Hidden Readmissions after Carotid Endarterectomy and Stenting.

BACKGROUND: Historically, carotid procedures incur a readmission rate of approximately 6%; however, these studies are not nationally representative and are limited to tracking only the index hospitals. We sought to evaluate a nationally representative database for readmission rates (including different hospitals) after both carotid endarterectomy (CEA) and carotid artery stenting (CAS) and determine risk factors for poor outcomes including postoperative mortality and myocardial infarction. METHODS: This study was a retrospective analysis utilizing the 2010-2014 Nationwide Readmissions Database to query patients aged >18 years undergoing CEA or CAS. Outcomes included initial admission mortality, and 30-day readmission, including mortality and myocardial infarction (MI). Univariable analysis of 39 demographic, clinical, and hospital variables was conducted with significance set at P < 0.05. Significant variables were included in a multivariable logistic regression to identify independent risk factors for readmission. Results were weighted for national estimates. RESULTS: There were 527,622 patients undergoing carotid procedures and 13% (n = 69,187) underwent CAS. The 30-day readmission rate was 7% (n = 35,782), and of those, 25% (n = 8,862) were readmitted to a different hospital. When controlling for other factors, CAS was a risk factor for mortality at both index admission (odds ratio [OR] 2.29 [2.11-2.49]) and 30-day readmission (OR 1.48 [1.3-1.69]) and 30-day readmissions at both index hospital (OR 1.11 [1.07-1.14]) and different hospital (OR 1.38 [1.29-1.48]). Readmission to a different hospital increased mortality risk (OR 1.45 [1.29-1.63]) but did not have an effect on MI. Postoperative infections comprised 15% of readmissions while 6% of all readmissions were for stroke. CONCLUSIONS: Previously unreported, one in 4 readmissions after carotid procedures occur at a different hospital and this fragmentation of care could increase mortality risk after carotid procedures particularly for CAS which was also an independent risk factor for postoperative mortality and readmissions. Further validation is required to decrease unnecessary hospital after carotid procedures.

Intramuscular E-selectin/adeno-associated virus gene therapy promotes wound healing in an ischemic mouse model.

BACKGROUND: Poor wound healing in critical limb ischemia (CLI) is attributed to impaired neovascularization and reperfusion. Optimizing the ischemic wound with adhesion molecules that enhance stem cell homing may revolutionize treatment. The purpose of this study is to test the efficacy of adhesion molecule E-selectin on wound healing in an ischemic mouse wound. METHODS: Adult FVB/NJ mice underwent unilateral femoral artery and vein ligation to induce CLI. A 4-mm punch biopsy wound was created on the anterior thigh to simulate ischemic wounds. Intramuscular injection of adeno-associated virus (AAV) carrying either E-selectin (E-selectin/AAV, n = 11) or LacZ as control (LacZ/AAV, n = 10) was performed. Gross wound size was measured for 10 d postoperatively. Ischemic hindlimb reperfusion was quantified using laser Doppler imaging. Wound tissue neovascularization was visualized using DiI perfusion and confocal microscopy. E-selectin expression in wounds was verified by immunofluorescence. RESULTS: Immunofluorescence confirmed E-selectin/AAV delivery in treatment versus control limbs. Wounds from E-selectin/AAV mice versus controls revealed surface area healing of 54% versus 20% (P < 0.01) on postoperative day (POD) 1, 78% versus 51% on POD 4 (P < 0.01), and 97% versus 84% on POD 10 (P < 0.01). Laser Doppler imaging revealed greater reperfusion in E-selectin/AAV mice versus controls by POD 10 (0.49 versus 0.27, P < 0.05). DiI perfused ligated hindlimb in E-selectin/AAV versus control mice revealed mean neovascularization intensity score of 30 versus 18 (P < 0.05) on POD 10. CONCLUSIONS: Intramuscularly injected E-selectin/AAV gene therapy in mice with CLI significantly increases wound angiogenesis and limb reperfusion, expediting overall wound healing.

Transverse versus Longitudinal Incisions for Femoral Artery Exposure in Treating Patients with Peripheral Vascular Disease.

