Galunisertib plus neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer: a single-arm, phase 2 trial.

BACKGROUND: TGF-ß is an immunosuppressive cytokine that is upregulated in colorectal cancer. TGF-ß blockade improved response to chemoradiotherapy in preclinical models of colorectal adenocarcinoma. We aimed to test the hypothesis that adding the TGF-ß type I receptor kinase inhibitor galunisertib to neoadjuvant chemoradiotherapy would improve pathological complete response rates in patients with locally advanced rectal cancer. METHODS: This was an investigator-initiated, single-arm, phase 2 study done in two medical centres in Portland (OR, USA). Eligible patients had previously untreated, locally advanced, rectal adenocarcinoma, stage IIA-IIIC or IV as per the American Joint Committee on Cancer; Eastern Cooperative Oncology Group status 0-2; and were aged 18 years or older. Participants completed two 14-day courses of oral galunisertib 150 mg twice daily, before and during fluorouracil-based chemoradiotherapy (intravenous fluorouracil 225 mg/m2 over 24 h daily 7 days per week during radiotherapy or oral capecitabine 825 mg/m2 twice per day 5 days per week during radiotherapy; radiotherapy consisted of 50·4-54·0 Gy in 28-30 fractions). 5-9 weeks later, patients underwent response assessment. Patients with a complete response could opt for non-operative management and proceed to modified FOLFOX6 (intravenous leucovorin 400 mg/m2 on day 1, intravenous fluorouracil 400 mg/m2 on day 1 then 2400 mg/m2 over 46 h, and intravenous oxaliplatin 85 mg/m2 on day 1 delivered every 2 weeks for eight cycles) or CAPEOX (intravenous oxaliplatin 130 mg/m2 on day 1 and oral capecitabine 1000 mg/m2 twice daily for 14 days every 3 weeks for four cycles). Patients with less than complete response underwent surgical resection. The primary endpoint was complete response rate, which was a composite of pathological complete response in patients who proceeded to surgery, or clinical complete response maintained at 1 year after last therapy in patients with non-operative management. Safety was a coprimary endpoint. Both endpoints were assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02688712, and is active but not recruiting. FINDINGS: Between Oct 19, 2016, and Aug 31, 2020, 38 participants were enrolled. 25 (71%) of the 35 patients who completed chemoradiotherapy proceeded to total mesorectal excision surgery, five (20%) of whom had pathological complete responses. Ten (29%) patients had non-operative management, three (30%) of whom ultimately chose to have total mesorectal excision. Two (67%) of those three patients had pathological complete responses. Of the remaining seven patients in the non-operative management group, five (71%) had clinical complete responses at 1 year after their last modified FOLFOX6 infusion. In total, 12 (32% [one-sided 95% CI ≥19%]) of 38 patients had a complete response. Common grade 3 adverse events during treatment included diarrhoea in six (16%) of 38 patients, and haematological toxicity in seven (18%) patients. Two (5%) patients had grade 4 adverse events, one related to chemoradiotherapy-induced diarrhoea and dehydration, and the other an intraoperative ischaemic event. No treatment-related deaths occurred. INTERPRETATION: The addition of galunisertib to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer improved the complete response rate to 32%, was well tolerated, and warrants further assessment in randomised trials. FUNDING: Eli Lilly via ExIST program, The Providence Foundation.

Transanal total mesorectal excision outcomes for advanced rectal cancer in a complex surgical population.

