Carotid stenting and endarterectomy and contralateral carotid occlusion.

BACKGROUND: The presence of contralateral carotid occlusion (CCO) has been controversial throughout the history of carotid intervention. Some studies cite a higher stroke risk in the setting of CCO, whereas other studies document no difference in stroke risk. We investigated the risk of stroke after intervention in the setting of CCO in a large, national, validated dataset. METHODS: Data were obtained from the 2011-2014 American College of Surgeons National Surgical Quality Initiative Project files using targeted carotid endarterectomy (CEA), carotid angioplasty, and carotid artery stenting (CAS) data. Patient and procedural characteristics, and 30-day postoperative outcomes were compared using Pearson χ2 tests for categorical variables and Wilcoxon rank-sum tests for continuous variables. Logistic regression was used for multivariable analysis. The primary outcome measure was the stroke rate, with a secondary outcome of major adverse cardiovascular events. RESULTS: During the study period, 11,948 CEA and 422 CAS procedures were available for study, with significantly fewer CEA (4.73% of all CEA) than CAS (9.95%; P < .0001) occurring in the setting of CCO. CAS was associated with more severe degree of stenosis than CEA (P = .045). Multivariable logistic regression showed that stroke after procedures was higher in patients with CCO than without CCO (odds ratio, 1.73; 95% confidence interval, 1.08-2.76; P = .02), but specific procedure (CEA vs CAS) was not associated with stroke while controlling for confounders. However, when evaluating our secondary composite outcome, CCO was not associated with the outcome while controlling for confounders. CONCLUSIONS: There is currently a bias that CCO confers a higher risk on patients undergoing carotid procedures and this notion is manifest in the proportion of CEA and CAS procedures done in the setting of CCO. Our study observes that CCO provides only a minor influence on periprocedural stroke risk and that other factors are more closely tied to outcomes of CEA and CAS.

Jejunal arterial access for retrograde mesenteric stenting.

Endovascular approaches have replaced open surgical revascularization in most patients with mesenteric ischemia; however, flush ostial occlusions may not be amenable to traditional antegrade access. Retrograde mesenteric stenting has been previously described, but this technique requires a formal laparotomy and dissection of the proximal superior mesenteric artery. We present here a modification of this technique that requires only a "mini-laparotomy" and no open vascular repair of the superior mesenteric artery as well as a review of our initial institutional experience with this procedure. Our approach differs from previously described work by minimizing mesenteric dissection, avoiding the need for repair of an arteriotomy, and limiting the size of the laparotomy incision in this population of profoundly comorbid patients.

Low mortality rates after endovascular aortic repair expand use to high-risk patients.

OBJECTIVE: The 2010 endovascular aneurysm repair (EVAR) trial 2 (EVAR 2) reported that patients with comorbidity profiles rendering them unfit for open aneurysm repair who underwent EVAR did not experience a survival advantage compared with those who did not undergo intervention. These patients experienced a 30-day mortality of 7.3%, whereas reports from similar cohorts reported far lower mortality rates. The primary objective of our study was to compare the incidence of 30-day mortality in low- and high-risk patients undergoing EVAR in a contemporary data set, using patient risk stratification criteria from EVAR 2. Secondarily, we sought to identify risk factors associated with a disproportionate contribution to 30-day mortality risk. METHODS: Data were obtained from the 2005 to 2013 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Participant Use Data Files (N = 24,813). Patients were included in the high-risk cohort with the presence of renal, respiratory, or cardiac preoperative criteria alone or in combination. Renal impairment criteria were defined as dialysis and creatinine concentration >2.26 mg/dL. Respiratory impairment criteria included history of chronic obstructive pulmonary disease and preoperative ventilator support. Cardiac impairment criteria included history of myocardial infarction, congestive heart failure, angina, and prior coronary intervention. Patient and procedural characteristics and 30-day postoperative outcomes were compared using Pearson χ2 tests for categorical variables and Wilcoxon rank sum tests for continuous variables. RESULTS: Among 24,813 patients undergoing EVAR, 12,043 (48%) patients were characterized as high risk (at least one impairment criterion); 12,770 (52%) patients were stratified as low risk. The 30-day mortality rate was 1.9% in the high-risk cohort compared with the 7.3% reported by EVAR 2, and it was higher in the high-risk cohort compared with the low-risk cohort (1.9% vs 0.9%; P < .001). Whereas the presence of each comorbidity increased the odds of 30-day mortality (respiratory odds ratio [OR], 1.62; 95% confidence interval [CI], 1.16-2.26; P = .005; cardiac OR, 1.55; 95% CI, 1.14-2.10; P = .005), the presence of renal criteria disproportionately increased the odds of mortality threefold (OR, 3.42; 95% CI, 2.31-5.09; P < .001). CONCLUSIONS: Contemporary 30-day mortality after EVAR in high-risk patients is substantially lower than that reported in the EVAR 2 trial. Whereas low- and high-risk stratification by current comorbidity criteria is appropriate, attention needs to be paid to disproportionate risk contribution from renal disease to mortality compared with cardiac and pulmonary comorbidities. Given the lower mortality risk than previously described, patients stratified as high risk should be thoughtfully considered for definitive EVAR.

