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.

Surgical resection provided cure in all the patients with benign tumors. As insufficiency of exeresis is associated with all recurrences in malignant tumors, completeness of resection is in our experience the best prognostic factor in these forms.

The hepatopulmonary syndrome (HPS) is characterized by intrapulmonary vascular dilatations and an increased alveolar-arterial oxygen difference (AaPO(2)). Exhaled nitric oxide (NO) concentrations are elevated, suggesting that pulmonary NO overproduction may be the mechanism underlying HPS. We investigated whether common bile duct ligation in rats results in lung NO overproduction and whether normalization of NO synthesis by a 6-wk course of N(G)-nitro-L-arginine methyl ester (L-NAME) (5 mg x kg(-)(1) x d(-)(1)) prevents HPS. Untreated cirrhotic rats showed increases in AaPO(2) and in cerebral uptake of intravenous (99m)Tc-labeled albumin macroaggregates (indicating intrapulmonary vascular dilatations), with decreases in pulmonary vascular resistance and in pulmonary vasoconstriction induced by angiotensin II and hypoxia. Increases were found in exhaled NO; pulmonary total and calcium-dependent NO synthase (NOS) activities; and pulmonary expression of inducible and, to a lesser extent, endothelial NOS. Accumulation of intravascular macrophages accounted for the inducible NOS expression. L-NAME normalized AaPO(2), brain radioactivity, pulmonary vascular resistance, reactivity to hypoxia and angiotensin II, exhaled NO, and NOS activities. These findings suggest that HPS and the associated reduced response to pulmonary vasoconstrictors seen in untreated cirrhotic rats are related to increased pulmonary NO production dependent primarily on increases in the expression and activities of inducible NOS within pulmonary intravascular macrophages.

Hepatopulmonary syndrome (HPS) is characterized by intrapulmonary vascular dilatations and an increased alveoloarterial oxygen difference (AaPO(2)). These abnormalities are related to augmented pulmonary nitric oxide (NO) production, dependent primarily on increases in the expression and activity of inducible NO-synthase (iNOS) within pulmonary intravascular macrophages and, to a lesser extent, of endothelial NOS (eNOS). Production of iNOS by pulmonary intravascular macrophages might be related to translocated gut bacteria present in the pulmonary circulation. To test this hypothesis, we determined whether macrophage sequestration, lung iNOS expression and activity, and HPS severity were decreased after norfloxacin was given for 5 weeks to prevent Gram-negative bacterial translocation in rats with common bile duct ligation-induced cirrhosis. Norfloxacin decreased the incidence of Gram-negative translocation from 70 to 0% and the percentage of pulmonary microvessels containing more than 10 macrophages from 52 +/- 7 to 21 +/- 8% (p < 0.01). AaPO(2) and cerebral uptake of intravenous (99m)Tc-labeled albumin macroaggregates (reflecting intrapulmonary vascular dilatations) were intermediate to those of untreated cirrhotic and sham-operated rats. The activity and expression of lung iNOS, but not eNOS, were reduced to normal. Norfloxacin may reduce HPS severity by inhibiting Gram-negative bacterial translocation, thereby decreasing NO production by pulmonary intravascular macrophages. Bacterial translocation may be the key to the pathogenesis of HPS.

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.

Background. The records of 98 consecutive patients (58 males and 40 females; median age, 27 years; age range, 2-64 years) who presented with a primary germ cell tumor (GCT) of the mediastinum between January 1960 and December 1990 were reviewed. There were 45 mature teratomas, 8 immature teratomas, 16 pure seminomas, and 24 malignant nonseminomatous GCT (MNSGCT).Results. All patients with mature teratomas were cured by radical resection alone, except one patient who died intraoperatively. Among the eight patients with immature teratomas, five were treated before the advent of cisplatin treatment (two children younger than 15 years were cured by surgery alone and three adults died within 7 months after operation). Three patients underwent surgery followed by cisplatin-based chemotherapy (two are still alive and one died of an associated rhabdomyosarcoma). Thirteen of 16 patients with seminomas (81%) were cured by surgery either alone (5 patients) or with adjuvant radiation therapy (8 patients). Among the 24 MNSGCT, 10 were treated before 1980 without cisplatin and all but 1 died of disease progression. Fourteen patients were treated by initial high-dose cisplatin combination chemotherapy and 8 (57%) achieved complete remission (2 died of systemic mastocytosis development).Conclusions. Results indicate the benignity of mature teratomas of the mediastinum, the age-dependent clinical course of immature teratomas, and the excellent prognosis of seminomas. The improved survival advantage resulting from cisplatin-based chemotherapy in MNSGCT is impaired by the propensity to nongerminal solid tumor development and hematologic malignancies.

( Table 1). This series include 126 leukemias and 124 lym-

1 Iloprost and cicaprost (IP-receptor agonists) induced relaxations in the histamine-(50 mM) contracted human bronchial preparations (pD 2 values, 6.63+0.12 and 6.86+0.08; E max values, 90+04 and 65+08% of the papaverine response for iloprost (n=6) and cicaprost (n=3), respectively).2 Prostaglandin E 2 (PGE 2 ) and misoprostol (EP-receptor agonist) relaxed the histamine-contracted human bronchial preparations (pD 2 values, 7.13+0.07 and 6.33+0.28; E max values, 67+04 and 57+08% of the papaverine response for PGE 2 (n=14) and misoprostol (n=4), respectively). In addition, both relaxations were inhibited by AH6809 (DP/EP 1 /EP 2 -receptor antagonist; 3 mM; n=5 ± 6). 3 The PGE 2 -induced relaxations of human bronchial preparations were not modi®ed by treatment with AH23848B (TP/EP 4 -receptor antagonist; 30 mM; n=4). 4 The contracted human bronchial preparations were signi®cantly relaxed by prostaglandin D 2 (PGD 2 ) 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 PGD 2 were signi®cantly inhibited by treatment with a DP-receptor antagonist BWA868C (0.1 mM; n=3). 5 These data suggest that the relaxation of human isolated bronchial preparations induced by prostanoids involved IP-, EP 2 -and to a lesser extent DP-receptors but not EP 4 -receptor.