Experimental study of tracheal allotransplantation with cryopreserved grafts

OBJECTIVE: Tracheal reconstruction is necessary in patients with extensive tracheal stenosis caused by neoplasm, trauma, and congenital disease. We investigated the possibility of tracheal allotransplantation with cryopreserved grafts in a canine model. METHODS: A seven-ring section of thoracic trachea was removed in 19 adult mongrel dogs. In group A (n = 4), a five-ring tracheal autograft was implanted. In group B (n = 6), a five-ring allograft was implanted without immunosuppression. In group C (n = 9), a five-ring cryopreserved tracheal allograft was implanted without immunosuppression. Omentopexy wrapping around the grafts and both anastomotic sites was used in all animals. RESULTS: All grafts survived without any evidence of atrophy or stenosis in group A. All animals in group B died of severe airway obstruction within 1 month, and postmortem examination of these grafts showed epithelial defect and necrotic tracheal cartilage in the scar tissue. In group C, no animals died of asphyxia caused by severe stenosis of the grafts. The graft epithelium was no longer present 20 days after transplantation, and the graft was covered with regenerated epithelium within about 60 days after the operation. CONCLUSION: These findings show that cryopreserved tracheal allografts can be transplanted by means of omentopexy without immunosuppression and that cryopreservation may reduce tracheal allogenicity.     

History of nurse-midwifery in reproductive health care

BACKGROUND: Recently, there have been a few reports recommending use of a 2 mm thick polytetrafluoroethylene soft tissue (Gore-Tex) patch for repair of thoracic wall defects. The potential role of these Gore-Tex patches was examined. METHODS: Five patients underwent chest wall tumor resection with thoracic wall reconstruction using a Gore-Tex patch (2 mm). We present a review of the complications experienced by five patients with Gore-Tex patches, as well as a review of the literature. RESULTS: Functionally and cosmetically, satisfactory results were obtained for 5 patients with Gore-Tex patch. There were no cases of infectious complications. However, we experienced one case of a flail chest postoperatively, in which reconstruction with two Gore-Tex patches of 30 x 15 cm, and 3 days of mechanical ventilation and chest wall support was needed. CONCLUSION: Our experience with Gore-Tex patches has been positive, and we recommend patch closure for thoracic wall defects.     

A model for tracheal study

While attempting to devise a valvular device to prevent aspiration in tracheo-esophageal anastomosis, we employed a model in the dog, which we feel would be very useful in the study of other tracheal problems. Essentially, a segment of trachea with its blood supply intact is isolated and turned through 90 degrees. One end of the segment is then anastomosed to the skin whereas the other end is either anastomosed to the gullet or covered with silastic, depending upon the required investigation. In both cases, after an interval of at least nine months, the segment continued to be lined by respiratory epithelium and no stenosis had occurred. Where silastic sheeting was employed to cover the end of the segment, the inner aspect of the silastic was covered with a thin layer of fibrous tissues lined by respiratory epithelium.     

Experimental trial of balloon-expandable, metallic Palmaz stent in the trachea

OBJECTIVE: To determine the effect of the Palmaz stent, which has been successfully used to relieve airway obstruction in a small group of children, on the normal and operated on animal trachea. DESIGN: In this experimental trial, stents were placed bronchoscopically in the thoracic tracheae of 4 groups of 50 anesthetized cats. The cats in group 1 (adults, n = 10) and group 2 (kittens, n = 10) had normal tracheae; the cats in group 3 (adults, n = 15) underwent horizontal tracheal incision and closure; and the cats in group 4 (adults, n = 15) underwent pericardial patch tracheoplasty. In group 3 and 4, the stents were inserted in 10 cats and 5 cats served as controls. Stents were inflated to a 15-mm diameter in group 1 and an 8-mm diameter in the other groups. Half of the animals with stents were killed 5 weeks after the procedure, and the others, 10 weeks after the procedure. SETTING: The Hospital for Sick Children, Toronto, Ontario. RESULTS: In group 1, 1 animal died of tracheal perforation. A mild cough was noted in 15 of the 39 cats with stents. In group 4, 3 cats had difficulty eating and lost weight. The results of esophagoscopy excluded esophageal inflammation or obstruction in these 3 animals. The results of bronchoscopy indicated a nonobstructing rim of granulation tissue at the end of the stent in 15 of 20 cats in groups 1 and 2 and 17 of 20 cats in groups 3 and 4 and at the repair site in all animals with stents from groups 3 and 4. The results of autopsy indicated the cross-sectional area at the site of the stent was greater than normal in group 1 (P < .003) and smaller than the normal trachea at the site of the tracheoplasty in group 4 controls without stents (P < .02); however, the cross-sectional area at the tracheoplasty site with the stent was not smaller (P < .13). The results of histologic examination indicated a mild inflammatory reaction, with granulation tissue in all animals with stents, but in group 1, with overexpanded stents, the reaction was more severe, with epithelial ulceration, fibrosis, and sealed-off perforations in most animals. In group 3, the tracheae with stents had significantly more inflammatory reaction, granulation tissue, and epithelial damage than the controls without stents. CONCLUSIONS: The Palmaz stent provokes an inflammatory reaction in the normal trachea and the trachea recently operated on. With the exception of the group 1 animals with overexpanded stents, this reaction is clinically insignificant. The Palmaz stent is able to maintain a normal lumen size after pericardial tracheoplasty in cats.     

