Yasumichi Yamamoto

The experimental replacement of a cervical esophageal segment with an artificial prosthesis with the use of collagen matrix and a silicone stent

OBJECTIVE Attempts have been made to replace esophageal defects with a variety of artificial materials. However, because of the artificial nature of the materials, problems such as infection, leakage, stricture, or dislocation could not be avoided. Therefore we have designed a new type of artificial esophagus that is gradually replaced by host tissue. METHODS Our artificial esophagus was a two-layered tube consisting of a collagen sponge matrix and an inner silicone stent. We used it to replace 5 cm esophageal segmental defects in 43 dogs, and the inner silicone stent was removed endoscopically at weekly intervals from 2 to 4 weeks. RESULTS In the 27 dogs from which the silicone stent was removed at 2 or 3 weeks, constriction of the regenerated esophagus progressed and the dogs became unable to swallow within 6 months. In the 16 dogs from which the silicone stent was removed at 4 weeks, highly regenerated esophageal tissue successfully replaced the defect, leaving no foreign body in the host. Moreover, the regenerated esophagi had stratified flattened epithelia, striated muscle tissue composed of an inner circular and an outer longitudinal muscle layer, and esophageal glands. CONCLUSIONS Even in mature adult higher mammals, esophageal high-order structures can be regenerated provided that an adequate three-dimensional extracellular structure is put in place for a sufficient period.

Intrathoracic esophageal replacement in the dog with the use of an artificial esophagus composed of a collagen sponge with a double-layered silicone tube

OBJECTIVES Intrathoracic esophageal replacement with an artificial esophagus is considered difficult. We attempted to replace the intrathoracic esophagus with an artificial esophagus composed of a collagen sponge with a double-layered silicone tube and examined the state of host tissue regeneration. METHODS A 5-cm long gap was created in the intrathoracic esophagus in 9 dogs and repaired by interposition of our prosthesis. The dogs were fed only by intravenous hyperalimentation for 28 days. The silicone tube was removed at 29 days after the operation, and oral feeding was reintroduced. RESULTS One dog was put to death at each of the following times: 1, 2, 3, 3, 6, 12, and 24 months after the operation. One dog is still surviving without problems after more than 26 months. One dog died of malnutrition at 10 months. In all dogs, the host regenerated tissue had replaced the resulting gap at the time of silicone tube removal. The mucosa had fully regenerated within 3 months and the glands within 12 months. The process of stenosis and shrinkage was complete within 3 months and did not advance thereafter. The lamina muscularis mucosae were observed as islets of smooth muscle within 12 months. Although the skeletal muscle regenerated close to the anastomoses, it did not extend to the middle of the regenerated esophagus even after 24 months. CONCLUSIONS Use of a collagen sponge with a double-layered silicone tube was shown to be feasible even in the thorax and to allow the regenerated host tissue, consisting of the mucosa, glands, and lamina muscularis mucosae, to replace the esophageal gap.

Porous-Type Tracheal Prosthesis Sealed With Collagen Sponge

BACKGROUND Reconstruction of a long section of the trachea is clinically problematic. Tracheal reconstructions using prostheses have met with limited success due to local infection, hemorrhage, luminal stenosis and prosthesis dislocation. METHODS We have designed a porous type of tracheal prosthesis in which the mesh is sealed with collagen sponge. We used this prosthesis (50 mm in length) to reconstruct the cervical trachea in 10 mongrel dogs and evaluated its efficacy. RESULTS One dog died due to an accident with anesthesia at 6 weeks and 1 of suffocation at 10 weeks. The other 8 dogs had an uneventful postoperative course until they were killed between 6 and 24 months after implantation. At sacrifice, all the prostheses had become completely incorporated into the host. Microscopic examination revealed advanced formation of a new epithelial lining in 1 dog at 6 months, and a confluent epithelial lining was observed in another dog at 12 months. Central stenosis was not significant in any of the animals. CONCLUSIONS This tracheal prosthesis gives good results in canine tracheal reconstruction, and appears very promising for the clinical repair of tracheal defects.

