative time in was 2.5 hours (range, 1.0-9.0 hours) for patients receiving operations on the left side, 2.25 hours (range, 1.0-8.5 hours) for patients receiving operations on the right side, and 5 hours (range, 3.0-10.5 hours) for those with bilateral operations. In this study, mean operative time for patients with obesity (2.9 hours) was longer than patients without obesity (2.7 hours; P = .02).
The overall conversion rate was 3.7%, with 9 patients (1.4%) requiring a hand-assisted conversion and 15 patients (2.3%) requiring open conversion. The most common reason for either conversion was extensive adhesions from prior surgery (particularly ipsilateral retroperitoneal operations) and difficulty in dissection of the primary tumor. In 4 patients (0.6%), control of bleeding that was difficult to visualize was the primary reason for open conversion.
The most common surgical complication was bleeding requiring perioperative blood transfusion. The median intraoperative blood loss was 20 mL (range, 0-1500 mL), with 8 patients (1.2%) requiring intraoperative blood transfusion, of which 4 (0.6%) were patients who also required conversion to an open operation.
In the full cohort, 55 patients (8.4%) experienced 76 complications with a Dindo-Clavien grade of 2 or greater, as detailed in Table 2. Most complications with Dindo-Clavien grade of 2 or greater were medical and associated with respiratory compromise and pneumonia. Fourteen patients required vasopressor support postoperatively with intensive care unit admission, of whom 12 (85.7%) were patients with pheochromocytoma. This was classified as a grade 4 complication because it deviates from the standard practice of 4 hours of monitoring in the postanesthesia care unit for patients with pheochromocytoma. Four patients (0.6%) required reoperation, 3 for bleeding and 1 because of a concern about a missed enterotomy.
Two patients (0.3%) died postoperatively (Dindo-Clavien grade 5). The first was a 63-year-old man with metastatic melanoma who underwent laparoscopic right adrenalectomy, recovered well from his operation, and was discharged after 2 days, but died of his metastatic disease 16 days after his procedure. The second was a 55-year-old man who had a concomitant left adrenal adenoma and left renal mass and was found to have primary aldosteronism. He had significant comorbidities, including atrial fibrillation, coronary artery disease, and a mechanical mitral valve, for which he was taking therapeutic anticoagulation. He underwent a laparoscopic left adrenalectomy and nephrectomy and recovered uneventfully with a 5-day hospital stay. He died 2 weeks postoperatively of unknown causes.
The median hospital LOS after the operation was 1 day (range, 0-32 days). A prolonged LOS was defined as any longer than 2 days (which was found to be longer than the 75th percentile of the cohort); this was seen in 102 patients (15.9%).
Table 3 describes factors associated with perioperative complications and prolonged LOS. Factors associated with perioperative complications include ASA class 3 or 4 (OR, 4.77 [95% CI, 2.64-8.63]; P < .001), diabetes (OR, 3.85 [95% CI, 2.15-6.86]; P < .001), pheochromocytoma (OR, 8.14 [95% CI, 3.10-21.39]; P < .001), cortisol-producing adenoma (OR, 4.65 [95% CI, 1.55-13.99]; P = .006), a tumor size of 6 cm or larger (OR, 5.17 [95% CI, 2.66-10.05]; P < .001), and a conversion to hand-assisted or open surgery (OR, 13.63 [95% CI, 5.78-32.14]; P < .001).
On multivariate analysis (Table 4), ASA class 3 or 4 was independently associated with perioperative complications (OR, 2.78 [95% CI, 1.39-5.55]; P = .004), as was diabetes (OR, 2.39 [95% CI, 1.14-5.01]; P = .02). Tumor-associated factors that increased the odds of complications included the diagnosis of pheochromocytoma (OR, 4.31 [95% CI, 1.43-13.05]; P = .01) and a tumor size of 6 cm or larger (OR, 2.47 [95% CI, 1.05-5.78]; P = .04). Conversion to either hand-assisted or open adrenalectomy was associated with greatest odds of perioperative complications (OR, 5.32 [95% CI, 1.84-15.41]; P = .002).
Patient factors that independently influenced prolonged LOS on multivariate analysis (Table 4) included age older than 65 years (OR, 2.44 [95% CI, 1.31-4.57]; P = .005) and ASA class 3 or 4 (OR, 3.48 [95% CI, 1.88-6.41]; P < .001). Patients experienced increased odds of prolonged LOS if they had a tumor of 4 cm or larger (4-6 cm: OR, 2.38 [95% CI, 1.21-4.67]; P = .01; ≥6 cm: OR, 2.46 [95% CI, 1.12-5.40]; P = .03), required bilateral adrenalectomy (OR, 7.10 [95% CI, 2.66-18.92]; P < .001), or required any procedural conversion (OR, 63.28 [95% CI, 12.53-319.59]; P < .001).
In this high-volume, single-institution analysis, we demonstrate that laparoscopic adrenalectomy by transabdominal lateral approach is a safe technique with low perioperative complications and extremely rare postoperative mortality for a range of indications. The overall complication rate of 8.4% in this study is similar to that described in many publications, both in single-center studies and national databases.6,11-14 Patients who required intensive care unit admission for vasopressor support might reflect that preoperative blockade and intraoperative management could be improved, but further study is needed. Infectious complications were rare, and perioperative antibiotics are not routinely used unless a patient has Cushing syndrome or is otherwise immunosuppressed.
