EPR spectroscopy solutions for assessment of decellularization of intrathoracic organs and tissues.

Using EPR spectroscopy it was established that the determination of the concentration of paramagnetic centers in lyophilized tissues allows indirect evaluation of the quality of decellularization of intrathoracic organs (diaphragm, heart, and lungs), since the content of paramagnetic particles in them can serve as a criterion of cell viability and points to the necessity to repeat decellularization. Experiments in rats showed that the EPR spectra of the native thoracic organs contained paramagnetic centers with g-factor values ranging from 2.007 to 2.011 at a concentration of 10(-8) to 6.62 × 10(-7) mol/g of lyophilized tissue, whereas in all decellularized tissues of the same organs paramagnetic particles were not detected.

Laryngeal transplantation in minipigs: early immunological outcomes.

Despite recent tissue-engineering advances, there is no effective way of replacing all the functions of the larynx in those requiring laryngectomy. A recent clinical transplant was a success. Using quantitative immunofluorescence targeted at immunologically relevant molecules, we have studied the early (48 h and 1 week) immunological responses within larynxes transplantated between seven pairs of National Institutes of Health (NIH) minipigs fully homozygous at the major histocompatibility complex (MHC) locus. There were only small changes in expression of some molecules (relative to interindividual variation) and these were clearest in samples from the subglottic region, where the areas of co-expression of CD25(+) CD45RC(-) CD8(-) and of CD163(+) CD172(+) MHC-II(-) increased at 1 week after transplant. In one case, infiltration by recipient T cells was analysed by T cell receptor (TCR) Vß spectratype analysis; this suggested that changes in the T cell repertoire occur in the donor subglottis mucosal tissues from day 0 to day 7, but that the donor and recipient mucosal Vß repertoires remain distinct. The observed lack of strong immunological responses to the trauma of surgery and ischaemia provides encouraging evidence to support clinical trials of laryngeal transplantation, and a basis on which to interpret future studies involving mismatches.

Laryngeal transplantation in minipigs: vascular, myologic and functional outcomes.

There is no effective way of replacing all the functions of the larynx in those requiring laryngectomy. Regenerative medicine offers promise, but cannot presently deliver implants with functioning neuromuscular units. A single well-documented laryngeal transplant in man was a qualified success, but more information is required before clinical trials may be proposed. We studied the early response of the larynx to laryngeal transplantation between 17 pairs of NIH minipigs full matched at the MHC2 locus. Following iterative technical improvements, pigs had good swallowing and a patent airway at 1 week. No significant changes in mucosal blood flux were observed compared with pre-operative measurements. Changes in muscle morphology and fibre phenotype were observed in transplant muscles retrieved after 7 days: the levels of fast and slow myosin heavy chain (MyHC) protein were reduced and embryonic MyHC was up regulated consistent with denervation induced atrophy. At 1 week laryngeal transplantation can result in good swallowing, and is not associated with clinical evidence of ischemia-reperfusion injury in MHC-matched pigs.

Artificial lung: current perspectives.

While the number of the patients suffering from end-stage pulmonary disease has been increasing, the most common treatment for this entity remains mechanical ventilation that entails the risks of lung damage by itself. Although the lung protective strategy for the prevention of further damage to the lung tissue has been elucidated and performed, mechanical ventilation alone as the management tactic coping with the patients of acute respiratory distress syndrome, chronic respiratory failure and lung transplantations has been a frustrated scenario. Extracorporeal membrane oxygenation or extracorporeal lung assist have been applied to these patients with occasional success, but it always accompanies difficulties such as multiple blood transfusion, labor intensity, technically complexity and tendency to infection. In contrast to advances in the development of cardiac or renal support systems for adults, the development of extra-, para- and intracorporeal mechanical systems for acute or chronic lung respiratory failure has logged far behind. It has been mostly due to the lack of the capable technologies. Entering 21st century with advent of new technology especially invention of the low resistance oxygenator, the developments of artificial lungs have entered the new stage. In this report current status of the artificial lungs will be reviewed.

p53 alterations in non-small cell lung cancers correlate with metastatic involvement of hilar and mediastinal lymph nodes.

