[Invasion of the pulmonary artery by an undifferentiated carcinoma]. / Obstruction tumorale de l'artère pulmonaire par un carcinome indifférencié

INTRODUCTION: The diagnosis of chronic obstruction of the pulmonary artery is difficult. We present the case of a woman with an invasive, undifferentiated carcinoma of the pulmonary artery. CASE REPORT: A 61 year old woman complained of increasing dyspnoea. This was evaluated by computed tomography which showed a defect in the main pulmonary artery. There was no clinical or radiological improvement following anticoagulant treatment for two months. A repeat CT scan showed a persisting intravascular defect and the diagnoses considered included post-embolic pulmonary arterial hypertension and angiosarcoma. A surgical biopsy was performed and pericardial and aortic tumour nodules were found during the operation. The pathological examination revealed undifferentiated carcinoma. Further investigations failed to reveal the primary site. CONCLUSION: Invasion of the pulmonary artery by angiosarcoma or other tumour is part of the differential diagnosis of chronic thromboembolic disease. The diagnosis rests on histology obtained by an intravascular or surgical procedure. Complete surgical excision may be possible in angiosarcoma but it was impossible in our patient. The patient died despite two courses of chemotherapy and targeted therapy with erlotinib.

Human herpes virus 8 (Kaposi's sarcoma herpes virus) and malignant lymphoproliferations in France: a molecular study of 250 cases including two AIDS-associated body cavity based lymphomas.

The new human herpes virus 8 (HHV8) was recently detected in cases of body cavity based lymphoma (BCBL), a rare B cell lymphoma, mostly AIDS-associated. We investigated for HHV8 DNA sequences a series of 250 B or T cell lymphoproliferative malignancies, as seen in France, including 126 leukemias and 124 lymphomas (232 non-AIDS-associated and 18 AIDS-associated tumors). HHV8 sequences were detected in only three patients. The first two were homosexual males, HIV-infected since 1985 who suffered from a BCBL initially characterized in one case by a pleural lymphomatous effusion and a peritoneal one in the other case. A high level of HHV8 copies was detected in the tumoral cells of these two BCBL. In contrast, in the third positive patient who had an AIDS-associated immunoblastic lymphoma, the HHV8 sequences level was quite low. In the two BCBL patients, the HHV8-infected clonal B cells had a large immunoblastic feature with an indeterminate phenotype and were also infected by Epstein-Barr virus. In one BCBL case, a semiquantitative PCR analysis revealed that the HHV8 sequences were much more abundant in the effusion tumor cells than in the cutaneous Kaposi's biopsy while no HHV8 sequence was detectable in the peripheral blood lymphocytes. This study reports HHV8-associated BCBL in European AIDS patients and confirms that HHV8 is present at a high copy number in the tumoral B cells of this malignancy. Furthermore, HHV8 does not seem to play a pathogenic role in any of the other T or B malignant lymphoid neoplasias studied so far. This study also stresses the necessity for quantification studies in interpretation of a positive PCR analysis for HHV8 sequences, especially in patients at risk for HIV infection or Kaposi's sarcoma.

Evidence for a M(1) muscarinic receptor on the endothelium of human pulmonary veins.

1. To characterize the muscarinic receptors on human pulmonary veins associated with the acetylcholine (ACh)-induced relaxation, isolated venous and arterial preparations were pre-contracted with noradrenaline (10 microM) and were subsequently challenged with ACh in the absence or presence of selective muscarinic antagonists. 2. ACh relaxed venous preparations derived from human lung with a pD(2) value of 5.82+/-0.09 (n=16). In venous preparations where the endothelium had been removed, the ACh relaxations were abolished (n=4). ACh relaxed arterial preparations with a pD(2) value of 7. 06+/-0.14 (n=5). 3. Atropine (1 microM), the non selective antagonist for muscarinic receptors, inhibited ACh-induced relaxations in human pulmonary veins. The affinity value (pK(B) value) for atropine was: 8.64+/-0.10 (n=5). The selective muscarinic antagonists (darifenacin (M(3)), himbacine (M(2),M(4)), methoctramine (M(2)) and pFHHSiD (M(1),M(3))) also inhibited ACh-induced relaxations in venous preparations. The pK(B) values obtained for these antagonists were not those predicted for the involvement of M(2 - 5) receptors in the ACh-induced relaxation in human pulmonary veins. 4. The pK(B) value for darifenacin (1 microM) was significantly greater in human pulmonary arterial (8.63+/-0.14) than in venous (7.41+/-0.20) preparations derived from three lung samples. 5. In human pulmonary veins, the pK(B) values for pirenzepine (0.5 and 1 microM), a selective antagonist for M(1) receptors, were: 7.89+/-0.24 (n=7) and 8.18+/-0.22 (n=5), respectively. In the venous preparations, the pK(B) values derived from the functional studies with all the different muscarinic antagonists used were correlated (r=0.89; P=0.04; slope=0.78) with the affinity values (pK(i) values) previously published for human cloned m1 receptors in CHO cells. 6. These results suggest that the relaxations induced by ACh are due to the activation of M(1) receptors on endothelial cells in isolated human pulmonary veins.

