Novel composite trachea grafts using 3-dimensional printing.

Objective: Porcine-derived small intestine submucosa (SIS) extracellular matrix (ECM) surgical patches claim to have greater regenerative properties compared with dermal extracellular matrices. We hypothesized that using SIS-ECM in a bioengineered composite tracheal graft would allow better incorporation into the native tissue. Methods: Two types of size-matched polycaprolactone support scaffolds were designed: rigid and flexible. The SIS-ECM was wrapped around the polycaprolactone supports lining the inside and outside of the graft. The grafts were implanted in 4 Yorkshire pigs, replacing an ∼2 cm segment of native trachea. Airway patency was evaluated with computed tomography scans and explanted grafts were examined grossly and histologically. Results: All animals survived through the immediate postoperative period. Generally, extraluminal examination showed a smooth transition between native and graft without significant volumetric loss. Animals that received the flexible design survived ∼10 days longer than those that received the rigid design; however, severe perianastomotic intraluminal granulation tissue was observed. The rigid design had less significant intraluminal granulation tissue development at the distal anastomosis, but partial dehiscence had occurred at the proximal anastomosis interrupting graft incorporation. Conclusions: The generally good extraluminal graft incorporation in our composite tracheal graft highlights some increased regenerative capabilities of SIS-ECM. However, the presence of intraluminal granulation tissue indicates that its use as an off-the-shelf, unaltered substrate in an airway graft is still not ideal. Further research must be conducted to determine whether a modification of the substrate is possible to enhance luminal airway incorporation and to exert control over the mechanisms responsible for granulation tissue development.

Successes and Failures in Tracheal Bioengineering: Lessons Learned.

BACKGROUND: Controversy in tracheal reconstruction using grafts and bioengineered constructs highlights the importance of animal studies before human application. Small animal models help to refine designs but do not adequately model sizes relevant to human anatomy. We have conducted extensive large animal studies and summarize our findings in 26 consecutive transplants. METHODS: We pooled 26 large animal studies together to investigate common elements related to successes and failures. In general the engineered tracheal graft consisted of a decellularized extracellular matrix surgical patch supported by a 3-dimensional-printed plastic polymer scaffold. Circumferential graft coverage ranged from 50% to 100%, spanning the length of 4 to 6 tracheal rings. Some grafts included embedded stem cells. Control grafts were fabricated without the support scaffold. At death grafts were harvested and examined grossly and through histology. RESULTS: The support scaffold prevented graft malacia and collapse. Luminal epithelialization was most extensive in grafts with smaller circumferential coverage. Smaller circumferential coverage was also associated with longest animal survival. Chondrogenesis was only observed in grafts with embedded stem cells. Survival time was shortest in 100% circumferential grafts. Granulation tissue was an issue for all graft designs. CONCLUSIONS: Large animal models capture challenges and complexities relevant to human anatomy. Development of granulation tissue remains a challenge, especially in circumferential grafts. Significant additional research is needed to investigate granulation tissue formation and to provide actionable insight into its management.

Adjuvant Radiation Therapy for Thoracic Soft Tissue Sarcomas: A Population-Based Analysis.

BACKGROUND: The role of adjuvant radiation therapy (RT) in the management of thoracic soft tissue sarcomas (STSs) remains unclear. We aimed to study the characteristics of patients with thoracic STS who received RT after surgical resection and investigate the impact of RT on survival outcomes. METHODS: We queried National Cancer Database to identify patients with surgically resected thoracic STS from 2004 to 2012. Factors associated with receiving adjuvant RT were identified. Analyses were performed to identify prognostic factors and compare overall survival (OS) in both unmatched and propensity score-matched cohorts. RESULTS: Overall, 1215 patients were identified, of whom 557 (45.8%) received adjuvant RT. Tumor grade (odds ratio [OR], 2.87; 95% confidence interval [CI], 2.18-3.77), tumor size (OR, 1.82; 95% CI, 1.36-2.42), and tumor margins (OR, 1.97; 95% CI, 1.43-2.72) were found to be significant predictors of receiving RT. Mean OS of patients receiving RT in the unmatched cohort was 91 months vs 88 months for patients who did not (P = .556). When adjusted for all variables, adjuvant RT was found to be associated with improved survival (hazard ratio, 0.79; 95% CI, 0.61-0.96). Survival analysis of the matched cohort also demonstrated improved survival with adjuvant RT (120 months vs 100 months; P = .02). Subgroup analysis in both the unmatched and matched cohorts showed patients with high-grade tumors more likely to benefit from adjuvant RT. CONCLUSIONS: This population-based analysis is the largest dataset of primary thoracic STSs to date and suggests significant survival benefit associated with adjuvant RT. The improvement in OS was more notable in patients with high-grade tumors. Randomized prospective studies are warranted to further understand the benefit of RT in this group.