BACKGROUND: Total mesorectal excision (TME) is the gold standard for oncologic resection in low and mid rectal cancers. However, abdominal approaches to TME can be hampered by poor visibility, inadequate retraction, and distal margin delineation. Transanal TME (taTME) is a promising hybrid technique that was developed to mitigate the difficulties of operating in the low pelvis and to optimize the circumferential resection and distal margins. METHODS: The objective of this study was to characterize our experience implementing taTME at our institution in a technically challenging patient population. We performed a retrospective review of consecutive patients who underwent taTMEs between November 2013 and May 2019 for rectal cancer at a tertiary community cancer center. Outcome measures included pathologic grading of TME specimen, post-operative complications, and oncologic outcomes. RESULTS: Forty-four patients with mid and low rectal cancer underwent low anterior resection via taTME. The most common staging modality was rectal MRI which demonstrated T3 or T4 tumors in 89% of our patients prior to neoadjuvant. Eighty-six percent of patients underwent neoadjuvant chemoradiation. The initial cases were performed sequentially as a single team, but we later transitioned to a synchronous, two-team approach. Ninety-one percent of TME grades were complete or near complete. Only one patient (2.3%) had a positive circumferential margin. Six patients developed anastomotic leaks with an overall anastomotic complication rate of 18.2%. Two patients (4.5%) with primary rectal cancer developed local recurrence, one of which developed multifocal local recurrence. CONCLUSIONS: Using the taTME approach on selected locally advanced low rectal cancers, especially in technically complex irradiated and obese male patients, has yielded comparably safe and effective outcomes to laparoscopic proctectomy.

TGFß suppresses CD8+ T cell expression of CXCR3 and tumor trafficking.

Transforming growth factor beta (TGFß) is a multipotent immunosuppressive cytokine. TGFß excludes immune cells from tumors, and TGFß inhibition improves the efficacy of cytotoxic and immune therapies. Using preclinical colorectal cancer models in cell type-conditional TGFß receptor I (ALK5) knockout mice, we interrogate this mechanism. Tumor growth delay and radiation response are unchanged in animals with Treg or macrophage-specific ALK5 deletion. However, CD8αCre-ALK5flox/flox (ALK5ΔCD8) mice reject tumors in high proportions, dependent on CD8+ T cells. ALK5ΔCD8 mice have more tumor-infiltrating effector CD8+ T cells, with more cytotoxic capacity. ALK5-deficient CD8+ T cells exhibit increased CXCR3 expression and enhanced migration towards CXCL10. TGFß reduces CXCR3 expression, and increases binding of Smad2 to the CXCR3 promoter. In vivo CXCR3 blockade partially abrogates the survival advantage of an ALK5ΔCD8 host. These data demonstrate a mechanism of TGFß immunosuppression through inhibition of CXCR3 in CD8+ T cells, thereby limiting their trafficking into tumors.

Enhanced Recovery After Surgery in Community Hospitals.

Multidisciplinary collaboration and administrative support are essential to enhanced recovery program (ERP) success. The key tenets for ERP are opiate-sparing pain regimen, decreased fasting, and minimizing intravenous fluids. Getting buy-in from community surgeons may be difficult due to varied practice patterns and clinical fragmentation. Prospective tracking of ERP outcomes will allow for more targeted interventions.

Benefit of Postresection Adjuvant Chemotherapy for Stage III Colon Cancer in Octogenarians: Analysis of the National Cancer Database.

