An Italian multicenter retrospective real-life analysis of patients with brain metastases from renal cell carcinoma: the BMRCC study.

BACKGROUND: The treatment of patients with brain-spread renal cell carcinoma (RCC) is an unmet clinical need, although more recent therapeutic strategies have significantly improved RCC patients' life expectancy. Our multicenter, retrospective, observational study investigated a real-world cohort of patients with brain metastases (BM) from RCC (BMRCC). PATIENTS AND METHODS: A total of 226 patients with histological diagnosis of RCC and radiological evidence of BM from 22 Italian institutions were enrolled. Univariate and multivariate models were performed to investigate the impact of clinicopathological features and multimodal treatments on both overall survival (OS) from the BM diagnosis and intracranial progression-free survival (iPFS). RESULTS: The median OS from the BM diagnosis was 18.8 months (interquartile range: 6.2-43 months). Multivariate analysis confirmed the following as positive independent prognostic factors: a Karnofsky Performance Status >70% [hazard ratio (HR) = 0.49, 95% confidence interval (CI) 0.26-0.92, P = 0.0026] and a single BM (HR = 0.51, 95% CI 0.31-0.86, P = 0. 0310); in contrast, the following were confirmed as worse prognosis factors: progressive extracranial disease (HR = 1.66, 95% CI 1.003-2.74, P = 0.00181) and only one line of systemic therapy after the BM occurrence (HR = 2.98, 95% CI 1.62-5.49, P = 0.029). Subgroup analyses showed no difference in iPFS according to the type of the first systemic treatment [immunotherapy (IT) or targeted therapy (TT)] carried out after the BM diagnosis (HR = 1.033, 95% CI 0.565-1.889, P = 0.16), and revealed that external radiation therapy (eRT) significantly prolonged iPFS when combined with IT (10.7 months, 95% CI 4.9-48 months, P = 0.0321) and not when combined with TT (9.01 months, 95% CI 2.7-21.2 months, P = 0.59). CONCLUSIONS: Our results suggest a potential additive effect in terms of iPFS for eRT combined with IT and encourage a more intensive multimodal therapeutic strategy in a multidisciplinary context to improve the survival of BMRCC patients.

Targeting androgen-independent pathways: new chances for patients with prostate cancer?

Androgen deprivation therapy (ADT) is the mainstay treatment for advanced prostate cancer (PC). Most patients eventually progress to a condition known as castration-resistant prostate cancer (CRPC), characterized by lack of response to ADT. Although new androgen receptor signaling (ARS) inhibitors and chemotherapeutic agents have been introduced to overcome resistance to ADT, many patients progress because of primary or acquired resistance to these agents. This comprehensive review aims at exploring the mechanisms of resistance and progression of PC, with specific focus on alterations which lead to the activation of androgen receptor (AR)-independent pathways of survival. Our work integrates available clinical and preclinical data on agents which target these pathways, assessing their potential clinical implication in specific settings of patients. Given the rising interest of the scientific community in cancer immunotherapy strategies, further attention is dedicated to the role of immune evasion in PC.

Advanced soft-tissue sarcoma in elderly patients: patterns of care and survival.

BACKGROUND: There are no data regarding the management of advanced soft-tissue sarcoma (STS) in elderly patients. PATIENTS AND METHODS: We retrospectively reviewed the charts of patients ≥75 years old diagnosed with metastatic or unresectable STS between 1991 and 2011 in 11 French and American centers. RESULTS: The study included 361 patients. Of these, 223 patients (62%) received systemic therapy, whereas 123 patients (34%) were managed with best supportive care (BSC) only. Patients who received BSC were more likely to be ≥80 years, with performance status (PS) ≥ 2, Charlson comorbidity score ≥ 10, and metastatic disease. The median progression-free survival of patients treated with systemic therapy was 4 months (95% CI: 2.9-5.1). Thirty-six patients (16%) stopped chemotherapy because of toxicity. Median overall survival (OS) of patients managed with specific therapy was 10.9 months (95% CI: 8.3-13.5) versus 5.3 months (95% CI: 3.6-7.1) for patients managed with BSC (P = 0.001). On multivariate analysis, age ≥ 80 years, PS ≥ 2, and number of metastatic sites were the only independent factors associated with OS. CONCLUSION: A high proportion of elderly patients with advanced STS were denied chemotherapy. Further efforts are needed to define better the optimal care for fit and unfit elderly patients with STS.

[Chlamydia trachomatis, pelvic inflammatory diseases and sterility]. / Chlamydia trachomatis, MIP e sterilità.

The authors analyse the results of direct (cervical, urethral, tubal) and serological research of Chlamydia trachomatis in a sample population of 420 women undergoing celioscopy due to sterility and pelvic pain, paying particular attention to a group of 193 who were found to be suffering from PID (acute, sequelae). In terms of absolute numbers the correlation between chlamydial contact-PID-sterility is confirmed, whereas in an analysis of the levels of direct positivity it is only significant for acute PID, and in cases of sequelae and in sterility with chronic infection with or without tubal damage the direct identification of Chlamydia trachomatis does not differ much from controls. Salpingo-peritoneal isolation was found to be completely lacking in significance.

