Clinical value of cervical mediastinoscopy in the staging of bronchial carcinoma

Whether mediastinoscopy is indicated in the preoperative staging of bronchogenic carcinoma is still a controversial issue. It may be performed routinely (to exclude locally inoperable patients from surgery), selectively, or it may be regarded as superfluous (in centers which prefer an extended lympho adenectomy at the time of thoracotomy). We regard mediastinoscopy as indicated for the following purposes: 1) staging of NSCLC and SCLC; 2) diagnostic (mediastinal masses or lung tumors without previous histology); 3) restaging after primary chemotherapy; 4) assessment of prognosis in patients with borderline operability. The indication for 224 mediastinoscopies performed at our institution in the period from September 1991 through March 1999 was mainly for staging (59.2%) or diagnostic (30.6%). Eight (5.4%) patients underwent mediastinoscopy for the assessment of operability, and 7 (4.8%) after primary chemotherapy for the restaging of loco-regionally advanced lung cancer. Sensitivity and specificity rates were 87% and 100%, respectively, with an accuracy of 93% for the mediastinoscopy performed for the staging of lung cancer at all stages. If we consider the N2 tumors (42 cases) alone, the sensitivity was 76.7% and the specificity 100%, with an accuracy of 83.3%. Overall positive and negative predictive value resulted 100% and 87%, respectively, according to the data reported in literature. Our data confirm the role of mediastinoscopy as the gold standard for regional staging of lung cancer.     

Preimplantation retrograde pneumoplegia in clinical lung transplantation.

OBJECTIVE: Retrograde pneumoplegia seems to improve early graft function in experimental and clinical lung transplantation. We evaluated the role of retrograde flushing in addition to antegrade pneumoplegia in clinical lung transplantation. METHODS: Fourteen patients undergoing lung transplantation were randomized into 2 groups: in group I we performed antegrade pulmonary artery flushing with alprostadil (prostaglandin E1) and modified Euro-Collins solution at the time of retrieval. In group II additional retrograde flushing through the pulmonary veins was performed at the back table, before reimplantation. Hemodynamic variables, mean airway pressure, and blood gas analysis were monitored at different time points. Postoperative volumetric monitoring was performed to assess extravascular lung water. The reimplantation response was assessed by a radiographic score; extubation time and intensive care unit stay were recorded. RESULTS: During retrograde flushing, blood and clots coming out from the pulmonary artery were observed; 2 lungs harvested from a donor with multiple bone fractures had fat emboli in the retrograde perfusate. Hemodynamic monitoring did not demonstrate any difference between the 2 groups. The ratio of arterial oxygen tension to inspired oxygen fraction, extravascular lung water, duration of intubation, and length of stay in the intensive care unit were improved in group II, but the differences did not reach statistical significance. Intrapulmonary shunt fraction was significantly improved in group II at each time point ( P =.02), as well as indexed alveolar-arterial oxygen tension gradient (P =.04), mean airway pressure (P =.04), and chest x-ray score ( P =.03). CONCLUSIONS: Preimplantation retrograde flushing is not detrimental and helps to improve early graft function.     

Mesenteric cystic neoformations: Report of two cases

(Received for publication on Apr. 28, 1997; accepted on May 15, 1998)     

Flow cytometric immunodissection of the human nephron in vivo and in vitro

In the present article, we show that flow cytometric immunodissection of cells immediately following their preparation from a tumor nephrectomy specimen is an accurate way of obtaining pure human primary cultures of proximal convoluted tubule origin, proximal straight tubule origin, distal tubular origin and/or collecting duct origin. By studying the expression of a panel of cell surface markers in these purified cultures, we could identify a number of markers that retain their lineage specificity in vitro. Using these appropriate stable markers, flow cytometry provides a simple yet accurate way of determining cell composition in previously unsorted (mixed type) tubular epithelial cultures in terms of proximal versus distal tubule/collecting duct subpopulations. Both subpopulations in mixed type cultures are shown to retain functional characteristics of their in vivo counterparts (glucose uptake, hormonal stimulation of adenylate cyclase) as well as cell type-specific response patterns (such as inducibility of cell adhesion and histocompatibility molecules), indicating the usefulness of studying cell responses in vitro in a cell-type-dependent way. Finally we illustrate that multi-parameter flow cytometry is a powerful tool for assessing constitutive characteristics of and/or responses by the distinct cell subpopulations present in mixed type cultures.     

p53 Accumulation Is a Prognostic Factor in Intestinal-Type Gastric Carcinoma but Not in the Diffuse Type

