Prognostic role of the PET parameter maximum standardized uptake value in non small cell lung cancer: analysis in tumour of diameter ≥ and <25 mm.

AIM: The aim of this study was to evaluate whether the primary tumour maximum standardized uptake value (SUV(max)) plays an independent prognostic role in patients with non small cell lung cancer (NSCLC) and whether this role is limited by partial volume effect (PVE) and motion artefacts. METHODS: One hundred and fifty-three consecutive patients underwent PET exam, surgery (R0 resection) and follow-up (mean 20.3; range 6-44.8 months). Correlation with Disease Free and Overall Survival (DFS, OS) was evaluated in the entire population for: SUV(max), clinical and histopathological features and pathological stage. To evaluate the PVE and motion artefacts' interferences on SUV calculation, the correlation between SUV(max) and DFS/OS was also calculated in the groups of patients with tumour diameter ≥ and < than 25 mm (group A and B, respectively). RESULTS: In the entire population only TNM and SUV(max) resulted correlated with DFS/OS. However, SUV(max) was significantly correlated with DFS/OS in group A but not in group B. Furthermore, only in the group of patients with primary tumour diameter ≥ 25 mm (group A), tumour diameter, tumour histotype, and tumour necrosis resulted significantly related with SUV(max) at both uni and multivariate analysis. CONCLUSION: TNM together with SUV(max) could be useful in giving a better prognostic stratification of patients with NSCLC; however technical limitations in the SUV calculation must be taken into account in patients with tumour diameter <25 mm.

CT features of solitary fibrous tumour of the pleura: experience in 26 patients.

PURPOSE: The purpose of this study was to identify the typical computed tomography (CT) features of solitary fibrous tumours of the pleura (SFTP) and determine which findings would allow confirmation of the pleural origin or benign behaviour of the tumour. MATERIALS AND METHODS: Twenty-six preoperative CT studies of the chest (23 enhanced and 14 unenhanced) were retrospectively reviewed. RESULTS: Up to 50% of SFTP were larger than 10 cm. At unenhanced CT, they showed homogeneous attenuation in 5 cases (35.7%) and inhomogeneous attenuation in 9 (64.3%). At contrast-enhanced CT, they were inhomogeneous in 21 cases (91.3%), with geographic pattern (61.9% of cases), serpiginous linear areas of enhancement (intralesional vessels) (23.8%), rounded (52.4%) or linear (33.3%) areas of low attenuation (necrosis). CONCLUSIONS: Depending on location, size and histological features, SFTP may produce a large spectrum of findings. Typical CT features of small SFTP were well-defined margins and smooth contours, homogeneous attenuation and right or obtuse angles with the pleura. Larger lesions were characterised by well-defined margins and lobulated contours, geographic pattern in enhanced CT scans, acute angles or smooth tapering margins with the pleura.

Prevalence of adrenal incidentaloma in a contemporary computerized tomography series.

Adrenal incidentalomas, defined as masses discovered incidentally during imaging investigation of non-adrenal disorders, have become a rather common finding in clinical practice. The prevalence is not well characterized and varies among studies. The aim of the present study was to perform a prospective evaluation of the prevalence of adrenal incidentalomas among subjects undergoing computerized tomography (CT) scan of the chest in a screening program of lung cancer (Tic TAC study) in Piedmont, a region of Northwestern Italy. This evaluation included 520 subjects (382 males and 138 females, aged between 55-82 yr), referred to our hospital from April to December 2001. Twenty-three patients with adrenal masses were identified: 21 adrenal adenomas, 1 myelolipoma, and 1 metastasis of lung cancer. Therefore, the overall prevalence of adrenal lesions was 4.4%, and that of benign adrenal masses was 4.2%. This prevalence is higher than those found in previous CT scan series reported in the literature, probably because of the use of high-resolution CT scanning technology. Another factor that influenced our results is that subject age is skewed towards the decades characterized by a greater occurrence of adrenal masses. The outcome of this study confirms that we are presently able to identify incidentally discovered adrenal masses more often than in early years and that the prevalence of adrenal incidentalomas on CT images is approaching that of autopsy series. The present study provides a reliable estimate of the prevalence of adrenal incidentaloma with currently used CT scanners. Notwithstanding that our subjects were at increased risk of lung cancer, the rate of adrenal metastases was low. We think that the present results can be generalized even if we may disclose the lack of histological diagnosis.

