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Biomedical subjects

A Mussi

Publications and source records attributed to A Mussi.

At least 73 records · Page 4Linked to original sources

Microvessel count predicts metastatic disease and survival in non-small cell lung cancer.

The growth of newly formed vessels, or neoangiogenesis, represents an important step in both physiological and pathological situations: in particular, tumour growth and metastasis require angiogenesis. Microvessel count (MC), which represents a measure of tumour angiogenesis, has been associated with metastatic spread in cutaneous, mammary, prostatic, head and neck, and early-stage lung cancer. In this study, the role of tumour angiogenesis as a prognostic indicator was examined in 253 primary non-small lung cancer (NSCLC) patients. Microvessels were counted by highlighting endothelial cells with anti-Factor VIII monoclonal antibody (Mab) in methacarn-fixed tumour samples. In univariat analysis, MC (P< 0.000001), sex (P=0.0036), histotype (P < 0.014), tumour status (P <0.007), and vessel invasion (P < 0.019) were significantly related to hilar and/or mediastinal nodal involvement. However, in the stepwise logistic regression analysis, MC (P<0.000003) retained the most important influence on nodal metastasis. The overall survival analysis calculated by the Kaplan-Meier method revealed that tumours with high MC ( > 25 vessels/field) were significantly associated with increased death risk (log-rank test P = 0.00067; Cox's test P = 0.00046; Gehan's Wilcoxon test P = 0.00108). In 94 patients, the development of metastatic disease during follow-up was significantly related to MC. Indeed, patients who developed metastasis during follow-up showed a higher MC, either as a dichotomous (P = 0.01) or as a continuous (P = 0.003) variable, than patients who had developed no metastasis at the time of the analysis. Moreover, in the stepwise logistic regression analysis, MC retained the most important influence on distant metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Epidermal growth factor receptor (EGFr) expression in non-small cell lung carcinomas correlates with metastatic involvement of hilar and mediastinal lymph nodes in the squamous subtype.

Epidermal growth factor receptor (EGFr) levels were evaluated in paraffin-embedded tumour specimens of non-small cell lung cancer (NSCLC) from 176 patients who underwent surgical resection. The EGFr expression was evaluated by immunocytochemical assay using a monoclonal antibody which recognises the external domain of the receptor. EGFr immunoreactivity was significantly higher in squamous than in non-squamous cell carcinomas (P = 0.0009). Hilar and/or mediastinal nodal involvement was found in 29 of 105 (27.4%) squamous cancers, and in this group of patients, the mean of EGFr positive cells was significantly higher than that of patients without nodal involvement (P = 0.01). No significant correlations were found between the expression of EGFr and other clinicopathological or biological parameters such as T-status, grading, proliferative activity. EGFR is suggested to represent a useful indicator of nodal metastasis in NSCLC.

Adenocarcinoma↗

Pre-operative chemotherapy for stage IIIa (N2) non-small cell lung cancer.

From June 1990 to December 1993, 36 patients were enrolled in a phase II study, aimed at determining the feasibility of surgery, patterns of disease recurrence and survival after neoajuvant chemotherapy in non-small cell lung cancer (NSCLC) stage IIIA-N2. Twenty-seven patients underwent invasive staging procedures (i.e. mediastinoscopy or needle biopsy). Two CHT schedules were used. Cisplatin (P) 90 mg/mq, day 1, mitomycin (M) 6 mg/mq, day 1, and vindesine (V) 5 mg/mq, days 1, 8, 15, were administered every 3 weeks for 3 cycles in the first 20 patients. The last 16 patients were treated with cisplatin (P) 90 mg/mq, day 1, mitomycin (M) 6 mg/mq, day 1, and vinorelbina 20 mg/mq, days 1, 8, 15. Thoracotomy was performed 15-20 days after haematological recovery in the objective-responders. Thirty-two patients were evaluable for response to CHT. The overall objective response (OR) rate was 78.1%. There were three complete (CR) (9.4%) and 22 partial responses (PR) (68.7%). The 25 patients with OR underwent radical surgery (16 pneumonectomies, one bilobectomy, seven lobectomies and one wedge resection). The only morbidity reported was a late broncho-pleural fistula (on post-operative day 37). There were three post-operative deaths in patients who underwent pneumonectomy: two due to an empyema following a broncho-pleural in fistula and one by pulmonary embolism. Histology was negative for the three CRs. Six patients with residual nodal involvement at surgery underwent radiotherapy. Relapse occurred in seven resected patients. Presently 14 patients are alive, all but one being disease-free, with a median follow-up of 30.5 months (15-47). Median survival was 31 months (5-47). Actuarial 3-year survival rate is 49%. Our results confirm the high response rate of CHT, as well as the feasibility and the overall low complication rate of both treatments (CHT and surgery).

