Bariatric Surgery in Youth.

Bariatric surgery provides a clinically effective and cost-effective means of achieving sustained weight reduction and management of associated comorbidities and has been met with increasing enthusiasm for application in obese youth. Following trends seen among obese adults, carefully selected obese youth are now undergoing bariatric surgical procedures with excellent short-term and intermediate-term outcomes. Although long-term data are not yet available, the results thus far hold great promise in the management of this population.

Disseminating surgery effectively and efficiently in Haiti.

The need for surgical care in Haiti remains vast despite the enormous relief efforts after the earthquake in 2010. As the poorest country in the Western hemisphere, Haiti lacks the necessary infrastructure to provide surgical care to its inhabitants. In light of this, a multidisciplinary approach led by Partners In Health and Dartmouth-Hitchcock Medical Center is improving the access to surgical care and offering treatment of a broad spectrum of pathology. This article discusses how postearthquake Haiti partnerships involving academic institutions can alleviate the surgical burden of disease and, in the process, serve as a profound educational experience for the academic community. The lessons learned from Haiti prove applicable in other resource-constrained settings and invaluable for the next generation of surgeons.

Pure transvaginal appendectomy versus traditional laparoscopic appendectomy for acute appendicitis: a prospective cohort study.

OBJECTIVE: This report describes the first cohort study comparing pure transvaginal appendectomies (TVAs) to traditional 3-port laparoscopic appendectomies (LAs). METHODS: Between August 2008 and August 2010, 42 patients were offered a pure TVA. Patients who did not wish to undergo a TVA underwent a LA and served as the control group. Demographic data, operative time, length of stay, patient controlled analgesia (PCA) 12-hour-morphine utilization, complications, return to normal activity, and return to work were recorded. RESULTS: Eighteen of 40 enrolled patients underwent a pure TVA. Two patients refused to participate in this study. Mean age (TVA: 31.3 ± 2.5 years vs. LA: 28.2 ± 2.3 years, P = 0.36), mean body mass index (TVA: 23.7 ± 1.2 kg/m2 vs. LA: 23.6 ± 0.7 kg/m2, P = 0.96) mean operative time (TVA: 44.4 ± 4.5 minutes vs. LA: 39.8 ± 2.6 minutes, P = 0.38), and mean length of hospital stay (TVA: 1.1 ± 0.1 days vs. LA: 1.2 ± 0.1 days, P = 0.53) were not statistically significant. However, mean postoperative morphine-use (TVA: 8.7 ± 2.0 mg vs. LA: 23.0 ± 3.4 mg, P < 0.01), return to normal activity (TVA: 3.3 ± 0.4 days vs. LA: 9.7 ± 1.6 days, P < 0.01), and return to work (TVA: 5.4 ± 1.1 days vs. LA: 10.7 ± 1.5 days, P = 0.01) were statistically significant. One conversion in the TVA group to a LA was necessary because of inability to maintain adequate pneumoperitoneum. Four complications were observed: 1 intraabdominal abscess and 1 case of urinary retention in the TVA group; 1 early postoperative bowel obstruction and 1 case of urinary retention in the LA group. CONCLUSIONS: Pure TVA is a safe and well-tolerated procedure with significantly less pain and faster recovery compared to traditional LA.

Outcomes of small bowel obstruction in patients with previous gynecologic malignancies.

BACKGROUND: Features predictive of malignant small bowel obstructions among patients with previous gynecologic malignancies remain undetermined. METHODS: Predictors of malignancy and mortality among patients with gynecologic malignancies and bowel obstructions were identified through a retrospective review of records. RESULTS: Malignancy was noted among 69.8% of 189 patients included in the analysis. Advanced-stage cancer (P = .006, odds ratio [OR] = 6.62), ovarian malignancy (P = .001, OR = 25.64), and early-onset obstruction (P = .014) predicted malignant etiology, whereas chemotherapy (P < .001, OR = .02) or radiation therapy (P = .027, OR = .09) predicted benign obstruction. The average survival was 9 months versus 49 months for malignant and benign obstructions, respectively. Ovarian cancer (P = .009, hazard ratio [HR] = 4.45), anemia (P = .001, HR = 1.11), and renal dysfunction (P < .001, HR 1.81) impaired survival. CONCLUSIONS: Palliative care should be considered for patients with advanced-stage cancer, ovarian malignancy, and a shorter time interval between cancer diagnosis and bowel obstruction, especially in the setting of anemia and renal dysfunction.

Tissue-engineered vascular grafts: does cell seeding matter?