Background: The prognostic value of p53 nuclear accumulation in gastric cancer is still unclear, as shown by the discordant results still reported in the literature. In this study, we evaluated the correlation between p53 accumulation and long-term survival of patients resected for intestinal and diffuse-type gastric cancer.Methods: Eighty-three patients with carcinoma of the intestinal type and 53 patients with carcinoma of the diffuse type were included in the study. Immunohistochemical staining of the paraffin sections was performed by using monoclonal antibody DO1; cases were considered positive when nuclear immunostaining was observed in 10% or more of the tumor cells. Prognostic significance of different variables was investigated by univariate and multivariate analysis.Results: p53 positivity was found in 51.8% of intestinal-type and 50.9% of diffuse-type cases. No significant correlation between the rate of p53 overexpression and age, sex, tumor location, tumor size, depth of invasion, lymph node involvement, distant metastases, and surgical radicality was found in the two groups of patients. A statistically significant difference in survival rate was observed between p53-negative and p53-positive cases in the intestinal type (P < .05), confirmed by multivariate analysis (P < .005; relative risk = 3.09). On the contrary, no correlation with survival was found in diffuse-type cases according to p53 overexpression.Conclusions: These results suggest that the immunohistochemical detection of p53 accumulation is a useful indicator of poor prognosis in the intestinal but not in the diffuse type of gastric cancer, and are indicative of distinct molecular pathways and pattern of progression in the two histotypes.     

Antiamphiphysin antibodies are associated with various paraneoplastic neurological syndromes and tumors

BACKGROUND: Antiamphiphysin antibodies react with a 128-kd protein found in synaptic vesicles.They were first described in patients with paraneoplastic stiff-man syndrome and breast cancer, but studies suggest that they can also occur in patients with other tumors and neurological disorders. OBJECTIVE: To determine if antiamphiphysin antibodies are associated with various paraneoplastic neurological syndromes and tumors. PATIENTS AND METHODS: Of 2800 serum samples tested by routine immunohistochemical procedures on sections of paraformaldehyde-fixed rat brain for the detection of autoantibodies associated with paraneoplastic neurological syndromes, 5 were selected because of labeling suggestive of antiamphiphysin antibodies and subsequently confirmed by the results of Western blot analysis using recombinant amphiphysin protein. Controls consisted of 40 patients with various nonparaneoplastic neurological diseases; 101 patients with cancer but without paraneoplastic neurological syndrome; 9 patients with small cell lung cancer, anti-Hu antibodies, and paraneoplastic neurological syndrome; 3 patients with M2-type antimitochondrial antibodies but no neurological disorder; and 30 normal subjects. RESULTS: Of the 5 patients with antiamphiphysin antibodies, patient 1 had sensory neuronopathy, encephalomyelitis, and breast cancer; patient 2 had limbic encephalitis, and small cell lung cancer was detected in the mediastinum after 24 months of follow-up; patient 3 had encephalomyelitis and ovarian carcinoma; and patients 4 and 5 had Lambert-Eaton myasthenic syndrome and small cell lung cancer (patient 4 subsequently developed cerebellar degeneration). None of the 5 had stiffness. Two patients (Nos. 2 and 4) had antimitochondrial antibodies. The two patients (Nos. 4 and 5) with Lambert-Eaton myasthenic syndrome had antibodies directed against the voltage-gated calcium channel, and patient 2 subsequently developed anti-Hu antibodies. In the controls, antiamphiphysin antibodies were detected by Western blot analysis in 3 of 8 patients with anti-Hu antibodies, but in none of the other groups. CONCLUSIONS: These data indicate that antiamphiphysin antibodies are not specific for one type of tumor or one neurological syndrome and can be associated with other neural and nonneural antibodies. The simultaneous association of several antibodies in some patients suggests multimodal autoantibody production.     

Tachykinin NK(3)receptor involvement in anxiety

This study investigates the effects of intracerebroventricular injection of selective agonists and antagonists of tachykinin NK(3)receptor on performance of mice in the elevated plus-maze test. Mice were treated with either vehicle or 1, 10, 100 or 500 pmol of neurokinin B or senktide ([succinil-Asp(6), MePhe(8)]substance P(6-11), a natural and synthetic selective NK(3)receptor agonists, respectively. Other mice received similar doses of [Trp(7)beta-Ala(8)]NKA(4-10)or SR 142801 ((S)-N-(1-(3-(1-benzoyl-3-(3, 4-dichlorophenyl)-piperidin-3-yl)propyl)-4-phenyl-piperidin- 4-yl)-N-m ethylacetamide) tachykinin NK(3)receptor selective peptide and non-peptide antagonists, respectively. Senktide significantly increased the frequency of entries and the time spent in the open arms, which is compatible with an anxiolytic action. Neurokinin B treatment did not alter the plus-maze parameters in a significant way. Conversely, the NK(3)peptide antagonist [Trp(7)beta-Ala(8)]NKA(4-10), but not SR142801 non-peptide antagonist, showed a reverse effect, i.e. an anxiogenic profile of action, reducing the frequency and the time spent in the open arms. Co-injection of either senktide plus [Trp(7)beta-Ala(8)]NKA((4-10)), or senktide plus SR 142801, blocked the effects promoted by senktide, indicating that centrally-administered NK(3)receptor agonists and antagonists can modulate experimental anxiety.