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Background . Results of antituberculous chemotherapy for Mycobacterium avium complex disease remain disappointing. Pulmonary resection during an early stage of the disease, therefore, may be beneficial to patients whose disease is localized and who can tolerate a resectional operation. Methods . Thirty-three patients with localized M avium complex disease underwent 33 pulmonary resections between 1979 and 1996. There were 17 males and 16 females, with a mean age of 50 years (range, 30 to 69 years). Lobectomy was performed in 26 patients, pleuropneumonectomy in 1, segmentectomy in 5, and wedge resection in 1. Results . There was no operative mortality. After pulmonary resection, 31 (94%) patients attained sputum-negative status. Bronchopleural fistula occurred in one patient who underwent a right upper lobectomy. There were two late deaths. A patient with bronchopleural fistula died of respiratory failure two years postoperatively. Another patient died of an unknown cause 12 years postoperatively. Of the 31 patients with negative sputum status postoperatively, only 2 patients (6%) had relapse at 1 and 9 years after operation. Conclusions . We recommend that patients with this disease be considered for pulmonary resection as early as possible.

Nitric oxide is crucial to the maintenance of vascular homeostasis. Because nitric oxide levels decline upon lung reperfusion, infusion of L-arginine, a nitric oxide precursor, during reperfusion might prove effective at ameliorating reperfusion injury.Neonatal piglet heart-lung blocks were preserved with Euro-Collins solution for 12 hours, rewarmed at room temperature for 1 hour, and reperfused for 10 minutes with either whole blood (n = 5), whole blood containing L-arginine (10 mmol/L; n = 6), or leukocyte-depleted blood (n = 6) on an isolated, blood-perfused, working heart-lung circuit. After the initial 10 minutes, all blocks received whole blood for 4 hours. Control blocks were continuously perfused on the circuit without intervening ischemia (n = 6).The partial pressure of oxygen in the whole blood group (113.8 +/- 33.1 mm Hg) was significantly less than in controls (417.3 +/- 6.2 mm Hg; p0.01). Lung compliance was significantly less in the whole blood group (0.8 +/- 0.2 mL/cm H2O) than in controls (2.9 +/- 0.4 mL/cm H2O; p0.01). The L-arginine and leukocyte-depleted blood groups showed no significant difference from controls.L-Arginine infusion during reperfusion improves pulmonary function, making it a simple alternative to leukocyte depletion.

Forty-eight-hr and 96-hr simple hypothermic preservations of the lung were studied on dogs using 4 kinds of solutions resembling extracellular electrolyte compositions (Ep1-Ep4). The pH of each solution was changed from 6.377 to 7.463 by HPO4(2-)/H2PO4- ratio. Twenty dogs were prepared as donors (12 for 48-hr preservation with Ep1, Ep2 and Ep3, and 8 for 96-hr preservation with Ep3 and Ep4, respectively). The heart-lung block was removed from the donor, and flushed with 500 ml of preservation solution via the pulmonary artery, then immersed in the same cold (4 degrees C) solution, after which it was stored in a cold (4 degrees C) room. After preservation, the left lung was separated from the heart-lung block and was transplanted into the recipient orthotopically. The function of the transplanted lung was evaluated with serial x-ray findings, contralateral pulmonary artery ligation test, and histologic findings. In the case of 48-hr preservation, all of the four recipients with Ep3 (pH: 7.225) showed good aeration of the grafted lungs on the chest x-ray in the early postoperative period. As for the 96-hr preservation cases, one with Ep3 and three with Ep4 (pH: 7.463) presented good x-ray findings. Of these successful cases, seven dogs (5 of 48-hr preservation cases, six dogs tolerated this procedure. On histopathological examination of the successful cases, the 48-hr preservation cases showed almost normal pulmonary structure, while the 96-hr preservation cases showed slight degenerative changes in the alveolar walls. From the present study, it becomes apparent that clinical application of 48-hr preservation may be possible by using a phosphate buffered extracellular solution.

