Hisashi Tsukada

Experimental study of a new tracheal prosthesis: Pored Dacron tube

OBJECTIVE This study was designed to evaluate how various sizes and densities of pores in Dacron tubing might enhance its utility as a tracheal prosthesis. METHODS A vascular prosthesis made of knitted external velour polyester was prepared for pore formation with a laser. The first set compared different pore sizes (300, 500, and 700 microm) and pore densities (25/cm(2) or 100/cm(2)). Grafts were reinforced with an externally heat-sealed silicone ring. The second set tested grafts with a pore density of 64/cm(2) and a pore size of 500 microm internally reinforced with a stainless-steel spiral stent. In all experiments, a canine mediastinal trachea 10 cartilage rings in length was resected, and the prosthesis was then implanted with an omental flap. RESULTS Lower pore size and density (300 microm, 25 pores/cm(2)) led to essentially no tissue ingrowth. Larger pore size (700 microm) and low density (25 pores/cm(2)) led to rapid and excessive ingrowth of granulation. Midrange pore size (500 microm) and high density (100 pores/cm(2)) invited steady tissue ingrowth, but marked luminal stenosis eventually developed. Stent-reinforced prostheses with 500-microm pores at 64 pores/cm(2), as used in the second set, maintained an average patency rate of 60% or more (range, 20%-100%) at least 12 months after implantation. CONCLUSION Our data show that porosity is a key factor for tissue growth through our Dacron tracheal prostheses. This artificial trachea model has led to long-term survivors up to 27 months after the operation and seems promising as a basic model for clinical tracheal repair.

Tracheal Replacement With a Silicone-Stented, Fresh Aortic Allograft in Sheep

BACKGROUND Tracheal tissue regeneration after allogeneic aortic transplants in sheep has been reported. We sought to confirm these findings and elucidate the mechanism of this transformation. METHODS Ten male sheep underwent cervical tracheal replacement with fresh, descending thoracic aortic allografts, 8 cm long, from female sheep, without postoperative immunosuppressive therapy. A 10-cm silicone stent was placed to prevent airway collapse. Graft evaluations with flexible bronchoscopy and computed tomography were conducted between 2 weeks and 1 year after surgery. RESULTS There were no procedural deaths, but 6 animals died or required euthanasia between 12 days and 3 months postoperatively owing to severe tracheitis, cervical lymphadenitis, pneumonia, graft necrosis, stent migration, or airway obstruction after stent removal. The 4 remaining sheep were euthanized as planned at 6 to 12 months after surgery. Harvested tracheas revealed no evidence of graft incorporation into the surrounding tissue, and there was no histologic evidence of any neocartilage within or around the graft at any point. Bronchoscopy revealed marked graft necrosis in the 4 animals surviving to planned euthanasia. In all sheep, computed tomography imaging revealed that the graft was replaced by connective tissue without any signs of cartilage regeneration. Image analysis also indicated profound shortening of the grafted area up to 87.5% at 1 year after implantation, secondary to axial shift of the native trachea. CONCLUSIONS Fresh aortic allografts appear to be unsuitable for primary tracheal replacement. However, the observed graft shortening may allow for two-staged, end-to-end reconstruction of large tracheal defects with temporary grafting techniques.

Drug infusion system manifold dead-volume impacts the delivery response time to changes in infused medication doses in vitro and also in vivo in anesthetized swine.

BACKGROUND: IV infusion systems can be configured with manifolds connecting multiple drug infusion lines to transcutaneous catheters. Prior in vitro studies suggest that there may be significant lag times for drug delivery to reflect changes in infusion rates set at the pump, especially with low drug and carrier flows and larger infusion system dead-volumes. Drug manifolds allow multiple infusions to connect to a single catheter port but add dead-volume. We hypothesized that the time course of physiological responses to drug infusion in vivo reflects the impact of dead-volume on drug delivery. METHODS: The kinetic response to starting and stopping epinephrine infusion ([3 mL/h] with constant carrier flow [10 mL/h]) was compared for high- and low-dead-volume manifolds in vitro and in vivo. A manifold consisting of 4 sequential stopcocks with drug entering at the most upstream port was contrasted with a novel design comprising a tube with separate coaxial channels meeting at the downstream connector to the catheter, which virtually eliminates the manifold contribution to the dead-volume. The time to 50% (T50) and 90% (T90) increase or decrease in drug delivery in vitro or contractile response in a swine model in vivo were calculated for initiation and cessation of drug infusion. RESULTS: The time to steady state after initiation and cessation of drug infusion both in vitro and in vivo was much less with the coaxial low-dead-volume manifold than with the high-volume design. Drug delivery after initiation in vitro reached 50% and 90% of steady state in 1.4 ± 0.12 and 2.2 ± 0.42 minutes with the low-dead-volume manifold and in 7.1 ± 0.58 and 9.8 ± 1.6 minutes with the high-dead-volume manifold, respectively. The contractility in vivo reached 50% and 90% of the full response after drug initiation in 4.3 ± 1.3 and 9.9 ± 3.9 minutes with the low-dead-volume manifold and 11 ± 1.2 and 17 ± 2.6 minutes with the high-dead-volume manifold, respectively. Drug delivery in vitro decreased by 50% and 90% after drug cessation in 1.9 ± 0.17 and 3.5 ± 0.61 minutes with the low-dead-volume manifold and 10.0 ± 1.0 and 17.0 ± 2.8 minutes with the high-dead-volume manifold, respectively. The contractility in vivo decreased by 50% and 90% with drug cessation in 4.1 ± 1.1 and 14 ± 5.2 with the low-dead-volume manifold and 12 ± 2.7 and 23 ± 5.6 minutes with the high-dead-volume manifold, respectively. CONCLUSIONS: The architecture of the manifold impacts the in vivo biologic response, and the drug delivery rate, to changes in drug infusion rate set at the pump.

