High dose, dual-release polymeric films for extended surgical bed paclitaxel delivery.

While surgery represents a major therapy for most solid organ cancers, local recurrence is clinically problematic for cancers such as sarcoma for which adjuvant radiotherapy and systemic chemotherapy provide minimal local control or survival benefit and are dose-limited due to off-target side effects. We describe an implantable, biodegradable poly(1,2-glycerol carbonate) and poly(caprolactone) film with entrapped and covalently-bound paclitaxel enabling safe, controlled, and extended local delivery of paclitaxel achieving concentrations 10,000× tissue levels compared to systemic administration. Films containing entrapped and covalently-bound paclitaxel implanted in the tumor bed, immediately after resection of human cell line-derived chondrosarcoma and patient-derived xenograft liposarcoma and leiomyosarcoma in mice, improve median 90- or 200-day recurrence-free and overall survival compared to control mice. Furthermore, mice in the experimental film arm show no film-related morbidity. Continuous, extended, high-dose paclitaxel delivery via this unique polymer platform safely improves outcomes in three different sarcoma models and provides a rationale for future incorporation into human trials.

Supraclavicular Approach for Neurogenic Thoracic Outlet Syndrome: Description of a Learning Curve.

BACKGROUND: The supraclavicular exposure represents an alternative approach for thoracic outlet decompression in neurogenic thoracic outlet syndrome with unique access to neurovascular structures. We aimed to evaluate the learning curve for this approach and associated patient outcomes. METHODS: Patients undergoing first-time, unilateral, supraclavicular thoracic outlet decompression for neurogenic thoracic outlet syndrome were included. Cumulative-sum and linear-spline-regression analyses were used to determine the operative time learning curve. Patients were consecutively organized into early (learning phase) and late (competency) cohorts. Primary endpoints were the operative time learning curve operation number and association of this learning curve on differences in self-reported postoperative symptomatic improvement between early and late cohorts, adjusting for American Society of Anesthesiology classification, body mass index, previous treatment (opioid/neuropathic medication/botulinum-injection), and length of stay. RESULTS: Among 114 patients, learning curve analyses showed decreasing operative times, plateauing at the 51st operation (ß = -1.63, 95% confidence interval [-2.30, -0.95], P < .001). No periprocedural differences existed between early (operations 1-50) and late (operations 51-114) cohorts. Self-reported 90-day outcomes were similar in early and late cohorts (odds ratio [OR]: 1.60 [0.65, 3.95], P = .31). Mediators of poor self-reported outcomes included increasing American Society of Anesthesiology classification (OR 0.21 [0.08, 0.54], P = .001), failed preoperative botulinum injection (OR 0.15 [0.03, 0.65], P = .01), and increased length of stay (OR 0.40 [0.22, 0.73], P = .003). CONCLUSIONS: The learning curve for supraclavicular thoracic outlet decompression in neurogenic thoracic outlet syndrome occurred after 51 operations with a trend towards improved 90-day self-reported outcomes from the early to late phases. These findings, along with mediators of poorer outcomes, may aid surgeons in adopting a new approach and counseling patients on expected outcomes.

Outcomes of Laparoscopic Heller Myotomy for Achalasia: 22-Year Experience.

INTRODUCTION: Laparoscopic Heller Myotomy is the most effective treatment of achalasia. We examined the durability of symptomatic relief, with and without fundoplication. METHODS: A single institution database between 1995 and 2017 was reviewed. Achalasia symptom severity was assessed by Eckardt scores (ES) obtained at 3-time points via patient questionnaire. Primary outcome was treatment success defined as ES of < 3. RESULTS: Completed surveys were returned by 130 patients (median follow-up of 6.6 years). A partial fundoplication was performed in 86%. At both 1-year and late follow-up, patients reported a significant improvement in ES compared to baseline (p < 0.05). Of those followed for ≥ 10 years (n = 44), 82% reported ES < 3 at 1-year (p < 0.001), and 78% at last follow-up (p < .001). Of patients who reported treatment success 1-year postoperatively (103/130), 85% continued to report symptomatic relief at last follow-up. Five-year cohort analysis did not show deterioration of dysphagia relief over time. The presence or absence of fundoplication had no impact on long-term outcome (p > 0.05). CONCLUSIONS: LHM provides immediate and durable symptomatic relief, with very few patients requiring further therapeutic intervention. Fundoplication does not appear to influence the durability of symptom relief. Treatment success at 1-year is predictive of long-lasting symptomatic relief.