Postoperative wound healing of the bronchial anastomosis was studied in dogs with autotransplantation (20 dogs, 7 days to 6 years postoperatively) and allotransplantation (62 dogs, 5 to 174 days postoperatively) of the left lung. In the group undergoing lung allotransplantation, the relationship among three histologic parameters was studied: the grade of lung allograft rejection, the degree of changes in the epithelium, and submucous lymphocyte infiltration along the donor bronchus within approximately a 0.5 cm area distal to the anastomosis. In lung autotransplantation, mucosal continuity began to be observed 1 week postoperatively. Mucosal continuity and apparent collagen formation on any bronchial contiguous site were demonstrated in most animals studied more than 3 weeks postoperatively. Bronchial anastomotic healing tended to be slower in lung allotransplantation than in autotransplantation, although a mucosal continuity at the anastomosis was sporadically observed in immunosuppressed dogs surviving more than 3 weeks postoperatively with a lung allograft. There were significant rank correlations among the three histologic parameters, which showed that lung allograft rejection is closely connected with wound healing of the bronchial anastomosis in lung allotransplantation. Meticulous mucosal approximation is most necessary during bronchial anastomotic procedures. Establishment of an exact method for early monitoring of lung allograft rejection is absolutely necessary for lung allotransplantation.

Thymomas, especially epithelial component were cultured, and differentiation between invasive and noninvasive thymoma was attempted.Materials were obtained at operations and were immediately minced. A portion was digested with 500-1000 u/mlof dispase, 0.25% trypsin or 0.05% collagenase and the remainder was placed in plastic tissue culture dishes, some of which were coated with type I collagen. Culture media were Dulbecco's modified MEM, Ham's F12 or Medium 199. These were supplemented with 10-20% fetal bovine serum, and some as the following additives were tested : 0.5 mg of ATP, 5ug/ml of dibutyryl cyclic AMP, 5 half-maximal units of IL-2, 0.05 u/ml of Insulin, 5 ng/ml of EGF, 10 ng/ml of phorbol 12-myristate 13-acetate, 10-9 M of chorela toxin, 2.5 mg/ml of methylprednisolone, autologous peripheral blood lymphocytes.Tissues were obtained from 9 patients with invasive and 7 with noninvasive thymoma. None of them was established and no additives promoted cell proliferation under the conditions described in this paper. Primary cultures from the invasive thymomas grew well and many epithelial cells were easily obtained. Tumor cells were dissociated easily by proteases or by physical forces. On the contrary, few or no tumor cells were obtained in the noninvasive cases. The growth of mesenchymal cells was always more dense in the noninvasive than in the invasive cases. Microscopic findings in the invasive cases were : dense cytoplasm and thick margin of nucleus, large nucleus, 1 or 2 clearly visible large nucleoli, sharply defined cell borders.Although we cannot necessarily distinguish between invasive and noninvasive thymoma from these results alone, this method may become a useful tool in the diagnosis of thymoma.

48-and 96-hour lung preservation were conducted using simple cooling method in dogs. The effect of buffer action of solutions to the lung preservation was examined.Phosphate buffered solutions with 2% of low molecular weight dextran (Ep1Ep3) were prepared with the change of pH by altering the ratio of H2PO4-and HPO42-. In Ep4, K2HPO4 was added for considering its availability to the heart-lung preservation. As to the electrolyte composition, all solutions were prepared as the extracellular fluid. For preservation, heart-lung bloc of the donor was used. After completion of the preservation, left lung was removed from the heart-lung bloc and transplanted to the recipient orthotopically. Recipient was immunosuppressed using 100 mg/day of azathioprine and 100 mg/day of methylprednisolone for 7 days after transplantation, thereafter each drug was decreased to 50 mg/day in dosage. Serial chest X-ray films were taken after transplantation. Contralateral pulmonary artery ligation was conducted on 11th day postoperatively in the successful cases.4 out of 4 (100%) were successful transplants after 48-hour preservation using Ep3 solution with the pH resembling to the physiological pH at 37°C. In 96-hour preservation, 3 out of 4 were successful cases, however, they did not give satisfactory results on chest X-ray films, contralateral pulmonary artery ligation and histologic findings comparing to successful cases in 48-hour preservation group. Further improvement in preservation solution is considered to be needed for 96-hour lung preservation.From this experiment, we concluded that our method of lung preservation using Ep3 solution may be reliable for 48-hour lung preservation in human lung transplantation.