PURPOSE: Use of tissue-engineered vascular grafts (TEVGs) in the repair of congenital heart defects provides growth and remodeling potential. Little is known about the mechanisms involved in neovessel formation. We sought to define the role of seeded monocytes derived from bone marrow mononuclear cells (BM-MNCs) on neovessel formation. METHODS: Small diameter biodegradable tubular scaffolds were constructed. Scaffolds were seeded with the entire population of BM-MNC (n = 15), BM-MNC excluding monocytes (n = 15), or only monocytes (n = 15) and implanted as infrarenal inferior vena cava (IVC) interposition grafts into severe combined immunodeficiency/bg mice. Grafts were evaluated at 1 week, 10 weeks, or 6 months via ultrasonography and microcomputed tomography, as well as by histologic and immunohistochemical techniques. RESULTS: All grafts remained patent without stenosis or aneurysm formation. Neovessels contained a luminal endothelial lining surrounded by concentric smooth muscle cell layer and collagen similar to that seen in the native mouse IVC. Graft diameters differed significantly between those scaffolds seeded with only monocytes (1.022 +/- 0.155 mm) and those seeded without monocytes (0.771 +/- 0.121 mm; P = .021) at 6 months. CONCLUSIONS: Monocytes may play a role in maintaining graft patency. Incorporation of such findings into the development of second-generation TEVGs will promote graft patency and success.

Tissue-engineered vascular grafts transform into mature blood vessels via an inflammation-mediated process of vascular remodeling.

Biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs) are the earliest tissue-engineered vascular grafts (TEVGs) to be used clinically. These TEVGs transform into living blood vessels in vivo, with an endothelial cell (EC) lining invested by smooth muscle cells (SMCs); however, the process by which this occurs is unclear. To test if the seeded BMCs differentiate into the mature vascular cells of the neovessel, we implanted an immunodeficient mouse recipient with human BMC (hBMC)-seeded scaffolds. As in humans, TEVGs implanted in a mouse host as venous interposition grafts gradually transformed into living blood vessels over a 6-month time course. Seeded hBMCs, however, were no longer detectable within a few days of implantation. Instead, scaffolds were initially repopulated by mouse monocytes and subsequently repopulated by mouse SMCs and ECs. Seeded BMCs secreted significant amounts of monocyte chemoattractant protein-1 and increased early monocyte recruitment. These findings suggest TEVGs transform into functional neovessels via an inflammatory process of vascular remodeling.

Cell-seeding techniques in vascular tissue engineering.

Previous studies have demonstrated the benefits of cell seeding in the construction of tissue-engineered vascular grafts (TEVG). However, seeding methods are diverse and no method is clearly superior in either promoting seeding efficiency or improving long-term graft function. As we head into an era during which a variety of different TEVG are under investigation in clinical trials around the world, it is important to consider the regulatory issues surrounding the translation of these technologies. In this review, we summarize important advances in the field of vascular tissue engineering, with particular attention on cell-seeding techniques for TEVG development and special emphasis placed on regulatory issues concerning the clinical translation of these various methods.

Tissue-engineered arterial grafts: long-term results after implantation in a small animal model.

BACKGROUND: Use of prosthetic vascular grafts in pediatric vascular surgical applications is limited because of risk of infection, poor durability, potential for thromboembolic complications, and lack of growth potential. Construction of an autologous neovessel using tissue engineering technology offers the potential to create an improved vascular conduit for use in pediatric vascular applications. METHODS: Tissue-engineered vascular grafts were assembled from biodegradable tubular scaffolds fabricated from poly-L-lactic acid mesh coated with epsilon-caprolactone and L-lactide copolymer. Thirteen scaffolds were seeded with human aortic endothelial and smooth muscle cells and implanted as infrarenal aortic interposition grafts in SCID/bg mice. Grafts were analyzed at time-points ranging from 4 days to 1 year after implantation. RESULTS: All grafts remained patent without evidence of thromboembolic complications, graft stenosis, or graft rupture as documented by serial ultrasound and computed tomographic angiogram, and confirmed histologically. All grafts demonstrated extensive remodeling leading to the development of well-circumscribed neovessels with an endothelial inner lining, neomedia containing smooth muscle cells and elastin, and a collagen-rich extracellular matrix. CONCLUSIONS: The development of second-generation tissue-engineered vascular grafts shows marked improvement over previous grafts and confirms feasibility of using tissue engineering technology to create an improved arterial conduit for use in pediatric vascular surgical applications.

Functional small-diameter human tissue-engineered arterial grafts in an immunodeficient mouse model: preliminary findings.