Degradation of acetylcholine in human airways: role of butyrylcholinesterase.

1. Neostigmine and BW284C51 induced concentration-dependent contractions in human isolated bronchial preparations whereas tetraisopropylpyrophosphoramide (iso-OMPA) was inactive on airway resting tone. 2. Neostigmine (0.1 microM) or iso-OMPA (100 microM) increased acetylcholine sensitivity in human isolated bronchial preparations but did not alter methacholine or carbachol concentration-effect curves. 3. In the presence of iso-OMPA (10 microM) the bronchial rings were more sensitive to neostigmine. The pD2 values were, control: 6.05 +/- 0.15 and treated: 6.91 +/- 0.14. 4. Neostigmine or iso-OMPA retarded the degradation of acetylcholine when this substrate was exogenously added to human isolated airways. A marked reduction of acetylcholine degradation was observed in the presence of both inhibitors. Exogenous butyrylcholine degradation was prevented by iso-OMPA (10 microM) but not by neostigmine (0.1 microM). 5. These results suggest the presence of butyrylcholinesterase activity in human bronchial muscle and this enzyme may co-regulate the degradation of acetylcholine in this tissue.

Prostanoid receptors involved in the relaxation of human bronchial preparations.

1. Iloprost and cicaprost (IP-receptor agonists) induced relaxations in the histamine- (50 microM) contracted human bronchial preparations (pD2 values, 6.63+/-0.12 and 6.86+/-0.08; Emax values, 90+/-04 and 65+/-08% of the papaverine response for iloprost (n=6) and cicaprost (n=3), respectively). 2. Prostaglandin E2 (PGE2) and misoprostol (EP-receptor agonist) relaxed the histamine-contracted human bronchial preparations (pD2 values, 7.13+/-0.07 and 6.33+/-0.28; Emax values, 67+/-04 and 57+/-08% of the papaverine response for PGE2 (n=14) and misoprostol (n=4), respectively). In addition, both relaxations were inhibited by AH6809 (DP/EP1/EP2-receptor antagonist; 3 microM; n=5-6). 3. The PGE2-induced relaxations of human bronchial preparations were not modified by treatment with AH23848B (TP/EP4-receptor antagonist; 30 microM; n=4). 4. The contracted human bronchial preparations were significantly relaxed by prostaglandin D2 (PGD2) or by BW245C a DP-receptor agonist. However, these responses did not exceed 40% of the relaxation induced by papaverine. In addition, the relaxations induced by PGD2 were significantly inhibited by treatment with a DP-receptor antagonist BWA868C (0.1 microM; n=3). 5. These data suggest that the relaxation of human isolated bronchial preparations induced by prostanoids involved IP-, EP2- and to a lesser extent DP-receptors but not EP4-receptor.

M1 and M3 muscarinic receptors in human pulmonary arteries.

1. Acetylcholine (ACh) and the M1 agonists (McN-A-343 or PD142505) relaxed human isolated pulmonary arteries which were pre-contracted with noradrenaline (10 microM). In preparations where the endothelium had been removed ACh induced a contractile response whereas the M1 agonists (McN-A-343 or PD142505) had no effect. 2. ACh- and McN-A-343-induced relaxations were abolished after treatment of endothelium-intact preparations with the drug combination NG-nitro-L-arginine (L-NOARG: 0.1 mM) and indomethacin (1.7 microM). 3. The affinity (pKB value) for pirenzepine was higher in human pulmonary arteries when tissues were relaxed with McN-A-343 as compared with ACh (pKB values, 7.71 +/- 0.30 (n = 4) and 6.68 +/- 0.15 (n = 8), respectively). In addition, the affinity for pFHHSiD against McN-A-343- and ACh-induced relaxations was 6.86 +/- 0.13 (n = 3) and 7.35 +/- 0.11 (n = 9) respectively. 4. The low affinities for methoctramine in human isolated pulmonary arteries with the endothelium either intact or removed, suggested the lack of involvement of M2 and M4 receptors in the Ach responses. 5. Phenoxybenzamine (3 microM: 30 min) abolished both ACh contraction and relaxation in human pulmonary artery. The ACh contraction was present when the phenoxybenzamine treatment was preceded by incubation with pFHHSiD (2 microM) but not with pirenzepine (1 microM). In addition, the ACh relaxation was present when preparations were treated with either pFHHSiD (2 microM) or pirenzepine (1 microM), before exposure to phenoxybenzamine. 6. These results in human isolated pulmonary arteries support the notion that only M3 receptors, on smooth muscle, mediate the ACh-induced contraction whereas M3 and M1 receptors are involved in the endothelium-dependent ACh-induced relaxation.