BACKGROUND: Clinical trials demonstrate that postresection chemotherapy conveys survival benefit to patients with stage III colon cancer. It is unclear whether this benefit can be extrapolated to the elderly, who are underenrolled in clinical trials. OBJECTIVE: The purpose of this study was to determine outcomes of selected octogenarians with stage III colon cancer with/without postresection adjuvant therapy. DESIGN: This was a retrospective cohort study (2006-2011) using unadjusted Kaplan-Meier and adjusted Cox proportional hazards analyses of overall survival. SETTING: The study was conducted with the National Cancer Database. PATIENTS: We included patients 80 to 89 years of age who were undergoing curative-intent surgery for stage III colon cancer and excluded patients who received neoadjuvant therapy, died within 6 weeks of surgery, or had high comorbidity. MAIN OUTCOME MEASURES: Overall survival was the main measure. RESULTS: A total of 8141 octogenarians were included; 3483 (42.8%) received postresection chemotherapy, and 4658 (57.2%) underwent surgery alone. Patients receiving chemotherapy were younger (82.0 vs 84.0 years; p < 0.001), healthier (73.1% vs 70.4% with no comorbidities; p = 0.009), and more likely to have N2 disease (40.4% vs 32.8%; p < 0.001). Overall survival was improved in patients receiving adjuvant chemotherapy (median = 61.7 vs 35.0 months; p < 0.001). Subgroup analysis of patients offered chemotherapy but refusing (n = 1315) demonstrated overall survival worse than those receiving adjuvant chemotherapy (median = 42.7 vs 61.7 months; p < 0.001). Multivariable analysis adjusting for potential confounders showed therapy with surgery alone to be independently associated with increased mortality hazard (HR = 1.83; p < 0.001), and the mortality hazard remained elevated in patients who voluntarily refused adjuvant therapy (HR = 1.45; p < 0.001). LIMITATIONS: The study was limited by its retrospective, nonrandomized design. CONCLUSIONS: In selected octogenarians with stage III colon cancer, postresection adjuvant chemotherapy was associated with superior overall survival. However, less than half of the octogenarians with stage III colon cancer in the National Cancer Database received it. The remaining majority, who were all fit and survived ≥6 weeks postsurgery, could have derived benefit from adjuvant chemotherapy. This represents a substantial opportunity for quality improvement in treating octogenarians with stage III colon cancer.

Using a modification of the Clavien-Dindo system accounting for readmissions and multiple interventions: defining quality for pancreaticoduodenectomy.

BACKGROUND: The Clavien-Dindo system (CD) does not change the grade assigned a complication when multiple readmissions or interventions are required to manage a complication. We apply a modification of CD accounting for readmissions and interventions to pancreaticoduodenectomy (PD). METHODS: PDs done between 1999 and 2009 were reviewed. CD grade IIIa complications requiring more than one intervention and II and IIIa complications requiring significantly prolonged lengths of stay including all 90-day readmissions were classified severe-adverse-postoperative-outcomes (SAPO). CD IIIb, IV, and V complications were also classified SAPOs. All other complications were considered minor-adverse-postoperative-outcomes (MAPO). RESULTS: Four-hundred forty three of 490 PD patients (90.4%) had either no complication or a complication of low to moderate CD grade (I, II, IIIa). When reclassified by the new metric, 92 patient-outcomes (19%) were upgraded from CD II or IIIa to SAPO. One-hundred thirty nine patients (28.4%) had a SAPO. Multivariable regression identified age >75 years, pylorus preservation and operative blood loss >1,500 ml as predictors of SAPO. Age was not associated with poor outcome using the unmodified CD system. CONCLUSIONS: Established systems may under-grade the severity of some complications following PD. We define a procedure-specific modification of CD accounting for readmissions and multiple interventions. Using this modification, advanced age, pylorus preservation, and significant blood loss are associated with poor outcome.

CA 19-9 nonproduction is associated with poor survival after resection of pancreatic adenocarcinoma.

BACKGROUND: Carbohydrate antigen (CA) 19-9 is the most common serum biomarker used in pancreatic adenocarcinoma (PC). Elevated preoperative levels have been shown to correlate with more advanced stage, greater risk of unresectability, and overall worse survival. The prognostic value of CA 19-9 nonproduction, which is present in an estimated 5% to 15% of the population, is unclear. We sought to determine whether CA 19-9 nonproduction was associated with worse survival after PC resection. METHODS: We retrospectively reviewed our institution's prospective pancreatic database for all PC patients with documented preoperative CA 19-9 values who underwent resection with curative intent from March 1992 to August 2009. After excluding 10 perioperative deaths, 200 patients remained for analysis. RESULTS: Mean and median follow-up was 23.3 and 16.1 months, respectively. Median survival in months for patients with preoperative CA 19-9 levels in U/mL by category was as follows: normal (5.1 to 36.9): 32, nonproduction (≤ 5): 21, mildly elevated (37 to 99.9): 35, highly elevated (100+): 16. Factors significantly associated with worse overall survival were: nonwhite race, nonproduction or highly elevated preoperative CA 19-9 (≥ 100 U/mL), estimated blood loss ≥ 1 L, tumor size (≥ 2 cm), lymph node-positivity, and advanced (3/4) histologic grade. On multivariate analysis, only CA 19-9 nonproduction or highly elevated production, estimated blood loss ≥ 1 L, advanced histologic grade, and node positivity remained significant in the final model. CONCLUSIONS: CA 19-9 nonproduction is not associated with improved survival after pancreatic cancer resection, as has previously been asserted, when compared with patients with normal and elevated levels.