HYPOTHESIS: The immunodeficient (severe combined immunodeficiency beige [SCID/bg]) mouse model provides a useful model for investigating vascular neotissue formation in human tissue-engineered arterial conduits (TEAC). DESIGN: Human aortic smooth muscle cells and endothelial cells were statically seeded on porous biodegradable polymeric scaffolds for vascular tissue engineering. These 2-cell tissue-engineered vascular conduits were implanted into immunodeficient female mice as aortic interposition grafts. Grafts were evaluated over a 30-week course to investigate their patency and structure. SETTING: In vivo animal study. PATIENTS: Thirteen female C.B-17 SCID/bg mice. INTERVENTION: The TEACs implanted as infrarenal abdominal aortic interposition grafts. MAIN OUTCOME MEASURES: Selective microcomputed tomography with intra-arterial contrast revealed graft patency and structure. Histological and immunohistochemical evaluations revealed cellularity and extracellular matrix composition. Species-specific immunohistochemical evaluation determined the source of cells within TEACs. RESULTS: All TEACs were patent without evidence of thrombosis or rupture over the 30-week course. Histological and immunohistochemical evaluation revealed a von Willebrand factor-positive luminal monolayer surrounded by concentric collagen-rich layers of alpha-smooth muscle actin-positive cells. CONCLUSIONS: The SCID/bg mouse is a useful model for investigating vascular neotissue formation in human TEACs. We see evidence that these grafts remain patent while developing into vascular neotissue histologically similar to native aorta. This chimeric animal model also enables determination of seeded cell retention, providing insight into cellular mechanisms underlying neotissue formation.

The development of tissue-engineered grafts for reconstructive cardiothoracic surgical applications.

Surgical correction of congenital heart defects often requires the use of valves, patches, or conduits to establish anatomic continuity. Homografts, xenografts, or mechanical prosthetic devices are frequently implanted during these surgical procedures. These grafts however lack growth potential, are associated with increased risk of thrombosis and infection and have limited durability, thus increasing the morbidity and mortality of their application in pediatric cardiac surgery. These limitations are being addressed through the development of living, biologic tissue-engineered valves, patches, and conduits. Pilot studies and phase 1 clinical trials are currently underway to evaluate their feasibility, safety, and efficacy. The optimal scaffold, cell source, and conditioning parameters, however, still remain to be determined and are areas of active research.

Small-diameter biodegradable scaffolds for functional vascular tissue engineering in the mouse model.

The development of neotissue in tissue engineered vascular grafts remains poorly understood. Advances in mouse genetic models have been highly informative in the study of vascular biology, but have been inaccessible to vascular tissue engineers due to technical limitations on the use of mouse recipients. To this end, we have developed a method for constructing sub-1mm internal diameter (ID) biodegradable scaffolds utilizing a dual cylinder chamber molding system and a hybrid polyester sealant scaled for use in a mouse model. Scaffolds constructed from either polyglycolic acid or poly-l-lactic acid nonwoven felts demonstrated sufficient porosity, biomechanical profile, and biocompatibility to function as vascular grafts. The scaffolds implanted as either inferior vena cava or aortic interposition grafts in SCID/bg mice demonstrated excellent patency without evidence of thromboembolic complications or aneurysm formation. A foreign body immune response was observed with marked macrophage infiltration and giant cell formation by post-operative week 3. Organized vascular neotissue, consisting of endothelialization, medial generation, and collagen deposition, was evident within the internal lumen of the scaffolds by post-operative week 6. These results present the ability to create sub-1mm ID biodegradable tubular scaffolds that are functional as vascular grafts, and provide an experimental approach for the study of vascular tissue engineering using mouse models.

Evidence for a hereditary neuroblastoma predisposition locus at chromosome 16p12-13.

Hereditary predisposition to develop neuroblastoma (Online Mendelian Inheritance in Man 256700), a pediatric cancer of the sympathetic nervous system, segregates as an autosomal dominant Mendelian trait. We performed linkage analysis on seven families with two or more first-degree relatives affected with neuroblastoma to localize a hereditary neuroblastoma predisposition gene. A single interval at chromosome bands 16p12-13 was the only genomic region consistent with linkage (LOD(MAX) = 3.30 at D16S764). Identification of informative recombination events in linked families defined a 28.0-cM region between D16S748 and D16S769 that cosegregated with the disease in each pedigree. Loss of heterozygosity was identified in 5 of 11 familial neuroblastomas and 68 of 336 nonfamilial neuroblastomas (20.2%) at multiple 16p polymorphic loci. A 14.5-cM smallest region of overlap of somatic deletions was identified within the interval defined by linkage analysis (tel-D16S500-D16S412-cen). Taken together, these data suggest that a hereditary neuroblastoma predisposition gene (HNB1) is located at 16p12-13 and that disruption of this gene may contribute to the pathogenesis of nonfamilial neuroblastomas.