Bleeding requiring perioperative transfusion with the most common surgical complication. Standard laparoscopic adrenalectomy patients do not receive prophylactic heparin, given their short LOS, and they are encouraged to ambulate as soon as possible.
The low perioperative mortality rate of 0.3% in this study compares well with the rates of 0% to 0.8% described in the literature.2,4,12 This highlights the overall safety of this surgical approach.
It is well described that patient-specific factors, such as increased ASA score and diabetes, play a significant role in rates of perioperative complications after adrenal surgery, which we also found in this study.3,4,8,12,13 Other studies have reported that increasing patient age is a predictor for postoperative complications.15,16 In this cohort, age was not independently associated with perioperative complications, but older patients were more likely to have prolonged LOS.
Obesity with a body mass index of 30 or more has also been previously reported to increase complication rates in laparoscopic adrenalectomy.17,18 Although in this study obesity was not associated with complications or prolonged LOS, it can often be challenging to identify small adrenal lesions amid an excess of retroperitoneal adipose tissue. For this reason, we encourage patients with obesity and aldosterone-secreting adenomas, which are typically small tumors, to lose weight before a surgical intervention.
The use of laparoscopic adrenalectomy for large tumors has been controversial because of concern about the potential for malignant conditions and tumor spillage.19,20 Our experience and comfort with minimally invasive adrenal surgery has grown, and many authors have shown that laparoscopy is technically safe and feasible for large adrenal tumors, even those larger than 10 cm.19,21,22 In this study, tumor size of 6 cm or larger was independently associated with postoperative complications and had a higher likelihood of requiring conversion. These patients also had a longer operative time and LOS. However, patients who undergo laparoscopic adrenalectomy still perform better than counterparts who received open procedures,23 and it should remain the first-line approach, especially for large, tumors that appear radiographically benign. However, patient and tumor selection are key, and in this study only 2 patients (2.6%) with a tumor of 6 cm or larger had a final pathological diagnosis of adrenal cortical carcinoma.
Aside from tumor size, the underlying adrenal pathology also has an important effect on perioperative outcomes. A multi-institutional review of 345 adrenalectomies found that patients with pheochromocytoma and malignant adrenal lesions had significantly higher perioperative complications rates than those with benign, nonpheochromocytoma tumors.24 Similarly, we found that patients with a diagnosis other than aldosterone-producing adenoma had a higher rate of complications. One of the postoperative deaths in this study was in a patient with adrenal metastasectomy; the role of adrenalectomy in this context is under constant evolution but has been shown to have the potential for long-term survival.25,26 In our practice, we perform adrenalectomy for isolated, completely resectable metastases or oligometastatic disease in selected patients, particularly those with melanoma or renal cell carcinoma. Surgeons need to be cognizant of the pathophysiology underlying different adrenal disorders, and adrenalectomy particularly in pheochromocytoma should be performed at specialized centers with expertise and resources to deal with the perioperative complications.
Conversion to either hand-assisted or open adrenalectomy was reported in 3.7% of cases in this study and was associated with increased postoperative complications and prolonged LOS. However, this does not mean that laparoscopy should be avoided as a first-line approach, even in patients with prior abdominal surgery.27 Even in difficult operations, laparoscopy affords improved visualization and can assist in the mobilization of surrounding structures. However, surgeons should not hesitate to convert to hand-assisted or open adrenalectomy when there is a concern about adrenal cortical carcinoma and capsular disruption or when scarring or bleeding obscures safe dissection.
This study is limited by its retrospective design. However, given the nature of adrenal surgery, where surgeons are considered high volume if they perform 4 or more adrenalectomies a year,28 this study represents the largest single-center experience of laparoscopic transabdominal adrenalectomy published in the literature (to our knowledge). This allows the delineation of specific patient-associated and disease-associated factors that influence postoperative complications and LOS, while largely removing confounders associated with institution or surgeon volume and specialty.7,28 Consequently, our findings may not translate to practices outside high-volume centers but can be used to inform patient selection and referral.
Laparoscopic adrenalectomy remains a safe procedure for most adrenal disorders. Careful selection of surgical candidates should be based on both patient and tumor factors, given that patients with more comorbidities, tumor sizes of 6 cm or larger, and pheochromocytoma are at risk for increased perioperative complications and longer LOSs. Laparoscopic adrenalectomy should be performed at experienced centers with multidisciplinary teams that are familiar with the perioperative care of these patients and their unique complications.
Corresponding Author: Yufei Chen, MD, Department of Endocrine Surgery, University of California San Francisco, 1600 Divisadero St, San Francisco, CA 94115 (email@example.com).
Accepted for Publication: May 13, 2018.
Published Online: August 8, 2018. doi:10.1001/jamasurg.2018.2648
Author Contributions: Dr Chen had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis
Concept and design: Chen, Scholten, Chomsky-Higgins, Shen, Suh, Duh.
Acquisition, analysis, or interpretation of data: Chen, Scholten, Chomsky-Higgins, Nwaogu, Gosnell, Seib, Suh, Duh.
Drafting of the manuscript: Chen, Scholten, Gosnell, Duh.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Chen, Scholten, Seib.
Administrative, technical, or material support: Chen, Scholten, Gosnell, Suh, Duh.
Supervision: Gosnell, Shen, Suh, Duh.
Conflict of Interest Disclosures: None reported.
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