Tracheal Replacement With a Bioabsorbable Scaffold in Sheep

BACKGROUND A significant native tracheal approximation phenomenon was observed in our previous study [Tsukada H, Ernst A, Gangadharan S, et al. Tracheal replacement with a silicone-stented fresh aortic allograft in sheep. Ann Thorac Surg 2010;89:253-8], in which sheep trachea was replaced with an allogenic aortic graft in order to attempt transplantation. Because an appropriate tracheal replacement graft has yet to be determined, other means to repair or replace tracheal tissue have to be evaluated. The aim of this study was to test a bioabsorbable scaffold for temporary tracheal grafting. METHODS Eight male sheep underwent cervical tracheal replacement (5 cm) using a copolymer of L-lactide and ε-caprolactone sponge tube reinforced by polyglycolic acid. A silicone stent (7 cm) was placed perioperatively to prevent graft collapse. Routine bronchoscopy and computed tomographic scans were scheduled for up to 9 months and necropsies with histologic examinations were scheduled at 9 months (n = 3), 6 months (n = 2), 4 months (n = 1), 3 months (n = 1), and 2 months (n = 1) after surgery. RESULTS No procedural deaths and postoperative complications occurred. Planned follow-up points were reached in all animals. Computed tomographic imaging of the grafted area showed tracheal approximation up to 75% at 9 months after surgery. Silicone stents were removed at 9 months in three animals. Symptomatic airway collapse was observed at 6 hours, 1 week, and 2 weeks after stent removal. Epithelialization of the entire grafted area was confirmed in all sheep that were followed beyond 4 months. CONCLUSIONS Tracheal axial approximation occurs consistently after tracheal resection and replacement. Our data suggest that bioabsorbable materials can be used as a reliable, temporary, tracheal replacement conduit.

Comparison of bioabsorbable materials for use in artificial tracheal grafts

Limited information exists regarding the usefulness of bioabsorbable materials in the design of tracheal grafts. The aim of this study was to evaluate the feasibility of three bioabsorbable materials for use as artificial trachea. Three sets of grafts were prepared: Group 1 (n=6), knitted polyglactin 910 mesh; Group 2 (n=3), copolymer of L-lactide and epsilon-caprolactone sponge reinforced with polyglycoride fibers; and Group 3 (n=8), copolymer of L-lactide and epsilon-caprolactone sponge covered with knitted poly-L-lactide mesh. All grafts were internally reinforced with a titanium stent. A 10-cartilage-ring-length of canine mediastinal trachea was resected and replaced by a bioabsorbable prosthesis with the aid of an omental flap. In Groups 1 and 2, the patency rates decreased below 50% within two months after surgery. In Group 3, six of eight dogs maintained patency rates above 50% from 10 months to 2 years after surgery. Grafts prepared with a copolymer of L-lactide and epsilon-caprolactone sponge covered with knitted poly-l-lactide mesh (Group 3) can function for up to two years after surgery. These results provide evidence toward the feasibility of utilizing bioabsorbable materials as a tracheal prosthesis.

