Daniel T. DeArmond

The first series of completely robotic esophagectomies with three-field lymphadenectomy: initial experience.

BackgroundThis study investigated the use of robotics to perform extended esophageal resection in a series of patients.MethodsA total of 14 patients with a median age of 64 years underwent esophagectomy using the da Vinci robot. At presentation, there were 12 cases of cancer, staged at T2N1 (n = 2), T3N0 (n = 2), T3N1 (n = 6), T4N1 (n = 1), and M1a (n = 1); 2 cases of high-grade dysplasia; 8 cases of adenocarcinoma; and 4 cases of squamous cell cancer; as well as 2 middle third, 9 lower third, and one gastroesophageal junction tumor. Nine patients had undergone preoperative chemoradiotherapy, and six had undergone prior abdominal surgery. The patients were categorized into three chronological groups according to the procedure performed. Group 1 consisted of the first three patients in the series, whose surgery was thoracic only (robotically assisted esophagectomy). Group 2, the next three patients, had robotically assisted thoracic esophagectomy plus thoracic duct ligation using a laparoscopic gastric conduit. Group 3, the last eight patients, underwent completely robotic esophagectomy.ResultsFor Group 3, the total operating room time was 11.1 ± 0.8 h (range, 11.3–13.2 h), with a console time of 5.0 ± 0.5 h (range, 4.8–5.8 h). The estimated blood loss was 400 ± 300 ml (range, 200–950 ml). One patient in group 1 had a thoracic duct leak. In groups 2 and 3, thoracic duct ligation resulted in no further leaks. Other postoperative complications included severe pneumonia (1 case), atrial fibrillation (5 cases), cervical anastomotic leak (2 cases), wound infection (1 case), and bilateral vocal cord paresis requiring tracheostomy (1 case). In seven of the cases, no intensive care unit time was required. There was one death from pneumonia 72 days after the procedure. The rate of disease-free survival was 87%.ConclusionThe robotic approach facilitates an extended three-field esophagolymphadenectomy even after induction therapy and abdominal surgery. Larger scale trials are needed to define the role of this technique.

Autocrine-mediated ErbB-2 kinase activation of STAT3 is required for growth factor independence of pancreatic cancer cell lines

Pancreatic ductal adenocarcinoma (PDAC) cell lines, MIA PaCa-2, and UK Pan-1, were used to investigate the role of ErbB2 in PDAC oncogenesis. Both these cell lines exhibit exogenous growth factor-independent proliferation that was attributed to the production of autocrine growth factors and/or overexpression of growth factor receptors. The exogenous growth factor-independent phenotype displayed by these PDAC cell lines was dependent on ErbB2 kinase activity since treatment of cells with tyrphostin AG879 prevented serum-free media (SFM) induction of cell proliferation. We determined that ErbB2 kinase contributed to aberrant cell cycle regulation in PDAC through the induction of cyclin D1 levels and the suppression of p21Cip1 and p27Kip1. Inhibition of ErbB2 kinase led to cell cycle arrest marked by an increased association of p27Kip1 with cdk2 and reduced levels of phosphorylated pRb. We further observed constitutive STAT3 activation in the PDAC cell lines and an increase in STAT3 activation upon stimulating quiescent cells with SFM. Inhibitors of ErbB2 kinase blocked STAT3 activation, whereas inhibition of EGFR kinase led to a slight reduction of STAT3 activation. STAT3 was coimmunoprecipitated with ErbB2. SFM stimulation caused an increase in the association of ErbB2 and STAT3, which was blocked by inhibition of ErbB2 kinase. Expression of a STAT3 dominant negative prevented SFM-stimulated cell proliferation of MIA PaCa-2 cells, suggesting that activation of STAT3 by ErbB2 is required for a growth factor-independent phenotype of these cells. Consistent with this observation in PDAC cell lines, we found that most PDAC tumor specimens (10 of 11) showed constitutive activation of STAT3 and that ErbB2 was readily detected in most of these tumors (nine of 11). We believe that these findings indicate a novel mechanism of oncogenesis in PDAC and may suggest future therapeutic strategies in the treatment of PDAC.

Alterations of cell signaling pathways in pancreatic cancer.

Pancreatic ductal adenocarcinomas continue to have the worst prognosis of any adult malignancy with a five-year survival rate of less than 4%. One approach to improve patient survival from pancreatic cancer is to identify new biological targets that contribute to the aggressive pathogenecity of this disease and to develop reagents that will interfere with the function of these targets. Apart from the identification of the genetic profile of pancreatic cancer, a number of studies have focused on aberrant cell signaling pathways and their role in pancreatic cancer biology and response to therapy. This review, although not comprehensive, will discuss the salient features of several of these pathways. These include the roles of TGF beta signaling in both tumor suppression and tumor promotion and the effects of deregulation of phosphotyrosine kinase receptor signaling pathways in pancreatic cancer.