Antineoplastic Combined Chemotherapy Protocols↗

Second primary lung cancer and relapse: treatment and follow-up.

During a 14-year period (1980-1993) second primary lung cancer or relapse was treated in 44 consecutive patients. Thirty-seven patients had synchronous (n = 18) or metachronous (n = 19) second primary lung cancer. Ten synchronous tumors were ipsilateral and treated contemporarily with five pneumonectomies, three lobectomies and two double wedge resections. The bilateral synchronous lesions (8 patients) were treated by staged bilateral thoracotomy (mean interval; 2 months). The first resection consisted of a lobectomy in six patients and wedge resection in two. The second one was a wedge resection in six patients and a lobectomy in two. In the metachronous presentation 15 patients (79%) were asymptomatic and detected by follow-up chest X-ray. In this group the first operation was a lobectomy in 12 patients, a wedge resection or segmentectomy in 6 and a pneumonectomy in 1. The second one was a wedge resection in nine patients, a lobectomy in six and completion pneumonectomy in four. Seven patients, all of them asymptomatic, had local recurrence from their primary lung cancer. The first lung resection was a lobectomy in five patients and a wedge resection in two. The second one was completion pneumonectomy in five patients and completion lobectomy in two. We had no operative death. The actuarial over-all 5-year survival rate after the second pulmonary resection for second primary lung cancer was 38.3% with a median survival time of 13.5 months. The synchronous presentation had a better survival than the metachronous one (46.2% and 25.9%), respectively). The actuarial overall 5-year survival rate for patients with relapse was 38.1% with a median survival time of 37 months. We may conclude that an aggressive surgical approach is safe, effective and warranted in patients with either a second primary lung cancer or relapse from their primary lung cancer. Moreover, for early detection of the second lesions, follow-up at a maximum of 6-monthly intervals should be continued for more than 5 years after the first resection.

Actuarial Analysis↗

Bcl-2 protein: a prognostic factor inversely correlated to p53 in non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) prognosis is strictly related to well-established clinicopathological parameters which have unfortunately become insufficient in the prognostic evaluation of this type of cancer. As p53 and bcl-2 gene deregulations are frequently involved in several types of epithelial malignancies, we investigated the Bcl-2 and p53 protein expression in 91 and 101 cases of NSCLC respectively. The expression was then compared with established indicators of prognosis and biological behaviour of the tumours. No relationship was observed between Bcl-2 and either clinicopathological or biological parameters such as histology, grading, tumour status, nodal metastasis and proliferative activity evaluated by scoring proliferating cell nuclear antigen expression and Ki-67 immunoreactivity. However, the mean Bcl-2 expression was significantly lower in patients who developed metastasis during follow-up or died of metastatic disease (P = 0.006 and P = 0.01 respectively). Moreover, survival probability was higher in patients who expressed the Bcl-2 protein (P = 0.0002). In contrast with this, p53 protein accumulation was observed in tumours with metastatic nodal involvement (P = 0.02) or in patients who developed metastasis during follow-up (P = 0.01), although no correlation was found between p53 expression and overall survival. An inverse relationship was also found between Bcl-2 and the anti-oncogene protein product p53 (P = 0.01). Thus, a high proportion of NSCLCs express p53 and Bcl-2 proteins and their expression may have prognostic importance.