Alterations of p53 are one of the most common molecular changes found in all types of lung tumors, suggesting a crucial role for p53 in bronchial carcinogenesis. However, the prognostic significance of p53 abnormalities in lung cancer patients is still unclear. By using genetic and immunohistochemical methods we have found p53 alterations in 40 of 53 (75%) primary, resected non-small cell lung cancer. A strong association (P = 0.0015) was found between deletions on chromosome region 17p13.3 and p53 mutations suggesting that loss of the wild-type p53 allele might be necessary for tumorigenesis. Correlations to clinicopathological parameters showed that p53 alterations (structural aberration of the gene and/or nuclear accumulation of the protein) are significantly linked with metastatic involvement of hilar and mediastinal lymph nodes (P < 0.01). Since the latter are well established prognostic factors for non-small cell lung cancer, p53 aberrations may also be a predictor of tumor aggressiveness.

A preclinical model for laryngeal transplantation: anatomy and mucosal immunology of the porcine larynx.

BACKGROUND: A major step in translating work on laryngeal transplantation into clinical practice is the establishment of a preclinical model. We have investigated the anatomy and mucosal immunology of the porcine larynx in eight Minnesota Minipigs (12-37 weeks). METHODS: Neck dissections were carried out and the vascular tree was mapped. Snap-frozen biopsies from epiglottis, supraglottis, glottis, and subglottis were prepared for conventional histology, immunohistochemistry (CD45), and single and two-color immunofluorescence (CD3, MHC-II, CD45). RESULTS: The anatomy of the laryngeal skeleton was broadly similar to that of the human larynx. The blood supply is predominantly via the caudal thyroid vessels, with assistance from the cranial laryngeal artery. The porcine larynx is clearly highly immunologically active. Structured collections of leukocytes were found in the mucosal epithelium, around tubuloacinar glands, and occasionally in the submucosa. MHC-II and CD 3 cells were predominantly found within the epithelium. The highest densities of all cell types were observed in the epiglottis, tailing off caudally. The lowest densities were seen in the vocal cords. CONCLUSIONS: The porcine larynx is both anatomically and immunologically similar to the human larynx and contains a high level of immunological organization. It presents an ideal preclinical model for laryngeal transplantation.

Use of embryonic human trachea grown in nude mice to patch-repair congenital tracheal stenosis.

BACKGROUND: Long congenital tracheal stenosis is a life-threatening condition, and the available surgical treatments do not give satisfactory long-term results. METHODS: Human embryonic tracheas were implanted in the abdominal cavities of nude mice until their differentiation was completed. These differentiated tracheas were used to patch-repair surgically induced tracheal stenosis in piglets. The human, mouse, or pig origin, of all the cells in the two successive xenotransplants in the nude mouse and the pig, was determined on tissue sections by in situ hybridization with species-specific DNA probes. RESULTS: The transplanted pigs thrived and reached normal adulthood, irrespective of the administration of immunosuppressive treatment. The human tracheal tissue developed in nude mice conserved human structures, with the exception of feeding capillaries, which were of mouse origin. The tracheal patch in the adult healthy pigs comprised only pig cells organized into a fibrous scar, which was covered by normal pig epithelium. CONCLUSIONS: Results suggest that human embryonic trachea grown in nude mice can be successfully used as patch tracheoplasty for long congenital tracheal stenosis without conventional immunosuppression.

Experimental and clinical evaluation of a new synthetic, absorbable sealant to reduce air leaks in thoracic operations.

BACKGROUND: Air leaks after pulmonary resections may contribute to increased patient morbidity, delayed removal of chest drainage tubes, and prolonged hospitalization. OBJECTIVE: The purpose of this study was to investigate the effects of a new synthetic, absorbable sealant on the healing of healthy bronchial and lung tissues (experimental study) and its safety and efficacy to stop air leaks after lung resection (clinical study). METHODS: Fifteen large white pigs underwent a left upper lobectomy. All parenchymal surgical sites were sealed; the bronchial stump was either stapled, sealed, or both (n = 5 each). In the clinical study, 26 consecutive patients were prospectively randomized, intraoperatively, to standard closure of parenchymal surgical sites with (n = 15) or without (n = 11) the sealant. RESULTS: In the experimental study, no postoperative air leaks occurred, with intact bronchial closures and normal tissues at death. In the clinical study, 100% of intraoperative leaks were sealed versus 18% of control patients (P =.001). Although 77% (n = 10) of treated patients remained leak-free from the end of the operation to chest tube removal versus 9% (n = 1) of control patients (P =.001), there was no statistical difference in the duration of postoperative chest tube time, hospital stay, or cost. There were no acute or late undesirable side-effects related to the sealant application. CONCLUSIONS: The surgical adhesive investigated here demonstrated a compelling safety profile and significant clinical efficacy to stop air leaks after lung resections.