Online Learning in Thoracic Surgical Training: Promising Results of Multi-Institutional Pilot Study

BACKGROUND Cardiothoracic surgical education faces numerous challenges, including reduced duty hours and diminishing prioritization of teaching, in the setting of rapidly advancing knowledge, skills, and case complexity. Pass rates on the American Board of Thoracic Surgery exam remain suboptimal, and new training formats are being evaluated. We hypothesize that Internet-based courses can be developed and implemented to supplement learning of basic topics in cardiothoracic surgery. METHODS After a needs assessment, 4 online self-study courses were developed by content experts using a Moodle [modular object-oriented dynamic learning environment] platform. As a pilot cohort, students from 4 thoracic surgery training programs participated, accessing courses at their own pace. Each course included general and detailed readings, multimedia content, discussion forum, and a question-bank supported quiz (90% required to pass, multiple attempts allowed). Utilization and exam data were tracked electronically. The t tests were used to compare first versus final-year traditional track trainees. Post-course surveys collected data on trainee attitudes. RESULTS Nineteen students completed 4 courses on tracheal disease. Mean time spent per course and quiz attempts to pass were 1.35 hours and 2.86, respectively. Scores improved with successive attempts. Senior trainees showed a trend toward less time per course and fewer quiz attempts. Post-course surveys uniformly demonstrated perceived benefits from the content and quizzes in an easy-to-navigate format. CONCLUSIONS Online courses can be developed and integrated within cardiothoracic training programs. This pilot demonstrates evidence of active learning as shown through the embedded assessments. Internet-based courses may serve as a means of supplementing modern thoracic surgical training. Further development and evaluation are warranted.

Effect of inhaled tacrolimus on ischemia reperfusion injury in rat lung transplant model

OBJECTIVE Systemic tacrolimus therapy has been shown to protect against lung ischemia-reperfusion injury in animal models. We sought to investigate on a functional and cellular level if inhaled nanoparticle tacrolimus administered to the donor lung before procurement could similarly attenuate ischemia-reperfusion injury after lung transplant. METHODS An isogenic orthotopic rat model of single left lung transplant was used. Donor animals were pretreated with inhaled tacrolimus (treatment group) or inhaled lactose (controls) before lung procurement. Lung grafts were subjected to 3 hours of cold ischemia followed by 4 hours of reperfusion after graft implantation. Recipient animal arterial blood gas measurement and isograft wet to dry weight ratios were obtained. Macrophage, neutrophil, and T-cell accumulation and activation in lung isografts, including γδ T-cell, T-helper, and cytotoxic T-cell subtypes were analyzed by flow cytometry. Tacrolimus levels were measured in the lung isograft using liquid chromatography/mass spectrometry. Isograft cytokine levels were measured with commercial enzyme-linked immunosorbent assay and microbead array kits. RESULTS Oxygenation in treatment group animals was significantly higher than in controls. The presence of macrophages, neutrophils, and all T-cell subtypes in the isografts as well as isograft levels of inflammatory cytokines were all less in the treatment group versus controls, although no single variable achieved statistical significance. CONCLUSIONS Inhaled nanoparticle tacrolimus treatment of lung donors is associated with an attenuation of ischemia-reperfusion injury on a functional and cellular level in lung transplant.

Traumatic Pseudoaneurysm of the Pulmonary Artery

A28-year-old woman, sustaining a gunshot wound to the left upper chest, arrived in the emergency department with CPR in progress for the last 2 minutes of transport. An emergency department thoracotomy was performed, finding a left hemothorax. The aorta and a bleeding left upper lobe were cross clamped. With further resuscitation, the patient regained vital signs and was transferred to the operating room. The bullet was noted to traverse the left upper lobe and exit through the left lower lobe. Through direct exploration of the upper lobe and tractotomy of the lower lobe, bleeding was controlled with suture ligation. Some persistent oozing from the bullet tract was controlled with direct pressure. The patient was transferred to the intensive care unit, where she remained hemodynamically stable with decreasing chest tube output. On postoperative day 3, because of a desaturation episode, a pulmonary embolism protocol chest computed tomography (CT) was performed revealing a 1.7 2.0 cm well-defined, oval-shaped, enhancing lesion within the left lingula, suspicious for a pseudoaneurysm (Fig. 1, A). Pulmonary angiography confirmed and further defined the pseudoaneurysm (Fig. 1, B) as arising from a branch of the lingular segment of the left pulmonary artery. Selective catheterization and coil embolization were performed, and ablation of the pseudoaneurysm was confirmed on a postembolization angiogram. The patient’s hospitalization was prolonged as a result of some psychiatric needs but was otherwise uncomplicated. She was ultimately discharged on postinjury day 30. A chest CT performed 1 year after the embolization showed persistent resolution of the pseudoaneurysm.