Aged↗

Correlation of lesional skin corneometry values with serum E-selectin levels and disease severity in patients affected by plaque-type psoriasis: recovery after effective therapy.

Ten subjects with plaque-type psoriasis (5 females, 5 males, median age 47, range 20-71 years, median psoriasis area and severity index [PASI] score = 15.5, range 8.1-23.0) were observed before (week 0) and at the second and sixth week after starting treatment (PASI = 10.5, range 7.8-14.6; PASI = 8.5, range 1.6-11.6, respectively). At each of these times, the patients were evaluated for both lesional and unlesional skin corneometry and serum E-selectin values, previously shown to be increased in psoriatic subjects. At time 0, both the corneometry and the E-selectin values were significantly correlated with the PASI, infiltration and desquamation scores. As expected, the corneometry was statistically higher in the unlesional than in the lesional areas (p < 0.001). After therapy, the lesion improvement was related both to the PASI scores and E-selectin level decreases (from median levels of 15.5 to 8.5 and from 18 to 13.2 ng/ml, respectively, p < 0.05) as well as to the corneometric level increases (from a median value of 34.5 to 42, p < 0.05). Considering the data obtained at all of these times, significant correlations were found between the PASI scores, lesional skin corneometry and serum E-selectin levels. In conclusion, lesional corneometry seems to represent an objective alternative method for reliably monitoring psoriatic patients.

Adult↗

Soluble E-selectin and soluble tumour necrosis factor receptor (60 kD) serum levels in patients with psoriasis.

BACKGROUND: Increased tumour necrosis factor alpha has been found in psoriatic skin. This cytokine activates endothelial cells and induces the membrane E-selectin molecule (E-selectin or endothelial leucocyte adhesion molecule 1); the same cytokine is able to induce its own receptors. Since the soluble forms of E-selectin and tumour necrosis factor receptor (TNF-R, 60 kD) may be reliably measured in body fluids, these determinations have been performed in the sera of psoriatic patients. OBJECTIVE: To evaluate endothelial activation in psoriatic patients, sE-selectin has been determined in patient sera and compared with those of a control group. sTNF-R (60 kD) was also measured in the same samples. METHODS: Two commercially available enzyme immunoassay methods have been used to determine sE-selectin and sTNF-R (60 kD) in the sera of 19 patients with plaque-type psoriasis; 22 healthy subjects were used as controls. CONCLUSIONS: Significantly increased amounts of sE-selectin serum levels were found in psoriatic patients as compared to healthy controls. Moreover, a direct correlation between sE-selectin and PASI scores was observed. On the contrary, sTNF-R (60 kD) serum levels presented no increases. These data suggest that sE-selectin serum levels are a reliable marker of disease activity in psoriatic patients.

Adolescent↗

Glutathione conjugation with 1-chloro-2,4-dinitrobenzene (CDNB): interindividual variability in human liver, lung, kidney and intestine.

The rate of glutathione conjugation with 1-chloro-2,4-dinitrobenzene (CDNB) was measured in specimens of human liver (n = 93), sigmoid colon (n = 56), renal cortex (n = 67) and lung (n = 68). In the liver there was a weak but significant (r = - 0.247 p = 0.017) negative correlation between the activity of glutathione transferase and the liver donor's age. Such a correlation was not found in the renal cortex, lung and colon. In the renal cortex and in lung the rate of glutathione conjugation with CDNB was a little but significantly (p < 0.05) higher in women than men, whereas no sex-dependent difference was observed in the liver and colon. The distribution of glutathione transferase activity was polymorphic in the mucosa of colon and renal cortex of men but not in that of women. Smoking seems not to affect the glutathione conjugation rate with CDNB in lung. The activity of glutathione transferase was 2-, 6-, and 7-fold greater in liver than in the renal cortex, lung and colon, respectively. There was a large interindividual variability of the hepatic glutathione transferase activity, and because this variability, 15% of the population studied catalyzed the glutathione conjugation with CDNB at a rate similar to those of the renal cortex and duodenum. The subjects with low expression of the hepatic glutathione transferase should be more exposed to the effects of toxic and carcinogenic compounds.