Colonoscopy is high yield in spinal cord injury.

OBJECTIVES/BACKGROUND: Colorectal cancer (CRC) can be prevented by routine colonoscopy. CRC screening in special populations, e.g. spinal cord injury and disorders, presents unique barriers and, potentially, a higher risk of complications. We were concerned about potentially higher risks of complications and sought to determine the safety of colonoscopy. METHODS: Retrospective observational design using medical record review for 311 patients who underwent 368 colonoscopies from two large VA SCI centers from 1997-2008. Patient demographics and peri-procedural characteristics, including indication, bowel prep quality, and pathological findings are presented. Descriptive statistics are presented. RESULTS: The population was predominantly male and Caucasian, and 199 (64%) had high-level injuries (T6 or above). Median age at colonoscopy was 61 years (interquartile range 53-69). Just <1/2 of the colonoscopies were diagnostic, usually for evidence of rectal bleeding. Although a majority of colonoscopies were reported as poorly prepped, the proportion that were adequately prepped increased over time (from 3.7 to 61.3%, P = <0.0001). Of the 146 polyps removed, 101 (69%) were adenomas or carcinomas. Ten subjects had 11 complications, none of which required surgical intervention. CONCLUSIONS: Although providing quality colonoscopic care in this population is labor intensive, the data suggests that it appears safe and therapeutically beneficial. The results indicate that the risk of screening is outweighed by the likelihood of finding polyps. Recognition of the benefit of colonoscopy in this population may have improved bowel prep and reporting over time. Spinal cord injury providers should continue to offer screening or diagnostic colonoscopy to their patients when indicated, while being aware of the special challenges that they face.

Is Illinois heeding the call to regionalize pancreatic surgery?

BACKGROUND AND OBJECTIVES: Recommendations to refer pancreatic procedures to high-volume centers have been in place for a decade. We sought to determine whether regionalization of pancreatic procedures to high-volume centers is occurring in Illinois. METHODS: We compared pancreatic procedures performed in Illinois hospitals from 2000 to 2004 [time period (TP) 1] versus 2005-2009 (TP2) for changes in inpatient mortality and hospital volume. Hospitals were categorized into low- (LVH), intermediate- (IVH), or high-volume (HVH). RESULTS: From TP1 to TP2, there was a 23% increase in absolute case volume (2,232-2,737), despite fewer hospitals performing pancreatic procedures (114-95). In hospital mortality decreased (5.5-3.3%, P < 0.01) and was lowest at HVHs. LVHs and IVHs were associated with a 4.7 and 3.0 higher odds of mortality, respectively (both P < 0.001). Overall, HVHs performed 659 (+73%) more procedures, whereas cumulative procedure volume dropped by 154 cases at LVHs (+1%) and IVHs (-18%). CONCLUSIONS: We observed limited evidence of regionalization of pancreatic procedures in Illinois. The increase in HVH case volume cannot be solely attributed to regionalization, given the corresponding modest decrease seen at non-HVHs. There is opportunity for Illinois hospitals to implement strategies such as selective referral to improve mortality after pancreatic resection.