The successful use of cardiopulmonary support for a transected bronchus.

A 20-year-old male was involved in a motor vehicle accident and computed tomography revealed a completely transected right mainstem bronchus. An Emergency Department (ED) right anterior thoracotomy was necessary soon after arrival at our institution secondary to acute desaturation that was unresponsive to ventilator and chest tube management. This allowed direct intubation and ventilation of the right middle and lower lobes directly through the thoracotomy incision, which stabilized the patient for transport to the operating room. Once there, percutaneous cardiopulmonary support (CPS) was initiated to allow primary surgical repair of the transected bronchus. Post surgery, the patient was transported to the surgical intensive care unit on CPS which he required for an additional two days. The patient eventually did well and was discharged home. To our knowledge this is the first successful reported case of using the Avalon Elite dual lumen veno-venous cannula for CPS in a patient with complete right main-stem bronchus transection and bilateral pulmonary contusions.

Photodynamic Therapy Followed by Thoracoscopic Sleeve Lobectomy for Locally Advanced Lung Cancer

Photodynamic therapy is an effective technique for debulking endobronchial tumors over an acceptably short time-course; however, to be effective, numerous treatment cycles may be required to achieve the desired results. We present a case in which photodynamic therapy was used with curative intent to downsize an obstructing endobronchial non-small cell lung cancer in advance of resection via video-assisted thoracoscopic surgery with right upper lobe sleeve lobectomy.

Anastomotic leak detection by electrolyte electrical resistance

ABSTRACT Objective: To characterize a new method of postoperative gastrointestinal leak detection based on electrical resistance changes due to extravasated electrolyte contrast. Background: Postoperative gastrointestinal leak results in increased patient morbidity, mortality, and hospital costs that can be mitigated by early diagnosis. A sensitive and specific diagnostic test that could be performed at the bedside has the potential to shorten the time to diagnosis and thereby improve the quality of treatment. Materials and Methods: Anaesthetized rats underwent celiotomy and creation of a 5-mm gastrotomy. In experimental animals, electrical resistance changes were measured with a direct current ohmmeter after the introduction of 5 cc of 23.4% NaCl electrolyte solution via gavage and measured with a more sensitive alternating current ohmmeter after the gavage of 1–5 cc of 0.9% NaCl. Comparison was made to negative controls and statistical analysis was performed. Results: Leakage from the gastrotomy induced by as little as 1 cc of gavage-delivered 0.9% NaCl contrast solution was detectable as a statistically significant drop in electrical resistance when compared to results from negative controls. Conclusion: Electrical resistance change associated with electrolyte-gated leak detection is highly sensitive and specific and has the potential to be rapidly translated into clinical settings.

The efficacy of inhaled nanoparticle tacrolimus in preventing rejection in an orthotopic rat lung transplant model

Objective: The immunosuppressive efficacy of inhaled nanoparticle tacrolimus was compared with systemic tacrolimus in a rodent allogeneic lung transplant model. Methods: Sixteen rats underwent allogeneic left orthotopic lung transplantation and were divided into 3 treatment groups: (1) inhaled nanoparticle tacrolimus: 6.4 mg tacrolimus/6.4 mg lactose twice per day; (2) intramuscular tacrolimus: 1 mg/kg tacrolimus once per day; and (3) inhaled lactose: 6.4 mg of lactose twice per day. Five days after transplant, the rats were necropsied and underwent histologic rejection grading and cytokine analysis. Trough levels of tacrolimus were measured in allograft, blood, and kidney. Results: Both intramuscular (n = 6) and nanoparticle tacrolimus (n = 6) rats displayed lower histologic grades of rejection (mean scores 3.4 ± 0.6 and 4.6 ± 0.9, respectively) when compared with lactose rats (n = 4) (mean score 11.38 ± 0.5, P = .07). Systemic tacrolimus trough levels (median) were lower in nanoparticle tacrolimus–treated rats versus intramuscular‐treated rats (29.2 vs 118.6 ng/g; P < .001 in kidney, and 1.5 vs 4.8 ng/mL; P = .01 in blood). Conclusions: Inhaled nanoparticle tacrolimus provided similar efficacy in preventing acute rejection when compared with systemic tacrolimus while maintaining lower systemic levels.