Mutational landscape of head and neck squamous cell carcinomas in a South Asian population.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type globally and contributes significantly to burden of disease in South Asia. In Pakistan, HNSCC is among the most commonly diagnosed cancer in males and females. The increasing regional burden of HNSCC along with a unique set of risk factors merited a deeper investigation of the disease at the genomic level. Whole exome sequencing of HNSCC samples and matched normal genomic DNA analysis (n=7) was performed. Significant somatic single nucleotide variants (SNVs) were identified and pathway analysis performed to determine frequently affected signaling pathways. We identified significant, novel recurrent mutations in ASNS (asparagine synthetase) that may affect substrate binding, and variants in driver genes including TP53, PIK3CA, FGFR2, ARID2, MLL3, MYC and ALK. Using the IntOGen platform, we identified MAP kinase, cell cycle, actin cytoskeleton regulation, PI3K-Akt signaling and other pathways in cancer as affected in the samples. This data is the first of its kind from the Pakistani population. The results of this study can guide a better mechanistic understanding of HNSCC in the population, ultimately contributing new, rational therapeutic targets for the treatment of the disease.

Robotic Thoracic Surgery Training for Residency Programs: A Position Paper for an Educational Curriculum.

OBJECTIVE: Robotic-assisted surgery is increasingly being used in thoracic surgery. Currently, the Integrated Thoracic Surgery Residency Program lacks a standardized curriculum or requirement for training residents in robotic-assisted thoracic surgery. In most circumstances, because of the lack of formal residency training in robotic surgery, hospitals are requiring additional training, mentorship, and formal proctoring of cases before granting credentials to perform robotic-assisted surgery. Therefore, there is necessity for residents in Integrated Thoracic Surgery Residency Program to have early exposure and formal training on the robotic platform. We propose a curriculum that can be incorporated into such programs that would satisfy both training needs and hospital credential requirements. METHODS: We surveyed all 26 Integrated Thoracic Surgery Residency Program Directors in the United States. We also performed a PubMed literature search using the key word "robotic surgery training curriculum." We reviewed various robotic surgery training curricula and evaluation tools used by urology, obstetrics gynecology, and general surgery training programs. We then designed a proposed curriculum geared toward thoracic Integrated Thoracic Surgery Residency Program adopted from our credentialing experience, literature review, and survey consensus. RESULTS: Of the 26 programs surveyed, we received 17 responses. Most Integrated Thoracic Surgery Residency Program directors believe that it is important to introduce robotic surgery training during residency. Our proposed curriculum is integrated during postgraduate years 2 to 6. In the preclinical stage postgraduate years 2 to 3, residents are required to complete introductory online modules, virtual reality simulator training, and in-house workshops. During clinical stage (postgraduate years 4-6), the resident will serve as a supervised bedside assistant and progress to a console surgeon. Each case will have defined steps that the resident must demonstrate competency. Evaluation will be based on standardized guidelines. CONCLUSIONS: Expansion and utilization of robotic assistance in thoracic surgery have increased. Our proposed curriculum aims to enable Integrated Thoracic Surgery Residency Program residents to achieve competency in robotic-assisted thoracic surgery and to facilitate the acquirement of hospital privileges when they enter practice.

Racial Disparity in Utilization of High-Volume Hospitals for Surgical Treatment of Esophageal Cancer.

BACKGROUND: Utilization of high-volume hospitals (HVH) for esophagectomy has been associated with improved perioperative outcomes and reduced mortality. We aimed to test the hypothesis that black-white racial disparities exist in HVH utilization and identify predictors of in-hospital surgical outcomes of esophageal cancer while adjusting for HVH utilization patterns. METHODS: We queried the New York Statewide Planning and Research Cooperative System database (1995 to 2012) for esophageal cancer patients who underwent surgical resection exclusively. Only records for patients with self-reported white or black race and a valid New York State ZIP code were included (n = 2,895). Analysis was performed to identify factors associated with HVH hospital (≥20 esophagectomies/year) utilization and determine predictors of complications and in-hospital mortality. RESULTS: Black patients (361 [12.5%]) were significantly different (p < 0.001) than their white counterparts in the proportion of women, Medicaid, income distribution, and privately insured individuals. Although 55% patients overall utilized an HVH, blacks were significantly less likely to utilize an HVH than whites (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.14 to 0.24), even though 74.5% resided within 8.9 miles of one. Operations performed at HVHs were associated with lower in-hospital mortality (OR, 0.48; 95% CI, 0.35 to 0.65); however, mortality remained higher for blacks (OR, 2.04; 95% CI, 1.65 to 3.30; propensity matched OR, 2.45; 95% CI, 1.5 to 4.03). CONCLUSIONS: Black patients were less likely to undergo esophagectomy at an HVH and experienced higher mortality. Efforts should be made to understand factors influencing patients' decision process and improve referral practices to ensure optimal care is provided across all segments of the population, irrespective of race, insurance, or income status.

