Anthony W. Castleberry

Surgical revascularization is associated with maximal survival in patients with ischemic mitral regurgitation: a 20-year experience.

Background— The optimal treatment for ischemic mitral regurgitation remains actively debated. Our objective was to evaluate the relationship between ischemic mitral regurgitation treatment strategy and survival. Methods and Results— We retrospectively reviewed patients at our institution diagnosed with significant coronary artery disease and moderate or severe ischemic mitral regurgitation from 1990 to 2009, categorized by medical treatment alone, percutaneous coronary intervention, coronary artery bypass grafting (CABG), or CABG plus mitral valve repair or replacement. Kaplan-Meier methods and multivariable Cox proportional hazards analyses were performed to assess the relationship between treatment strategy and survival, with the use of propensity scores to account for nonrandom treatment assignment. A total of 4989 patients were included: medical treatment alone=36%, percutaneous coronary intervention=26%, CABG=33%, and CABG plus mitral valve repair or replacement=5%. Median follow-up was 5.37 years. Compared with medical treatment alone, significantly lower mortality was observed in patients treated with percutaneous coronary intervention (adjusted hazard ratio, 0.83; 95% confidence interval, 0.76–0.92; P=0.0002), CABG (adjusted hazard ratio, 0.56; 95% confidence interval, 0.51–0.62; P<0.0001), and CABG plus mitral valve repair or replacement (adjusted hazard ratio, 0.69; 95% confidence interval, 0.57–0.82; P<0.0001). There was no significant difference in these results based on mitral regurgitation severity. Conclusions— Patients with significant coronary artery disease and moderate or severe ischemic mitral regurgitation undergoing CABG alone demonstrated the lowest risk of death. CABG with or without mitral valve surgery was associated with lower mortality than either percutaneous coronary intervention or medical treatment alone.

Concomitant Vascular Reconstruction During Pancreatectomy for Malignant Disease: A Propensity Score–Adjusted, Population-Based Trend Analysis Involving 10 206 Patients

OBJECTIVE To assess trends in the frequency of concomitant vascular reconstructions (VRs) from 2000 through 2009 among patients who underwent pancreatectomy, as well as to compare the short-term outcomes between patients who underwent pancreatic resection with and without VR. DESIGN Single-center series have been conducted to evaluate the short-term and long-term outcomes of VR during pancreatic resection. However, its effectiveness from a population-based perspective is still unknown. Unadjusted, multivariable, and propensity score-adjusted generalized linear models were performed. SETTING Nationwide Inpatient Sample from 2000 through 2009. PATIENTS A total of 10,206 patients were involved. MAIN OUTCOME MEASURES Incidence of VR during pancreatic resection, perioperative in-hospital complications, and length of hospital stay. RESULTS Overall, 10,206 patients were included in this analysis. Of these, 412 patients (4.0%) underwent VR, with the rate increasing from 0.7% in 2000 to 6.0% in 2009 (P < .001). Patients who underwent pancreatic resection with VR were at a higher risk for intraoperative (propensity score-adjusted odds ratio, 1.94; P = .001) and postoperative (propensity score-adjusted odds ratio, 1.36; P = .008) complications, while the mortality and median length of hospital stay were similar to those of patients without VR. Among the 25% of hospitals with the highest surgical volume, patients who underwent pancreatic surgery with VR had significantly higher rates of postoperative complications and mortality than patients without VR. CONCLUSIONS The frequency of VR during pancreatic surgery is increasing in the United States. In contrast with most single-center analyses, this population-based study demonstrated that patients who underwent VR during pancreatic surgery had higher rates of adverse postoperative outcomes than their counterparts who underwent pancreatic resection only. Prospective studies incorporating long-term outcomes are warranted to further define which patients benefit from VR.