Laparotomy during endovascular repair of ruptured abdominal aortic aneurysms increases mortality.

OBJECTIVE: Subset analyses from small case series suggest patients requiring laparotomy during endovascular repair of ruptured abdominal aortic aneurysms (REVAR) have worse survival than those undergoing REVAR without laparotomy. Most concomitant laparotomies are performed for abdominal compartment syndrome. This study used data from the American College of Surgeons National Surgical Quality Improvement Program to determine whether the need for laparotomy during REVAR is associated with increased mortality. METHODS: Data were obtained from the 2005 to 2013 National Surgical Quality Improvement Program participant user files based on Current Procedural Terminology (American Medical Association, Chicago, Ill) and International Classification of Diseases-9 Edition coding. Patient and procedure-related characteristics and 30-day postoperative outcomes were compared using Pearson χ2 tests for categoric variables and Wilcoxon rank sum tests for continuous variables. A backward-stepwise multivariable logistic regression model was used to identify patient- and procedure-related factors associated with increased death after REVAR. RESULTS: We identified 1241 patients who underwent REVAR, and 91 (7.3%) required concomitant laparotomy. The 30-day mortality was 60% in the laparotomy group and 21% in the standard REVAR group (P < .001). The major complication rate was also higher in the laparotomy group (88% vs 63%; P < .001). Multivariable analysis showed laparotomy was strongly associated with 30-day mortality (odds ratio, 5.91; 95% confidence interval, 3.62-9.62; P < .001). CONCLUSIONS: Laparotomy during REVAR is a commonly used technique for the management of elevated intra-abdominal pressure and abdominal compartment syndrome development. The results of this study strongly confirm findings from smaller studies that the need for laparotomy during REVAR is associated with significantly worse 30-day survival.

Perioperative Optimization of Geriatric Lower Extremity Bypass in the Era of Increased Performance Accountability.

BACKGROUND: The initiation of bundled payment for care improvement by Centers for Medicare and Medicaid Services (CMS) has led to increased financial and performance accountability. As most vascular surgery patients are elderly and reimbursed via CMS, improving their outcomes will be critical for durable financial stability. As a first step in forming a multidisciplinary pathway for the elderly vascular patients, we sought to identify modifiable perioperative variables in geriatric patients undergoing lower extremity bypass (LEB). METHODS: The 2011-2013 LEB-targeted American College of Surgeons National Surgical Quality Improvement Program database was used for this analysis (n = 5316). Patients were stratified by age <65 (n = 2171), 65-74 (n = 1858), 75-84 (n = 1190), and ≥85 (n = 394) years. Comparisons of patient- and procedure-related characteristics and 30-day postoperative outcomes stratified by age groups were performed with Pearson χ2 tests for categorical variables and Wilcoxon rank-sum tests for continuous variables. RESULTS: During the study period, 5316 total patients were identified. There were 2171 patients aged <65 years, 1858 patients in the 65-74 years age group, 1190 patients in the 75-84 years age group, and 394 patients in the ≥85 years age group. Increasing age was associated with an increased frequency of cardiopulmonary disease (P < 0.001) and a decreased frequency of diabetes, tobacco use, and prior surgical intervention (P < 0.001). Only 79% and 68% of all patients were on antiplatelet and statin therapies, respectively. Critical limb ischemia occurred more frequently in older patients (P < 0.001). Length of hospital stay, transfusion requirements, and discharge to a skilled nursing facility increased with age (P < 0.001). Thirty-day amputation rates did not differ significantly with age (P = 0.12). CONCLUSIONS: Geriatric patients undergoing LEB have unique and potentially modifiable perioperative factors that may improve postoperative outcomes. These modifiers will be the basis of a multidisciplinary care path targeting the geriatric vascular surgery patients.