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.

Extramedullary hematopoietic tumors of the posterior mediastinum related to asymptomatic refractory anemia.

Two asymptomatic paravertebral thoracic masses occurred in a 65-year-old patient with isolated macrocytosis. The largest one measured 8 cm and was surgically resected with a presumptive diagnosis of schwannoma. This thoracic mass was hemorrhagic, encapsulated, and composed of fat and hematopoietic tissue. While extramedullary hematopoietic tumors usually occur in patients with severe chronic hemolytic anemia, our report suggests that such lesions must be considered in the differential diagnosis of posterior mediastinal mass in patients without clinical evident anemia.

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.

Bronchioloalveolar lung carcinoma: results of surgical treatment and prognostic factors.

STUDY DESIGN: To determine the long-term results after surgical treatment of bronchioloalveolar lung carcinoma (BALC) and to identify prognostic factors. PATIENTS AND METHODS: A retrospective study of 70 patients (49 men, 21 women), mean age 61+/-10 years, was carried out. Their carcinomas were classified into three clinicopathologic types: nodular or tumoral, pneumonic, and diffuse types. All the diagnosed BALC cases were reviewed and were classified into histologic types: mucinous, nonmucinous (including fibrotic center), and mixed tumors. Univariate and multivariate analyses were carried out. RESULTS: The nodular or tumoral type was identified in 42 patients, pneumonic in 21, and diffuse in seven. Histologically, there were 36 mucinous, 25 nonmucinous, and nine mixed tumors. Resection was complete in 61 instances (87%) and incomplete in five. The 5-year survival rate was 34% in patients with curative resections. Five prognostic factors were identified by univariate analysis, but in multivariate analysis, only three factors remained significant: the absence of symptoms, the TNM stage, and completeness of resection. Thirty-six patients with curative resection (59%) developed recurrences (in the lung in 26 patients; mediastinal lymph nodes, four; distant metastases, nine). The frequency of recurrence was significantly greater in patients with pneumonic-type BALC than in nodular or tumoral types (p<0.01), and pulmonary recurrences were significantly more frequent in pneumonic than in tumoral types (p<0.02). CONCLUSIONS: This study confirmed that the overall prognosis of BALC is not significantly different from that of the other non-small cell lung cancers. We found that the lungs are the predominant site of recurrence in BALC, especially in the pneumonic types. The complete surgical resection of localized BALC offers the best chances of long-term survival.

Heterotopic pig model for direct revascularization and venous drainage of tracheal allografts. Paris-Sud University Lung Transplantation Group.

A macrosurgical technique of thyrotracheal harvesting and direct revascularization with and without venous drainage in a heterotopic thyrotracheal and immunosuppressed allograft in the pig model is described. Harvesting included en bloc cervicothoracic exenteration of the aortic arch and its supraortic trunks, anterior vena cava, jugular veins, subclavian vessels, thyroid gland, cervicothoracic trachea, and esophagus. This technique conserves the tracheal arterial supply provided by either the right or left subclavian artery, directly or indirectly via the inferior thyroid artery, and venous return provided by the anterior vena cava, directly or indirectly via the descending cervical vein. In recipients, implantation included (1) arterial end-to-end anastomoses of the proximal and postscalenic stumps of donor's subclavian artery to the proximal and prescalenic stumps of recipient's subclavian artery; (2) end-to-side venous anastomosis of the donor's anterior vena cava to the recipient's brachiocephalic venous trunk; and (3) heterotopic implantation of the proximal and distal orifices of the grafted trachea into the neck. Ten adult Large White pigs underwent direct revascularization of a thyrotracheal allograft with (n = 6, group 1) and without (n = 4, group 2) venous drainage. All grafts of group 2 exhibited a venous infarction, extensive inferior thyroid artery thrombosis, and ischemic and suppurative thyrotracheal necrosis 1 to 2 days after transplantation. In group 1, the length of the grafted trachea and number of rings were 9.75 +/- 1.5 cm and 22.1 +/- 3.3, respectively; ischemic time was 236.3 +/- 338.3 minutes. Group 1 pigs were put to death 4 (n = 4) and 3 (n =2) weeks after transplantation. All tracheal grafts had histologically normal airway epithelium; isolated areas of necrotic ischemia of the chorion and submucosa lasted for the first 7 days after transplantation but disappeared after epithelial regeneration. Premortem angiograms showed that all vascular anastomoses were patent. Grafts were histologically normal at postmortem examinations and all but one had no rejection. This large animal model demonstrates that long tracheal allografts might be transplanted by means of this direct revascularization and venous drainage technique.