Adult↗

[Pulmonary carcinoma and solitary intracranial metastasis: results of the combined surgical treatment].

Previous reports have shown the utility of combined lung and brain surgery in patients with a primary non small cell lung cancer (-NSCLC) and solitary brain metastasis. This paper reports our recent data with the aim to rationalize the indication of this surgical approach. Over a period of eighteen years (1975-1992), 50 patients with NSCLC and solitary brain metastasis underwent combined lung and brain surgery. Fifteen of these patients had a synchronous presentation while the remaining 35 had a metachronous presentation of lung cancer and single brain metastasis. There were no operative deaths and complete remission of neurological symptoms was obtained in 46 patients (92%). Actuarial overall five year survival was 16% with a median survival of 21 months. Age, gender, histology, T status, size and site of NSCLC, site and location of brain metastasis and the association with adjuvant therapy did not significantly affect survival. The variables that were associated with a significantly prolonged survival were type of lung surgery, N status and interval between the two operations. Patients with synchronous presentation had a five-year survival of 6.6%. By contrast the actuarial five-year survival of those patients with the diagnosis of brain metastasis after the removal of NSCLC was 19%. In this subset of patients those with N0 status and a median interval between lung and brain surgery longer than 14.5 months had a significantly longer survival. We may conclude that combined lung and brain surgery is recommended both for relieving neurological symptoms and for prolonging survival. This is particularly true in those patients with limited loco-regional involvement and a late single brain metastasis.

Adult↗

[The role of adjuvant therapy in the management of pN2 non-small-cell carcinoma of the lung].

Over a period of eleven years (1983-1993), the role of adjuvant chemo and/or radiotherapy was evaluated on 222 resected patients (pts) with NSCLC at atage IIIA(N2). All the patients underwent an attentive mediastinal limphoadenectomy. Fifty-five patients had a clinical mediastinal node involvement. 174 pts had a single mediastinal node station involved while 48 had two or more stations involved. One hundred and seventy-one pts (77%) underwent adjuvant therapies, consisting of citotoxic chemotherapy in 40 pts, radioterhapy in 97 pts and chemoradioterhapy in 34 pts. Follow-up lasted until September 1994. Overall 5-yr survival was 17.5%, the median being 17 months. Forty-two pts were, at that moment, still living (median 43.5 months, min 11-max 120) with 37 disease free. We verified a significant difference concerning survival among the three histologic types (p = 0.03), with the squamous achieving the best result (21.3% at 5-yrs). Surgical N2 had a better survival (20/5% at 5-yrs) than the clinical one (9%), (p = 0.01). In particular, if only one nodal station was involved, survival was 21.3% compared to 4.5% when metastases were present at two or more nodal station (p = 0.0001). Considering the level of mediastinal node involvement, the worst prognosis was linked to the carina node metastases (p = 0.02). Survival benefits were obtained by means of adjuvant therapies (20/2% vs 8.1%), (p = 0.0002). Analyzing all the pts, the best survival was achieved in those treated by surgery plus chemo-radiotherapy (32.4%), (p = 0.0001). As regards the squamous cell tumors, pts who underwent surgery plus radiotherapy had the best prognosis (24.2%), (p = 0.0026). Further, in non-squamous cell tumor, chemo-radiotherapy increased survival (45%), (p = 0.0001). At multivariate analysis, only the level of nodal involvement and the adjuvant therapy maintained their statistical significance. Our results prompt us to conclude that: 1) Squamous cell tumors and single nodal station involvement are linked to the best prognosis; 2) Squamous cell carcinoma should be treated by adjuvant radiotherapy; 3) Non-squamous tumors should undergo to chemo-radiotherapy; 4) Clinical N2 (according to our recent experience) may benefit from neoadjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

[Treatment of malignant pleural effusion by percutaneous catheter drainage and chemical pleurodesis].