Significant variation in P2Y12 inhibitor use after peripheral vascular intervention in Medicare beneficiaries.

UNLABELLED: There is no consensus regarding whether to use antithrombotic medications in patients with peripheral artery disease after lower-extremity peripheral vascular intervention. OBJECTIVES: The main hypothesis is that significant variation exists regarding use of antithrombotic medications after lower-extremity peripheral vascular intervention. We sought to examine the patterns of postprocedural antithrombotic medication use and associated factors in Medicare patients. METHODS: We measured rates of P2Y12 inhibitor use after peripheral vascular intervention in a 100% national sample of Medicare beneficiaries with Part D prescription drug coverage. We used logistic regression modeling to examine associations between patient and clinical factors and P2Y12 inhibitor use. RESULTS: Between 2010 and 2012, a total of 85,830 patients underwent peripheral vascular intervention and had prescription drug claims. Overall, 18.3% of patients were treated with an oral anticoagulant, 19.1% received no P2Y12 inhibitor, 30.8% received a P2Y12 inhibitor before and after the procedure, 6.2% received a P2Y12 inhibitor for up to 30 days after the procedure, and 25.6% received a P2Y12 inhibitor for more than 30 days after the procedure. After adjustment, factors associated with P2Y12 inhibitor use included male sex; black race; history of renal disease, dementia, or heart failure; physician specialty; and clinical setting of the procedure. We observed a strong interaction effect between clinical setting and physician specialty (P < .001). CONCLUSIONS: One-fifth of patients who underwent lower-extremity peripheral vascular intervention did not fill a prescription for a P2Y12 inhibitor. Patients whose operators were surgeons or radiologists had lower odds of P2Y12 inhibitor use. More research to determine the optimal use and duration of antithrombotic medications after the procedure is warranted.

Mitogen-activated protein kinase (MAPK) hyperactivation and enhanced NRAS expression drive acquired vemurafenib resistance in V600E BRAF melanoma cells.

Although targeting the V600E activating mutation in the BRAF gene, the most common genetic abnormality in melanoma, has shown clinical efficacy in melanoma patients, response is, invariably, short lived. To better understand mechanisms underlying this acquisition of resistance to BRAF-targeted therapy in previously responsive melanomas, we induced vemurafenib resistance in two V600E BRAF+ve melanoma cell lines, A375 and DM443, by serial in vitro vemurafenib exposure. The resulting approximately 10-fold more vemurafenib-resistant cell lines, A375rVem and D443rVem, had higher growth rates and showed differential collateral resistance to cisplatin, melphalan, and temozolomide. The acquisition of vemurafenib resistance was associated with significantly increased NRAS levels in A375rVem and D443rVem, increased activation of the prosurvival protein, AKT, and the MAPKs, ERK, JNK, and P38, which correlated with decreased levels of the MAPK inhibitor protein, GSTP1. Despite the increased NRAS, whole exome sequencing showed no NRAS gene mutations. Inhibition of all three MAPKs and siRNA-mediated NRAS suppression both reversed vemurafenib resistance significantly in A375rVem and DM443rVem. Together, the results indicate a mechanism of acquired vemurafenib resistance in V600E BRAF+ve melanoma cells that involves increased activation of all three human MAPKs and the PI3K pathway, as well as increased NRAS expression, which, contrary to previous reports, was not associated with mutations in the NRAS gene. The data highlight the complexity of the acquired vemurafenib resistance phenotype and the challenge of optimizing BRAF-targeted therapy in this disease. They also suggest that targeting the MAPKs and/or NRAS may provide a strategy to mitigate such resistance in V600E BRAF+ve melanoma.