A novel technique for tumor localization and targeted lymphatic mapping in early-stage lung cancer

Objective: To investigate safety and feasibility of navigational bronchoscopy (NB)‐guided near‐infrared (NIR) localization of small, ill‐defined lung lesions and sentinel lymph nodes (SLN) for accurate staging in patients with non–small cell lung cancer (NSCLC). Methods: Patients with known or suspected stage I NSCLC were enrolled in a prospective pilot trial for lesion localization and SLN mapping via NB‐guided NIR marking. Successful localization, SLN detection rates, histopathologic status of SLN versus overall nodes, and concordance to initial clinical stage were measured. Ex vivo confirmation of NIR+ SLNs and adverse events were recorded. Results: Twelve patients underwent NB‐guided marking with indocyanine green of lung lesions ranging in size from 0.4 to 2.2 cm and located 0.1 to 3 cm from the pleural surface. An NIR+ “tattoo” was identified in all cases. Ten patients were diagnosed with NSCLC and 9 SLNs were identified in 8 of the 10 patients, resulting in an 80% SLN detection rate. SLN pathologic status was 100% sensitive and specific for overall nodal status with no false‐negative results. Despite previous nodal sampling, one patient was found to have metastatic disease in the SLN alone, a 12.5% rate of disease upstaging with NIR SLN mapping. SLN were detectable for up to 3 hours, allowing time for obtaining a tissue diagnosis and surgical resection. There were no adverse events associated with NB‐labeling or indocyanine green dye itself. Conclusions: NB‐guided NIR lesion localization and SLN identification was safe and feasible. This minimally invasive image‐guided technique may permit the accurate localization and nodal staging of early stage lung cancers.

Cost-effectiveness associated with the diagnosis and staging of non-small-cell lung cancer.

OBJECTIVE We evaluated how much time and money could be saved without compromising overall results in treating lung cancer. SUBJECTS AND METHODS We retrospectively evaluated 318 patients for T- and M-factors and 335 for N-factor. If bronchoscopy failed to diagnose a mass lesion believed to be malignant in x-ray computed tomography (CT), we proceeded to direct thoracotomy without needle or video-assisted biopsy. When mediastinal nodes were negative in CT, we proceeded to direct thoracotomy without mediastinoscopy. We searched routinely for distant metastasis with brain and abdominal CTs and bone scans. RESULTS Lesions suspected of malignancy in CT were pathologically malignant in 93%. A total of 82.8% of patients with CT-negative mediastinum were without metastasis. The remainder, with metastasis, had a postoperative 5-year survival of 23.5%. Brain CT scans were positive in only 2.2%, abdominal CT scans in 2.4%, and bone scans in 5.0%, for patients with a cT1/T2 non-cN2 lesion. CONCLUSION Brain and abdominal CT scans and bone scans may be omitted for cT1/T2 and non-cN2 lesions in CT. CT-negative mediastinum then leads to direct thoracotomy. The vast majority of patients may thus undergo surgery earlier with less physical and financial burden. The cost saving was calculated to be 59.4% per cT1/T2 non-cN2 patient, or US

Computer control of drug delivery by continuous intravenous infusion: bridging the gap between intended and actual drug delivery.

666,815, for population evaluated based on cost-effectiveness.

Reconstruction of the Hemidiaphragm and Hemipericardium Using Combined Reversed Latissimus Dorsi and Serratus Anterior Muscle Flaps

Background:Intravenous drug infusion driven by syringe pumps may lead to substantial temporal lags in achieving steady-state delivery at target levels when using very low flow rates (“microinfusion”). This study evaluated computer algorithms for reducing temporal lags via coordinated control of drug and carrier flows. Methods:Novel computer control algorithms were developed based on mathematical models of fluid flow. Algorithm 1 controlled initiation of drug infusion and algorithm 2 controlled changes to ongoing steady-state infusions. These algorithms were tested in vitro and in vivo using typical high and low dead volume infusion system architectures. One syringe pump infused a carrier fluid and a second infused drug. Drug and carrier flowed together via a manifold through standard central venous catheters. Samples were collected in vitro for quantitative delivery analysis. Parameters including left ventricular max dP/dt were recorded in vivo. Results:Regulation by algorithm 1 reduced delivery delay in vitro during infusion initiation by 69% (low dead volume) and 78% (high dead volume). Algorithmic control in vivo measuring % change in max dP/dt showed similar results (55% for low dead volume and 64% for high dead volume). Algorithm 2 yielded greater precision in matching the magnitude and timing of intended changes in vivo and in vitro. Conclusions:Compared with conventional methods, algorithm-based computer control of carrier and drug flows can improve drug delivery by pump-driven intravenous infusion to better match intent. For norepinephrine infusions, the amount of drug reaching the bloodstream per time appears to be a dominant factor in the hemodynamic response to infusion.

Intrathoracic retroesophageal goiter causing tracheal stenosis

We used autologous tissue for the reconstruction of intrathoracic structures after extrapleural pneumonectomy in six patients. The resected areas of the hemidiaphragm and hemipericardium were reconstructed using combined reversed latissimus dorsi and serratus anterior muscle flaps. Based on our results, we conclude that the combined reversed latissimus dorsi and serratus anterior muscle flaps are broad enough to cover any defect within the hemithorax. Thus, we think that this technique is the best choice for multisite reconstruction after extrapleural pneumonectomy.