Antegrade versus retrograde cerebral perfusion for hemiarch replacement with deep hypothermic circulatory arrest: Does it matter? A propensity-matched analysis

OBJECTIVE The choice of cerebral perfusion strategy for aortic arch surgery has been debated, and the superiority of antegrade (ACP) or retrograde (RCP) cerebral perfusion has not been shown. We examined the early and late outcomes for ACP versus RCP in proximal (hemi-) arch replacement using deep hypothermic circulatory arrest (DHCA). METHODS A retrospective analysis of a prospectively maintained database was performed for all patients undergoing elective and nonelective hemiarch replacement at a single referral institution from June 2005 to February 2013. Total arch cases were excluded to limit the analysis to shorter DHCA times and a more uniform patient population for whom clinical equipoise regarding ACP versus RCP exists. A total of 440 procedures were identified, with 360 (82%) using ACP and 80 (18%) using RCP. The endpoints included 30-day/in-hospital and late outcomes. A propensity score with 1:1 matching of 40 pre- and intraoperative variables was used to adjust for differences between the 2 groups. RESULTS All 80 RCP patients were propensity matched to a cohort of 80 similar ACP patients. The pre- and intraoperative characteristics were not significantly different between the 2 groups after matching. No differences were found in 30-day/in-hospital mortality or morbidity outcomes. The only significant difference between the 2 groups was a shorter mean operative time in the RCP cohort (P = .01). No significant differences were noted in late survival (P = .90). CONCLUSIONS In proximal arch operations using DHCA, equivalent early and late outcomes can be achieved with RCP and ACP, although the mean operative time is significantly less with RCP, likely owing to avoidance of axillary cannulation. Questions remain regarding comparative outcomes with straight DHCA and lesser degrees of hypothermia.

Surgical management of complex rectourethral fistulas in irradiated and nonirradiated patients.

BACKGROUND: Rectourethral fistulas are an uncommon, yet devastating occurrence after treatment for prostate cancer or trauma, and their surgical management has historically been nonstandardized. Anecdotally, irradiated rectourethral fistulas portend a worse prognosis. OBJECTIVE: To review outcomes after surgical treatment of rectourethral fistulas in radiated and nonirradiated patients to construct a logical surgical algorithm. DESIGN AND SETTING: A retrospective review was undertaken of all patients presenting to Duke University with the diagnosis of rectourethral fistula from 1996 to 2012. PATIENTS: Thirty-seven patients presented with and were treated for rectourethral fistulas: 21 received radiation, and a rectourethral fistula from trauma or iatrogenic injury developed in 16. MAIN OUTCOME MEASURES: The groups were compared regarding their functional outcomes, including healing, time to healing, continence, and recurrence. RESULTS: There were no significant differences in patient characteristics between groups. Patients who had irradiated rectourethral fistulas had a significantly higher rate of passage of urine through the rectum and wound infections, a higher rate of crystalloid infusion and blood transfusion requirements, and a longer time to ostomy reversal than nonirradiated patients. Patients who had irradiated rectourethral fistulas underwent more complex operative repairs, including gracilis interposition flaps (38%) and pelvic exenterations (19%), whereas nonirradiated patients most commonly underwent a York-Mason repair (50%). There were no statistically significant differences in rectourethral fistula healing or in postoperative and functional outcomes. Only 55% of irradiated patients had their ostomy reversed versus 91% in the nonirradiated group. LIMITATIONS: This study was limited by the small sample size and the retrospective nature of the review. CONCLUSIONS: Repair of rectourethral fistulas caused by radiation has a significantly higher wound infection rate and median time to healing, and lower overall stomal reversal rate than nonradiation-induced rectourethral fistulas. Patients who had irradiated rectourethral fistulas required significantly more complex operations, likely contributing to the higher morbidity, mortality, and lower fistula closure rate. We propose an algorithm for approaching rectourethral fistulas based on etiology.

Modest improvement in overall survival for patients with metastatic pancreatic cancer: a trend analysis using the surveillance, epidemiology, and end results registry from 1988 to 2008.

Objectives Patients with pancreatic adenocarcinoma often present with distant metastatic disease. We aimed to assess whether improvements in survival of clinical trials translated to a population-based level. Methods The US Surveillance, Epidemiology, and End Results registry was queried. Adult patients with distant metastatic adenocarcinoma of the pancreas were included from 1988 to 2008. Overall survival was analyzed using Kaplan-Meier curves as well as multivariable-adjusted Cox proportional hazards models. Results In total, 32,452 patients were included. Mean age was 67.6 (SD: 11.7) years, and 15,341 (47.3%) were female. Median overall survival was 3 months (95% confidence interval [CI], 3–3 months), which increased from 2 (CI, 2–2) months in 1988 to 3 (CI, 3–4) months in 2008. After adjustment for multiple covariates, the hazard ratio (HR) decreased by 0.977 per year (CI, 0.975–0.980). In multivariable-adjusted survival analyses, tumor location in the pancreatic body/tail (HR, 1.10), male sex (HR, 1.09), increasing age (HR, 1.016), African American ethnicity (HR, 1.16), nonmarried civil status (HR, 1.18), and absence of radiotherapy (HR, 1.41) were associated with worse survival (P < 0.001 for all predictors). Conclusions The improvement in overall survival over the past 2 decades among patients with metastatic pancreatic adenocarcinoma is modest and disappointing. More effective therapeutic strategies for advanced disease are desperately needed.