BACKGROUND: This study evaluates differences in wound complication rate when transverse versus longitudinal incision is utilized to expose femoral vessels in managing patients with peripheral vascular disease. METHODS: A retrospective review from 2013 to 2015 was conducted of 150 patients undergoing 156 lower extremity revascularizations with femoral artery exposure through a groin incision. Patients were stratified into 2 groups, transverse versus longitudinal groin incision. Data were reviewed for 3 surgeons that utilize either transverse or longitudinal groin incision in patients undergoing common or iliofemoral endarterectomies, or where femoral artery was used as inflow and/or outflow vessel for limb revascularization. Each group had a comparative outcomes analysis based on incision type. The primary outcome was wound complication, defined as any wound infection, lymphocele, hematoma, dehiscence, pseudoaneurysm, or necrosis. Other outcomes studied included unplanned return to operating room for wound complication, wound vacuum therapy, and soft-tissue flap closure. Data were analyzed using 2-tailed chi-squared test and Student's t-test. RESULTS: Patients in the transverse (n = 85 cases) versus longitudinal (n = 71 cases) cohorts were similar in relation to demographics and comorbidities. Overall mean follow-up was 220 days. Patients with a transverse as compared to longitudinal incision had a significantly lower overall wound complication rate, 7% vs. 42%, respectively (P < 0.001). Furthermore, transverse incisions were associated with lower incidence of unplanned return to the operating room to manage wound complications than patients with a longitudinal incision (5% vs. 23%, respectively; P < 0.001). Transverse versus longitudinal incisions were also associated with significantly lower need for wound vacuum therapy (6% vs. 15%, respectively; P < 0.05) and muscle flap closure (0% vs. 13%, respectively; P < 0.001) for wound complications. CONCLUSIONS: Transverse groin incisions for femoral artery exposure may offer a lower risk of wound complications for open procedures as compared to a longitudinal incision. While longitudinal incisions may have higher wound complication rates, incisional approach is contingent on anatomical circumstance and treated disease pattern. Patients should undergo appropriate preoperative counseling regarding wound healing in preparation for limb revascularization.

A Reliable Mouse Model of Hind limb Gangrene.

BACKGROUND: Lack of a reliable hind limb gangrene animal model limits preclinical studies of gangrene, a severe form of critical limb ischemia. We develop a novel mouse hind limb gangrene model to facilitate translational studies. METHODS: BALB/c, FVB, and C57BL/6 mice underwent femoral artery ligation (FAL) with or without administration of NG-nitro-L-arginine methyl ester (L-NAME), an endothelial nitric oxide synthase inhibitor. Gangrene was assessed using standardized ischemia scores ranging from 0 (no gangrene) to 12 (forefoot gangrene). Laser Doppler imaging (LDI) and DiI perfusion quantified hind limb reperfusion postoperatively. RESULTS: BALB/c develops gangrene with FAL-only (n = 11/11, 100% gangrene incidence), showing mean limb ischemia score of 12 on postoperative days (PODs) 7 and 14 with LDI ranging from 0.08 to 0.12 on respective PODs. Most FVB did not develop gangrene with FAL-only (n = 3/9, 33% gangrene incidence) but with FAL and L-NAME (n = 9/9, 100% gangrene incidence). Mean limb ischemia scores for FVB undergoing FAL with L-NAME were significantly higher than for FVB receiving FAL-only. LDI score and capillary density by POD 28 were significantly lower in FVB undergoing FAL with L-NAME. C57BL/6 did not develop gangrene with FAL-only or FAL and L-NAME. CONCLUSIONS: Reproducible murine gangrene models may elucidate molecular mechanisms for gangrene development, facilitating therapeutic intervention.

Nationwide review of hormonally active adrenal tumors highlights high morbidity in pheochromocytoma.