Prognostic factors and long-term results after thymoma resection: a series of 307 patients.

Three hundred seven cases of patients who underwent operation for thymoma (196 of whom had myasthenia gravis) were analyzed to assess the prognostic values of Masaoka clinical staging, completeness of resection, histologic classification, history of myasthenia gravis, and postoperative radiotherapy. According to the Masaoka staging system, 135 thymomas were stage I, 70 were stage II, 83 were stage III, and 19 were stage IV. According to the Verley and Hollmann histologic classification system, 67 thymomas were type 1, 77 were type 2, 139 were type 3, and 24 were type 4. Two hundred sixty patients underwent complete resection, 30 underwent incomplete resection, and 17 underwent biopsy. Postoperative radiotherapy was performed mainly in cases of invasive or metastatic thymoma. Mean follow-up was 8 years; eight patients were unavailable for follow-up. The overall 10- and 15-year survivals were 67% and 57%, respectively. In univariate analysis, three prognostic factors were established: completeness of resection, Masaoka clinical staging, and histologic classification. Furthermore, among patients with stage III thymomas, survival was significantly higher for patients with complete resection than for patients with incomplete resection (p < 0.001). Completeness of resection should therefore be taken into account in clinical-pathologic staging. We did not find any significant difference with respect to disease-free survival between patients who had postoperative radiotherapy and those who did not. In multivariate analysis, the sole significant prognostic factor was completeness of resection. On the basis of these findings, a new clinical-pathologic staging system is proposed.

Ex vivo lung model of pig-to-human hyperacute xenograft rejection.

OBJECTIVE: Our objective was to study lung hyperacute rejection in the pig-to-human xenotransplantation combination. METHODS: Pig lungs were harvested and continuously ventilated and perfused ex vivo, using a neonatal oxygenating system, with either xenogeneic unmodified human blood (n = 6) or autogeneic pig blood (n = 6). RESULTS: Autoperfused lungs displayed normal hemodynamics, oxygen extraction (arteriovenous oxygen difference), and histologic characteristics throughout the 3-hour study period. By contrast, xenoperfused lungs displayed, within 30 minutes, severe pulmonary hypertension and abolishment of arteriovenous oxygen difference culminating in massive pulmonary edema, hemorrhage, and lung failure after 115 +/- 44.2 minutes of reperfusion. Within 30 minutes, the human blood showed a significant drop of anti-alpha Gal immunoglobulin M and G xenoreactive antibodies (enzyme-linked immunosorbent assay) and complement activity, consumption of clotting factors, and hemolysis; total circulating human immunoglobulins remained substantially normal. Histologically, lungs perfused with human blood were congestive and showed alveolar edema and hemorrhage and multiple fibrin and platelet thrombi obstructing the small pulmonary vessels (arterioles, capillaries, and venules) but not large (segmental or lobar) pulmonary vessels. On immunohistologic examination, deposits of human immunoglobulin M and complement (C1q and C3) proteins were observed on the alveolar capillaries. CONCLUSIONS: This pig-to-human xenograft model suggests that the pig lung perfused with human blood has an early and violent hyperacute rejection that results in irreversible pulmonary dysfunction and failure within approximately 150 minutes of reperfusion.

Experimental tracheal and tracheoesophageal allotransplantation. Paris-Sud University Lung Transplantation Group.