Thymic neuroendocrine carcinoma (carcinoid): a clinicopathologic study of fourteen cases.

The medical records and histologic documents of 14 patients treated at our institution for a thymic carcinoid tumor were reviewed. There were 3 women and 11 men with an age range from 35 to 71 years. One patient had a multiple endocrine neoplasia syndrome; another had a neurofibromatosis. Twelve tumors were revealed by local symptoms and two were asymptomatic. One patient had Cushing's syndrome that appeared secondarily and was related to metastases. Tumors ranged from 6 to 20 cm and had the characteristic histologic appearance of atypical carcinoid tumor. Immunohistochemical evaluations were done. Tumors were positive for cytokeratin (92%), neuroendocrine markers (100%), and p53 oncoprotein (29%). S-100 protein antibody revealed numerous sustentacular cells in one case. Overall survival was 46% and 31% at 3 and 5 years, respectively. However, all patients died of the disease within 109 months as a result of local progression (n = 5), local relapse (n = 3), distant metastases (n = 8), or a combination of these reasons. Median survival was 71, 30, and 5 months for patients who had total resection (n = 4), partial resection (n = 5), or simple biopsy (n = 4), respectively (p = 0.023). In conclusion, thymic carcinoid tumors can be considered thymic neuroendocrine carcinomas because of their malignant behavior and histologic appearance of atypical carcinoid tumors. Complete surgical resection offers the best hope for long-term survival.

Partial cricoidectomy with primary thyrotracheal anastomosis for postintubation subglottic stenosis.

OBJECTIVE: We describe a Pearson-type technique and evaluate its results for postintubation subglottic stenosis. METHODS: Forty-five patients underwent a partial cricoidectomy with primary thyrotracheal anastomosis, and 5 underwent simultaneous repair of a tracheoesophageal fistula as well. Twenty-four (53%) patients were referred to us after initial conservative (n = 21) or operative (n = 3) management. There were 27 cuff lesions, 7 stomal lesions, and 11 at both levels. The upper limit of the stenosis was 1.5 cm (range, 1-2.5 cm) below the cords, and the subglottic diameter was reduced by 60% in 38 (84%) of the patients. The length of airway resection ranged from 2 to 6 cm (median, 3 cm). Despite 23 thyrohyoid or suprahyoid releases, 8 anastomoses were under tension. RESULTS: Thirty-seven (82%) patients were extubated after the operation (n = 30) or within 24 hours (n = 7). Six patients required postoperative airway stenting (median, 5.5 days). Early (<30 days) complications occurred in 18 (41%) patients, mainly as transient airway and voice complaints, aspiration, and dysphagia. One (2%) patient died of myocardial infarction. Late morbidities were 2 failures occurring as bilateral recurrent nerve paralysis and restenosis requiring definitive tracheostomy. Patients had excellent or good anatomic (n = 42 [96%]), functional (n = 41 [93%]), or both types of long-lasting results, with no stenotic relapse. CONCLUSIONS: Partial cricoidectomy with primary thyrotracheal anastomosis can be applied in patients with postintubation stenosis extending up to 1 cm below the cords and measuring up to 6 cm in length with excellent-to-good definitive results. The association with a tracheoesophageal fistula does not contraindicate surgical repair.

Evaluation and outcome of different surgical techniques for postintubation tracheoesophageal fistulas.