Pulmonary Resection for Second Lung Cancer After Pneumonectomy: A Population-Based Study.

BACKGROUND: Pulmonary resection for a second lung cancer after pneumonectomy is generally considered to be at prohibitive risk. Using a population-based database, we examined treatment patterns and survival in patients who underwent pulmonary resection after pneumonectomy for lung cancer. METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER) database (1988-2012) to identify patients who underwent pneumonectomy and subsequently experienced contralateral non-small cell lung cancer (NSCLC). Multivariate logistic regression was performed to identify the factors associated with the receipt of surgical resection. Survival was estimated with the Kaplan-Meier method. RESULTS: Of 13,370 patients who underwent pneumonectomy, 402 (3.0%) experienced subsequent contralateral NSCLC, and 170 (42%) met the selection criteria. Surgical resection was performed in 63 (37.1%) cases (sublobar n = 56, lobectomy, n = 7). Patients with stage I/II disease and tumor size 2 cm or smaller were more likely to undergo surgical procedures. The 1-month and 3-month mortality after resection was 11.1% (sublobar resection 10.7%, lobectomy 14.3%) and 12.7% (sublobar 12.5%, lobectomy 14.3%), respectively. The overall 1-year and 3-year survival after surgical resection was 79% and 54%, respectively. The patients who underwent sublobar resection had higher median overall survival than did those who underwent lobectomy (42 vs 18 months). Similarly, median survival after resection for metachronous tumors was higher than after resection for metastatic cancers (40 vs 28 months). CONCLUSIONS: On the basis of our analysis of the SEER database, sublobar resection can be performed in selected patients with small tumors (≤2 cm) and early-stage disease (stage I/II). Although perioperative mortality is significant, the favorable 1-year and 3-year survival may justify the role of an additional procedure on the single lung.

Three-Dimensional-Printed Bioengineered Tracheal Grafts: Preclinical Results and Potential for Human Use.

BACKGROUND: We aimed to develop a process using three-dimensional (3D) printing to create bioengineered tracheal grafts (BETGs) for reconstruction of anterior tracheal defects in a large-animal model (porcine) that would have translational relevance for potential human use. METHODS: Preoperative computed tomographic scans were used to create virtual 3D models of the animal airways. Anatomically scaled tracheal grafts were subsequently developed using 3D-printed polycaprolactone and extracellular matrix. A 4-cm anterior tracheal defect (about 50% of the length of the subject trachea) was surgically created in 4-week-old female Yorkshire pigs and reconstructed using the customized grafts. Gross and microscopic analyses of the grafts were performed. RESULTS: The BETGs were implanted in 7 animals. There was adequate graft-native trachea size match at the operation. The trachea was successfully reconstructed in all cases. Gross examination at autopsy showed a structurally intact, well-incorporated graft. Histologic evaluation showed respiratory mucosal coverage and vascularity of the graft. Five of 7 animals outlived the 3-month study period. The animals had approximately 100% growth during the study period. CONCLUSIONS: We report of a 3D-printed BETG to repair long-segment anterior tracheal defects in a large-animal model. Although the study duration is short, this work presents an efficient strategy for tracheal graft bioengineering with potential translational relevance for human use.

Circumferential Three-Dimensional-Printed Tracheal Grafts: Research Model Feasibility and Early Results.