Defining quality for distal pancreatectomy: does the laparoscopic approach protect patients from poor quality outcomes?

INTRODUCTION: Established systems for grading postoperative complications do not change the assigned grade when multiple interventions or readmissions are required to manage a complication. Studies using these systems may misrepresent outcomes for the surgical procedures being evaluated. We define a quality outcome for distal pancreatectomy (DP) and use this metric to compare laparoscopic distal pancreatectomy (LDP) to open distal pancreatectomy (ODP). METHODS: Records for patients undergoing DP between January 2006 and December 2009 were reviewed. Clavien-Dindo grade IIIb, IV, and V complications were classified as severe adverse--poor quality--postoperative outcomes (SAPOs). II and IIIa complications requiring either significantly prolonged overall lengths of stay including readmissions within 90 days or more than one invasive intervention were also classified as SAPOs. RESULTS: By Clavien-Dindo system alone, 91 % of DP patients had either no complication or a low/moderate grade (I, II, IIIa) complication. Using our reclassification, however, 25 % had a SAPO. Patients undergoing LDP demonstrated a Clavien-Dindo complication profile identical to that for SDP but demonstrated significantly shorter overall lengths of stay, were less likely to require perioperative transfusion, and less likely to have a SAPO. CONCLUSIONS: Established systems undergrade the severity of some complications following DP. Using a procedure-specific metric for quality, we demonstrate that LDP affords a higher quality postoperative outcome than ODP.

How is the Department of Veterans Affairs addressing the new Accreditation Council for Graduate Medical Education intern work hour limitations? Solutions from the Association of Veterans Affairs Surgeons.

BACKGROUND: The Accreditation Council for Graduate Medical Education implemented new intern work-hour regulations in July 2011 that have unique implications for surgical training at Veterans Affairs (VA) medical centers. Implementation of these new regulations required profound restructuring of trainee night coverage systems at many VA medical centers. This article offers approaches and potential solutions to the Accreditation Council for Graduate Medical Education regulations used by different surgery programs throughout the country that are applicable to the VA training environment. METHODS: The information contained in this article was derived from the opinion of a panel of academic surgical leaders in the VA system and responses to a survey that was sent to national VA surgical leaders. RESULTS: The most common solution chosen by the VA centers was hiring physician extenders (37%). The most common type of extender was a nonphysician extender, that is, nurse practitioner or physician assistant (70%), followed by a surgical hospitalist (33%), and surgical resident moonlighter (24%). Other common solutions included the following: night float for residents (22%) or interns (19%), establishing early versus late shifts (19%), or establishing cross-institutional or disciplinary coverage (19%). CONCLUSIONS: The public expects the medical community to produce safe, experienced surgeons, while demanding they are well rested and directly supervised at all times. The ability to meet these expectations can be challenging.

Assessing compliance with national quality measures to improve colorectal cancer care at the VA.

BACKGROUND: The US Department of Veterans Affairs (VA) Office of Quality and Performance's July 2009 report detailed the quality of VA colorectal cancer (CRC) care on the basis of 10 quality indicators (QIs). Of 21 Veterans Integrated Service Networks (VISNs), the authors' VISN ranked last or near last on more than half of the QIs. The aim of this study was to compare a national-level assessment of performance with an institutional-level clinical review. METHODS: The authors reabstracted all patients seen at surgical hospitals within their VISN during the time period of the Office of Quality and Performance report and reanalyzed their performance on the 10 QIs. A number of quality improvement efforts were also implemented to further boost performance, including the creation of a computerized patient record system CRC order set and quarterly surveillance meetings. RESULTS: After reanalysis of the VISN's QI performance for CRC patients during the time period of the OQP report, the VISN performed 18% better than reported and 2% better than the national average. Since that time, a multidisciplinary CRC committee has implemented quality improvement measures that have further improved QI performance. CONCLUSIONS: There is variability between administrative quality assessments and clinically abstracted data. Care must be taken when analyzing QIs at the national level.