BACKGROUND: Adrenal adenomas are benign tumors often discovered incidentally, and >70% are hormonally inactive. The remaining subset may produce excess aldosterone, cortisol, or catecholamine. Perioperative outcomes after adrenalectomy for such "hormonally active" tumors remain unclear. This study examines in-hospital outcomes after unilateral adrenalectomy for hormonally active tumors. METHODS: A retrospective review was performed using the Nationwide Inpatient Sample (2006-2011) to identify patients undergoing unilateral adrenalectomy for hormonally active or inactive tumors. Malignant adrenal tumors were excluded. Demographics, comorbidities, and postoperative complications were evaluated by univariate analysis, using two-tailed Chi-square and t-tests and multivariate logistic regression. RESULTS: Of 27,312 patients who underwent adrenalectomy, 78% (n = 21,279) had hormonally inactive and 22% (n = 6033) had hormonally active adrenal tumors. Among the latter, 65% (n = 4000) had primary hyperaldosteronism (Conn's syndrome), 33% (n = 1996) had hypercortisolism (Cushing's syndrome), and 1.4% (n = 85) had pheochromocytoma. Patients with pheochromocytoma had higher rate of comorbidities including congestive heart failure, chronic lung disease, and malignant hypertension compared with remaining hormonally active tumors (12% versus 4%, 18% versus 11%, 6% versus 2%; P < 0.01). For patients with pheochromocytoma versus other hormonally active tumors, mean length of stay was 5 versus 3 d and total in-hospital cost was $50,000 versus $41,000 (P < 0.01). On multivariate analysis, pheochromocytoma had an independently higher risk for intraoperative blood transfusion (4.2, 95% confidence interval [CI] 2.4-7.2), postoperative cardiac (7.6, 95% CI 2.8-20.2), and respiratory (1.9, 95% CI 1.0-3.3) complications. CONCLUSIONS: Patients with pheochromocytoma have high rates of preoperative comorbidities, postoperative cardiopulmonary complications, and longer and more costly hospitalizations. Such high-risk patients should undergo appropriate preoperative medical optimization in preparation for adrenalectomy.

Intraoperative Parathormone Monitoring Mitigates Age-Related Variability in Targeted Parathyroidectomy for Patients with Primary Hyperparathyroidism.

BACKGROUND: Preoperative parathyroid localization studies, namely, sestamibi (MIBI) and surgeon-performed ultrasound (SUS), are commonly used for targeted parathyroidectomy (PTX) with intraoperative parathormone monitoring (IPM) in patients with primary hyperparathyroidism (pHPT). This study examined age-related variability in abnormal parathyroid gland localization for targeted PTX and the value of IPM across age groups. METHODS: A retrospective review examined prospectively collected data of 833 patients who underwent targeted PTX guided by IPM. The patients were stratified into three age groups as follows: younger [<47 years; mean -1 standard deviation (SD)], typical (47-73 years), and older (>73 years; mean +1 SD) based on an age distribution curve for pHPT. The accuracy, sensitivity, and positive predictive value (PPV) for MIBI, SUS, and IPM were analyzed and compared among age groups. Operative success was defined as eucalcemia for 6 months or longer after PTX, and operative failure was defined as elevated calcium and PTH levels within 6 months after PTX. RESULTS: Of the 833 patients, the youngest group had the highest accuracy and sensitivity for MIBI, SUS, and IPM compared with the older groups (p < 0.05). The accuracy and sensitivity of MIBI and SUS also decreased significantly with increased age (p < 0.05). Within all three age groups, IPM was consistently more accurate and sensitive than SUS or MIBI (p < 0.05). CONCLUSIONS: Age can significantly affect the accuracy and sensitivity of MIBI and SUS in targeted PTX for patients with pHPT. Across all age groups, IPM remains more accurate than preoperative localization studies. For the elderly, in whom multiglandular disease appears increased, surgeons should have a lower threshold for conversion to bilateral neck exploration.

A nationwide analysis of clinical outcomes among newborns with esophageal atresia and tracheoesophageal fistulas in the United States.