The Calvin cycle enzyme sedoheptulose-1,7-bisphosphatase is encoded by a light-regulated gene in Chlamydomonas reinhardtii

OBJECTIVES: Current surgical treatment for a glottic cancer with significant subglottic extension is a total laryngectomy. The objective of this study was to expand laryngeal conservation procedures by using a reconstructive technique that allows for the repair of hemicricolaryngectomy defects. STUDY DESIGN: After resection of the ipsilateral thyroid, cricoid, and arytenoid for advanced T3 glottic cancer, the laryngeal defect was reconstructed by means of an autotransplanted segment of trachea in four patients. The reconstruction consisted of a transferable patch that was constructed from a segment of revascularized cervical trachea. METHODS: During a 14-day period, a 4-cm segment of cervical trachea was wrapped by a free radial forearm fascial flap. In the second stage, the glottic cancer was removed and the cervical trachea was isolated on its fascial blood supply and transformed into a patch that was used to repair the extended hemilaryngectomy defect. Two different patch designs were used. Two patients underwent reconstruction with a patch augmented at the glottic level (group A); two patients underwent reconstruction without glottic augmentation on the patch (group B). Tracheal continuity was restored by an end-to-end reanastomosis. The postreconstruction morphology of the two patch designs was compared with the preoperative laryngeal morphology. RESULTS: The autotransplantation technique led to complete restoration of the subglottic airway lumen in all four patients. Although the anterior-posterior glottic diameter was reduced by 36% in group A patients and by 43.5% in group B patients, a sufficient glottic airway lumen was obtained. The glottic sphincteric function was restored in both groups. CONCLUSIONS: Tracheal autotransplantation may be used reliably to repair hemicricolaryngectomy defects. Augmentation of the patch at the level of the glottis is not essential for successful rehabilitation.     

Experimental biliary reconstruction with a Dacron graft which preserves the function of papilla Vater

Roux-en-Y cholangiojejunostomy has been widely accepted as a method of biliary reconstruction after resection of the bile duct, however complications such as cholestasis, cholangitis and peptic ulcer attributable to the loss of papillary functions are frequently encountered after this procedure. In this point of view, the author experimentally studied biliobiliary anastomosis with a Dacron vascular graft to preserve normal bile passage through the duodenal papilla. End-to-end choledocho-graft-choledochostomy with a Dacron vascular graft coated with collagen (Hemashield) was carried out in 10 pigs. Out of them three died of complications during the 13th to 26th the POD, and seven were sacrificed 6 weeks after the operation. Two weeks after biliary grafting (n = 3) the grafts were surrounded by thin fibrous tissue and microscopically collagen fibers infiltrating into pores of the graft were noted, however after 6 weeks the grafts were spontaneously detached from the bile duct and floated in bile. The covered fibrous tissue was remained and the anastomotic site was replaced with soft granulation tissue, where infiltration of inflammatory cells were microscopically noted. Caliber of the anastomotic site was not smaller and but for slight elevation of total bile acid level blood biochemistry did not show cholestasis and cholangitis. The papillary function was manometrically well maintained. A Dacron graft shielded by collagen seemed to be inadequate material as a permanent bile duct graft, however granulation tissue after spontaneous removal of the graft may be covered with biliary epithelium, and may heal maintaining normal papillary function.     