Targeting N-cadherin increases vascular permeability and differentially activates AKT in melanoma.

OBJECTIVE: We investigate the mechanism through which N-cadherin disruption alters the effectiveness of regional chemotherapy for locally advanced melanoma. BACKGROUND: N-cadherin antagonism during regional chemotherapy has demonstrated variable treatment effects. METHODS: Isolated limb infusion (ILI) with melphalan (LPAM) or temozolomide (TMZ) was performed on rats bearing melanoma xenografts after systemic administration of the N-cadherin antagonist, ADH-1, or saline. Permeability studies were performed using Evans blue dye as the infusate, and interstitial fluid pressure was measured. Immunohistochemistry of LPAM-DNA adducts and damage was performed as surrogates for LPAM and TMZ delivery. Tumor signaling was studied by Western blotting and reverse-phase protein array analysis. RESULTS: Systemic ADH-1 was associated with increased growth and activation of the PI3K (phosphatidylinositol-3 kinase)-AKT pathway in A375 but not DM443 xenografts. ADH-1 in combination with LPAM ILI improved antitumor responses compared with LPAM alone in both cell lines. Combination of ADH-1 with TMZ ILI did not improve tumor response in A375 tumors. ADH-1 increased vascular permeability without effecting tumor interstitial fluid pressure, leading to increased delivery of LPAM but not TMZ. CONCLUSIONS: ADH-1 improved responses to regional LPAM but had variable effects on tumors regionally treated with TMZ. N-cadherin-targeting agents may lead to differential effects on the AKT signaling axis that can augment growth of some tumors. The vascular targeting actions of N-cadherin antagonism may not augment some regionally delivered alkylating agents, leading to a net increase in tumor size with this type of combination treatment strategy.

SRC family kinase inhibition as a novel strategy to augment melphalan-based regional chemotherapy of advanced extremity melanoma.

BACKGROUND: Src kinase inhibition has been shown to augment the efficacy of chemotherapy. Dasatinib, a dual Src/Abl kinase inhibitor approved for the treatment of CML, is under investigation as monotherapy for tumors with abnormal Src signaling, such as melanoma. The goal of this study was to determine if Src kinase inhibition using dasatinib could enhance the efficacy of regionally administered melphalan in advanced extremity melanoma. METHODS: The mutational status of c-kit and patterns of gene expression predictive of dysregulated Src kinase signaling were evaluated in a panel of 26 human melanoma cell lines. The effectiveness of dasatinib was measured by quantifying protein expression and activation of Src kinase, focal adhesion kinase, and Crk-associated substrate (p130(CAS)), in conjunction with in vitro cell viability assays using seven melanoma cell lines. Utilizing a rat model of regional chemotherapy, we evaluated the effectiveness of systemic dasatinib in conjunction with regional melphalan against the human melanoma cell line, DM443, grown as a xenograft. RESULTS: Only the WM3211 cell line harbored a c-kit mutation. Significant correlation was observed between Src-predicted dysregulation by gene expression and sensitivity to dasatinib in vitro. Tumor doubling time for DM443 xenografts treated with systemic dasatinib in combination with regional melphalan (44.8 days) was significantly longer (p = 0.007) than either dasatinib (21.3 days) or melphalan alone (24.7 days). CONCLUSIONS: Systemic dasatinib prior to melphalan-based regional chemotherapy markedly improves the efficacy of this alkylating agent in this melanoma xenograft model. Validation of this concept should be considered in the context of a regional therapy clinical trial.

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.

Ureteral stenting in laparoscopic colorectal surgery.