OBJECTIVE: We evaluated the outcome of different surgical techniques for postintubation tracheoesophageal fistula. METHODS: Thirty-two consecutive patients aged 51 +/- 23 years had tracheoesophageal fistulas resulting from a median of 30 days of mechanical ventilation via endotracheal (n = 12) or tracheostomy (n = 20) tubes. Tracheoesophageal fistulas were 2.5 +/- 1.2 cm long and were associated with a tracheal (n = 10) or subglottic (n = 3) stenosis in 13 patients. RESULTS: All but 3 patients were weaned from respirators before repair. All operations were done through cervical incisions and included direct division and closure (n = 9), esophageal diversion (n = 3), muscle interposition (n = 6), or, more recently, tracheal or laryngotracheal resection and anastomosis with primary esophageal closure (n = 14). Nine thyrohyoid and two supralaryngeal releases reduced anastomotic tension. Twenty-three patients (74%) were extubated after the operation (n = 16) or within 24 hours (n = 7), and 7 required a temporary tracheotomy tube. One postoperative death (3%) was associated with recurrent tracheoesophageal fistula. Seven complications (22%) included recurrent tracheoesophageal fistula (n = 1), delayed tracheal stenosis (n = 2), dysphagia (n = 2), and recurrent nerve palsy (n = 2). Complications necessitated reoperation (n = 1), dilation (n = 2), definitive tracheostomy (n = 1), Montgomery T tubes (n = 1), and Teflon injection of the vocal cords (n = 1). Twenty-nine patients (93%) had excellent (n = 24) or good (n = 5) anatomic and functional long-term results. Complications have been less common (7% vs 38%) and long-term results better (93% vs 65%) recently with tracheal or laryngotracheal resection and anastomosis with primary esophageal closure as compared with previous procedures. CONCLUSIONS: Postintubation tracheoesophageal fistula is usually best treated with tracheal or laryngotracheal resection and anastomosis with primary esophageal closure even in the absence of tracheal damage.

Most peripheral, node-negative, non-small-cell lung cancers have low proliferative rates and no intratumoral and peritumoral blood and lymphatic vessel invasion. Rationale for treatment with wedge resection alone.

We investigated the tumor aggressiveness (intratumoral and peritumoral lymphatic and blood vessel invasion by tumor emboli) and proliferative activity (mitotic count) of 45 patients with peripheral, superficially seated, node-negative (T1-2 N0 M0), non-small-cell lung cancer treated with wedge resection alone between January 1982 and June 1988. Most patients were male (n = 39) with T1 (n = 25), small (mean diameter, 2.6 +/- 0.8 cm), squamous (n = 24), right-sided (n = 29) tumors located in either upper lobe (n = 35). The surgical specimens were studied by immunohistochemical staining with a monoclonal antibody targeting the factor VIII-related antigen. None of the tumors had lymphatic peritumoral or intratumoral invasion. Seven neoplasms (15%) harbored blood vessel invasion by tumor cells; all but one of these invasions were within the substance of the tumor. The median mitotic count was 8 mitoses per 10 high-power fields (range, 1 to 42 mitoses), significantly (p = 0.003) higher in patients with blood vessel invasion than in those without. With a 24-month minimum follow-up, projected 3- and 5-year survivals are 79% and 68%, respectively. Eleven patients had relapses and died of their tumors because of either local (n = 5) or extrathoracic (n = 6) recurrence; three patients died without tumors of comorbidity. Among the six tumors recurring in extrathoracic sites, five (83%) harbored intratumoral (n = 4) or peritumoral (n = 1) blood vessel invasion. Both recurrence of disease and death from non-small-cell lung cancer were significantly (p = 0.0009) higher for tumors with blood vessel invasion. By univariate analysis, significant predictors of survival were tumor stage (T1 vs T2, p = 0.008), size (< or = 2.6 cm vs > 2.6 cm, p = 0.039), mitotic count (< or = 8 vs > 8 mitoses, p = 0.0007), and blood vessel invasion (absence vs presence, p = 0.0001). By multivariate analysis, however, only blood vessel invasion retained its level of prognostic significance (p = 0.006). Data demonstrate that peripheral, node-negative non-small-cell lung cancers have a low metastatic potential. Whenever anatomically feasible, wedge resection seems to be an appropriate method of primary treatment.

