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Introduction: A pathologic grading system (PGS) for malignant pleural mesothelioma (MPM) is warranted to better identify different risk categories of patients, plan therapeutic options, and activate clinical trials., Methods: A series of 940 patients with MPM (328 in a training set and 612 in a validation set) that was diagnosed between October 1980 and June 2015 at the participant institutions was retrospectively assembled. A PGS was constructed by attributing to each histologic parameter, independent at multivariate analysis with excellent reproducibility (κ > 0.75), different scores based on the increase in corresponding hazard ratios. The relevant PGS score thus ranged from 0 to 8 points for individual patients with MPM., Conclusions: The PGS was constructed by taking into consideration the histological subtyping of MPM (epithelioid/biphasic = 0 points; sarcomatoid = 2 points), necrosis (absent = 0 points versus present = 1 point), mitotic count per 1 mm 2 (cutoffs as follows: 1-2 = 0 points, 3-5 = 1 point, 6-9 = 2 points, or ≥10 = 4 points), and Ki-67 labeling index based on 2000 cells (<30% = 0 points versus ≥30 = 1 point), all of which are independent factors in both patient sets after adjustment for stage and age at diagnosis. No heterogeneity was seen across the validation centers (p = 0.19). Epithelioid/biphasic MPM patterning and biopsy versus resection did not affect survival, whereas the PGS outperformed mitotic count and Ki-67 LI in both the training (area under the curve receiver operating characteristic = 0.76) and validation sets (area under the curve receiver operating characteristic = 0.73) (p < 0.01). Patient survival progressively deteriorated from a score of 0 (median times of 26.3 and 26.9 months) to a score 1 to 3 (median times of 12.8 and 14.4 months) and a score of 4 to 8 (median times of 3.7 and 7.7 months) in both sets of patients, with the hazard ratio for a 1-point increase in score being 1.46 (95% confidence interval: 1.36-1.56) in the training set and 1.28 (95% confidence interval: 1.22-1.34) in the validation set (after adjustment for age and [when available] tumor stage). The PGS was effective even in subgroup analysis (epithelioid, biphasic, and sarcomatoid tumors)., Discussion: A simple and reproducible multiparametric PGS effectively predicted survival in patients with MPM., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Primary chemotherapy as part of multidisciplinary approach is the established treatment for inoperable stage III B breast cancer. The primary endpoints were conversion to operable disease and feasibility of conservative surgery (breast-conserving therapy: BCT); secondary were clinical and pathological complete response rate, local and distant control and safety of the primary regimen., Methods: Between 1998 and 2001, 40 inoperable breast cancer patients < or =60 years, 72% T4abc and 28% T4d, received 6 cycles of primary PEV dose-dense regimen: cisplatin 50 mg/m2, epirubicin 100 mg/m2 and vinorelbine 25 mg/m2, i.v. (q 14). Modified radical mastectomy (MRM) or BCT was performed, followed by adjuvant chemotherapy, radiotherapy and hormone therapy., Results: All patients were converted to operable disease, and BCT was feasible in 24% of T4abc patients. After a median follow-up of 84 months (range 58-96), local and distant relapses were 7.5% (0% in BCT ) and 25% (25% in BCT), respectively. Clinical response was 80% (clinical complete response [cCR]: 20%); pathological complete response (pCR) was 40% in breast, 50% in axilla (pLN0); 32% both in breast and axilla. Neutropenia (G4, 30%), leukopenia (G4, 25%), alopecia (G2, 100%), nausea and vomiting (G4, 20%) were the most common toxicities., Conclusions: The PEV dose-dense regimen seems to be highly effective in terms of resectability and pCR. Toxicity, mainly hematological, was acceptable. Successful BCT is feasible, in selected patients, without compromising local and distant control., (Copyright 2007 S. Karger AG, Basel.)