BACKGROUND: Few studies have examined the current status of ureteral stent use or the indications for stenting, particularly in laparoscopic colorectal surgery. This study examines current national trends and predictors of ureteral stenting in patients undergoing major colorectal operations and the subsequent effects on perioperative outcomes. METHODS: The 2005-2011 National Surgical Quality Improvement participant user files were used to identify patients undergoing laparoscopic segmental colectomy, low anterior resection, or proctectomy. Trends in stent use were assessed across procedure types. To estimate the predictors of stent utilization, a forward-stepwise logistic regression model was used. A 3:1 nearest neighbor propensity match with subsequent multivariable adjustment was then used to estimate the impact of stents. RESULTS: A total of 42,311 cases were identified, of which 1795 (4.2%) underwent ureteral stent placement. Predictors of stent utilization included diverticular disease, need for radical resection (versus segmental colectomy), recent radiotherapy, and more recent calendar year. After adjustment, ureteral stenting appeared to be associated with a small increase in median operative time (44 min) and a trivial increase in length of stay (5.4%, P<0.001). However, there were no significant differences in morbidity or mortality. CONCLUSIONS: We describe the clinical predictors of ureteral stent usage in this patient population and report that while stenting adds to operative time, it is not associated with significantly increased morbidity or mortality after adjusting for diagnosis and comorbidities. Focused institutional studies are necessary in the future to address the utility of ureteral stents in the identification and possible prevention of iatrogenic injury.

Age and gender differences in substance screening may underestimate injury severity: a study of 9793 patients at level 1 trauma center from 2006 to 2010.

BACKGROUND: Although the relationship between psychoactive substance use and injury is known, evidence remains conflicting on the impact of substance use on clinical outcomes after injury. We hypothesized that preinjury substance use would negatively impact clinical outcomes. METHODS: National Trauma Registry American College of Surgeons identified patients (n = 9793) presenting to Duke Hospital from 2006 to 2010. Logistic regression models assessed potential predictors of receiving substance screening, mortality, length of stay, ventilator requirement, intensive care admission, or emergency department disposition. RESULTS: Forty-seven percent (4607/9793) of patients received blood alcohol screen (BAS) and 31% (3017/9793) received urine drug screen (UDS). Men were more likely to receive both BASs (P < 0.001) and UDSs (P = 0.001) than women after controlling for potential confounders. There was no significant difference between men and women over the legal limit for alcohol (OLLA; 27.2%, 95% confidence interval [CI]: 25.7%-28.8% versus 24.8%, 95% CI: 22.3%-27.5%). Similarly, younger patients more likely received both BASs (P < 0.001) and UDSs (P < 0.001) compared with older patients. The proportion of patients aged ≤45 y OLLA (26.5 %, 95% CI: 24.9%-28.2%) was similar to those aged >45 y OLLA (26.8%, 95% CI: 24.5%-29.3%). After controlling for potential confounders neither alcohol, nor tetrahydrocannabinol, nor cocaine was predictive of mortality, ventilator requirement, length of stay, or emergency department disposition, but a higher alcohol level (P = 0.0174) predicted intensive care admission. CONCLUSIONS: Females and those aged >45 y are less likely to receive BASs and UDSs. Differential screening that is biased may place patients at risk for receiving inadequate care.

Atypical aortic thrombus: should nonoperative management be first line?

BACKGROUND: Aortic thrombus in the absence of atherosclerotic plaque or aneurysm is rare, and its optimal management remains unclear. Although atypical aortic thrombus (AAT) has been historically managed operatively, successful nonoperative strategies have been recently reported. Here, we report our experience in treating patients with AAT that has evolved from a primarily operative approach to a first-line, nonoperative strategy. METHODS: Records of patients treated for AAT between 2008 and 2011 at our institution were reviewed. RESULTS: Ten female and three male patients with ages ranging from 27 to 69 were identified. Seven were treated operatively and 6 nonoperatively. Initial presentation was variable and included limb thromboembolic events (n = 6), visceral ischemia (n = 5), and stroke (n = 1). Associated risk factors included hypercoagulability (76%; n = 10) and hyperlipidemia (38%, n = 5). In the nonoperative group, complete thrombus resolution was obtained via anticoagulation (n = 5) or systemic thrombolysis (n = 1). Complete thrombus extraction was achieved in all operative patients. There were 11 significant complications in 5 of the 7 patients (71%) in the operative group, including intraoperative lower extremity embolism, pericardial effusion, stroke, and 1 death. There was 1 complication in the patients treated nonoperatively. The median hospital length of stay was 9 days (range 3-49) for those treated nonoperatively and 30 days (range 4-115) for those undergoing operative thrombectomy. CONCLUSIONS: Although AAT has traditionally been treated operatively, nonoperative management of AAT with anticoagulation or thrombolysis is feasible in selected patients and may lessen morbidity and length of hospitalization in those patients for whom it is appropriate.