Three-year findings of an early lung cancer detection feasibility study with low-dose spiral computed tomography in heavy smokers.

BACKGROUND: Low-dose spiral computed tomography (sCT) showed a four-fold increase in the detection rate in high-risk subjects and a higher percentage of stage I lung cancer in comparison with chest X-ray. However, there is a considerable discrepancy among studies in the percentage of lung nodules, overall lung cancer and stage I detection rate. SUBJECTS AND METHODS: From April to December 2001, 520 asymptomatic volunteers aged >or=55 years with a history of cigarette smoking >or=20 pack-years and no previous cancer were enrolled to receive an annual sCT of the chest for five consecutive years. RESULTS: Seventy three per cent were male, median age was 59 years and 91% were current smokers. At baseline, nodules >or=5 mm were detected in 114 (22%) undergoing sCT; the size of lung nodules ranged from 5 to 9.9 mm in 81.5% of the cases. Five (1%) cases of lung cancer were detected. In two additional cases a pathological diagnosis of atypical adenomatous hyperplasia was made. Three new cases of lung cancer were detected in the second and third year of the study. One interval case was detected during the third year. CONCLUSIONS: Despite some promising data, convincing evidence from ongoing randomized trials is needed to support the routine use of sCT as a recommended tool for screening of lung cancer.

Management of neuroendocrine differentiated breast carcinoma.

In neuroendocrine differentiated breast cancer, the coexistence of both neuroendocrine and exocrine components may raise some uncertainty about the best clinical approach to adopt. We describe the case of a patient with neuroendocrine differentiated breast carcinoma with lung metastases, who experienced a partial response after epirubicin chemotherapy. During subsequent maintenance hormone therapy with letrozole, plasma chromogranin A was consistently elevated even though CT showed disease stabilization. The patient was scheduled for surgery and radical resection was performed. She is still alive and disease free after over 37 months. Anthracyclines are effective in the treatment of neuroendocrine differentiated breast carcinoma. Surgical resection of metastatic lesions can lead to a durable disease-free status. Serial evaluation of circulating chromogranin A is useful in the follow-up of these patients.

Multimodal management of stages III-IVa malignant thymoma.

PURPOSE: The optimal therapy for locally advanced malignant thymoma is controversial. We review our experience with a multimodal approach in 63 consecutive cases. PATIENTS AND METHODS: Forty-three patients had stage III and 20 stage IVa disease. Surgery with radical intent was initially performed in 30 cases, while 33 cases not amenable to radical surgery underwent neoadjuvant treatment (radiotherapy in 8 and chemotherapy in 25) before surgical reassessment. All patients, whether or not surgically resected, received radiation therapy. RESULTS: Radical resection (RR) was performed in 20 patients ab initio (all stage III) and in 12 patients after neoadjuvant treatment (eight stage III and four stage IVa). With the addition of patients radically operated with neoadjuvant treatment, the radical resection rate increased from 46 to 65% in stage III patients, and from 0 to 20% in those with stage IVa disease, respectively. Radical surgery was associated with longer progression free survival and overall survival according to both univariate analysis ( P< 0.001 and P<0.01, respectively) and multivariate analysis after adjustment for age, gender, histology and disease stage ( P<0.001 and <0.02, respectively). Progression free survival (median 56.9 months) was slightly lower in patients undergoing radical surgery after neoadjuvant approaches than in those radically resected ab initio (median not achieved), but overall survival (median not achieved) was similar in both groups. Subtotal surgical resection promoted complete response to subsequent radiation therapy. This condition significantly correlated with a better outcome. CONCLUSIONS: Complete surgical resection is an independent prognostic parameter in locally advanced thymoma treated with a multimodal approach. Preoperative treatment to increase the complete resection rate could improve the overall survival of these patients.

Epidermal growth factor receptor overexpression correlates with a poor prognosis in completely resected non-small-cell lung cancer.