BACKGROUND: The aim of this study was to examine national outcomes in newborn patients with esophageal atresia and tracheoesophageal fistula (EA/TEF) in the United Sates. METHODS: Kids' Inpatient Database (KID) is designed to identify, track, and analyze national outcomes for hospitalized children in the United States. Inpatient admissions for pediatric patients with EA/TEF for kids' Inpatient Database years 2000, 2003, 2006, and 2009 were analyzed. Patient demographics, socioeconomic measures, disposition, survival and surgical procedures performed were analyzed using standard statistical methods. RESULTS: A total of 4168 cases were identified with diagnosis of EA/TEF. The overall in-hospital mortality was 9%. Univariate analysis revealed lower survival in patients with associated acute respiratory distress syndrome, ventricular septal defect (VSD), birth weight (BW) < 1500 g, gestational age (GA), time of operation within 24 h of admission, coexisting renal anomaly, imperforate anus, African American race, and lowest economic status. Multivariate logistic regression identified BW < 1500 g (odds ratio [OR] = 4.5, P < 0.001), operation within 24 h (OR = 6.9, P < 0.001), GA <28 wk (OR = 2.2, P < 0.030), and presence of VSD (OR = 3.8, P < 0.001) as independent predictors of in-hospital mortality. Children's general hospital and children's unit in a general hospital were found to have a lower mortality rate compared with not identified as a children's hospital after excluding immediate transfers (P = 0.008). CONCLUSIONS: BW < 1500 g, operation within 24 h, GA < 28 wk, and presence of VSD are the factors that predict higher mortality in EA/TEF population. Despite dealing with more complicated cases, children's general hospital and children's unit in a general hospital were able to achieve a lower mortality rate than not identified as a children's hospital.

Surgical treatment of patients with mildly elevated parathormone and calcium levels.

BACKGROUND: Patients with mildly elevated parathormone (PTH) and calcium levels consistent for primary hyperparathyroidism (pHPT) may present with more underlying multiglandular disease (MGD) and higher operative failure and recurrence rates than those with conventional, or "classic" pHPT. This study compared the clinical characteristics and surgical outcomes of patients with biochemically mild versus conventional pHPT. METHODS: A series of 707 consecutive patients underwent initial targeted parathyroidectomy with intraoperative parathormone monitoring (IPM) at a single institution. Biochemically mild (BM) pHPT was defined as PTH > 65 and <100 pg/ml with serum calcium >10.4 and <11 mg/dl. Conventional pHPT was defined as calcium ≥11 mg/dl and PTH ≥ 100 pg/ml. Prospectively collected data for all patients, including operative indication, preoperative laboratory values, imaging, IPM dynamics, and postoperative laboratory values were retrospectively reviewed. Additional assessments included presence of MGD, bilateral neck exploration (BNE), single-gland volume, and operative failure or success, and recurrence. RESULTS: Of 60 patients with BM-pHPT, 46 reported preoperative bone pain, kidney stones, fatigue, and/or mental disturbances. The remaining 14 BM-pHPT patients underwent parathyroidectomy based on published asymptomatic guidelines. Patients with BM-pHPT had significantly more kidney stones, MGD, and BNE. Average single-gland volume and postoperative PTH levels were significantly lower in BM-pHPT patients. There were no significant differences between groups regarding preoperative localization accuracy, IPM dynamics, or operative success/failure, recurrence rates. CONCLUSIONS: BM-pHPT patients had more MGD requiring BNE but achieved operative success rates similar to those of patients with conventional disease. IPM successfully identifies MGD in BM-pHPT patients, who should be counseled regarding more extensive operations than limited parathyroidectomy.

Surgeon-performed ultrasound predictors of malignancy in patients with Hürthle cell neoplasms of the thyroid.

BACKGROUND: Fine-needle aspiration cannot reliably determine malignancy in patients with Hürthle cell neoplasms (HCNs) of the thyroid. Thyroid nodule size and characteristics determined by surgeon-performed ultrasound (SUS) may be useful for predicting malignancy in HCN preoperatively. This study examined whether tumor size and features by SUS can reliably predict malignancy in patients with HCN. MATERIALS AND METHODS: We performed a retrospective review of 84 patients with HCN by fine-needle aspiration, who underwent SUS and thyroidectomy from 2002 to 2010. All patients underwent thyroid lobectomy with isthmusectomy unless there was a history of radiation exposure, familial thyroid cancer, obstructive symptoms, bilateral nodules, and/or patient preference, in which case total thyroidectomy was performed. Tumor size and malignant features by SUS were correlated with final histopathology using multivariate regression analysis. RESULTS: On final histopathology, 29 patients had malignant thyroid nodules and 55 patients had benign ones. There were no statistically significant differences in terms of age, race, ethnicity, or gender between HCN patients who revealed malignant or benign nodules on final pathology. Tumor size ≥ 4 cm measured by SUS did not predict malignancy in HCN. Hypoechogenicity and hyperechogenicity were significantly associated with malignancy, whereas isoechogenicity was predictive of benignity (P = 0.044). No other ultrasonographic features were predictive for thyroid carcinoma by multivariate analysis. CONCLUSIONS: Tumor size and features determined by SUS do not reliably predict malignancy in patients with HCN. Such patients at risk for malignancy should initially undergo thyroid lobectomy for definitive diagnosis.