Laparoscopic versus open Hartmann procedure for the emergency treatment of diverticulitis: a propensity-matched analysis.

BACKGROUND: A laparoscopic approach has been proposed to reduce the high morbidity and mortality associated with the Hartmann procedure for the emergency treatment of diverticulitis. OBJECTIVE: The objective of our study was to determine whether a laparoscopic Hartmann procedure reduces early morbidity or mortality for patients undergoing an emergency operation for diverticulitis. DESIGN: This is a comparative effectiveness study. A subset of the entire American College of Surgeons National Surgical Quality Improvement Program patient sample matched on propensity for undergoing their procedure with the laparoscopic approach were used to compare postoperative outcomes between laparoscopic and open groups. SETTING: This study uses data from the American College of Surgeons National Surgical Quality Improvement Program Participant User Files from 2005 through 2009. PATIENTS: All patients who underwent an emergency laparoscopic or open partial colectomy with end colostomy for colonic diverticulitis were reviewed. MAIN OUTCOME MEASURES: The main outcome measures were 30-day mortality and morbidity. RESULTS: Included in the analysis were 1186 patients undergoing emergency partial colectomy with end colostomy for diverticulitis. Among the entire cohort, the laparoscopic group had fewer overall complications (26% vs 41.7%, p = 0.008) and shorter mean length of hospitalization (8.9 vs 11.6 days, p = 0.0008). Operative times were not significantly different between groups. When controlling for potential confounders, a laparoscopic approach was not associated with a decrease in morbidity or mortality. In comparison with a propensity-match cohort, the laparoscopic approach did not reduce postoperative morbidity or mortality. LIMITATIONS: This study is limited by its retrospective nature and the absence of pertinent variables such as postoperative pain indices, time for return of bowel function, and rates of readmission. CONCLUSIONS: A laparoscopic approach to the Hartmann procedure for the emergency treatment of complicated diverticulitis does not significantly decrease postoperative morbidity or mortality in comparison with the open technique.

Hepatic resection for metastatic gastrointestinal stromal tumors in the tyrosine kinase inhibitor era.

BACKGROUND: Before the advent of tyrosine kinase inhibitors (TKIs), surgical resection was the primary treatment for hepatic gastrointestinal stromal tumor (GIST) metastases. Although TKIs have improved survival in the metastatic setting, outcomes after multimodal therapy comprised of hepatectomy and TKIs for GIST are unknown. The objective of this study was to determine whether combination therapy for hepatic GIST metastases is associated with improved overall survival compared with reported outcomes from surgery or TKI therapy alone. METHODS: Demographics, clinicopathologic tumor characteristics, treatments, and outcomes of patients who underwent hepatic resection at 3 high-volume centers from 1995 to 2010 were reviewed. RESULTS: In total, 39 patients underwent hepatectomy for metastatic GISTs, and 27 patients received postoperative TKI therapy. At a median follow-up of 39.7 months, 23 patients (59%) experienced recurrence at a median of 18 months. The 1-year, 2-year, and 3-year overall survival rates were 96.7%, 76.8%, and 67.9%, respectively. Median survival was not reached at 5 years. The rates of severe complication and mortality were 10.2% (4 patients) and 2.5% (1 patient), respectively. When controlling for confounders, postoperative TKI therapy was associated with improved survival (hazard ratio, 0.04; 95% confidence interval, 0.01-0.50; P = .006), and extrahepatic disease was associated with worse survival (hazard ratio, 9.51; 95% confidence interval, 1.63-55.7; P = .012). CONCLUSIONS: Overall survival after combination therapy exceeded previous reports for the treatment of metastatic GIST with hepatic resection or TKI therapy alone and was significantly enhanced by postoperative TKI therapy. The results from this study support findings that combination therapy for GIST liver metastases comprised of surgical resection and TKI therapy is more effective than surgery or TKI therapy alone.

A multi-institution experience comparing the clinical and physiologic differences between upper extremity and lower extremity melphalan-based isolated limb infusion.