[HPV infections in the lower genital tract in the female. Results of beta-interferon treatment]. / Lesioni da HPV del tratto genitale inferiore femminile. Risultati del trattamento con beta-interferone.

The Authors have analyzed the results obtained by treating 60 patients affected by HPV lesions of the lower female genital tract (flat vulvar, vaginal and cervical condylomatosis) with beta-interferon. At vulvovaginal level, the action of the drug is independent from the colposcopic aspect of the lesion but is closely correlated to its extension. The drug proved to be more efficacious at cervical level in case of condylomatous cervicitis rather than ANTZ with a reduction in the size of the lesion and disappearance, if present, of the dysplasia. The positive action of the beta-interferon has never occurred before 2-6 months from the end of the farmacologic treatment. The best results have been obtained in case of condylomatous cervicitis with complete remission in 58% of the cases, and in vaginal condylomatosis (CR at 6 months: 45%). On the basis of these results we may conclude that in these HPV lesions priority should be given to medical treatment whereas in vulvar condylomatosis (especially if extended greater than 1/3) where results are not very satisfactory (not more than 20% of CR) physical therapy is advisable.

The incidence of Chlamydia trachomatis-induced infection in women suffering from cervicovaginitis.

The results of a research on Chlamydia T. (direct survey of both the antigen in the uterine cervix and plasmatic antibodies) in a group of subjects suffering for cervico-vaginitis are provided. The incidence of the Chlamydia infection (proved by either the presence of this bacterium or antibody positivity) is not different from the values reported in literature. Conversely, the presence of neither specific cytological or colposcopic patterns nor of priviledged comites at vaginal level could be demonstrated. Our data, however, confirm a greater incidence of this infection in women reporting early sexual life and a high number of partners. As for the relationship between Chlamydia and contraceptives a slightly higher incidence of positivity in the cervix of patients using oestro-progestinics was registered, whereas no significant difference was noted in the use of other contraceptives IUD included.

PIP: Physicians examined 173 sexually active, non pregnant women suffering from lower genitalia inflammation. They responded to questions pertaining to their past and recent obstetric/gynecological history, to their partner's possible urogenital inflammations, the age of 1st intercourse, number of partners, and contraceptive use. 27.2% of the patients tested positive using immunoenzymatic techniques for Chlamydia trachomatis (CT). No specific symptoms of CT were observed. A correlation exists between early sexual intercourse and a large number of partners and a greater incidence of CT infections. Almost 98% of all CT positive patients reported 1st sexual intercourse between 16 and 21 years. Antibody positivity ranged from 33% (1st intercourse before 15 years) to 24% (1st intercourse between 16-21 years) and decreased to 5.89% when 1st intercourse occurred 21 years. In addition, CT positive patients had many partners. A greater positivity in the cervix occurred in those using oral contraceptives, however. On the other hand, no positivity was noted for those who used IUDs. Those women who used several contraceptives, such as oral contraceptives, IUD, and barrier methods, had a higher incidence of CT positivity (53.2%) than other groups. Perhaps this is due to clinical cervicovaginitis symptoms prompting the women to change techniques. Specific colposcopy patterns and cytological alterations which some physicians believe indicate CT infections did not identify patients with Chlamydia. These data suggest that it is impossible to make a diagnosis based on symptoms, past sexual history, and contraceptive use. Therefore the data indicate that immunoenzymatic tests are needed.

Puerperal lactation, gonadotropin release and estradiol release: effects of metergoline and bromocriptine.

The exact cause of amenorrhea during the puerperium is still a matter of debate. PRL might inhibit primarily the release of FSH and LH or their stimulating effects on the ovary. In the study presented here, 28 healthy women were investigated, 13 of them lactating puerperae. In the other 15, lactation was prevented by drugs (metergoline in 9, bromocriptine in 6). The women's serum PRL, FSH, LH, beta-HCG and 17 beta-estradiol as well as their FSH and LH response to LHRH (100 micrograms i.v.) were tested 1, 3, 7 and 14 days after vaginal delivery. Serum PRL levels remained elevated in the lactating puerperae and dropped in the puerperae treated with metergoline or bromocriptine. The pattern of FSH, LH and beta-HCG levels as well as the FSH and LH response to LHRH were superimposable in lactating and in nonlactating women. 17 beta-estradiol levels dropped in all puerperae from day 1 to 7, but rose from day 7 to 14 only in the puerperae treated with metergoline or bromocriptine and not in the lactating women. These data indicate that PRL directly affects the ovarian response to FSH and LH, whereas the release of FSH and LH remains unaffected. A stimulatory effect of metergoline and bromocriptine on the ovarian steroidogenesis cannot be excluded.