Risk of concomitant malignancy in hyperfunctioning adrenal incidentalomas.

BACKGROUND: Adrenal masses are common incidental findings on radiologic imaging. The association between malignancy and hormonal hyperactivity found in incidentally discovered adrenal tumors, however, remains unclear. METHODS: A retrospective analysis of prospectively collected data from patients who underwent adrenalectomy for incidentally discovered adrenal tumors at a single institution. Outcomes and operative data were compared by univariate analysis. Area under the curve was used to analyze the effect of tumor size in predicting malignancy. RESULTS: There were 49 patients who initially presented with adrenal incidentalomas that underwent adrenalectomy. Most patients were Caucasian women with an average age of 51 ± 14 years. Of this group, 24 patients underwent resection for hyperfunctioning adrenal glands. There were no significant differences in malignancy rates between hyperfunctional and nonfunctional tumors (4.1% vs. 12.0%, P = 0.32). On final histopathology, there were four patients with adrenal malignancies: two adrenocortical carcinomas and two metastatic from renal carcinoma. Only one patient with a hyperfunctioning adrenal tumor had underlying malignancy. Overall, invasion of adjacent structures (P < 0.001), presence of lymphadenopathy (P = 0.02), metastasis (P = 0.03), irregular tumor margins (P = 0.01), heterogeneity (P = 0.05), and tumor size >6 cm (P = 0.04) on radiologic imaging were strongly associated with malignancy in adrenal incidentalomas. CONCLUSIONS: The risk of concomitant malignancy and hormonal hyperactivity in adrenal incidentalomas is very low. Tumor size (>6 cm) and radiographic features remain the most important predictors of adrenal malignancy, regardless of tumor function.

An analysis of 73 cases of pediatric malignant tumors of the thymus.

BACKGROUND: Tumors of the thymus are very rare in the pediatric population. This study examines the current trends and outcomes of children with thymus tumors. METHODS: The Surveillance, Epidemiology and End Results (SEER) registry was queried for all patients <20 y of age with primary thymic malignancies from 1973 to 2008. RESULTS: A total of 73 pediatric patients were identified with malignant thymic tumors. The median age at diagnosis was 13 y old. Among the 20 patients that presented with distant disease, 70% died. Conversely, among the 23 patients that presented with locoregional disease, 70% survived. Although the overall mean survival time was 89 ± 116 mo, 45% of patients died over the study period. Patients with Hodgkin lymphomas and germ cell tumors exhibited the highest survival (76% and 60% at 10 y, respectively). Multivariate analysis was used to identify local or regional tumor stage (odds ratio = 4.5, 95% confidence interval = 1.4-14.5) and surgical resection (OR = 3.8, 95% confidence interval = 1.4-10.8) as independent predictors of survival. CONCLUSIONS: Malignant thymomas and lymphomas are the most common histological variants of pediatric thymus tumors, and patients with Hodgkin lymphomas exhibit the highest survival. Surgery is more commonly performed on malignant thymomas and is an independent prognostic indicator of survival.

A schwannoma of the greater petrosal nerve located within the petrous apex and treated with stereotactic radiotherapy.

A 26 year-old female experienced progressive left sided pulsatile tinnitus and conductive hearing loss for two years, which following an extensive clinical workup, was diagnosed as a left greater petrosal nerve schwannoma located within the petrous apex of the temporal bone. Between neurosurgical management and radiation therapy, multiple therapeutic options were presented to the patient, who ultimately chose stereotactic radiotherapy as an alternative to surgical resection due to the potential morbidity associated with surgery. The patient received three fractions of 600 cGy without subsequent worsening of her symptoms, new onset neurologic symptoms or radiation induced side effects reported at a 3, 6 and 12 month clinic visits. A follow-up MRI at 6 and 12 months post radiation administration demonstrated no further tumor growth.

