Celecoxib for the prevention of nonmuscle invasive bladder cancer: Results from a matched control study

New targets and approaches are under investigation for the treatment of nonmuscle invasive bladder cancer (NMIBC). Preclinical data suggest cyclooxygenase-2 (COX-2) as a promising target. Celecoxib, a COX-2 selective inhibitor, inhibits tumor development and enhances survival, both in vitro and in vivo models of bladder cancer. Therefore, we conducted a pilot study of celecoxib to prevent recurrence in patients with intermediate risk NMIBC

Results of D-IMPACT

Summary Aims:  Diagnosis IMprovement in PrimAry Care Trial (D-IMPACT) was a prospective, multicentre epidemiological study in three European countries to identify the optimal subset of simple tests applied in primary care to diagnose benign prostatic hyperplasia (BPH) in men who spontaneously present with lower urinary tract symptoms (LUTS). Methods:  Consecutive male patients aged ≥ 50 years who spontaneously attended their regular general practitioner (GP) office with LUTS were eligible for inclusion if they had not previously undergone BPH diagnostic tests or received treatment for BPH. Patients were assessed on three occasions, twice by their regular GP (visits 1 and 2) and once by a urologist (visit 3). The diagnostic accuracy of each variable was determined using the urologists' final BPH diagnosis (at visit 3) as gold-standard. Independent variables analysed were as follows: age; BPH diagnosis performed by GP in visit 1 (yes/no); probability of BPH diagnosis assessed by GP in visit 1; urinalysis (normal/abnormal); prostate-specific antigen (PSA); International Prostate Symptom Score (IPSS); diagnosis of BPH performed by GP in visit 2 (yes/no); and probability of BPH diagnosis assessed by GP in visit 2. Statistically significant variables (p 1.5 ng/ml and prostate volume ≥ 30 cm3). Among the independent variables analysed, only age, IPSS and PSA showed a statistically significant relationship with BPH diagnosis. In a logistic regression model including age, IPSS, PSA and probability of BPH (based on physical examination and symptoms), positive predictive value (PPV) was 77.1%. Exclusion of BPH probability resulted in a PPV of 75.7%. Conclusions:  A diagnostic algorithm including only objective variables (age, IPSS and PSA), easily implemented in any GP office, allows GPs to accurately diagnose BPH in approximately three-quarters of patients spontaneously reporting LUTS

Prognostic role of amenorrhea induced by adjuvant chemotherapy in premenopausal patients with early breast cancer.

The prognostic role of drug-induced amenorrhea (DIA) was restrospectively evaluated in 221 out of 254 consecutive premenopausal patients treated with adjuvant CMF or a CMF-containing regimen; 33 patients were eliminated because of lack of menstrual data. All patients had metastatic axillary nodes; drug regimens were: CMF x 9 courses +/- Tamoxifen (TM) and CMF x 6 courses; median age was 43 (range 26-54). Premenopausal status was defined as last normal menses within the 6 weeks preceding initiation of chemotherapy: DIA as cessation of menses for at least 3 months not later than 3 months from the end of chemotherapy. DIA occurred in 166,221 (75.1%) patients and was strictly related to the age of the patients; also, the older the patients the shorter the time required to develop DIA. At median follow up of 69 months, Mantel-Byar analysis showed a longer disease free survival (DFS) for patients who developed DIA as compared with non amenorrheic women (P less than 0.001). DIA prognostic value was independent of age, number of involved nodes, tumour size and number of CMF cycles, as assessed by the Cox model (RH 0.43, 95% C.I. 0.24-0.77), in which DIA was entered as a time dependent covariate

Prolactin receptor does not correlate with oestrogen and progesterone receptors in primary breast cancer and lacks prognostic significance. Ten year results of the Naples adjuvant (GUN) study.

The correlation between prolactin (PRLR) and oestrogen (ER) or progesterone receptors (PgR) in breast cancer and a possible prognostic significance of PRLR at 10 year follow-up have been investigated in the Naples (GUN) adjuvant trial. A total of 308 pre- and post-menopausal patients with early breast cancer, who entered the trial from 1 February 1978 to 31 December 1983, received randomly Tamoxifen (TM), 30 mg per die for 2 years, or no therapy. PRLR status was known in 229 (74.3%) patients. Values of specific binding less than 1% were considered negative. PRLR was positive in 75/229 (32.8%). ER was assayed in 210/229 (91.7%) patients and PgR in 188/229 (82.1%). No significant correlation, by the Spearman test, was found between PRLR and ER or PgR, while ER status was highly interrelated with PgR status. By the Cox model no evidence of an independent prognostic role of PRLR on disease-free survival (DFS) was observed, nor an interaction between PRLR and adjuvant treatment with TM was found

CMF vs alternating CMF/EV in the adjuvant treatment of operable breast cancer. A single centre randomised clinical trial (Naples GUN-3 study).