From June 1989 to December 1991, 93 patients affected by malignant pleural effusion (MPE) were treated as out patients using a ultrasound (US) guided catheter drainage (10F Percuflex pig-tail catheter-Medi-tech@(PTC) and chemical pleurodesis. The PTC was positioned when the MPE had been diagnosed by X-ray and all the patients had undergone some thoracentesis (mean 3.2, range 2-6). We started a chemical pleurodesis when the MPE was inferior to 100cc/day injecting Epidoxorubicin (EDX 30 mg/mq) in the pleural space on alternate day for three administrations, and then, a lyophilized Corynebacterium Parvum (Wellcome strain CN 6134) (CBP 14 mg) on alternate day for two administrations. The complete response rate of this treatment was 90% (86 pt) with a mean treatment period of 32.9 days (range 12-62). Complete response was assessed as total resolution of pleural effusion. Side effects were short-term hyperpyrexia in 65 cases (69.8%) and pleurodynia in 15 cases (15.7%). Three patients (3.1%) were complicated by a pleural infection which was resolved in 1 case and became chronic in 2. These findings indicate that this technique is an adequate treatment for the control of MPE inducing a clinical and quality-life improvement.

Adult↗

[The diagnosis of primary lesions of the anterior mediastinum].

The treatment of anterior mediastinal tumours is often subordinated to histological diagnosis. Sometimes topographic, radiographic and clinical criteria are sufficient to indicate surgical therapy. From January 1988 to June 1992, 31 patients (40.7%) underwent immediate surgery, while 47 patients (59.3%) underwent fine needle aspiration and Trucut biopsy under ultrasonographic or computed tomographic guidance. Thirteen of these patients had also an anterior mediastinotomy according to McNeill-Chamberlain technique. In 36 patients it was possible to verify accuracy of diagnostic procedures comparing these specimens with surgical histological reports. Only 3 patients had minimal complications. No patients undergone anterior mediastinotomy had morbidity or mortality. Our reports show that transthoracic fine needle aspiration and Trucut biopsy have a diagnostic accuracy of 72% and 83% respectively in identifying malignant from benign lesions. These procedures are not adequate to detail diagnosis for tumours with pleomorphic pathologic characteristics (diagnostic accuracy of 39% and 75% respectively). This disagreement is due to false-positive results (one for fine needle aspiration and four for tru-cut biopsies), this discordance occurred in lymphomas and thymomas groups. Such correct diagnosis is very important either for frequency of these tumours either for different therapeutic approach: chemo-radiotherapy in lymphomas and surgery in thymomas.

Adolescent↗

Relationship between acute suppression of plasma renin activity and lymphocyte Na+:H+ exchange rate in young patients with borderline hypertension.

The participation of the cellular sodium content and renin-angiotensin-aldosterone system in the development of high blood pressure has been frequently suggested. To elucidate the role of a mechanism responsible for renal sodium reabsorption on the time-course of renin suppression, 16 young borderline hypertensive patients were studied by analyzing the relationship between the level of baseline activation of lymphocyte Na+:H+ exchange and the degree of plasma renin activity (PRA) suppression in response to saline loading. In the whole hypertensive population, a significant correlation (R = 0.64; p < 0.01) was found between the lymphocyte Na+:H+ exchange activity and the percentage degree of PRA suppression induced by saline loading. Urinary sodium excretion was enhanced in patients with lesser activation of lymphocyte Na+:H+ exchange and greater PRA suppression (3.5 +/- 5 vs. 2.4 +/- .1 umol/min/kg; p < 0.05). These findings suggest that a mechanism influencing renal sodium reabsorption as Na+:H+ exchange could also affect the control of plasma renin activity, and concur with the development of salt-sensitive high blood pressure.

Adult↗

Traumatic callosotomy.

In a 33 years-old epileptic woman with a traumatic impact to the vertex, clinical and radiological studies (skull X-R, CT and MRI) disclosed an extensive callosal section under the topography of the falx, associated to fronto-basal contusions. There was a significant improvement in the epileptic syndrome. No interhemispheric disconnection syndrome could be determined, which is compatible with the posterior regions of the corpus callosum having been spared. This is, to the best of our knowledge, the most extensive callosal injury documented by MRI to date.