Predictors of survival and incidence of hepatoblastoma in the paediatric population.

OBJECTIVES: This study evaluates current trends in incidence, clinical outcomes and factors predictive of survival in children with hepatoblastoma (HB). METHODS: The Surveillance, Epidemiology and End Results (SEER) database was queried for the period 1973-2009 for all patients aged <20 years with HB. RESULTS: A total of 606 patients were identified. The age-adjusted incidence was 0.13 patients per 100 000 in 2009. An annual percentage change of 2.18% (95% confidence interval (CI) 1.10-3.27; P < 0.05) was seen over the study period. Overall survival rates at 5, 10 and 20 years were 63%, 61% and 59%, respectively. Ten-year survival rates significantly improved in patients with resectable disease who underwent operative treatment in comparison with those with non-resectable HB (86% versus 39%; P < 0.0001). Multivariate analysis showed surgical treatment (hazard ratio (HR) = 0.23, 95% CI 0.17-0.31; P < 0.0001), Hispanic ethnicity (HR = 0.61, 95% CI 0.43-0.89; P = 0.01), local disease at presentation (HR = 0.43, 95% CI 0.29-0.63; P < 0.0001) and age < 5 years (HR = 0.63, 95% CI 0.41-0.95; P < 0.03) to be independent prognostic factors of survival. CONCLUSIONS: The incidence of paediatric HB has increased over time. Hepatoblastoma is almost exclusively seen in children aged < 5 years. When HB presents after the age of 5 years, the prognosis is most unfavourable. Tumour extirpation markedly improves survival in paediatric patients with local disease.

Gangrene, revascularization, and limb function improved with E-selectin/adeno-associated virus gene therapy.

OBJECTIVE: Novel therapeutic angiogenic concepts for critical limb ischemia are still needed for limb salvage. E-selectin, a cell-adhesion molecule, is vital for recruitment of the stem/progenitor cells necessary for neovascularization in ischemic tissues. We hypothesized that priming ischemic limb tissue with E-selectin/adeno-associated virus (AAV) gene therapy, in a murine hindlimb ischemia and gangrene model, would increase therapeutic angiogenesis and improve gangrene. METHODS: FVB/NJ mice were given intramuscular hindlimb injections of either E-selectin/AAV or LacZ/AAV and then underwent induction of gangrene via femoral artery ligation and concomitant systemic injections of the nitric oxide synthesis inhibitor L-NAME (L-NG-Nitro arginine methyl ester; 40 mg/kg). Gangrene was evaluated via the Faber hindlimb appearance score. The rate of ischemic limb reperfusion and ischemic tissue angiogenesis were evaluated using laser Doppler perfusion imaging and DiI perfusion with confocal laser scanning microscopy of the ischemic footpads, respectively. The treadmill exhaustion test was performed on postoperative day (POD) 8 to determine hindlimb functionality. RESULTS: The E-selectin/AAV-treated mice (n = 10) had decreased Faber ischemia scores compared with those of the LacZ/AAV-treated mice (n = 7) at both PODs 7 and 14 (P < .05 and P < .01, respectively), improved laser Doppler perfusion imaging reperfusion indexes by POD 14 (P < .01), and greater gangrene footpad capillary density (P < .001). E-selectin/AAV-treated mice also had improved exercise tolerance (P < .05) and lower relative muscular atrophy (P < .01). CONCLUSION: We surmised that E-selectin/AAV gene therapy would significantly promote hindlimb angiogenesis, reperfusion, and limb functionality in mice with hindlimb ischemia and gangrene. Our findings highlight the reported novel gene therapy approach to critical limb ischemia as a potential therapeutic option for future clinical studies.

E-Selectin-Overexpressing Mesenchymal Stem Cell Therapy Confers Improved Reperfusion, Repair, and Regeneration in a Murine Critical Limb Ischemia Model.