BACKGROUND: Methods for tracheal graft research have presented persistent challenges to investigators, and three-dimensional (3D)-printed biosynthetic grafts offer one potential development platform. We aimed to develop an efficient research platform for customizable circumferential 3D-printed tracheal grafts and evaluate feasibility and early structural integrity with a large-animal model. METHODS: Virtual 3D models of porcine subject tracheas were generated using preoperative computed tomography scans. Two designs were used to test graft customizability and the limits of the construction process. Designs I and II used 270-degree and 360-degree external polycaprolactone scaffolds, respectively, both encompassing a circumferential extracellular matrix collagen layer. The polycaprolactone scaffolds were made in a fused-deposition modeling 3D printer and customized to the recipient's anatomy. Design I was implanted in 3 pigs and design II in 2 pigs, replacing 4-ring tracheal segments. Data collected included details of graft construction, clinical outcomes, bronchoscopy, and gross and histologic examination. RESULTS: The 3D-printed biosynthetic grafts were produced with high fidelity to the native organ. The fabrication process took 36 hours. Grafts were implanted without immediate complication. Bronchoscopy immediately postoperatively and at 1 week demonstrated patent grafts and appropriate healing. All animals lived beyond a predetermined 1-week survival period. Bronchoscopy at 2 weeks showed significant paraanastomotic granulation tissue, which, along with partial paraanastomotic epithelialization, was confirmed on pathology. Overall survival was 17 to 34 days. CONCLUSIONS: We propose a rapid, reproducible, resource efficient method to develop various anatomically precise grafts. Further graft refinement and strategies for granulation tissue management are needed to improve outcomes.

Reconstruction of Anterior Tracheal Defects Using a Bioengineered Graft in a Porcine Model.

BACKGROUND: Reconstruction of long-segment tracheal defects can be challenging and a suitable tracheal substitute remains lacking. We sought to create a bioengineered tracheal graft to repair such lesions using acellullar bovine dermis extracellular matrix (ECM) and male human mesenchymal stem cells (hMSCs) and implant it in a porcine model. METHODS: hMSCs were seeded on the ECM and incubated for 1 week with chondrogenic factors. An anterior 4 cm × 3 cm defect was surgically created in the trachea of 4-week-old female Yorkshire pigs. The defect was reconstructed using the bioengineered graft (n = 7) or control (n = 3, ECM only). The study duration was 3 months. RESULTS: Survival ranged from 7 days (n = 3) to 3 months (n = 7). Early death was due to graft malacia (n = 1, control), graft infection (n = 1, bioengineered), and pneumonia (n = 1, bioengineered). There was substantial animal growth at 3 months (>200% weight). Surveillance bronchoscopy showed patent airway, mild stenosis, and integration of the graft with the native trachea. On histology, luminal epithelialization and neovascularization with scant submucosa were observed in both the bioengineered graft and control groups. Chondrogenesis was seen only in the bioengineered graft. The neocartilage was less mature and organized compared to native cartilage. SRY immunostain was positive in the neocartilage but not control or native trachea. CONCLUSIONS: We demonstrate the feasibility of the bioengineered graft for reconstruction of long anterior tracheal defects with favorable short-term outcomes. Furthermore, we show its ability to facilitate chondrogenesis, neovascularization, and epithelialization. Importantly, it supported rapid animal growth offering potential solutions for both pediatric and adult applications.

Robotically Assisted Thoracic Surgery: Proposed Guidelines for Privileging and Credentialing.

OBJECTIVE: Increased use of robotically assisted thoracic surgery (RATS) necessitates effective credentialing guidelines to ensure safe outcomes. We provide a stepwise algorithm for granting privileges and credentials in RATS. This algorithm reflects graduated responsibility and complexity of the surgical procedures performed. Furthermore, it takes into account volume, outcomes, surgeon's competency, and appropriateness of robot usage. METHODS: We performed a literature review for available strategies to grant privileges and credentials for implementing robotic surgery. The following terms were queried: robot, robotic, surgery, and credentialing. We provide this algorithm on the basis of review of the literature, our institutional experience, and the experience of other medical centers around the United States. RESULTS: Currently, two pathways for robotic training exist: residency and nonresidency-trained. In the United Sates, Joint Commission: Accreditation, Health Care, Certification requires hospitals to credential and privilege physicians on their medical staff. In the proposed algorithm, a credentialing designee oversees and reviews all requests. Residency-trained surgeons must fulfill 20 cases with program directors' attestation to obtain full privileges. Nonresidency-trained surgeons are required to fulfill simulation, didactics including online modules, wet laboratories (cadaver or animal), and observation of at least two cases before provisional privileges can be granted. A minimum number of cases (10 per year) are required to maintain privileges. All procedures are monitored via departmental QA/QI committee review. Investigational uses of the robot require institutional review board approval, and complex operations may require additional proctoring and QA/QI review. CONCLUSIONS: Safety concerns with the introduction of novel and complex technologies such as RATS must be paramount. Our algorithm takes into consideration appropriate use and serves as a basic guideline for institutions that wish to implement a RATS program.