Aims and Background: Urothelial cancer is a chemosensitive disease. However, cisplatin or anthracycline-containing regimens still provoke severe toxicity mainly due to reduced renal function and poor performance status (PS) of patients. The aim of this study was to verify the possibility of substituting carboplatin for cisplatin and epirubicin for doxorubicin in the M-VAC regimen in order to reduce toxicity and improve patient tolerance., Methods: Twenty patients with advanced urothelial tract tumors were treated with a chemotherapeutic regimen composed of methotrexate (30 mg/mq iv on days 1, 15, 22), vinblastine (3 mg/m2 iv on days 2, 15, 22), epidoxorubicin (35 mg/m2 iv on day 2) and carboplatin (250 mg/m2 iv on day 2) every four weeks (M-VECA). All patients had bidimensionally measurable disease., Results: Of the 18 evaluable patients, 3 (17%) obtained complete response and 7 (33%) obtained partial response (50% overall response). The median duration of response was 50 weeks (range, 28-88+). Grade III-IV toxicity (leukothrombocytopenia and mucositis) was observed in 20% of cases. Nevertheless, recovery was prompt in all but 2 patients with poor PS who died of nadir sepsis., Conclusions: M-VECA was an effective regimen for the treatment of patients with metastatic urothelial tumors and was safely employed in patients with a good PS. However, the possibility of substituting carboplatin for cisplatin as neoadjuvant therapy for less advanced stages needs further investigation in randomized studies.

Using a new immunoradiometric assay (ELSA pS2 Cis-France), a total of 200 cytosols obtained from primary breast tumors were examined for pS2 content, which is an estrogen-regulated protein actually studied as a marker of hormone sensitivity and favorable prognostic factor in breast cancer. In our patient group, the median pS2 value corresponding to 5.3 ng/mg of cytosolic proteins was used as cutoff. pS2 content was not related to menopause status, tumor size, or nodal involvement, whereas a positive correlation was found between pS2 and ER/PgR status. Moreover, the association of pS2 with steroid receptors seems to identify subgroups of patients better than ER/PgR alone.

A prospective randomised clinical trial in patients with node-negative, fast-proliferating breast cancer was initiated in January 1990 to verify the feasibility and reliability of a 3H-thymidine (3H-Tdr) autoradiographic assay in a prospective and consecutive series of node-negative patients and the therapeutic effect of adjuvant chemotherapy in patients with node-negative breast cancer and high tumour proliferative activity. Node-negative patients with a high 3H-Tdr Labelling Index (3H-Tdr-LI) were randomised to receive either no further treatment or combination chemotherapy consisting of fluorouracil, epirubicin plus cyclophosphamide (FEC) for 6 cycles. The autoradiographic assay was performed in 307 of 317 patients (97%) and was evaluable in 291 of 317 patients (92%). A total of 176 patients with a high 3H-Tdr-LI entered the clinical randomised study: 91 in the FEC arm and 85 in the control arm. Patient groups were fairly well balanced regarding the most important clinical and pathological characteristics. In total, 530 FEC cycles have been administered with an actual dose intensity of 90%. Patients receiving FEC demonstrated leucopenia in 35% of cases, alopecia in 70%, and loss of menses in premenopausal patients in an age-dependent manner. Patients are still being entered into the study.

Humoral and cellular immune responses to Salmonella typhi have been studied in nine children with typhoid fever. By using dot immunobinding assay, anti-O-polysaccharide chain and antilipid A antibody titers have been evaluated during the course of the disease. Anti-O-polysaccharide chain antibody titers are lower at the first week and increase up to the third week of the infection. On the other hand, antilipid A antibody levels, which are already higher at the beginning of the disease, progressively augment during the following weeks. Concerning cellular immunity to S. typhi, antibacterial activity mediated by typhoid peripheral mononuclear cells has been determined. Results show this function to be depressed in the initial phase of typhoid, increasing with the time. Together, these data bring new insight on immunity in typhoid patients.