BACKGROUND: Although studies of melphalan-based isolated limb infusion (ILI) combine data from upper extremity (UE) treatments with those from lower extremity (LE) treatments, differences between the 2 may be clinically important. METHODS: Candidates for UE ILI (n = 51) and LE ILI (n = 192) were identified from prospective databases at 2 institutions. The Response Evaluation Criteria in Solid Tumors and Wieberdink toxicity scale were used as appropriate. RESULTS: The following patients had indications for UE ILI: melanoma, 36 of 47 patients (77%); sarcoma, 5 of 47 patients (11%); Merkel cell sarcoma, 3 of 47 patients (6%), and squamous cell carcinoma, 3 of 47 patients (6%). The patients who underwent UE ILI, as expected, had lower limb volumes (mean, 2.5 L vs 8.6 L; P < .001) and lower mean melphalan doses (20.7 mg vs 49.5 mg; P < .001). On perfusate blood gas analysis, the mean base excess at 30 minutes (-13.9 vs -9.1; P < .001) and the mean pH at 30 minutes (7.06 vs 7.15; P < .001) were lower for UE procedures than for LE procedures, although the mean ischemic time was longer in LE procedures (67.2 minutes) than in UE procedures (61.6 minutes; P = .03). The rate of regional toxicity grade ≥3 for UE ILI was 7% compared with 24% (P = .005) for LE ILI. There was no difference in the complete response rate for melanoma UE procedures (28%; 95% confidence interval, 16%-44%) compared with LE ILI procedures (32%; 95% confidence interval, 25%-39%). CONCLUSIONS: ILI for UE disease was associated with similar complete response rates but lower toxicity than ILI for LE disease and with different physiologic sequelae despite comparable methods. The UE appears relatively resistant to toxic effects of melphalan-based ILI as currently performed, which suggests a potential for further optimization of drug dosing for UE ILI.

Patterns of recurrence following complete response to regional chemotherapy for in-transit melanoma.

BACKGROUND: Even after complete response (CR) to regional chemotherapy for in-transit melanoma, many patients develop recurrence. Understanding the probability, location, and timing of recurrences can optimize management strategies for this patient population. METHODS: A prospective database identified patients who underwent 81 first-time hyperthermic isolated limb perfusions (HILPs) and 133 first-time isolated limb infusions (ILIs). Response was defined using the response evaluation criteria in solid tumors; recurrence was defined as development of new disease after in-field CR. RESULTS: HILP exhibited a significantly higher CR rate than ILI (44 vs. 28 %, p = .01). Among 36 HILP-CRs and 37 ILI-CRs, the 3-year recurrence rate was 65 % (95 % confidence interval [95 % CI]: 43-79 %) and 85 % (95 % CI: 63-94%), respectively. Median time to first recurrence was longer for HILP-CR than ILI-CR (23 vs. 8 months, p = .02). There was no statistically significant difference in median time to in-field recurrence between HILP-CR and ILI-CR (46 vs. 25 months, p = .15), but HILP-CR showed a longer median time to out-of-field recurrence (42 vs. 14 months, p = .02). Finally, the overall survival (OS) difference between HILP-CR and ILI-CR (3-year survival: 77 vs. 54 %) did not achieve statistical significance (p = .10). CONCLUSIONS: In the largest series comparing patterns of recurrence, we demonstrate that out-of-field recurrence after CR to HILP occurs later than after CR to ILI, though control of in-field disease remains similar. There remains no statistically significant difference in overall survival after CR to the 2 procedures.

Management and recurrence patterns of desmoids tumors: a multi-institutional analysis of 211 patients.