Zone I gunshot neck injury treated with common carotid and esophageal stent grafts.

Management of zone I gunshot injuries to the neck is controversial. Endovascular and endoscopic therapies are appealing minimally invasive alternatives, but they are still evolving. This case report demonstrates effective stent grafting of an arterial and an esophageal zone I neck injury after a civilian gunshot.

A multicenter analysis of distal pancreatectomy for adenocarcinoma: is laparoscopic resection appropriate?

BACKGROUND: As compared with open distal pancreatectomy (ODP), laparoscopic distal pancreatectomy (LDP) affords improved perioperative outcomes. The role of LDP for patients with pancreatic ductal adenocarcinoma (PDAC) is not defined. STUDY DESIGN: Records from patients undergoing distal pancreatectomy (DP) for PDAC from 2000 to 2008 from 9 academic medical centers were reviewed. Short-term (node harvest and margin status) and long-term (survival) cancer outcomes were assessed. A 3:1 matched analysis was performed for ODP and LDP cases using age, American Society of Anesthesiologists (ASA) class, and tumor size. RESULTS: There were 212 patients who underwent DP for PDAC; 23 (11%) of these were approached laparoscopically. For all 212 patients, 56 (26%) had positive margins. The mean number of nodes (+/- SD) examined was 12.6 +/-8.4 and 114 patients (54%) had at least 1 positive node. Median overall survival was 16 months. In the matched analysis there were no significant differences in positive margin rates, number of nodes examined, number of patients with at least 1 positive node, or overall survival. Logistic regression for all 212 patients demonstrated that advanced age, larger tumors, positive margins, and node positive disease were independently associated with worse survival; however, method of resection (ODP vs. LDP) was not. Hospital stay was 2 days shorter in the matched comparison, which approached significance (LDP, 7.4 days vs. ODP, 9.4 days, p = 0.06). CONCLUSIONS: LDP provides similar short- and long-term oncologic outcomes as compared with OD, with potentially shorter hospital stay. These results suggest that LDP is an acceptable approach for resection of PDAC of the left pancreas in selected patients.

Prevalence and predictors of hepatic steatosis in adults with newly diagnosed chronic liver disease due to hepatitis C.

Obesity appears to be a risk factor for hepatic steatosis, which has been implicated in the development of hepatic fibrosis in patients with hepatitis C virus infection. We conducted the current study to examine whether obesity is associated with hepatic steatosis among patients with chronic hepatitis C identified from a population-based cohort. Study participants were persons with chronic hepatitis C who had had a liver biopsy, identified from a population-based study of persons with newly identified chronic liver disease conducted in gastroenterology practices. Data were collected through patient interviews, medical record abstraction, and review of previously performed liver biopsies. The outcome variable of interest was significant steatosis, defined as steatosis grade > or =2 determined from liver biopsy samples. Univariate and multivariate analyses were performed using logistic regression techniques. The analysis included 450 patients with chronic hepatitis C with available liver biopsy slides. Overall, only 15.8% of subjects had significant hepatic steatosis (grade > or =2), while 35.9% of obese subjects had significant steatosis. In multivariate analysis, significant fibrosis (defined as > or = grade 2) (odds ratio [OR], 3.43; 95% confidence interval [CI], 1.59-7.37), obesity (OR, 3.32; 95% CI, 1.84-5.98), genotype 3 (OR, 2.5; 95% CI, 1.09-5.75), and the presence of multiple metabolic comorbidities (OR, 1.91; 95% CI, 0.88-4.11) were independently associated with steatosis. In this unique United States cohort of patients with newly diagnosed chronic liver disease due to hepatitis C, obesity was independently associated with hepatic steatosis. The results of this study provide additional evidence that obesity worsens liver damage in patients with chronic hepatitis C, and suggest a role for weight loss as a treatment modality in these patients.

Effect of surgeon training, specialization, and experience on outcomes for cancer surgery: a systematic review of the literature.