BACKGROUND: We designed a prospective study to test epidermal growth factor receptor (EGFR) expression by immunohistochemistry (IHC) in resected stage I-IIIA non-small-cell lung cancer (NSCLC) and to correlate overexpression with survival. PATIENTS AND METHODS: EGFR expression was evaluated in 130 consecutive NSCLC patients after radical surgery (60 squamous cell carcinomas, 48 adenocarcinomas, 22 large cell carcinomas: stage I, 41 (31%); stage II, 37 (29%) and stage IIIA, 52 (40%). RESULTS: Overall, 101 of 130 (78%) specimens expressed EGFR, and with a cut-off value of 10% positive cells 48 cases (37%) were classified as positive. At univariate analysis, EGFR was significantly more expressed in stage III (50%) than stage I (20%) and stage II (25%) (P <0.03). No correlation with histotype was found. After a median follow-up of 84 months, both median survival time (18 versus 50 months), 2-year (43% versus 70%) and 5-year (31% versus 46%) survival rates of positive cases were significantly lower than negative ones [P <0.001; hazard ratio 1.96; 95% confidence interval (CI) 1.16-3.30]. At the multivariate analysis, EGFR overexpression and stage emerged as independent factors for cancer-related mortality. CONCLUSION: In patients with radically resected stage I-IIIA NSCLC, EGFR overexpression predicts shorter survival, thus representing a valuable prognostic factor.

Primary chemotherapy with adriamycin, cisplatin, vincristine and cyclophosphamide in locally advanced thymomas: a single institution experience.

From 1990 to 1997, 16 consecutive patients with stage III and IVa invasive thymoma were treated in a single institution with primary chemotherapy consisting in adriamycin (40 mg m(-2)), cisplatin (50 mg m(-2)) administered intravenously on day 1, vincristine (0.6 mg m(-2)) on day 2 and cyclophosphamide (700 mg m(-2)) on day 4 (ADOC). The courses were repeated every 3 weeks. The aim was to evaluate the impact of this cytotoxic regimen with respect to response rate, per cent of patients radically resected, time to progression and overall survival. Two complete responses (one clinical and one pathological) and 11 partial responses were observed (overall response rate 81.2%); two patients had stable disease and one progressed. Toxicity was mild as only two patients developed grade III/IV neutropenia and one patient grade III nausea/vomiting. Nine patients were radically resected (five out of ten with stage III, and four out of six with stage IVa). Median time to progression and overall survival was 33.2 and 47.5 months respectively. Three patients were alive and disease free after more than 5 years. The ADOC scheme is highly active and manageable in the treatment of locally advanced thymoma. As a preoperative approach it should be offered to patients not amenable to surgery or to those surgically resectable but with a great deal of morbidity.

Gas exchange threshold as a predictor of severe postoperative complications after lung resection in mild-to-moderate chronic obstructive pulmonary disease.

Low exercise capacity is considered predictive for postoperative complications or death after thoracic and general surgery. However, in recent literature no agreement has been found about the predictive cut-off values for preoperative exercise parameters. The aim of this work was to investigate whether peak oxygen consumption (V'o2) and noninvasive anaerobic threshold (AT) determined by gas exchange threshold (GET) can be reliable preoperative predictors of mortality and morbidity after lung resection in patients with mild-to-moderate (forced expiratory volume in one second (FEV1) > 50% predicted) chronic obstructive pulmonary disease (COPD). Fifty tour COPD patients were studied before lung surgery: 12 had severe complications, 16 had mild and 26 had no complications. Peak V'O2 sensitivity and specificity in predicting severe postoperative complications were 41.6% and 95.5% respectively (using 75% of the predicted value as cut-off), while for GET they were 91.6% and 97.6% respectively (using 14.5 mL.kg-1.min-1 as cut-off value). Only one patient (3.5%) with a peak V'O2 > 20 mL.kg-1.min-1 suffered severe complications. On the other hand 11 out of the 26 patients (42.3%) with peak V'O2 < 20 mL.kg-1.min-1 had serve complications. In patients with peak V'O2 < 20 mL.kg-1.min-1, 11 out of 12 (91.6%) with a GET < or = 14.5 mL.kg-1.min-1 suffered severe complications, whereas 15 out of 15 (100%) with a GET > 14.5 mL.kg-1.min-1 showed no or mild complications. In conclusion, peak oxygen consumption values > 20 mL.kg-1.min-1 can be considered a safe upper cut-off limit for pulmonary resection. In patients with a peak oxygen consumption value < 20 mL.kg-1.min-1, gas exchange threshold determination can improve significantly the predictivity of a cardiopulmonary test for severe complications and must be routinely considered.