BACKGROUND: Desmoid tumors are rare soft-tissue neoplasms with limited data on their management. We sought to determine the rates of recurrence following surgery for desmoid tumors and identify factors predictive of disease-free survival. METHODS: Between January 1983 and December 2011, 211 patients with desmoid tumors were identified from three major surgical centers. Clinicopathologic and treatment characteristics were analyzed to identify predictors of recurrence. RESULTS: Median age was 36 years; patients were predominantly female (68 %). Desmoid tumors most commonly arose in extremities (32 %), abdominal cavity (23 %) or wall (21 %), and thorax (15 %); median size was 7.5 cm. Most patients had an R0 surgical margin (60 %). The 1- and 5-year recurrence-free survival was 81.3 and 52.8 %, respectively. Factors associated with worse recurrence-free survival were: younger age (for each 5-year increase in age, hazard ratio [HR] = 0.90, 95 % confidence interval [95 % CI] 0.82-0.98) and extra-abdominal tumor location (abdominal wall referent: extra-abdominal site, HR = 3.28, 95 % CI, 1.46-7.36) (both P < 0.05). CONCLUSIONS: Recurrence remains a problem following resection of desmoid tumors with as many as 50 % of patients experiencing a recurrence within 5 years. Factors associated with recurrence included age, tumor location, and margin status. While surgical resection remains central to the management of patients with desmoid tumors, the high rate of recurrence highlights the need for more effective adjuvant therapies.

Presentation and management of gastrointestinal stromal tumors of the duodenum: a multi-institutional analysis.

BACKGROUND: Duodenal gastrointestinal stromal tumors (GISTs) are a small subset of GISTs, and their management is poorly defined. We evaluated surgical management and outcomes of patients with duodenal GISTs treated with pancreaticoduodenectomy (PD) versus local resection (LR) and defined factors associated with prognosis. METHODS: Between January 1994 and January 2011, 96 patients with duodenal GISTs were identified from five major surgical centers. Perioperative and long-term outcomes were compared based on surgical approach (PD vs LR). RESULTS: A total of 58 patients (60.4%) underwent LR, while 38 (39.6%) underwent PD. Patients presented with gross bleeding (n = 25; 26.0%), pain (n = 23; 24.0%), occult bleeding (n = 19; 19.8%), or obstruction (n = 3; 3.1%). GIST lesions were located in first (n = 8, 8.4%), second (n = 47; 49%), or third/fourth (n = 41; 42.7%) portion of duodenum. Most patients (n = 86; 89.6%) had negative surgical margins (R0) (PD, 92.1 vs LR, 87.9%) (P = 0.34). Median length of stay was longer for PD (11 days) versus LR (7 days) (P = 0.001). PD also had more complications (PD, 57.9 vs LR, 29.3%) (P = 0.005). The 1-, 2-, and 3-year actuarial recurrence-free survival was 94.2, 82.3, and 67.3%, respectively. Factors associated with a worse recurrence-free survival included tumor size [hazard ratio (HR) = 1.09], mitotic count >10 mitosis/50 HPF (HR = 6.89), AJCC stage III disease (HR = 4.85), and NIH high risk classification (HR = 4.31) (all P < 0.05). The 1-, 3-, and 5-year actuarial survival was 98.3, 87.4, and 82.0%, respectively. PD versus LR was not associated with overall survival. CONCLUSIONS: Recurrence of duodenal GIST is dependent on tumor biology rather than surgical approach. PD was associated with longer hospital stays and higher risk of perioperative complications. When feasible, LR is appropriate for duodenal GIST and PD should be reserved for lesions not amenable to LR.

Effect of surgeon specialization on long-term survival following colon cancer resection at an NCI-designated cancer center.

BACKGROUND: Recent studies have documented improved outcomes for patients undergoing colorectal cancer resection at NCI cancer centers compared to hospitals without this designation. Proposed contributory factors include a higher proportion of surgeons with specialty training in colorectal surgery and surgical oncology. The purpose of this study was to assess whether surgeon specialization is associated with differences in overall survival following colon cancer resection at an NCI cancer center. METHODS: We conducted a retrospective review of patients undergoing colectomy for colon cancer from 1994 to 2009 at Duke University Medical Center. Patients were divided into two groups based on specialization status of the attending surgeon, and several clinicopathologic variables were compared. A multivariate analysis was then performed examining variables influencing overall survival. RESULTS: Total of 395 patients were included in the study, with 335 patients operated on by specialty-trained surgeons and 60 patients operated on by non-specialists. Overall, the two groups were similar with respect to demographic and pathologic variables. On multivariate analysis, surgeon specialization was found to be an independent predictor of improved overall survival [HR 0.43 (CI: 0.25-0.75), P = 0.003]. CONCLUSION: Surgeon specialization appears to be associated with improved overall survival in the setting of an NCI-designated cancer center.