BARD1: an independent predictor of survival in non-small cell lung cancer.

BRCA1 mRNA overexpression is correlated with poor survival in NSCLC. However, BRCA1 functions depend on the interaction with BARD1 for its stability, nuclear localization and ubiquitin ligase activity. Expression of alternatively spliced BARD1 isoforms that lack the BRCA1-interaction domain was found upregulated and correlated with poor prognosis in breast and ovarian cancer. These BARD1 isoforms are essential for proliferation of cancer cells in vitro. We investigated whether BARD1 isoforms are expressed in NSCLC. While in lung tissues from healthy controls BARD1 expression was undetectable on the mRNA level and protein level, we found two novel isoforms in addition to previously identified mRNAs expressed in all NSCLC samples tested. Furthermore, the pattern of BARD1 isoform expression was similar in tumor and morphologically normal peri-tumor tissues, and only one novel isoform π was specifically upregulated in tumors. Immunohistochemistry revealed that all 100 NSCLC cases tested expressed isoform-specific BARD1 epitopes, while BARD1 expression was undetectable in biopsies from healthy controls. Statistical analysis showed that the expression of epitopes PVC and WFS, present on isoform π, or epitope WFS alone, expressed on isoforms π, κ and ß, were significantly correlated with decreased patient survival. These findings were corroborated in a mouse model of chemically induced lung cancer. Immunostaining of mouse tumors showed that BARD1 epitopes PVC and WFS were specifically upregulated in invasive, but not in confined lung tumors. Thus, BARD1 isoforms might be involved in tumor initiation and invasive progression and might represent a novel prognostic marker for NSCLC.

Dose-intense phase II study of weekly cisplatin and epidoxorubicin plus medroxyprogesterone acetate and recombinant interleukin 2 in stage IIIB-IV non-small cell lung cancer.

The purpose of the study was to evaluate the effectiveness in terms of response rates, toxicity and survival of the combination chemotherapy regimen cisplatin and epidoxorubicin (epirubicin) including medroxyprogesterone acetate (MPA), recombinant IL-2 (rIL-2) and antioxidants in patients with advanced (stage IIIB-IV) non-small cell lung cancer (NSCLC). Thirty-three chemotherapy-naive patients with NSCLC were enrolled in the study and 30 of them were evaluable. The mean age of the patients was 61 years. Twenty (66.7%) out of 30 patients were >or=60 years, and 5 (16.7%) patients were >or=70 years. The ECOG performance status was 0 to 1 in 30 patients and 2 in 3 patients. Twenty-six patients (78.8%) had stage IIIB disease and 7 (21.2%) had stage IV; histology was mainly squamous cell carcinoma (72.7%). The treatment consisted of cisplatin 40 mg/m2/week and epirubicin 40 mg/m2/week both intravenously on day 1, rIL-2 1.8 MIU/day subcutaneously, MPA 1 g/day orally, alpha-lipoic acid 300 mg/day orally and N-acetyl cysteine 1.8 g/day orally. The treatment was administered for 6 weeks. Patients with a complete response (CR), partial response (PR) or stable disease (SD) continued the treatment, according to response re-evaluation, until 15 weeks. The present study reports the results of 6, 9, 12 and 15-week treatment. After 6 weeks, 30 patients were assessable for response: no CR was observed, a PR was achieved in 15 patients (50%; ORR 50%). After 15 weeks, 1 CR and 8 PR were observed (ORR 30.0%). The median follow-up period was 13 months. The median duration of response was 9 months. The median overall survival (OS) was 15 months. The one-year survival rate was 55.8%. The median progression-free survival (PFS) was 10 months. The toxicity was, as expected, mainly hematologic: neutropenia was the most significant symptom. The non-hematologic toxicity was quite low. Therefore, the treatment's toxicity was quite acceptable. There was no toxic death. The 30.0% ORR, the 15 month OS and the 10 month PFS obtained in this study are comparable with those observed with cisplatin plus epirubicin (ORR 39-54%) in phase II studies and in a previous phase III study (ORR 33%, OS 10.5 months). Moreover, the toxicity was acceptable and it was mainly hematologic. Serum levels of proinflammatory cytokines significantly decreased after treatment.

Radiofrequency ablation in the management of advanced stage thymomas: a case report on a novel multidisciplinary therapeutic approach.

We describe in this report a case of successful radiofrequency ablation of an unresectable stage III-type B3 thymoma, and we discuss the role of this novel approach in the management of patients with advanced stage thymoma. The patient, a 59-year-old Caucasian male underwent neoadjuvant chemotherapy with only a slight reduction of the mass. Subsequently, an explorative sternotomy and debulking were performed; before closing the thorax, radiofrequency ablation of the residual tumor was carried out and a partial necrosis of the mass was achieved. A further percutaneous radiofrequency ablation was performed subsequently, obtaining complete necrosis of the lesion. Successively, the patient underwent adjuvant radiotherapy. As a result of this multidisciplinary treatment, complete and stable response was obtained. It is hard to say which of the single treatments had the major impact on cure; nevertheless, the results obtained suggest that radiofrequency ablation must be taken into account for the treatment of advanced stage thymomas, and its effectiveness must be further assessed in future studies.

[Pericardial cyst with intracystic hemorrhage. A case report and review of the literature]. / Cisti pericardica complicata da emorragia intracistica. Descrizione di un caso e revisione della letteratura.

Pericardial cysts are rare benign intrathoracic lesions, more often located in the right rather than in the left cardiophrenic angle. At echocardiography, they appear as echolucent unilocular structures, which are in contact with the pericardium. They contain a clear water-like fluid and, thus, are referred to as "spring water cysts". They are usually discovered incidentally in asymptomatic patients. Sometimes they can cause symptoms (dyspnea, chest pain, dysphagia, cough), depending on their dimensions and location, or severe complications such as cardiac tamponade. Asymptomatic cases are managed conservatively with a close follow-up, being surgical excision recommended only in symptomatic patients. Actually, the treatment options include excision via thoracotomy, video-assisted thoracoscopic surgery, and percutaneous echo-guided aspiration. We describe the case of a patient for whom the echocardiographic follow-up allowed to disclose intracystic hemorrhage, leading to surgical treatment before the patient became symptomatic.