Use of Lung Allografts from Brain-Dead Donors after Cardiopulmonary Arrest and Resuscitation

RATIONALE Patients who progress to brain death after resuscitation from cardiac arrest have been hypothesized to represent an underused source of potential organ donors; however, there is a paucity of data regarding the viability of lung allografts after a period of cardiac arrest in the donor. OBJECTIVES To analyze postoperative complications and survival after lung transplant from brain-dead donors resuscitated after cardiac arrest. METHODS The United Network for Organ Sharing database records donors with cardiac arrest occurring after brain death. Adult recipients of lung allografts from these arrest/resuscitation donors between 2005 and 2011 were compared with nonarrest donors. Propensity score matching was used to reduce the effect of confounding. Postoperative complications and overall survival were assessed using McNemars test for correlated binary proportions and Kaplan-Meier methods. MEASUREMENTS AND MAIN RESULTS A total of 479 lung transplant recipients from arrest/resuscitation donors were 1:1 propensity matched from a cohort of 9,076 control subjects. Baseline characteristics in the 1:1-matched cohort were balanced. There was no significant difference in perioperative mortality, airway dehiscence, dialysis requirement, postoperative length of stay (P ≥ 0.38 for all), or overall survival (P = 0.52). A subanalysis of the donor arrest group demonstrated similar survival when stratified by resuscitation time quartile (P = 0.38). CONCLUSIONS There is no evidence of inferior outcomes after lung transplant from brain-dead donors who have had a period of cardiac arrest provided that good lung function is preserved and the donor is otherwise deemed acceptable for transplantation. Potential expansion of the donor pool to include cardiac arrest as the cause of brain death requires further study.

Survival for stage IB cervical cancer with positive lymph node involvement : a comparison of completed vs. abandoned radical hysterectomy

PURPOSE Management for stage IB cervical cancer with intraoperative positive pelvic lymph nodes (LNs) is controversial. We compare 5-year survival rates for women with completed vs. abandoned radical hysterectomy (RH) who were treated with postoperative radiation therapy (RT). PATIENTS AND METHODS We identified all women diagnosed with stage IB cervical carcinoma from the Surveillance, Epidemiology, and End Results database from 1988-1998. Women with positive LN involvement who had undergone a complete pelvic and para-aortic lymphadenectomy were compared for 5-year survival based on whether a RH was completed or abandoned at the time of surgery. All women then received postoperative RT. Survival rates were calculated using the Kaplan-Meier method, and the Chi square test was used for all univariate analysis. RESULTS From a cohort of 3116 women diagnosed with stage IB cervical cancer, 265 (8.7%) had positive pelvic LNs and a complete pelvic and para-aortic lymphadenectomy. Of these women, 163 had completion of their RH while RH was abandoned in 55. Positive pelvic LNs averaged 2.58+/-2.37 in the completed RH group and 2.42+/-1.63 in the abandoned RH group. Median follow-up was 6.42 years in the completed RH group and 5.75 years in the abandoned RH group. Five-year survival for the completed RH group was 69% compared with 71% in patients with abandoned RH (p=0.46). CONCLUSIONS Treatment for patients with positive pelvic LNs at the time of RH should be determined by overall morbidity of therapy since equivalent 5-year survival was found between the completed and abandoned RH groups.