AIMS: Novel cell-based therapeutic angiogenic treatments for patients with critical limb ischemia may afford limb salvage. Mesenchymal stem cells (MSCs) do not overexpress E-selectin; however, we have previously demonstrated the cell-adhesion molecule's vital role in angiogenesis and wound healing. Thus, we created a viral vector to overexpress E-selectin on MSCs to increase their therapeutic profile. METHODS AND RESULTS: Femoral artery ligation induced hind limb ischemia in mice and intramuscular injections were administered of vehicle or syngeneic donor MSCs, transduced ex vivo with an adeno-associated viral vector to express either GFP+ (MSCGFP) or E-selectin-GFP+ (MSCE-selectin-GFP). Laser Doppler Imaging demonstrated significantly restored reperfusion in MSCE-selectin-GFP-treated mice vs. controls. After 3 weeks, the ischemic limbs in mice treated with MSCE-selectin-GFP had increased footpad blood vessel density, hematoxylin and eosin stain (H&E) ischemic calf muscle sections revealed mitigated muscular atrophy with restored muscle fiber size, and mice were able to run further before exhaustion. PCR array-based gene profiling analysis identified nine upregulated pro-angiogenic/pro-repair genes and downregulated Tumor necrosis factor (TNF) gene in MSCE-selectin-GFP-treated limb tissues, indicating that the therapeutic effect is likely achieved via upregulation of pro-angiogenic cytokines and downregulation of inflammation. CONCLUSION: This innovative cell therapy confers increased limb reperfusion, neovascularization, improved functional recovery, decreased muscle atrophy, and thus offers a potential therapeutic method for future clinical studies.

Nationwide analysis of adrenocortical carcinoma reveals higher perioperative morbidity in functional tumors.

BACKGROUND: Current adrenalectomy outcomes for functional adrenocortical carcinoma (ACC) remain unclear. This study examines nationwide in-hospital post-adrenalectomy outcomes for ACC. METHODS: A retrospective analysis of the Nationwide Inpatient Sample database (2006-2011) to identify unilateral adrenalectomy patients for functional or nonfunctional ACC was performed. Patient demographics, comorbidities and postoperative outcomes were evaluated by t-test, Chi-square and multivariate regression. RESULTS: Of 2199 patients who underwent adrenalectomy, 87% had nonfunctional and 13% had functional ACC (86% hypercortisolism, 16% hyperaldosteronism, 4% hyperandrogenism). Functional ACC patients had significantly more comorbidities, and experienced certain postoperative complications more frequently including wound issues, adrenocortical insufficiency and acute kidney injury with longer hospital stay compared to nonfunctional ACC (P < 0.01). On multivariate analysis, functional ACC was an independent prognosticator for wound complications (28.1, 95%CI 4.59-176.6). CONCLUSION: Patients with functional ACC manifest significant comorbidities with certain in-hospital complications. Such high-risk patients require appropriate preoperative medical optimization prior to adrenalectomy.

Nationwide overview of survival and management of appendiceal tumors in children.

INTRODUCTION: There remains a paucity of literature on survival related to pediatric appendiceal tumors. The purpose of this study was to determine the incidence, surgical management, and survival outcomes of appendiceal tumors in pediatric patients. METHODS: The Surveillance, Epidemiology, and End Results (SEER) Registry was analyzed for pediatric appendiceal tumors from 1973 to 2011. Parameters analyzed were: tumor type, surgical management (appendectomy vs. extensive resection), tumor size, and lymph node sampling. Chi-square analysis for categorical and Student's t test for continuous data were used. RESULTS: Overall, 209 patients had an appendiceal tumor, including carcinoid (72%), appendiceal adenocarcinoma (16%), and lymphoma (12%). Patients undergoing appendectomy vs. extensive resection had similar 15-year survival rates (98% vs. 97%; p=0.875). Appendectomy vs. extensive resection conferred no 15-year survival advantage when patients were stratified by tumor type, including adenocarcinoma (87% vs. 89%; p=0.791), carcinoid (100% vs. 100%; p=0.863), and lymphoma (94% vs. 100%; p=0.639). There was no significant difference in 15-year survival between tumor size groups ≥2 and <2cm (both 100%) and presence or absence of lymph node sampling (96% and 97%; p=0.833) for all patients with a carcinoid tumor. CONCLUSION: Appendectomy may be adequate for pediatric appendiceal tumors. Extensive resection may be of limited utility for optimizing patient survival, placing patient at greater operative risk. TYPE OF STUDY: Retrospective Prognostic Study. LEVEL OF EVIDENCE: III.