Tracheal growth after slide tracheoplasty.

OBJECTIVE: Our goal was to investigate the effects of slide tracheoplasty on tracheal growth in newborn piglets. METHODS: Slide tracheoplasty was performed on normal trachea (n = 6) and a model of tracheal stenosis resembling that seen in infants (n = 6). After division of the trachea at its midportion between the second cartilaginous ring above and the right upper lobe takeoff below (around 23 rings), the proximal and distal segments were incised vertically on opposite anterior and posterior surfaces and reconstructed together. RESULTS: The reconstructed tracheas lengthened and their cross-sectional areas enlarged linearly at a rate of 0.94 cm per month and 1.55 mm2/kg, respectively, as the piglets grew over a 6-month period from 4.7 +/- 0.6 to 64.4 +/- 5.7 kg (+/- standard deviation). Growth was not different between the two studied groups. There was no narrowing or late restenosis. The mean anastomotic cross-sectional area was overall 1.63 +/- 0.28 times larger (range 1.2 to 2.7) than the cross-sectional area of the unreconstructed trachea. When the animals were put to death, all tracheal lumina were completely lined with normal respiratory epithelium and all layers were histologically intact; anastomotic trachealis muscles contracted less (p < 0.001) but relaxed similarly to those muscles lining normal tracheas. Tracheal blood supply was macroscopically and microscopically normal in both groups; however, newborn piglets had an almost twofold increased number of intramural capillary vessels as opposed to adult pigs (p < 0.001). CONCLUSIONS: Results suggest that slide tracheoplasty is not limited by the length of stenosis, provides a permanent enlargement of the cross-sectional airway diameter, does not compromise tracheal vascular supply, and does not impair tracheal growth as somatic growth continues.

Characterization of a pig-to-goat orthotopic lung xenotransplantation model to study beyond hyperacute rejection.

BACKGROUND: A pig-to-goat orthotopic lung xenograft model was developed to test whether depletion of goat xenoreactive antibodies against pig red blood cells would prolong pig lung xenograft survival. METHODS: Adult goats with anti-pig xenoreactive antibodies underwent left pneumonectomy followed by orthotopic transplantation of pig left lung (group 1) or immunodepletion of their xenoreactive antibodies by extracorporeal right pig lung perfusion before transplantation without (group 2) or with (group 3) complete clampage of the right pulmonary artery. In group 4, goat left lungs were orthotopically transplanted into pigs and served as negative controls (pig serum does not have anti-goat xenoreactive antibodies). Each study group included 5 animals. Immunosuppression in surviving recipients included cyclosporine and azathioprine. RESULTS: Group 1 recipients died 7 +/- 3 hours after xenograft reimplantation of severe pulmonary hypertension and dysfunction and vasogenic shock, with little evidence of histologic xenograft injury. Group 2 xenografts had a stable circulatory and respiratory function on reperfusion and survived 9 +/- 4 days. Group 3 animals also tolerated complete occlusion of the right pulmonary artery, and xenografts assured the total respiratory support for 4 +/- 1 days. After immunodepletion, goat serum showed no detectable titers of xenoreactive antibodies, which began to reappear by postoperative day 2, where xenografts showed histologic stigmata of acute (humoral and cellular-mediated) rejection that evolved to a complete xenograft necrose at death. Group 4 xenografts showed scattered features of acute rejection 5 +/- 1 days after the operation. CONCLUSIONS: Pig left lung xenografts can provide prolonged and complete respiratory support after depletion of goat xenoreactive antibodies, but they ultimately necrose once recipient xenoreactive antibodies return to pretransplantation values.

Surgical treatment of pulmonary aspergilloma: current outcome.