Post-intubation tracheal rupture. A report on ten cases.

OBJECTIVE: We wanted to evaluate the role of surgical and conservative therapy in the treatment of post-intubation tracheal rupture. METHODS: A retrospective study was performed on 10 consecutive patients (9 women and 1 man) treated over a 7-year period. RESULTS: A tracheal rupture following double-lumen intubation was recognized and repaired at the time of lobectomy for lung cancer. Five patients with rents ranging from 2.5 cm to 5 cm underwent primary repair through a cervical collar incision (n = 3) or right posterolateral thoracotomy (n = 2). Three patients had small tears (about 1 cm in length) and were treated conservatively. Tracheostomy was performed in one patient with a 1.5-cm long laceration and extensive subcutaneous emphysema. Results were uniformly good. CONCLUSIONS: Early surgical repair is the preferred treatment for most patients with post-intubation tracheal ruptures. Conservative treatment may be a viable alternative for patients with small rents, in the absence of gross air leak, or for those judged unsuitable for surgery. The role of tracheostomy is limited by its potential for late sequelae.

Adenosine analogs inhibit acetylcholine release and cyclic AMP synthesis in the guinea-pig superior cervical ganglion.

The ability of adenosine agonists to modulate the electrically evoked release of acetylcholine (ACh) from [3H]choline preloaded guinea-pig superior cervical ganglia (SCG) was investigated. The adenosine A1-receptor selective agonist N6-cyclohexyladenosine (CHA) and 2-chloroadenosine (2-CADO) inhibited the evoked transmitter release, the effect being reversed by the A1-receptor selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), and by sulmazole (SUL), which blocks both the A1-receptor and the adenylate cyclase inhibitory regulator Gi. In whole ganglia, CHA decreased both the basal and the forskolin (FSK)-stimulated cyclic AMP synthesis. The latter effect was again prevented by the A1 antagonist DPCPX. These results are compatible with the existence, in the guinea-pig SCG, of adenosine A1-receptors, part of which are located on the presynaptic nerve terminals mediating an inhibition of ACh release.

[The use of metal vascular prosthesis in the palliative treatment of neoplastic esophago-gastric stenosis]. / Impiego di protesi metalliche vascolari nel trattamento palliativo delle stenosi neoplastiche esofago-gastriche.

The paper reports the authors' experience regarding the use of expandable metal prostheses designed for vascular stenoses but adapted for unoperable esophago-gastric stenoses. Their first impressions are very positive so much so that they affirm that these prostheses are close to being ideal since they are flexible and have an insertion diameter of 3 mm which does not therefore require dilatation. As a result: 1) they involve limited trauma to the patient; 2) reduce the risk of perforation to virtually zero. Moreover: 3) they can be inserted in twisted and angled stenoses and in esophaguses with difficult access due to axial deviations and restriction of the upper cervical aperture; 4) they function well even in notoriously "difficult" sections such as the cardia and esophago-jejunal anastomoses; 5) the unfastening system is easy and rapid. On the strength of these characteristics the authors suggest that these prostheses should be used in an outpatient setting, as occurred in the case of the last of the 10 patients treated, and even at a preoperative stage in preparation for resective surgery so as to preserve normal oral feeding. The structure of these prostheses renders them contraindicated for use in stenoses associated with fistulas in air paths and requires an evaluation of long-term results to verify the incidence with which the following occur: 1) tumoral growth between the mesh; 2) food obstruction; 3) hemorrhage due to compressive necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Neoadjuvant chemotherapy with adriamycin, cisplatin, vincristine and cyclophosphamide (ADOC) in invasive thymomas: results in six patients.