Sixty-six patients with thymoma have undergone surgical treatment since 1965 and have been assessed from the viewpoint of clinical manifestations and prognosis. Thirty-one patients with encapsulated thymoma were treated with total surgical resection alone, and they had no postoperative tumor recurrence. With the exception of one patient who died of respiratory insufficiency on the fourth day after the operation, 34 patients with invasive thymoma were evaluated on the basis of their postoperative prognosis. Fifteen patients with invasive thymoma died from 1 1/2 months to 10 years, 1 month postoperatively; 9 died of local or metastatic tumor and 6 died of other diseases. Associated autoimmune diseases, as well as the invasive tendency of the tumors, apparently affected the prognosis. Ten-year survival rates of the patients who underwent surgical treatment were as follows: 61.6% for the total group, 74.3% for those with encapsulated thymoma, and 49.4% for those with invasive thymoma. In the surgical treatment for invasive thymomas, one should aim to resect the tumor totally, even though adjacent tissues are resected simultaneously. Even for the patient with total resection of invasive tumor, postoperative radiation should be required. Finally, if residual tumor must be left during the operation, postoperative radiation as well as anticancer chemotherapy should be aggressively scheduled, because postoperative distant metastasis may appear in these patients with residual thymoma.

This study introduces a model for intracoronary gene transfer in murine cardiac isografts using adenovirus vectors. This approach may offer an opportunity to modulate alloreactivity after cardiac transplantation. Donor hearts were infected via the coronary arteries with a volume of 10 9 plaque-forming units per milliliter of a recombinant adenovirus containing the β-galactosidase–encoding gene (Ad.CMVLacZ). In a control group, 200 μl of normal saline solution was infused. The grafts were stored in 4º C cold saline solution for 15 minutes, then transplanted heterotopically into syngeneic hosts (B10.BR). The grafts were harvested at 3, 7, 15, or 30 days (n = 5 for each group) after transplantation, and β-galactosidase activity was assessed by histochemical staining (X-gal). All grafts were functioning when harvested. X-gal staining pattern was nonuniform with positive staining appearing in epicardial, myocardial, and endocardial cells, as well as in the vessel walls. The cells permissive to infection consisted predominantly of myocardial cells. The mean total numbers of β-gal–positive staining cells per slice were 68.7 ± 27.3 in the 3-day group, 330.4 ± 53.8 in the 7-day group, 151.3 ± 48.0 in the 15-day group, and 39.9 ± 10.8 in the 30-day group, thus peaking in the 7-day group (p < 0.05). Control isografts (n = 5), retrieved at day 30, revealed no staining activity. In conclusion, our model demonstrates that intracoronary gene transfer to the transplanted murine cardiac grafts is feasible at the time of harvest. Adenovirus-mediated gene transfer produces widespread gene expression which, though perhaps transient, does not adversely affect myocardial structure or function. This technology may allow modification of graft immunogenicity in the future through the production of therapeutic proteins sufficient to modulate local immune responses. (J THORAC CARDIOVASC SURG 1996;111:246-52)