OBJECTIVE: This retrospective study was designed to confirm that aggressive pulmonary resection can provide effective long-term palliation of disease for patients with pulmonary aspergilloma. METHODS AND RESULTS: From 1959 to 1998, 84 patients underwent a total of 90 operations for treatment of pulmonary aspergilloma in the Marie-Lannelongue Hospital. The mean follow-up period was 9 years, and 83% of the patients were followed up for 5 years or until death, if the latter occurred earlier. The median age was 44 years. The most common indications were hemoptysis (66%) and sputum production (15%). Fifteen patients (18%) had no symptoms. Tuberculosis and lung abscess were the most common underlying causes of lung disease (65%). The procedures were 70 lobar or segmental resections, 8 cavernostomies, and 7 pneumonectomies. Five thoracoplasties were required after lobectomy (3 patients) or pneumonectomy (2 patients). The operative mortality rate was 4%. The major complications were bleeding (23 patients), prolonged air leak (31 patients), respiratory failure (10 patients), and empyema (5 patients). The actuarial survival curve showed 84% survival at 5 years and 74% survival at 10 years. During the first 2 years, death was related to the surgical procedure and the underlying disease. In contrast, 85% of the survivors had a good late result. CONCLUSION: Lobar resection in both the symptomatic and the asymptomatic patients was conducted in low-risk settings. For patients whose condition is unfit for pulmonary resection, cavernostomy may need to be undertaken despite the high operative risk. The better survival rate in this study may have been due to the selection of patients with better lung function and localized pulmonary disease.

Anterior transcervical-thoracic approach for radical resection of lung tumors invading the thoracic inlet.

We describe an original anterior transcervical-thoracic approach required for a safe exposure and radical resection of non-small-cell lung cancer that has invaded the cervical structures of the thoracic inlet. Through a large L-shaped anterior cervical incision, after the removal of the internal half of the clavicle, the following steps may be performed: (1) dissection or resection of the subclavian vein; (2) section of the anterior scalenus muscle and resection of the cervical portion of the phrenic nerve, if invaded; (3) exposure of the subclavian and vertebral arteries; (4) dissection of the brachial plexus up to the spinal foramen; (5) section of invaded ribs; and (6) en bloc removal of chest wall and lung tumor, either directly or through an extension of the cervical incision into the deltopectoral groove. An additional posterior thoracotomy may be required for resection of the chest wall below the second rib. Between 1980 and 1991, 29 patients underwent radical en bloc resection of the inlet tumor, chest wall (ribs 1 and 2), and underlying lung, either through the anterior transcervical approach alone (n = 9) or with an additional posterior thoracotomy (n = 20). The inferior root of the brachial plexus, either alone (n = 11) or with the phrenic nerve (n = 4), was involved and resected in 15 patients (52%). Twelve patients (41%) had a vascular involvement that included the subclavian artery alone (n = 3); subclavian artery and subclavian vein (n = 3); subclavian artery, subclavian vein, and vertebral artery (n = 2); subclavian artery and vertebral artery (n = 1); subclavian vein alone (n = 1); vertebral artery alone (n = 1), or subclavian artery and vertebral artery (n = 1). The subclavian artery was revascularized either with a prosthetic replacement (n = 7) or an end-to-end anastomosis (n = 2), and the median graft patency was 18.5 months (range, 6 to more than 73 months); only 1 patient had postradiotherapy graft occlusion in the revascularized artery 6 months after operation. We performed 14 wedge resections, 14 lobectomies, and 1 pneumonectomy. There were no operative or hospital deaths. Postoperative radiotherapy (median, 56 Gy) was given to 25 (86%) patients, either alone (n = 14) or in combination with adjuvant systemic chemotherapy (n = 11). With a median follow-up time of 2.5 years, overall 2- and 5-year survivals were 50% and 31%, respectively. This transcervical-thoracic approach affords a safe exposure and radical resection of non-small-cell lung cancer involving the thoracic inlet and results in encouraging long-term survival.

Double lung transplantation in situs inversus with Kartagener's syndrome. Paris-Sud University Lung Transplant Group.

En bloc double lung transplantation with bilateral bronchial anastomoses was successfully performed in three patients with complete situs inversus and end-stage Kartagener's syndrome. Dextrocardia was not a technical problem for institution of cardiopulmonary bypass, but a large azygos vein draining the systemic venous return was systematically preserved. The major technical difficulty was restoration of airway continuity, because patients with situs inversus have an inverse direction and length of the main stem bronchi. The right and left main bronchi of the recipients were approached in the aortocaval sinus and transected approximately at 1.5 cm from the carina. The donor right main stem bronchus was divided at its origin and the donor left main stem bronchus was divided proximal to the upper lobe takeoff. The different bronchial angulation was not an obstacle, and airway continuity was reestablished twice with an end-to-end anastomosis and once with a telescopic technique. Because of the midline position of the left atrium and pulmonary artery, the anastomoses with the respective recipient's structures were made as in patients with situs solitus. One patient required a right lower lobectomy because the position of the right side of the heart interfered with lobar expansion. One patient died of obliterative bronchiolitis 36 months after the operation. The remaining two are alive and doing well after 48 and 6 months, respectively.