Reconstruction of posterior mandibular defects with soft tissue using the rectus abdominis free flap

Nitric oxide (NO) plays an important regulatory role in airway function and seems to be implicated in the pathophysiology of several airway diseases. We studied the presence of NO synthase activity in human nasal mucosa and nasal polyp tissues obtained from patients undergoing septoplasty or polypectomy, respectively. NO synthase activity was quantified in tissue homogenates using citrulline release assay and was located in tissue sections using NADPH-diaphorase histochemistry. The results indicated that nasal polyps contain higher levels of total NO synthase activity than nasal mucosa tissue. In addition, nasal polyps contained mainly inducible NO synthase activity whereas all NO synthase activity detected in the nasal mucosa was in constitutive form. In both cases, NO synthase activity was localized in epithelial cells. In view of these results, we conclude that NO may be an important inflammatory mediator in the respiratory system and that the epithelium may be a source of NO production.     

Two studies of the clinical effectiveness of the nicotine patch with different counseling treatments

OBJECTIVE: To assess the effectiveness of transdermal nicotine therapy for smoking cessation and suppression of withdrawal severity in conjunction with two different adjuvant counseling treatments. DESIGN: Two independent randomized placebo-controlled double-blind trials. SETTING: Smoking cessation clinic. SUBJECTS: Eighty-eight (study 1) and 112 (study 2) adult volunteers motivated to quit smoking. INTERVENTIONS: Eight weeks of 22-mg transdermal nicotine therapy with group counseling (study 1); 4 weeks of 22 mg followed by 2 weeks of 11-mg transdermal nicotine therapy with brief individual counseling (study 2). MAIN OUTCOME MEASURES: Modified point prevalence (7 consecutive days of nonsmoking) at the end of patch treatment and 6 months after treatment initiation was assessed by self-report and biochemically confirmed; survival analyses were also conducted for both studies to compare treatment efficacy. Also, we examined the impact of the nicotine patch on specific withdrawal symptoms (anger, anxiety, awakening, difficulty concentrating, depression, hunger, impatience, and craving). RESULTS: Transdermal nicotine treatment produced higher cessation rates at the end of treatment than did placebo with both adjuvant counseling interventions: 59 percent vs 40 percent (p < 0.05 in study 1) and 37 percent vs 20 percent (p < 0.05 in study 2), respectively. Smoking cessation efficacy was maintained 6 months after initiation of treatment: 34 percent vs 21 percent (p = 0.08 in study 1) and 18 percent vs 7 percent (p = 0.05 in study 2). Survival analyses also revealed significant group differences in efficacy in both studies. Nicotine patches also suppressed a variety of withdrawal symptoms, including craving in the first weeks after patients quit smoking. CONCLUSION: Transdermal nicotine effectively augments smoking cessation rates with two different types of counseling treatment. Overall, the nicotine patch approximately doubles the sustained rate of smoking cessation. Additionally, the nicotine patch provides relief from some tobacco withdrawal symptoms.     

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.     

Allograft replacement of the trachea. Experimental synchronous revascularization of composite thyrotracheal transplant

We describe a method for experimental tracheal transplantation that uses synchronous revascularization based on the blood supply of the related thyroid gland. This study compares the structural integrity and histologic features of nonvascularized tracheal transplants, revascularized thyrotracheal composite allografts, with and without immunosuppression. Eighteen adult beagle dogs underwent tracheal transplant operations with one of the preceding methods. Postmortem specimens were studied macroscopically and histologically, 3 to 28 days postoperatively. Proximal, mid, and distal segments of each graft (twelve-ring segments) were examined microscopically. Nonvascularized tracheal transplants necrosed completely as early as 3 days postoperatively. The vascularized composite thyrotracheal allografts survived for up to 28 days. Six dogs did not receive immunosuppressive agents; tracheal cartilage was preserved in this group, but soft tissue necrosis developed. Six dogs received cyclosporine; tracheal cartilages and all soft tissues remained histologically intact. This difference may be due to early tracheal cartilage ischemia in the nonvascularized group, rejection of the soft tissues in the nonimmunosuppressed group, and viability of all structures in the vascularized and immunosuppressed group. Revascularization of the transplanted trachea with the thyroid arteries maintains the vascularity and hence the viability of the trachea. A reliable substitute for long-segment tracheal resections is finally found. We predict that clinical application of this technique will solve a major problem in the surgery of the airways.     

Pectoralis major muscle island flaps. Personal experiences

Fifty-six pectoralis major island flap procedures were carried out in 52 patients for the immediate reconstruction of defects after resection of head, neck or thoracic tumors. In 28 we used only a part of the muscle covered with meshgraft, in another 28 as a myocutaneous island flap. The complication rate was low: One partial flap necrosis, two bleedings postoperatively on the donor site, four fistulas (one required a second operation). One necrosis of ribs required the resection and covering with a latissimus dorsi flap. One patient died with mediastinitis. The functional aspects of the muscle donor site is stressed out.     