Looped suture versus stapler device in pediatric laparoscopic appendectomy: a comparative outcomes and intraoperative cost analysis.

BACKGROUND: Appendiceal ligation during pediatric laparoscopic appendectomy (LA) may be performed using looped suture versus stapler. Controversy regarding the utility of either method exists. Clinical outcomes and cost analysis of LA with both methods were compared. METHODS: All pediatric LA were performed from fiscal years 2013 and 2014 by two pediatric surgeons. While one surgeon used looped suture, the other used stapler exclusively. chi-Square tests were performed to analyze associations. RESULTS: Two hundred thirty-eight cases were analyzed where looped suture versus stapler LA was performed in 46% and 54% of patients, respectively. Operating room costs were $317.10 and $707.12/person for looped suture and stapler LA, respectively (P<0.0001). Difference in cost of $390.02/person was attributed solely to ligation type. On bivariate analysis, rate of in-hospital complications, length of stay, return-to-ER and readmission within 30 days did not significantly differ between groups. CONCLUSION: A comparative analysis of looped suture versus stapler device during LA for pediatric appendicitis revealed that postoperative complications, length of stay, ER visits and readmissions were not significantly different. Looped suture LA was significantly more cost efficient than stapler LA. In pediatric appendicitis, appendiceal ligation during LA may be performed safely and cost effectively with looped suture versus stapler. TYPE OF STUDY: Cost effectiveness LEVEL OF EVIDENCE: III.

Incidence and outcomes of pediatric extremity melanoma: A propensity score matched SEER study.

BACKGROUND: There is a paucity of literature on treatment of melanoma in children with surgical management extrapolated from adult experience. The incidence and clinical outcomes of pediatric extremity melanoma were studied. METHODS: SEER registry was analyzed between 1973 and 2010 for patients <20years old with extremity melanoma. Multivariate and propensity-score matched analyses were performed to identify independent predictors of survival. RESULTS: Overall, 917 patients were identified with an age-adjusted incidence of 0.2/100,000 persons, annual percent change 0.96. Most had localized disease (77%), histology revealing melanoma-not otherwise specified (52%). Surgical procedures performed included wide local excision (50%), excisional biopsy (32%), lymphadenectomy (LA) (28%), and sentinel lymph node biopsy (SLNB) (15%). Overall, 30-year disease specific mortality was 7% with lower survival for extremity melanoma (90%), males (89%), nodular histology (69%), and distant disease (36%) (all P<0.05). Post-treatment multivariate analysis revealed localized disease (HR 9.76; P=0.006) as an independent prognosticator of survival; earlier diagnostic years 1988-1999 (HR 2.606; P=0.017) were a negative prognosticator of survival. Propensity-score matched analysis found no difference in survival between SLNB/LA vs no sampling for regional/distant disease. CONCLUSIONS: Pediatric extremity melanoma in SEER demonstrate no survival advantage between children undergoing sampling procedures vs no sampling for regional/distant disease. TYPE OF STUDY: Retrospective, prognostic study. LEVEL OF EVIDENCE: III.

A Molecular and Clinical Review of Stem Cell Therapy in Critical Limb Ischemia.

Peripheral artery disease (PAD) is one of the major vascular complications in individuals suffering from diabetes and in the elderly that can progress to critical limb ischemia (CLI), portending significant burden in terms of patient morbidity and mortality. Over the last two decades, stem cell therapy (SCT) has risen as an attractive alternative to traditional surgical and/or endovascular revascularization to treat this disorder. The primary benefit of SCT is to induce therapeutic neovascularization and promote collateral vessel formation to increase blood flow in the ischemic limb and soft tissue. Existing evidence provides a solid rationale for ongoing in-depth studies aimed at advancing current SCT that may change the way PAD/CLI patients are treated.