BACKGROUND: Outcomes after cancer resections have been shown to be better for high-volume surgeons compared with low-volume surgeons; however, reasons for this relationship have been difficult to identify. The objective of this study was to assess studies examining the effect of surgeon training and experience on outcomes in surgical oncology. METHODS: A systematic review of the literature was performed to assess articles examining the impact of surgeon training, certification, and experience on outcomes. Studies were included if they examined cancer resections and performed multivariable analyses adjusting for relevant confounding variables. RESULTS: An extensive literature search identified 29 studies: 27 examined surgeon training/specialization, 1 assessed surgeon certification, and 4 evaluated surgeon experience. Of the 27 studies examining training/specialization, 25 found that specialized surgeons had better outcomes than nonspecialized surgeons. One study found that American Board of Surgery (ABS)-certified surgeons had better outcomes than noncertified surgeons. Of the two studies examining time since ABS certification, both found that increasing time was associated with better outcomes. Of the four studies that examined experience, three studies found that increasing surgeon experience was associated with improved outcomes. CONCLUSIONS: Although numerous studies have examined the impact of surgeon factors on outcomes, only a few cancers have been examined, and outcome measures are inconsistent. Most studies do not appear robust enough to support major policy decisions. There is a need for better data sources and consistent analyses which assess the impact of surgeon factors on a broad range of cancers and help to uncover the underlying reasons for the volume-outcome association.

Deadly partners: interdependence of alcohol and trauma in the clinical setting.

Trauma is the leading cause of death for Americans aged 1 to 45. Over a third of all fatal motor vehicle collisions and nearly eighty percent of completed suicides involve alcohol. Alcohol can be both a cause of traumatic injury as well as a confounding factor in the diagnosis and treatment of the injured patient. Fortunately, brief interventions after alcohol-related traumatic events have been shown to decrease both trauma recidivism and long-term alcohol use. This review will address the epidemiology of alcohol-related trauma, the influence of alcohol on mortality and other outcomes, and the role of prevention in alcohol-related trauma, within the confines of the clinical setting.

Improved quality of life after bilateral laparoscopic adrenalectomy for Cushing's disease: a 10-year experience.

OBJECTIVE: To determine long-term quality of life after bilateral adrenalectomy for persistent Cushing's disease after transsphenoidal pituitary tumor resection. SUMMARY BACKGROUND DATA: Bilateral adrenalectomy for symptomatic relief of persistent hypercortisolism appears to be an effective treatment option. However, few studies have examined long-term outcomes in this patient population. METHODS: Retrospective review of 39 patients treated by bilateral laparoscopic adrenalectomy for Cushing's disease from 1994 to 2004. Patients completed a follow-up phone survey, including our Cushing-specific questionnaire and the SF-12v2 health survey. Patients then refrained from taking their steroid replacement for 24 hours, and serum cortisol and ACTH levels were measured. RESULTS: Three patients died at 12, 19, and 50 months following surgery from causes unrelated to adrenalectomy. The remaining 36 patients all responded to the study questionnaire (100% response rate). Patients were between 3 months and 10 years post-adrenalectomy. We had zero operative mortalities and a 10.3% morbidity rate. Our incidence of Nelson's syndrome requiring clinical intervention was 8.3%; 89% of patients reported an improvement in their Cushing-related symptoms, and 91.7% would undergo the same treatment again. Twenty of 36 (55%) and 29 of 36 (81%) patients fell within the top two thirds of the national average for physical and mental composite scores, respectively, on the SF-12v2 survey. An undetectable serum cortisol level was found in 79.4% of patients. CONCLUSIONS: Laparoscopic bilateral adrenalectomy for symptomatic Cushing's disease is a safe and effective treatment option. The majority of patients experience considerable improvement in their Cushing's disease symptoms, and their quality of life equals that of patients initially cured by transsphenoidal pituitary tumor resection.