Objective The prevalence of pulmonary disease caused by nontuberculous mycobacteria (NTM) has been increasing in Japan. Adjuvant resectional surgery is often recommended to lessen disease progression when the response to drug therapy is poor. In all likelihood, as affected cases of NTM disease increase, so will the number of operations. The goal of this study was to determine the current status of NTM surgery in Japan by analyzing data from the annual survey of the Japanese Association for Thoracic Surgery (JATS). Methods Data were obtained from annual surveys conducted between 2008 and 2012. The annual number of operations for pulmonary NTM disease was tabulated nationwide and in each region (Hokkaido, Tohoku, Kanto, Tokyo, Chubu, Kinki, Chugoku/Shikoku, and Kyushu). For comparison, the numbers for pulmonary tuberculosis and tuberculoma operations were also obtained. Results The annual number of operations for pulmonary NTM disease nationwide increased each year between 2008 and 2012: 292 (2008), 323 (2009), 452 (2010), 440 (2011), and 514 (2012); an overall increase of 76 %. Conversely, the annual numbers of operations for pulmonary tuberculosis were stable: 145 (2008), 181 (2009), 117 (2010), 113 (2011), and 107 (2012), as were the annual numbers of operations for tuberculoma: 386 (2008), 341 (2009), 320 (2010), 390 (2011), and 351 (2012). Conclusion Data from the JATS annual survey demonstrate a steady increase in the number of NTM surgeries in Japan. General thoracic surgeons will continue to increasingly encounter NTM patients who are candidates for surgery until a magic bullet against NTM disease is available.

Objective Because extensively drug-resistant tuberculosis has emerged, adequate control of drug-resistant tuberculosis has become increasingly important. We report on our experience using liberal adjuvant resectional surgery as part of aggressive treatment for multidrug-resistant tuberculosis. Methods We retrospectively reviewed the records of 56 consecutive patients who underwent pulmonary resections for multidrug-resistant tuberculosis between January 2000 and June 2007. There were 42 males and 14 females (mean age, 46 years; range, 22-64 years). Isolates were resistant to a mean of 5.6 drugs (range, 2-10 drugs). Multi-drug regimens employing 3 to 7 drugs (mean, 4.6 drugs) were initiated in all patients. Indications for surgery were a high risk of relapse for 37 patients, persistent positive sputum for 18, and 1 with associated empyema. Results The 56 patients underwent 61 pulmonary resections (3 completion pneumonectomies, 19 pneumonectomies, 33 lobectomies, and 6 segmentectomies). Bronchial stumps were reinforced with muscle flaps in 54 resections. Operative mortality and morbidity rates were 0% and 16%, respectively. All patients attained postoperative sputum-negative status. Relapse occurred in 5 patients; 3 were converted by a second resection, and 1 responded to augmentation of chemotherapy. Late death occurred for 2 patients without evidence of relapse. Among 54 survivors, 53 (98%) were considered cured. Conclusion Surgical treatment that complements medical treatment has proved safe and efficacious for patients with multidrug-resistant tuberculosis. In an era with extensively drug-resistant tuberculosis, an aggressive treatment approach to multidrug-resistant tuberculosis continues to be justified until a panacea for this refractory disease is available.

KONDO, T., SHIONOZAKI, F., FUJIMURA, S., YAMAUCHI, A., HANDA, M., OKABE, T., SAITO, R., ICHINOSE, T., SHIRAISHI, Y. and NAKADA, T. A Rat Model for Monitoring Homograft Rejection of the Lung. Tohoku J. exp. Med., 1986, 149 (3), 323-328 - A new surgical procedure was devised for the experimental homograft of the lung. The pulmonary artery and vein and bronchus were anastomosed under the operation microscope using interrupted sutures in group W (30 outbred Wistar rats) and continuous sutures in group F (7 inbred F344/Ducrj Rats). Mean ischemia time during the operation was 95.3±10.3min in the group W and 55.6± 5.8 in group F. Eight out of 30 rats (27%) of group W and all rats of group F survived more than 24hr after the surgery. Pulmonary functions of grafted lungs were evaluated by serial x-rays and the perfusion ratio was 27.4±11.6% (mean± S.D.) in group W and 25.4±7.7% in group F. A patent opening of the hilar anastomosis in these rats was confirmed at autopsy. This model with continuous suture would be useful for the rat lung transplantation.