Intrathoracic tracheal reconstruction with a collagen-conjugated prosthesis: Evaluation of the efficacy of omental wrapping

Reconstructions of the intrathoracic trachea in 24 dogs were done with the use of 50 mm long collagen-conjugated tracheal prostheses. Omental wrapping was also done in 14 of the dogs (omentopexy group) to evaluate the efficacy of this option in comparison with results in the other 10 dogs (control group). All 24 dogs had uneventful postoperative courses and were killed at 4 weeks or 3, 6, or 12 months after the operation. Better epithelialization and fewer complications, such as mesh exposure and luminal stenosis, were observed in the omentopexy group than in the control group. Angiography and analysis of regenerated blood vessels revealed that vessel ingrowth had started within 4 weeks and that vessel formation reached its maximal point within 6 to 12 months in the omentopexy group. In contrast, revascularization of the subepithelial region in the control group was poor even after 3 months, and vessel formation continued for as long as 12 months. The differences between the two groups were considered to be mainly a result of the speed of blood vessel ingrowth into the regenerated mucosa. We conclude that our prosthesis can be used safely for intrathoracic tracheal reconstruction and that omental wrapping is a useful supplementary method that reduces the occurrence of complications.

11C-acetate PET in the evaluation of brain glioma: comparison with 11C-methionine and 18F-FDG-PET.

PurposeThe aim of the study is to retrospectively investigate the usefulness of 11C-acetate (ACE)-positron emission tomography (PET) for evaluation of brain glioma, in comparison with 11C-methionine (MET) and 2-deoxy-2-18F-fluoro-d-glucose (FDG).ProceduresFifteen patients with brain glioma referred to initial diagnosis were examined with ACE, MET, and FDG-PET. Five patients had low-grade gliomas (grade II), three had anaplastic astrocytomas (grade III), and seven had glioblastomas (grade IV). PET results were evaluated by visual and semiquantitative analysis. For semiquantitative analysis, the standardized uptake value (SUV) and tumor to contralateral normal gray matter (T/N) ratio were calculated. The sensitivity for detection of high-grade gliomas was calculated using visual analysis.ResultsSensitivities of ACE, MET, and FDG were 90%, 100%, and 40%, respectively. ACE and MET T/N ratios were significantly higher than that of FDG. ACE and FDG SUV in high-grade gliomas were significantly higher than that in low-grade gliomas. No significant differences were observed using MET.ConclusionsACE PET is a potentially useful radiotracer for detecting brain gliomas and differentiating high-grade gliomas.

Intrathoracic esophageal replacement with a collagen sponge-silicone double layer tube : Evaluation of omental-pedicle wrapping and prolonged placement of an inner stent

In a previous study, we replaced a 5 cm gap created in the canine intrathoracic esophagus with an artificial esophagus. However, although newly formed esophageal tissue subsequently bridged the gap, mild stenosis occurred, and this seemed to be caused by inadequate regeneration of the skeletal muscle. In the present study, we evaluated whether omental pedicle wrapping (OMPx) of the prosthesis could promote tissue regeneration and whether prolonged retention of the silicone tube within the prosthesis could prevent stenosis. A gap was created in 14 dogs, and the defect was repaired by our prosthesis. OMPx was performed in 5 of the 14 dogs (OMPx group) but not in the rest (control group). The silicone tube was retained for 4 weeks in the control group and for 8 weeks in the OMPx group. All of the dogs in the control group survived for more than 3 months, except for those that were killed. Four dogs in the OMPx group died within 3 months, one caused by perforation at 7 months. Only the thin epithelial and submucosal layer regenerated in the OMPx group. OMPx is not effective for promoting tissue regeneration, and prolonged retention of the silicone tube interrupts epithelial regeneration.

Use of a newly developed artificial nerve conduit to assist peripheral nerve regeneration across a long gap in dogs.