BACKGROUND: Locally advanced malignant thymomas are usually radically resectable in about 60% of stage III but hardly ever in stage IVA. Neoadjuvant chemotherapy followed by surgery could improve both resection rate and curability. Cisplatin containing regimens have repeatedly been found to be highly active in advanced disease, with overall response rates ranging from 80%-90%. PATIENTS AND METHODS: 3 patients with stage III and 3 with stage IVA invasive thymomas, according to Masaoka staging, entered the study. Histology was: lymphoepithelial 4 cases, epithelial 2 cases. 4 cycles of the ADOC scheme--Adriamycin (40 mg/sqm), cisplatin (50 mg/sqm) on day 1, vincristine (0.6 mg/sqm) on day 2, and cyclophosphamide (700 mg/sqm) on day 3, every 21 days--were administered to 5 patients, while 1 patient received 5 cycles. RESULTS: 5/6 patients (83.3%) attained partial responses and underwent radical surgery followed by two further ADOC cycles. The disease-free intervals were 5+, 6+, 15+, 16+, 26+ months. One patient showing stable disease at the end of the fifth cycle was referred to radiotherapy. Toxicity was tolerable: grade III (WHO) nausea/vomiting and leukopenia grade III occurred in 2 patients each. CONCLUSIONS: These results suggest that the ADOC scheme is active as a neoadjuvant approach in invasive thymoma stages III and IVA, rendering possible radical resectability in 83% of patients.

Prognostic significance of Ki67 labelling in resected non small cell lung cancer.

One hundred and eleven tissue samples of primary non small cell lung cancer obtained from patients undergoing radical surgery for resectable disease were investigated for the presence and distribution of Ki67 related antigen using an immunohistochemical technique, as a marker of the proliferative activity of the tumour. No correlation was seen between Ki67 expression and clinico-pathological variables (sex, age, histology, grading and pTNM stage) but disease-free survival was significantly lower in patients with higher Ki67 score (> 25% positive cells) at diagnosis (P < 0.03). Growth fraction evaluated by Ki67 labelling may provide a complementary prognostic parameter in non small cell lung cancer.

Sulmazole effects on PGE2 and D-Ala2-Met-enkephalinamide modulation of cyclic AMP synthesis and neurotransmitter release in a sympathetic ganglion.

In the guinea-pig superior cervical ganglion, the Gi blocking agent sulmazole enhanced the basal and prostaglandin E2-induced stimulation of cyclic AMP synthesis but had no effect on the prostaglandin-dependent inhibition of acetylcholine release. On the contrary sulmazole counteracted the inhibitory effect of D-Ala2-Met-enkephalinamide both on cyclic AMP formation and acetylcholine release. Moreover sulmazole eliminated the supra-additive effect of the combination of prostaglandin + opiate on cyclic AMP synthesis. The presence of a Gi-coupled opiate receptor at the pre-and postsynaptic levels is suggested.

Detection of multidrug resistance associated P-170 glycoprotein in previously untreated non small cell lung cancer.

Samples of Non Small Cell Lung Cancer (NSCLC) and normal bronchial tissue obtained in patients submitted to radical surgery and without previous exposure to cytotoxic drugs were investigated for the expression of P-170 glycoprotein using C-219 monoclonal antibody and an immunohistochemistry technique. In normal bronchial tissue the immunostaining was confined to the lumenal surface of the epithelium. Fifteen out of 86 NSCLC had more than 1/4 of examined cells positive for P-170 glycoprotein, but the heterogeneity of the expression ranged from rare scattered cells to a positive pattern for nearly all cells considered, without any relationship with pathologic and clinical prognostic variables.

Receptor-mediated supra-additive activation of guinea pig superior cervical ganglion adenylate cyclase: role of Mn2+ ions and calmodulin.

The effects of Mn2+ and calmodulin were studied on the basal and agonist-modulated adenylate cyclase activity of the guinea pig superior cervical ganglion. The divalent cation strongly stimulates the basal and agonist-modulated enzyme in a concentration-dependent manner. Moreover, in the presence of Mn2+ the inhibitory effects of "high" GTP concentrations and of D-Ala2-Met-enkephalinamide on adenylate cyclase are eliminated, while the stimulation exerted by prostaglandin E2 and the supra-additive activation of the enzyme by the combination of the two drugs are unaffected. In EGTA-washed, calmodulin-depleted membrane preparations, Mn2+ still activates the cyclase but the enkephalin inhibition and the superactivation of the enzyme induced by the combination of opiate and prostaglandin are lost, both in the absence and in the presence of the cation. Reconstituting the depleted membranes with exogenous Ca2+/calmodulin fully restored the enzyme responsivity to the combination and, partially, to the enkephalin. The findings suggest the existence in the guinea pig superior cervical ganglion of both the calmodulin-sensitive and differently regulated calmodulin-insensitive adenylate cyclase.