Carboplatin and vindesine in advanced non-small cell lung cancer. A feasibility study.

Twenty-eight patients affected by advanced non-small cell lung cancer (NSCLC) were enrolled in a feasibility study evaluating toxicity and activity of carboplatin-vindesine combination chemotherapy, according to two different schedules. Fourteen patients were treated with carboplatin 350 mg/m2 monthly and vindesine 3 mg/m2 weekly for 5 doses, then every other week (schedule 1). The activity observed was promising with 3 partial remissions, but the toxicity was substantial, preventing full dose administration in 11 out of 14 patients. The subsequent 14 patients were treated with carboplatin 350 mg/m2 monthly and vindesine 3 mg/m2 on days 1 and 8 of each cycle. Activity was maintained with 4 partial remissions and toxicity was quite tolerable, allowing all patients to receive the planned treatment. The combination of carboplatin 350 mg/m2 on day 1 and vindesine 3 mg/m2 on days 1 and 8 seems active and well tolerated in advanced NSCLC patients and deserves further evaluation in a larger phase II study.     

Right heart chamber geometry and tricuspid annulus morphology in patients undergoing mitral valve repair with and without tricuspid valve annuloplasty

According to current recommendations, patients could benefit from tricuspid valve (TV) annuloplasty at the time mitral valve (MV) surgery if tricuspid regurgitation is severe or if tricuspid annulus (TA) dilatation is present. Therefore, an accurate pre-operative echocardiographic study is mandatory for left but also for right cardiac structures. Aims of this study are to assess right atrial (RA), right ventricular (RV) and TA geometry and function in patients undergoing MV repair without or with TV annuloplasty. We studied 103 patients undergoing MV surgery without (G1: 54 cases) or with (G2: 49 cases) concomitant TV annuloplasty and 40 healthy subjects (NL) as controls. RA, RV and TA were evaluated by three-dimensional (3D) transthoracic echocardiography. Comparing the pathological to the NL group, TA parameters and 3D right chamber volumes were significantly larger. RA and RV ejection fraction and TA% reduction were lower in pathological versus NL, and in G2 versus G1. In pathological patients, TA area positively correlated to systolic pulmonary pressure and negatively with RV and RA ejection fraction. Patients undergoing MV surgery and TV annuloplasty had an increased TA dimensions and a more advanced remodeling of right heart chambers probably reflecting an advanced stage of the disease.     

Late thrombosis of a Transcatheter aortic valve: the border between a proactive and reactive management

Background

Valve thrombosis – either biological or mechanical – is proved to increase patient’s morbidity and mortality. No consensus exist on the best management in such cases.

Case presentation

We report the case of a 69-year-old man presenting with a late thrombosis of a transcatheter aortic valve who was medically managed until he acutely worsened, developing myocardial ischemia and cardiogenic shock.

Conclusion

This unlucky case raises a word of caution about the safety of a reactive management.

     

Epidermal growth factor receptor expression and gene copy number in sinonasal intestinal type adenocarcinoma

Sinonasal intestinal type adenocarcinoma (ITAC) is a rare subtype of adenocarcinoma strongly associated with professional exposure to wood or leather dusts. It is an aggressive tumor, with an estimated 5-year survival of 40%. Herein, we report a series of 55 cases tested for epidermal growth factor receptor protein expression and epidermal growth factor receptor gene copy gains, through immunohistochemistry and fluorescence in situ hybridization. Eighteen tumors (32.7%) showed EGFR positivity, seven of which exhibited high expression levels of the receptor. The frequency of EGF-R overexpression was significantly higher in tumors from woodworkers (6 of 14, 42.8%) than in tumors from leatherworkers (2 of 21, 9.5%), or arising in subjects with no known occupational history (0 of 8) (P = 0.015, Pearson chi square). No correlation was found with other clinico-pathological parameters, including histologic subtype, stage, overall, and disease free survival. In cases with EGFR overexpression, fluorescent in situ hybridization analysis revealed disomy in three adenocarcinomas, chromosome 7 polysomy in two, and EGFR gene amplification in three. In conclusion, a subset of ITAC, mostly occurring in woodworkers, express high levels of EGFR and this is often associated with either gene amplification or chromosome 7 polysomy. EGFR targeted therapies could therefore be investigated prospectively in this group of tumors.     

Unfavorable experience with hypofractionated radiotherapy in unresectable lung cancer.

The use of a reduced number of large-sized fractions in radiotherapy (hypofractionation) is usually associated with poor therapeutic results and severe adverse effects, in accord with radiobiologic concepts. However by some authors unresectable lung cancer patients have been treated with hypofractionated radiotherapy with the main aim of "convenience". Result and damage rates are reported to be comparable to those of conventional treatment. In our experience, based on palliative irradiation of 86 advanced-stage, nonmicrocytoma patients, objective remission rates, subjective and performance status improvement, and survival overall were as poor as could be expected in this kind of presentation, with no striking impact of this treatment modality. Severe adverse effects were shown by a large proportion of cases involving skin and soft tissues of the chest wall (40%) and lungs (55.5%). The incidence of severe damage was in agreement with BED (biologic effective dose) values, differently from other experiences of radiotherapeutic management of advanced lung cancer with large fractions.     

An investigation into the adjuvanticity and immunogenicity of zein microspheres being researched as drug and vaccine carriers

We have determined whether zein microspheres could act as vaccine adjuvants i.e. increase the immune responses to co-administered immunogens. Ovalbumin (model antigen)-loaded zein microspheres, blank zein microspheres and ovalbumin solution were intramuscularly administered to mice and the sera antibody levels were determined by ELISA. Another group of mice was orally dosed with blank zein microspheres, and serum and faecal antibody levels were determined. As expected, negligible antibody titres were obtained with the ovalbumin solution. Surprisingly, intramuscular administrations of blank zein microspheres elicited high levels of serum IgG which bound to the ovalbumin antigen coated on ELISA microtitre plates. This indicated that anti-zein antibodies had been elicited by blank zein microspheres and that these antibodies were cross-reacting with ovalbumin antigen coated onto ELISA plates. Such cross-reactivity inhibited the determination of the adjuvant activity of zein microspheres, if any. Additional ELISA assays, where zein was used as the coating antigen, confirmed the generation of anti-zein antibodies by blank zein microspheres i.e. zein microspheres were immunogenic following intramuscular administration. Upon oral administration of blank zein microspheres, serum IgG levels remained low but intestinal IgA levels increased following booster doses i.e. systemic tolerance, but not mucosal tolerance, to oral zein particles was achieved. Zein microspheres were immunogenic when administered intramuscularly and orally.