Postintubation Tracheal Stenosis: Management and Results 1993 to 2017.

BACKGROUND: To evaluate the management, complications of treatment, and outcomes of postintubation tracheal stenosis. METHODS: A retrospective review was performed of records from a prospective database of all patients undergoing tracheal or laryngotracheal resection from 1993 to 2017 for postintubation tracheal stenosis. Redo operations after failure of initial resection and reconstruction for postintubation tracheal stenosis were included. RESULTS: There were 392 patients whose ages ranged from 3 months to more than 84 years. A tracheostomy was performed in 275 as part of their care before surgery (present at time of resection in 123), dilations in 201, laser treatment in 82, T tubes in 66, and stents in 44 patients. Median length of resection was 3 cm. Laryngeal release was required in 15 of 392 (3.8%). Operative mortality was 0.8% (3 of 392); T tubes, tracheostomy present at resection, requirement for postoperative tracheostomy, and laryngeal involvement adversely impacted outcomes. Patients having tracheal resection and reconstruction had good or satisfactory outcomes in 96% (289 of 301) compared with 85% (77 of 91) having laryngotracheal resection. Complications within 30 days and at more than 30 days occurred in 116 patients and 14 patients, respectively. There were 96 anastomotic complications-68% minor (65 of 96), and 32% major (31 of 96). Necrosis of cartilage occurred in 12 patients and dehiscence in 14 patients. CONCLUSIONS: Despite advances in care postintubation tracheal stenosis remains a challenging problem. Laryngotracheal resection and tracheostomy lead to worse outcomes. Excellent surgical results can be obtained for postintubation tracheal stenosis. Good results require careful evaluation, management of comorbid conditions, meticulous technique, minimizing tension, and preservation of blood supply.

Carinal surgery: A single-institution experience spanning 2 decades.

OBJECTIVES: Complete resection of neoplasms involving the carina are technically challenging and have high operative morbidity and mortality. This study examines the last 2 decades of clinical experience at our institution. METHODS: Medical records were retrospectively reviewed between 1997 and 2017 to identify all patients who underwent carinal resection. Primary outcome measures include risk factors for complications and overall survival. RESULTS: In total, 45 carinal resections were performed with a median follow-up of 3.4 years (interquartile range 0.8-8.5). Procedures included 21 neocarinal reconstructions (48%), 14 right carinal pneumonectomies (30%), 9 left carinal pneumonectomies (20%), and 1 carinal plus lobar resection (2%). Age ranged from 27 to 74 years, and 23 of 45 patients were female. Eight received neoadjuvant chemotherapy and 6 preoperative radiation. Extracorporeal membrane oxygenation and cardiopulmonary bypass were intraoperatively used for 4 patients with no mortality. Four patients underwent superior vena cava resection and reconstruction. Anastomotic complications occurred in 5 patients, all of which were managed conservatively: 1 required stent placement and a second underwent hyperbaric oxygen therapy. Postoperative events were observed in 26 patients (58%), including pneumonia (n = 11), blood transfusion (n = 8), and atrial arrhythmias (n = 8). More serious complications, such as acute respiratory distress syndrome, occurred in 3 patients. Postoperative events were most closely associated with pulmonary resection (P = .040). There were 3 deaths, yielding an overall operative 30- and 90-day mortality of 6.8% and 7%, respectively. CONCLUSIONS: Despite advances in perioperative management, carinal resection poses challenges for both patient and surgeon. Preoperative chemotherapy, radiation, and concomitant pulmonary resection were associated with increased risk of complications. Patient selection and meticulous surgical technique contribute to reduction in morbidity and mortality.