Impact of donor cardiac arrest on heart transplantation

BACKGROUND Cardiac transplantation is an effective therapy for patients with end-stage heart failure, but it is still hindered by the lack of donor organs. A history of donor cardiac arrest raises trepidation regarding the possibility of poor post-transplant outcomes. The impact of donor cardiac arrest following successful cardiopulmonary resuscitation on heart transplant outcomes is unknown. Therefore, we sought to evaluate the impact of donor cardiac arrest on orthotropic heart transplantation using the United Network for Organ Sharing database. METHODS We performed a secondary longitudinal analysis of all cardiac transplants performed between April 1994 and December 2011 through the United Network for Organ Sharing registry. Multiorgan transplants, repeat transplants, and pediatric recipients were excluded. Survival analyses were performed using Kaplan-Meier methods as well as multivariate adjusted logistic regression and Cox proportional hazard models. RESULTS A total of 19,980 patients were analyzed. In 856 cases, the donors had histories of cardiac arrest, and in the remaining 19,124 cases, there was no history of donor cardiac arrest. The unadjusted 1-, 5-, and 10-year actuarial survival rates between the arrest and the nonarrest groups were not significantly different. Multivariate logistic regression demonstrated no difference in survival in the donor arrest group at 30 days, 1 year, or 3 years. Furthermore, the adjusted Cox proportional hazard model for cumulative survival also showed no survival difference between the 2 groups. CONCLUSION If standard recipient and donor transplantation criteria are met, a history of donor cardiac arrest should not prohibit the potential consideration of an organ for transplantation.

The Utility of Preoperative Six-Minute-Walk Distance in Lung Transplantation.

RATIONALE The use of 6-minute-walk distance (6MWD) as an indicator of exercise capacity to predict postoperative survival in lung transplantation has not previously been well studied. OBJECTIVES To evaluate the association between 6MWD and postoperative survival following lung transplantation. METHODS Adult, first time, lung-only transplantations per the United Network for Organ Sharing database from May 2005 to December 2011 were analyzed. Kaplan-Meier methods and Cox proportional hazards modeling were used to determine the association between preoperative 6MWD and post-transplant survival after adjusting for potential confounders. A receiver operating characteristic curve was used to determine the 6MWD value that provided maximal separation in 1-year mortality. A subanalysis was performed to assess the association between 6MWD and post-transplant survival by disease category. MEASUREMENTS AND MAIN RESULTS A total of 9,526 patients were included for analysis. The median 6MWD was 787 ft (25th-75th percentiles = 450-1,082 ft). Increasing 6MWD was associated with significantly lower overall hazard of death (P < 0.001). Continuous increase in walk distance through 1,200-1,400 ft conferred an incremental survival advantage. Although 6MWD strongly correlated with survival, the impact of a single dichotomous value to predict outcomes was limited. All disease categories demonstrated significantly longer survival with increasing 6MWD (P ≤ 0.009) except pulmonary vascular disease (P = 0.74); however, the low volume in this category (n = 312; 3.3%) may limit the ability to detect an association. CONCLUSIONS 6MWD is significantly associated with post-transplant survival and is best incorporated into transplant evaluations on a continuous basis given limited ability of a single, dichotomous value to predict outcomes.

Posterior Reversible Encephalopathy Syndrome Independently Associated With Tacrolimus and Sirolimus After Multivisceral Transplantation

Posterior reversible encephalopathy syndrome (PRES) is a small vessel microangiopathy of the cerebral vasculature that occurs in 0.5–5% of solid organ transplant recipients, most commonly associated with tacrolimus (Tac). Clinical manifestations include hypertension and neurologic symptoms. We report an adult multivisceral transplant recipient who experienced recurrent PRES initially associated with Tac and subsequently with sirolimus. A 49‐year‐old woman with short bowel syndrome underwent multivisceral transplantation due to total parenteral nutrition–related liver disease. She was initially maintained on Tac, mycophenalate mofetil (MMF) and prednisone. Three months after transplantation, she developed renal dysfunction, leading to a reduction in Tac and the addition of sirolimus. Eight months after transplantation, she developed PRES. Tac was discontinued and PRES resolved. Sirolimus was increased to maintain trough levels of 12–15 ng/mL. Fourteen months after transplant, she experienced recurrent PRES which resolved after discontinuing sirolimus. Currently 3 years posttransplant, she is maintained on cyclosporine, MMF and prednisone with no PRES recurrence. In addition to calcineurin inhibitors, sirolimus may also be associated with PRES after solid organ transplantation. Ours is the first report of sirolimus‐associated PRES in the setting of multivisceral transplantation. Identifying a safe alternative immunosuppression regimen was challenging but ultimately successful.