Accidental Falls↗

Results and prognostic factors of surgery in the management of non-small cell lung cancer with solitary brain metastasis.

Between 1975 and 1988, 37 patients with resectable non-small cell lung cancer (NSCLC) and synchronous (within 1 month, n = 10) or metachronous (n = 27) solitary brain metastasis (SBM) underwent combined excision of their lesions. Overall 5-year and median survival were 30% and 27 months (range, 3 to 125+ months), respectively. Twenty-seven patients had a relapse, and their median disease-free interval (DFI) was 17.5 months (range, 1 to 108 months). The most frequent (78%, n = 20) site of first recurrence locally was either the ipsilateral thorax (n = 14) or brain (n = 6). In univariate analysis, age, primary tumor and lymph node status; tumor histology, size, and side; type of pulmonary resection; side and location of SBM; and onset of presentation did not affect survival and DFI. By contrast, the interval (less than or equal to versus greater than 12 months) between the two operations significantly affected survival (P = 0.0096) and DFI (P = 0.046). The DFI was also affected by the administration of adjuvant chemotherapy (AC) for the primary tumor (P = 0.02). Using the Cox model, AC was the most independent predictor of DFI. These data support the inclusion of surgery in the therapeutic armamentarium for patients with NSCLC and SBM.

Adult↗

Results of treatment and lessons learned from pathologically staged T4 non-small cell lung cancer.

Depending on the local extension of primary non-small cell lung cancer (NSCLC) and invaded T4 structure(s), 49 patients underwent complete (CR, n = 14) or palliative (PR, n = 13) resection of exploratory thoracotomy (ET, n = 22) between January 1982 and June 1988. Thoracic radiotherapy (TR) was given to all patients receiving PR (median dose, 43 Gy) and ET (median dose, 53 Gy). With a median follow-up of 44 months, overall 2- and 5-year survival was 25 and 5%, respectively. Patients undergoing ET plus TR had a significantly worse survival than those treated by CR (P = 0.041) and PR plus TR (P = 0.046). Only completely resected patients became long-term survivors (5-year survival, 29%) and significant predictors of their survival were previous weight loss, hemoglobin, and creatinine level, in univariate analysis, and previous weight loss in multivariate analysis. The site of initial treatment failure was mainly local for PR plus TR (85%) and systemic for CR (71%) and ET plus TR (86%). Presented results suggest that surgery might play a role for selected patients with T4 NSCLC, but advances in systemic and local therapy are necessary.

Antineoplastic Combined Chemotherapy Protocols↗

Possible prognostic value of pulmonary AH-locus-linked enzymes in patients with tobacco-related lung cancer.

As prognosis in breast cancer patients has been related to the AHH activity in their breast tissue, we have conducted a similar analysis on pulmonary drug metabolizing enzymes as prognostic markers for male lung cancer patients, primarily investigated for other reasons. A subset of 50 patients with lung cancer related to tobacco use, who had undergone thoracic surgery, was re-analyzed. The activity of parenchymal aryl hydrocarbon hydroxylase (AHH) and epoxide hydrolase (EH) that had been determined previously in homogenates of non-neoplastic surgical lung specimens, was used for comparisons of the patients' survival after surgery. When the crude mortality percentages at 1 and 2 years by AHH or EH activity, subdivided into quarters of the distribution, were calculated, a lower mortality was related to lower enzyme levels. Subjects in the 1st and 4th quarters of the distribution showed significant differences in their 1-year survival for AHH (p = 0.05) and EH (p less than 0.01) activities. This relationship could not be accounted for by age, cumulative lifetime smoking, recent or continuing smoking, stage or histological type of disease. Thus, the levels of pulmonary AHH and EH may have some prognostic significance in tobacco-related lung cancer.

Aryl Hydrocarbon Hydroxylases↗