We investigated the effects of allograft perfusion with a preservative technique and of combined thyrotracheoesophageal implantation on airway epithelium of long segments of thyrotracheal grafts allotransplanted on their own vascular pedicles into immunosuppressed pigs. Four groups of five animals each underwent heterotopic (into the neck) thyrotracheal (group 1) and thyrotracheoesophageal (group 2) and orthotopic thyrotracheal (group 3) and thyrotracheoesophageal (group 4) allotransplantation. Allograft revascularization included (1) interposition of donor right subclavian artery--incorporating the inferior thyroid artery--to recipient right carotid artery (end-to-end fashion) and (2) end-to-side anastomosis of donor anterior vena cava to recipient right external jugular vein. All thyrotracheoesophageal blocks were harvested after inferior thyroid artery perfusion with 4 degrees C Euro-Collins solution. The overall lengths of tracheal and esophageal grafts were 10.7 +/- 2.7 cm and 13.4 +/- 3.6 cm, respectively. In the heterotopic groups, all allografts were viable and histologically normal at postmortem examination and the incidence and severity of airway ischemia and rejections (at equal residual levels of cyclosporine) were not different between groups 1 and 2. In the orthotopic groups, the first two pigs died of airway collapse with histologically normal grafts. In the remaining pigs, temporary airway stenting was inserted and allografts remained viable and histologically intact for their entire length 30 days after transplantation. Transplanted tracheal smooth muscles had concentration-dependent contractions and relaxations similar to those of nontransplanted (native) tracheas. This study documents the feasibility of allotransplanting long tracheal and esophageal segments on their own vascular pedicles and demonstrates that allograft preservation and thyrotracheoesophageal transplantation are equally effective in minimizing airway ischemia. Thyrotracheoesophageal transplantation does not enhance recipient alloimmune response compared with thyrotracheal transplantation alone.

Pulmonary thromboendarterectomy for chronic thromboembolic obstruction of the pulmonary artery in piglets.

OBJECTIVE: The 2 main causes of death after thromboendarterectomy for chronic pulmonary thromboembolism are incomplete repermeabilization responsible for persistent pulmonary hypertension and acute high-permeability pulmonary edema. We wish to establish an experimental model of chronic pulmonary thromboembolism to replicate the conditions encountered during and after pulmonary thromboendarterectomy. METHODS: Multiple-curled coils and tissue adhesive were embolized in 6 piglets to induce complete obstruction of the left pulmonary artery, documented by angiography. After 5 weeks, the main pulmonary artery was repermeabilized by thromboendarterectomy during circulatory arrest. The left lung was reperfused ex vivo with autologous blood at constant flow, and patency of the pulmonary artery was evaluated on a barium angiogram. The endarterectomy-reperfusion procedure was also done in 6 nonembolized piglets that served as the controls. The severity of lung injury induced by 60 minutes of reperfusion was assessed on the basis of measurements of the lung filtration coefficient and of lung myeloperoxidase activity. RESULTS: Marked hypertrophy of the bronchial circulation was seen in the chronic pulmonary thromboembolism group. Thromboendarterectomy removed the organized obstructing thrombus that was incorporated into the arterial wall and restored patency of the pulmonary artery. Acute lung inflammation and high-permeability edema occurred after reperfusion, as indicated by a 1.5-fold increases in both lung filtration coefficient and lung myeloperoxidase values in the chronic pulmonary thromboembolism group; these 2 variables being correlated. CONCLUSIONS: Our model replicated the perioperative conditions of pulmonary thromboendarterectomy, suggesting that it may prove useful for improving the repermeabilization technique and for investigating the mechanisms and prevention of reperfusion injury.

Amelioration of reperfusion injury by pentoxifylline after lung transplantation. The Université Paris-Sud Lung Transplant Group.

BACKGROUND: Pentoxifylline attenuates neutrophil-mediated lung injury in several models of acute lung inflammation. METHODS: Because pulmonary neutrophil sequestration is the main determinant of lung reperfusion injury, we sought to determine whether pentoxifylline prevented reperfusion injury in isolated perfused rat lung (4-hour cold ischemia, 1-hour reperfusion; pentoxifylline intravenously 40 mg) and in pigs after left lung allotransplantation (24-hour cold ischemia, 4-hour reperfusion; pentoxifylline 1.5 mg/kg/hr intravenously). In the pigs, inflatable cuffs placed around each pulmonary artery enabled us to evaluate each lung separately. RESULTS: In rat lungs, the coefficient of lung permeability increased by 75% +/- 10% in controls and by 3% +/- 2% (p < 0.01) in pentoxifylline-treated lungs. In the pigs, with blood flow to the transplanted lung alone and ventilation with an inspired oxygen fraction of 1, the arterial oxygen tension was greater in the pentoxifylline group than in the control group (423 +/- 49 versus 265 +/- 43 mm Hg, p < 0.05), whereas the total pulmonary vascular resistance was lower (15 +/- 1 versus 30 +/- 9 mm Hg/L/min, p < 0.02). After reperfusion, the decrease in circulating leukocyte count fell by 35% +/- 3% in the control group and remained unchanged in the pentoxifylline group, and the leukocytes count per microscopic field in the transplanted lung was lower in the pentoxifylline group than in the control group (15 +/- 2 versus 140 +/- 50, p < 0.02). CONCLUSIONS: These data suggest that pentoxifylline prevented reperfusion injury by decreasing neutrophil lung sequestration.