Relative Incremental Cost of Postoperative Complications of Esophagectomy.

The purpose of this study was to quantify the cost impact of complications of esophagectomy and identify opportunities for reducing costs while optimizing outcomes. Patients undergoing esophagectomy at a single institution between 2002 and 2017 were included. Complications were tabulated from clinical data. Direct hospital costs were determined for all encounters between the day of surgery and postoperative day 90. Risk factors were assessed using logistic regression. The relative incremental cost of complications was assessed using multivariable linear regression. A total of 761 patients were included in this study. 428 patients (56%) experienced at least 1 complication. Factors associated with increased likelihood of complications included age (P < 0.001), female sex (P = 0.005), pack-years (P = 0.006), cerebrovascular disease (P = 0.021), and diabetes (P = 0.052). The most common complications were atrial arrhythmia (18%), transfusion (15%), and atelectasis requiring bronchoscopy (8%). The complications incurring the greatest incremental cost per event were anastomotic complications requiring surgical treatment (200%, P < 0.001) or those treated nonoperatively (96%, P < 0.001), and renal failure (178%, P < 0.001). Pneumonia increased costs by 40% (P < 0.001) and other major pulmonary complications increased costs by 75% (P < 0.001). Though the cost of complications was unaffected by surgical approach (minimally invasive esophagectomy vs open), MIE was associated with decreased cost vis-à-vis a lower complication rate (41% vs 60%, P < 0.001). Complications accounted for 28% of the aggregate 90-day direct hospital cost for all patients. Pulmonary complications accounted for 35% of all complication-attributable costs, while anastomotic complications accounted for 17%. Anastomotic and pulmonary complications after esophagectomy with gastric conduit reconstruction represent high-yield targets for cost reduction and quality improvement.

Relative incremental costs of complications of lobectomy for stage I non-small cell lung cancer.

OBJECTIVE: To evaluate the relative incremental cost of complications after lobectomy for stage I non-small cell lung cancer (NSCLC). METHODS: Patients treated with open or video-assisted thoracoscopic surgery (VATS) lobectomy for stage I NSCLC between 2008 and 2014 were selected. A patient registry was queried for all complications recorded during a 90-day postoperative interval. Hospital cost data for each patient was concatenated with clinical data. Linear regression was used to assess the impact on direct hospital costs of specific complications. RESULTS: Among the 488 patients included in this study, 34% experienced ≥1 complication and 17% experienced ≥1 major complication. In patients experiencing complications, atrial arrhythmia (13%), prolonged air leak (8.6%), atelectasis (6.4%), and transfusion requirement (4.5%) were most common. Minor complications increased the relative cost of lobectomy by 29% (95% confidence interval [CI], 23%-34%; P < .001) compared to the cost of an uncomplicated lobectomy. Major complications increased costs by 57% (95% CI, 53%-62%; P < .001). The greatest predictor of increased 90-day cost was major pulmonary complications, which increased cost by 111% (95% CI, 96%-126%; P < .001). Prolonged air leak increased relative mean cost by 22% (95% CI, 10%-33%; P < .001) and pneumonia by 96% (95% CI, 75%-117%; P < .001). CONCLUSIONS: Complications, both major and minor, contribute significantly to the total 90-day direct hospital cost of lobectomy for stage I NSCLC. Analysis of 90-day postoperative outcomes more accurately captures costs. Major pulmonary complications, atrial arrhythmia, pneumonia, and prolonged air leak represent 4 high-yield targets for cost reduction. Efforts to control health care spending while improving patient outcomes might optimally focus on reducing complications that incur the greatest relative incremental cost.