Comparative outcome of heart-lung and lung transplantation for pulmonary hypertension.

Despite the development of several lung transplantation procedures, the most advantageous for pulmonary hypertension remains controversial. Between 1986 and February 1992, 30 patients with end-stage primary pulmonary hypertension (n = 24), chronic pulmonary embolism (n = 4), and hystiocytosis X (n = 2) underwent heart-lung (n = 21), double lung (n = 8), or single lung (n = 1) transplantation. Indications for double lung transplantation were similar to those for heart-lung transplantation, and the preoperative clinical and hemodynamic parameters were not significantly different between the two groups. There were no intraoperative deaths, but two reoperations were needed for pleural hematoma. Five early deaths were related to graft failure (two heart-lung transplantations), mediastinitis (one heart-lung transplantation), multiorgan failure (one double lung transplantation), and aspergillosis (one double lung transplantation). There was a similar improvement in early (days 0 and 2) and late (6 months postoperatively) right-sided hemodynamic function in patients undergoing heart-lung and double lung transplantation. Three double lung transplant recipients had early and reversible left ventricular-failure. The early postoperative course of the one patient who had single lung transplantation was characterized by severe pulmonary edema, left ventricular failure, and persistent desaturation and later on by moderate pulmonary hypertension and an important ventilation/perfusion mismatch. The pulmonary function results were also similar in the heart-lung and double lung transplantation groups. The overall projected 2- and 4-year survivals were 49% and 41%, respectively, and were not significantly different between the heart-lung and double lung recipients. Results demonstrate that heart-lung and double lung transplantation are equally effective in obtaining early and durable right-sided hemodynamic and respiratory improvement and similar respiratory function. In patients with pulmonary hypertension, double lung transplantation should be preferred to single lung transplantation because of the critical postoperative course and the uncertain long-term results of single lung transplantation.

Blood vessel invasion by tumor cells predicts recurrence in completely resected T1 N0 M0 non-small-cell lung cancer.

The prognostic significance of traditional and newer tumor cell-related biologic parameters, like deoxyribonucleic acid ploidy (flow cytometry), proliferative activity (expression of proliferating cell nuclear antigen by immunohistochemistry), mitotic count, and intratumoral or peritumoral (or both) blood or lymphatic vessel invasion by tumor cells was investigated in 95 consecutive patients who had T1 N0 M0 non-small-cell lung cancer and who had operation alone between 1975 and 1985. The median follow-up for the entire group is now 8.3 years, and overall 5-, 10-, and 15-year-survivals were 75%, 69%, and 61%, respectively. Twenty-two patients died of either local (n = 3) or systemic (n = 19) recurrent non-small-cell lung cancer, 5 of non-cancer-related causes, 2 of new primary lung cancer, and 1 of an extrathoracic cancer. By multivariate analysis, blood vessel invasion by tumor cells (p = 0.0001) and mitotic count (p = 0.016) were independent predictors of survival; by contrast, the disease-free survival was influenced only by blood vessel invasion (p = 0.0004). The relative risk of death of recurrent non-small-cell lung cancer for low-risk patients (n = 79) was 13.3 (95% confidence interval, 6.1 to 28.7) times lower than that of high-risk patients (n = 16) (p < 0.0001). The relative risk of manifesting recurrent disease as distant metastasis for high-risk patients was 25.64 (95% confidence intervals, 8.4 to 77.6) times higher than that of their low-risk counterparts (p < 0.0001). These results provide a rationale for effective systemic adjuvant treatment in completely resected T1 N0 M0 non-small-cell lung cancer tailored to the individual patients' risk of development of recurrent non-small-cell lung cancer.