The incidence of trocar-site hernia in minimally invasive bariatric surgery: a comparison of multi versus single-port laparoscopy.

INTRODUCTION: Single-port laparoscopy (SPL) employs a 1.5- to 2.5-cm incision at the umbilicus for the placement of a single working port. We hypothesized that the longer incision created by SPL compared with multiport laparoscopy may increase the incidence of trocar-site hernias. We examined our experience with SPL in bariatric operations. METHODS: There were 734 laparoscopic sleeve gastrectomy and laparoscopic adjustable gastric banding procedures performed at our institution between 2001 and 2011. Fifty-eight patients were lost to follow-up or had a short duration of follow-up (<1 month). Of the remaining 676 cases, 163 were performed via SPL. All laparoscopic wounds created by trocar size greater than 12 mm were closed with absorbable suture. RESULTS: Patient demographics of the SPL group and the multiport group were similar in terms of age, gender, and comorbidities. The average body mass index (BMI) of the SPL group was lower than the multiport group (43.5 ± 5.3 vs. 45.8 ± 7.7, p < 0.01). The mean follow-up for the SPL group was 11 months versus 24 months for the multiport group. There were three trocar-site hernias out of 513 cases in the multiport compared to one hernia out of 163 cases in the SPL group (0.6 vs. 0.6 %, p = 0.967). All trocar-site hernias occurred at the 15-mm port site. The median time to hernia occurrence for the multiport group was 13 months (range, 1-18). In the SPL group, the hernia occurred at 8 months. On multivariate analysis, age, BMI, SPL, procedure type, and the postoperative weight loss were not associated with the development of trocar-site hernias. CONCLUSIONS: SPL did not increase the rate of trocar-site hernia in this series. A low rate of trocar-site hernia can be achieved with the use of SPL in bariatric surgery.

Surgical residents' perception of the 16-hour work day restriction: concern for negative impact on resident education and patient care.

BACKGROUND: Effective July 1, 2011, the Accreditation Council for Graduate Medical Education (ACGME) instituted a 16-hour duty period limitation for postgraduate year I (PGY I) residents. Our aim was to assess the attitudes and perception of general surgery residents regarding the new duty hour limitation as well as the transfer of care process under the new guidelines. STUDY DESIGN: An anonymous, web-based survey was conducted nationally 7 months after the institution of the 16-hour duty limitation. RESULTS: A total of 464 completed surveys were analyzed. Overall, 75% of residents expressed dissatisfaction with the new duty hour limitation. PGY II to V residents reported a higher level of dissatisfaction compared with PGY I residents (87% vs 54%, p < 0.01). Eighty-nine percent of PGY II to V residents responded that there has been a shift of responsibilities from the PGY I class to PGY II to V residents, with 73% reporting increased fatigue as a result. Seventy-five percent of PGY I and 94% of PGY II to V residents expressed concerns about the adverse impact of the restrictions on the education of PGY I residents (p < 0.01). Residents at all PGY training levels reported encountering problems due to inadequate sign-outs (PGY I, 59%; PGY II to V, 85%; p < 0.01). Sixty-two percent of PGY I residents and 54% of PGY II to V residents believed that the new 16-hour duty restriction contributes to inadequate sign-outs (p = NS). Most PGY II to V residents (86%) believe there is a decreased level of patient ownership due to the work hour restrictions. CONCLUSIONS: The results of the survey suggest that the majority of general surgery residents are concerned over the potential negative impact of the duty limitation on resident education and patient care. Further research is needed to address these concerns.

The spread of HIV in Pakistan: bridging of the epidemic between populations.

In the last two decades, 'concentrated epidemics' of human immunodeficiency virus (HIV) have established in several high risk groups in Pakistan, including Injecting Drug Users (IDUs) and among men who have sex with men (MSM). To explore the transmission patterns of HIV infection in these major high-risk groups of Pakistan, 76 HIV samples were analyzed from MSM, their female spouses and children, along with 26 samples from a previously studied cohort of IDUs. Phylogenetic analysis of HIV gag gene sequences obtained from these samples indicated a substantial degree of intermixing between the IDU and MSM populations, suggesting a bridging of HIV infection from IDUs, via MSM, to the MSM spouses and children. HIV epidemic in Pakistan is now spreading to the female spouses and offspring of bisexual MSM. HIV control and awareness programs must be refocused to include IDUs, MSM, as well as bisexual MSM, and their spouses and children.