Effects of load and tone on the mechanics of isolated human bronchial smooth muscle.

Isotonic and isometric properties of nine human bronchial smooth muscles were studied under various loading and tone conditions. Freshly dissected bronchial strips were electrically stimulated successively at baseline, after precontraction with 10(-7) M methacholine (MCh), and after relaxation with 10(-5) M albuterol (Alb). Resting tension, i.e., preload determining optimal initial length (Lo) at baseline, was held constant. Compared with baseline, MCh decreased muscle length to 93 +/- 1% Lo (P < 0.001) before any electrical stimulation, whereas Alb increased it to 111 +/- 3% Lo (P < 0.01). MCh significantly decreased maximum unloaded shortening velocity (0.045 +/- 0.007 vs. 0.059 +/- 0.007 Lo/s), maximal extent of muscle shortening (8.4 +/- 1.2 vs. 13.9 +/- 2.4% Lo), and peak isometric tension (6.1 +/- 0.8 vs. 7.2 +/- 1.0 mN/mm2). Alb restored all these contractile indexes to baseline values. These findings suggest that MCh reversibly increased the number of active actomyosin cross bridges under resting conditions, limiting further muscle shortening and active tension development. After the electrically induced contraction, muscles showed a transient phase of decrease in tension below preload. This decrease in tension was unaffected by afterload levels but was significantly increased by MCh and reduced by Alb. These findings suggest that the cross bridges activated before, but not during, the electrically elicited contraction may modulate the phase of decrease in tension below preload, reflecting the active part of resting tension.

Leiomyosarcoma of the superior vena cava.

Leiomyosarcoma of the superior vena cava is exceptional. A case in a 52-year-old man is described. A treatment by means of neoadjuvant chemotherapy, operation, and adjuvant radiotherapy was performed. This aggressive treatment has permitted the patient to obtain a relatively long survival with a good quality of life.

Angiogenesis: an indicator of metastasis in non-small cell lung cancer invading the thoracic inlet.

We have attempted to identify a biologic rationale for the local aggressiveness and late treatment failure of resected non-small cell lung cancer involving the thoracic inlet. Tumor specimens from 28 patients who underwent a new transcervical approach were analyzed for the expression of tumor proliferative activity, suppressor-gene p53, intratumoral and peritumoral blood vessel invasion by tumor cells, the presence and degree of angiogenesis (induction of new capillaries and venules), and other biologic variables. Eighty-nine percent of the neoplasms were moderately or poorly differentiated, 89% expressed either an intermediate or high proliferative activity, 39% showed p53 aberrations, 71% exhibited induction of angiogenesis, and 39% had tumors that were positive for blood vessel invasion. With a median follow-up time of 3.5 years (range, 8 to 145+ months), the overall projected 5-year survival was 29% and the median disease-free interval was 23 months. Results of univariate and multivariate analysis of survival and the disease-free interval identified the degree of angiogenesis (density less than 1 versus more than 1 and number of neovessels less than 6 versus more than 6) as the only independent and significant predictors of the disease-free interval. Patients whose tumor showed a density of angiogenesis of 1 or greater and a number of neovessels of 6 or greater faced a significantly (p = 0.0001) higher relative risk of suffering systemic recurrence of their primary tumor than did their low-risk counterparts. Results demonstrate that angiogenesis significantly correlates with late treatment failure (metastasis), and this is acquired at a critical density and number of vessels.

Tracheoesophageal fistula caused by mycobacterial tuberculosis adenopathy.

Tracheoesophageal fistulas resulting from a Mycobacterium tuberculosis infection are uncommon. We describe a patient with such a lesion that had the radiologic and clinic appearance of a malignant tracheoesophageal fistula. Use of an anterior cervical approach with one-stage esophageal repair along with tracheal resection and anastomosis allowed definitive diagnosis and treatment of this life-threatening complication.