The aim of this study was to test the hypothesis of Goldie and Coldman that the use of non-cross-resistant regimens of chemotherapy could lead to maximal anti-tumour effect. We compared standard CMF (cyclophosphamide, methotrexate, fluorouracil) with alternating CMF/EV (epirubicin, vincristine) in the adjuvant therapy of early breast cancer. Stage II premenopausal node-positive or post-menopausal node-positive oestrogen receptor-negative and stage III breast cancer patients were eligible for the study. From January 1985 to December 1990, 220 patients were randomised (115 to CMF and 105 to CMF/EV). Toxicity was mild; neurotoxicity, vomiting and hair loss were more frequent in the CMF/EV group, while permanent amenorrhoea, diarrhoea, stomach ache and minor infections occurred more often in the CMF arm. At a follow-up of 48 months, 113 patients (51.4%) had had recurrence (62 on CMF and 51 on CMF/EV) and 54 (24.5%) had died (30 on CMF and 24 on CMF/EV). There was no significant difference in disease-free and overall survival between the two arms. After adjusting for menopausal status and stage, the relative risk (RR) of recurrence for CMF/EV patients was 0.93 (95% CL 0.64-1.35), while the RR of death was 0.85 (95% CL 0.49-1.47). In conclusion, the Goldie-Coldman model of alternating therapy is not confirmed in this trial of adjuvant therapy of early breast cancer, although in view of its design a difference of less than 20% in 3 year disease-free survival could not be excluded

Central nervous system metastases from castration-resistant prostate cancer in the docetaxel era.

Central nervous system (brain or leptomeningeal) metastases (BLm) are considered rare in castration-resistant prostate cancer (CRPC) patients. Now that docetaxel has become the reference drug for first-line treatment of CRPC, patients whose disease is not controlled by hormonal manipulations may live much longer than before and have higher risk of developing BLm. We retrospectively reviewed the records of all patients with CRPC attending our centres from 2002 to 2010, and identified all of those who were diagnosed as having BLm and received (or were considered to have been eligible to receive) docetaxel-based treatment. We identified 31 cases of BLm (22 brain metastases and 9 leptomeningeal metastases) with an incidence of 3.3%. BLm-free survival was 43.5 months, and survival after BLm discovery was 4 months. With six patients surviving for more than 1 year after developing BLm, the projected 1-year BL-S rate was 25.8%. The findings of our study may be relevant in clinical practice as they indicate that incidence of BLm in CRPC patients in the docetaxel era seems to be higher than in historical reports, meaning that special attention should be paid to the appearance of neurological symptoms in long-term CRPC survivors because they may be related to BLm

\u201cA randomised factorial trial of sequential doxorubicin and CMF vs CMF and chemotherapy alone vs chemotherapy followed by goserelin plus tamoxifen as adjuvant treatment of node-positive breast cancer\u201d

The sequential doxorubicin \u2192 CMF (CMF = cyclophosphamide, methotrexate, fluorouracil) regimen has never been compared to CMF in a randomised trial. The role of adding goserelin and tamoxifen after chemotherapy is unclear. In all, 466 premenopausal node-positive patients were randomised to: (a) CMF 7 6 cycles (CMF); (b) doxorubicin 7 4 cycles followed by CMF 7 6 cycles (A \u2192 CMF); (c) CMF 7 6 cycles followed by goserelin plus tamoxifen 7 2 years (CMF \u2192 GT); and (d) doxorubicin 7 4 cycles followed by CMF 7 6 cycles followed by goserelin plus tamoxifen 7 2 years (A \u2192 CMF \u2192 GT). The study used a 2 7 2 factorial experimental design to assess: (1) the effect of the chemotherapy regimens (CMF vs A 7 CMF or arms a + c vs b + d) and (2) the effect of adding GT after chemotherapy (arms a + b vs c + d). At a median follow-up of 72 months, A \u2192 CMF as compared to CMF significantly improved disease-free survival (DFS) with a multivariate hazard ratio (HR) = 0.740 (95% confidence interval (CI): 0.556-0.986; P = 0.040) and produced a nonsignificant improvement of overall survival (OS) (HR = 0.764; 95% CI: 0.489-1.193). The addition of GT after chemotherapy significantly improved DFS (HR = 0.74; 95% CI: 0.555-0.987; P = 0.040), with a nonsignificant improvement of OS (HR = 0.84; 95% CI: 0.54-1.32). A \u2192 CMF is superior to CMF. Adding GT after chemotherapy is beneficial for premenopausal node-positive patients. \ua9 2005 Cancer Research UK

Tidal notches in Mediterranean Sea: a comprehensive analysis

Recent works (Evelpidou et al., 2012) suggest that the modern tidal notch is disappearing worldwide due sea level rise over the last century. In order to assess this hypothesis, we measured modern tidal notches in several of sites along the Mediterranean coasts. We report observations on tidal notches cut along carbonate coasts from 73 sites from Italy, France, Croatia, Montenegro, Greece, Malta and Spain, plus additional observations carried outside the Mediterranean. At each site, we measured notch width and depth, and we described the characteristics of the biological rim at the base of the notch. We correlated these parameters with wave energy, tide gauge datasets and rock lithology. Our results suggest that, considering \u2018the development of tidal notches the consequence of midlittoral bioerosion\u2019 (as done in Evelpidou et al., 2012) is a simplification that can lead to misleading results, such as stating that notches are disappearing. Important roles in notch formation can be also played by wave action, rate of karst dissolution, salt weathering and wetting and drying cycles. Of course notch formation can be augmented and favoured also by bioerosion which can, in particular cases, be the main process of notch formation and development. Our dataset shows that notches are carved by an ensemble rather than by a single process, both today and in the past, and that it is difficult, if not impossible, to disentangle them and establish which one is prevailing. We therefore show that tidal notches are still forming, challenging the hypothesis that sea level rise has drowned them