Acceleration in the rate of CNS remyelination in lysolecithin-induced demyelination

One important therapeutic goal during CNS injury from trauma or demyelinating diseases such as multiple sclerosis is to develop methods to promote remyelination. We tested the hypothesis that spontaneous remyelination in the toxic nonimmune model of lysolecithin-induced demyelination can be enhanced by manipulating the inflammatory response. In PBS-treated SJL/J mice, the number of remyelinating axons per square millimeter of lesion area increased significantly 3 and 5 weeks after lysolecithin injection in the spinal cord. However, methylprednisolone or a monoclonal antibody (mAb), SCH94.03, developed for its ability to promote remyelination in the Theiler's virus murine model of demyelination, further increased the number of remyelinating axons per lesion area at 3 weeks by a factor of 2.6 and 1.9, respectively, but did not increase the ratio of myelin sheath thickness to axon diameter or the number of cells incorporating tritiated thymidine in the lesion. After 3 weeks, the number of remyelinating axons in the methylprednisolone or mAb SCH94.03 treatment groups was similar to the spontaneous remyelination in the 5 week PBS control-treated group, indicating that these treatments promoted remyelination by increasing its rate rather than its extent. To address a mechanism for promoting remyelination, through an effect on scavenger function, we assessed morphometrically the number of macrophages in lesions after methylprednisolone and mAb SCH94.03 treatment. Methylprednisolone reduced the number of macrophages, but SCH94.03 did not, although both enhanced remyelination. This study supports the hypothesis that even in toxic nonprimary immune demyelination, manipulating the inflammatory response is a benefit in myelin repair.     

Inflammatory bronchial polyps with a foreign body-like substance

A 68-year-old male complaining of hemosputum was admitted to our hospital. Fiberoptic bronchoscopic examinations revealed bronchial polyps and a flat foreign body-like substance in the left main bronchus. A closer inspection of a biopsied bronchial inflammatory polyp showed inflammatory edema with hypervascularization in the submucosal space and inflammatory cell infiltration. Following complete removal of this foreign body-like substance, the polyps disappeared within six weeks. It is therefore feasible to assume that the polyps appeared as a reaction to this extrinsic substance. The origin of the foreign matter is not obvious because the patient had no history of aspiration and because the histological examination did not confirm that it was a foreign body. The substance could have been formed out of the organization and calcification of some secretes in the bronchus.     

Prosthetic reconstruction of the trachea and carina

Twenty-six patients with tracheal stenosis owing to benign stricture and malignancy have had airway reconstruction with a molded silicone rubber prosthesis. In 8 patients the distal trachea and carina were replaced with a bifurcated graft. One individual with respiratory insufficiency could not be weaned from the respirator and died in 3 weeks. Two other patients with malignancy died 15 and 18 months following operation from disseminated cancer. The remainder are living from 1 to 5 years postoperatively. Eighteen individuals have had the trachea reconstructed with a straight graft of silicone rubber. In 5 patients with long strictures the prosthesis was invaginated into the upper and lower ends of the trachea. Thirteen individuals had circumferential resection of the airway with end-to-end anastomosis of the graft to the trachea. There was one early death from erosion of the innominate artery and 5 late deaths unrelated to the prosthesis.     

Effect of an adrenergic agonist and a cholinergic antagonist on the airway epithelium

The ultrastructure of the rabbit tracheal epithelium was studied 30 minutes after intratracheal administration of two puffs of salbutamol and ipratropium bromide, respectively. The injury to the tracheal epithelium due to the treatment with both bronchospasmolytic drugs was considered moderate to severe. In both experimental groups, the degree of goblet cells' stimulation did not differ significantly, the ciliated cells were less damaged compared with the goblet ones and the morphological signs of the impaired self-cleaning ability were revealed.     

Ileocecal tuberculosis as a cause of lower gastrointestinal hemorrhage in lupus erythematosus

BACKGROUND AND AIMS OF THE STUDY: The use of living, untreated autologous pericardium for patch repair in the left ventricular outflow tract was considered attractive in children. METHODS: Ventricular septal defect (VSD) closure with an untreated autologous pericardial patch was performed in 102 children of mean age 13.4 months (range: 1 to 73 months). Postoperative transthoracic Doppler echocardiography was performed in all children at a mean of nine weeks (range: one day to 50 weeks) after surgery. One pericardial patch, which was explanted at autopsy two months after surgery, was studied microscopically. RESULTS: At short-term follow up, no or only minor residual VSD was found in 97 patients, moderate VSD in two and severe VSD in one patient. One patient was reoperated for residual VSD and an aneurysmic patch first diagnosed seven days after surgery. Two more patients showed ballooning of the patch without VSD after five and seven days respectively. All aneurysmic patches were attributed to intraoperative patch oversizing. Patch integrity was confirmed in all other patients. No inflammatory or degenerative changes were observed at microscopy, rather a remodeling response had caused the patch to thicken, indicating an adaptation of the living tissue. CONCLUSIONS: The untreated autologous pericardial patch has shown to be a safe alternative for VSD closure, provided that the patch is properly sized.     