There is now considerable evidence that peripheral nerves have the potential to regenerate if an appropriate microenvironment is provided. However, there are only a few reports of the successful use of artificial nerve conduits to repair major nerve defects more than 30 mm in length. In this study, we examined nerve regeneration across a long gap in the dog peroneal nerve using a novel artificial nerve conduit developed by our group. The conduit consists of a polyglycolic acid (PGA) collagen tube filled with laminin coated collagen fibers. In 12 dogs, the nerve conduit was implanted across an 80 mm gap in the left peroneal nerve. Three months after surgery, compound muscle action potentials (CMAPs) and somatosensory evoked potentials (SEPs) were detected. Evaluation of locomotor function revealed obvious limping for up to 3 months, but no marked difficulty in walking by 6 months. Microscopic observation of the regenerated nerve segment at 12 months showed numerous myelinated nerve fibers, which were smaller in diameter and enclosed in a thinner myelin sheath than normal axons. These results suggest that our artificial nerve conduit has potential usefulness in enhancing peripheral nerve regeneration, even across large gaps.

Early Assessment of Therapeutic Response using FDG PET in Small Cell Lung Cancer

PurposeWe evaluated the ability of 2-deoxy-2-18F-fluoro-d-glucose (FDG) positron emission tomography (PET) in the early assessment of therapeutic response in patients with small cell lung cancer (SCLC).ProceduresFDG PET studies were performed before (baseline PET), after the first cycle of chemotherapy (early PET), and after completion of therapy (final PET) in 12 patients with SCLC. The standardized uptake value (SUVmax) was measured. Metabolic response was defined as a reduction in SUVmax of more than 20% on the early PET, compared with the baseline PET. Tumor response after completion of therapy was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST).ResultsEleven patients were classified as metabolic responders and had a mean (±SD) reduction in SUVmax of 57.9 ± 10.3%. The remaining one patient was classified as a metabolic nonresponder with a reduction in SUVmax of 13.5%. In all patients, metabolic response after the first cycle of chemotherapy was associated with subsequent response according to RECIST.ConclusionsFDG PET has the potential to identify the therapeutic response in patients with SCLC as early as after the first cycle of chemotherapy.

A novel method for determining adjacent lung segments with infrared thoracoscopy.

OBJECTIVES We investigated a new technique for identifying the lung intersegmental line using infrared thoracoscopy with intravenous injection of indocyanine green. METHODS This was an experimental animal study, and target segments were established preoperatively. Six adult beagle dogs underwent thoracotomy. After the corresponding pulmonary artery of the target segment had been ligated, indocyanine green was administered intravenously during infrared thoracoscopy. The lung was separated into 2 areas, white and blue, according to the blood flow on the monitor. We marked the visceral pleura with electrocautery along the transition zone showing a change in color from blue to white. The experimental lung was removed and subjected to pathologic and radiologic analysis. RESULTS After injection of indocyanine green, infrared thoracoscopy showed that the area of normal perfusion changed to blue, whereas the area at which perfusion was absent remained white. The transition zone between colors was distinct, and the blue stain remained visible during the marking procedure. Three-dimensional computed tomographic analysis indicated that the marking separated the target segmental bronchus from the adjacent one. Detailed macroscopic and microscopic study confirmed that the marking corresponded to the intersegmental line. CONCLUSION By using infrared thoracoscopy with indocyanine green, it is possible to detect the intersegmental line without inflating the lung.

Cartilage regeneration using slow release of bone morphogenetic protein-2 from a gelatin sponge to treat experimental canine tracheomalacia: A preliminary report

We investigated whether saber sheath-type tracheomalacia could be treated by the slow release of bone morphogenetic protein (BMP)-2 from a gelatin sponge. A 1 cm gap was made in the middle portion of each of 10 consecutive tracheal cartilage rings in the canine cervix (control group, n = 3), then a gelatin sponge containing 12 &mgr;g of BMP-2 solution was implanted in the gap (12 &mgr;g group, n = 3). In another group (120 &mgr;g + P group, n = 3), the implanted gelatin sponge contained 120 &mgr;g of BMP-2 solution, and the gap was covered with periosteum. All of the control dogs developed saber sheath-type tracheomalacia, whereas tracheomalacia was not observed in the 12 &mgr;g and 120 &mgr;g + P groups. In the 12 &mgr;g group, fibrous cartilage was observed at the ends of the cartilage stumps. In the 120 &mgr;g + P group, newly formed bone and cartilage were observed to form a bridge between the cartilage stumps. The regeneration of cartilage or bone induced by the slow release of BMP-2 from a gelatin sponge might be useful for treatment of tracheomalacia.