CO2 laser conization for cervical intraepithelial neoplasia grade II-III: complications and efficacy

PURPOSE: Functional outcome after anterior resection for rectal cancer is improved by colonic J-pouch reconstruction compared with straight anastomosis. The indications for colonic J-pouch reconstruction have yet to be determined. Therefore, we attempted to determine the level at which J-pouch reconstruction provides an advantage over straight anastomosis. METHODS: A total of 48 patients who underwent 5-cm colonic J-pouch reconstruction (J-pouch group) and 80 patients who underwent straight anastomosis (straight group) underwent functional assessment one year postoperatively. RESULTS: The functional outcome in the J-pouch group was significantly better than that in the straight group when the distance of the anastomosis from the anal verge was less than 8 cm. The difference was particularly obvious when the level of the anastomosis was below 4 cm. However, functional outcome in the straight group when the anastomosis was between 9 and 12 cm from the anal verge was also satisfactory and did not differ from that in the J-pouch group when the anastomosis was between 5 and 8 cm from the anal verge. CONCLUSIONS: Colonic J-pouch reconstruction is indicated when the distance of anastomosis from the anal verge is less than 8 cm, and it is essential when the distance is less than 4 cm.     

Performance of small diameter synthetic vascular prostheses with confluent autologous endothelial cell linings

Autologous grafts are superior to their synthetic counter-parts for grafting arteries smaller than 6-mm diameter both in terms of acute thrombogenicity and chronic intimal hyperplasia. Endothelial cell (EC) coating of the blood contacting surface may reduce thrombogenicity of synthetic small diameter vascular prostheses. In this study, the survival of EC monolayers on synthetic 4-mm diameter arterial prostheses over short-term implantations (< or = 6 weeks) was examined. Graft types examined were expanded polytetra-fluoroethylene (ePTFE) and microporous polyurethane (PU). Lumenal coverage with ECs was achieved by culturing ovine ECs on prostheses treated by either physical adsorption or covalent binding of ovine fibronectin (Fn). An ovine carotid interposition model was used to examine the performance of EC coated ePTFE and microporous PU over implantation periods of 1, 3, and 6 weeks. Outcomes assessed at the end of each experiment were graft patency, area covered by ECs, and thrombus free surface area (TFSA). Fn concentration, cell density at the time of coating and prostacyclin production in vitro were similar for both graft types. Occlusion occurred more frequently in unseeded grafts compared with EC coated grafts over 3 and 6 week implantation periods; however, the difference was not significant (p = 0.099). In prostheses precoated with ECs, approximately 40-60% of the surface area remained covered with endothelial-like cells following the first postoperative week. Recovery of EC layers occurred rapidly thereafter with 80-90% coverage at 3 weeks. TFSA remained low in comparison to EC cover in these prostheses until between 3 and 6 weeks postoperatively, suggesting a lag phase in recovery of EC function of seeded cells. In contrast, EC cover of unseeded prostheses only achieved 10-30% at 3 weeks, primarily by pannus EC ingrowth from the adjacent artery. TFSA of unseeded grafts increased in direct proportion to EC cover over time suggesting that there was no lag phase in function of these ingrowing cells.     

Induction of atypical squamous metaplasia with benzo[a]pyrene in cultured hamster tracheas

Areas of hyperplasia were produced in hamster tracheal epithelium maintained in vitro by exposure to a suspension of benzo[a]pyrene (BP) in gelatin. Typical and atypical epiodermoid metaplasia were seen by 2 weeks. In atypical areas, cell nuclei were enlarged with prominent nucleoli, the cytoplasm contained dense bundles of tonofilaments and the cells were joined by numerous desmosomes. The peak response to the carcinogen was reached 4 weeks after the application of BP and consisted of extensive atypical epidermoid metaplasia. Tracheas treated with gelatin alone maintained a columnar epithelium for 6 weeks of culture. The characteristics of the metaplastic changes in vitro are essentially identical to those described after exposure of the hamster tracheobronchial epithelium to benzo[a]pyrene-ferric oxide in vivo.