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Cinisello Balsamo, Italy

Fruscio R.,University of Milan Bicocca | Villa A.,Bassini Hospital | Chiari S.,University of Milan Bicocca | Vergani P.,University of Milan Bicocca | And 8 more authors.
Gynecologic Oncology | Year: 2012

Objective: Treatment of locally invasive cervical cancer diagnosed during pregnancy in women who desire to retain their pregnancy is a major challenge to physicians. Neoadjuvant chemotherapy followed by radical hysterectomy has been reported to be an attractive option to delay delivery until fetal viability has been reached. Methods: Between 1994 and 2009 9 patients were treated at San Gerardo Hospital (Monza, Italy) for cervical cancer during pregnancy. Results: FIGO stage was IB1 in four patients and IB2 in five. Tumor diameter ranged between 20 and 70 mm. After neoadjuvant platinum-based chemotherapy partial response was achieved in 5 patients, while 4 had a stable disease. One patient received a second-line chemotherapy during pregnancy due to progressive disease, achieving a partial response. Median duration of therapy delay until cesarean section was 16 weeks. Between 30 and 36 weeks of gestation all patients underwent cesarean section. Piver II radical hysterectomy with pelvic lymphadenectomy was performed. Two children had mild perinatal morbidities and were discharged in good conditions after 14 and 40 days. Three patients received adjuvant therapy for pathological risk factors. Four patients relapsed (44%) and two of them (23%) died because of tumor progression. Conclusion: During pregnancy, the oncological outcome of cervical cancer patients is similar to non-pregnant ones. Chemotherapy does not seem to affect fetal health and development, even if longer follow-up is required. Therefore, neoadjuvant chemotherapy for the treatment of locally invasive cervical cancer during pregnancy seems to be a reasonable option for delay definitive treatment until fetal viability is obtained. © 2012 Elsevier Inc. All rights reserved.

Messina G.,Psychological Service | Lissoni P.,Institute of Biological Medicine | Marchiori P.,Natur Spiritual | Bartolacelli E.,Psychological Service | And 2 more authors.
Journal of Research in Medical Sciences | Year: 2010

BACKGROUND: The anti-oxidant and immunomodulating natural agents may enhance the efficacy of cancer chemotherapy. One of the most important agents is the pineal hormone melatonin (MLT) which may exert both anti-oxidant and antiproliferative immunostimulating anticancer effects. This study was performed to evaluate the efficacy of a biochemotherapeutic regimen in metastatic cancer patients, and its therapeutic activity in relation to the psychospiritual status of patients. METHODS: The study included 50 metastatic non-small cell lung cancer (NSCLC) patients and a control group of 100 patients. Chemotherapy consisted of cisplatin plus gemcitabine. MLT was given orally at 20 mg/day in the evening. Patients were subdivided into 5 psychic profiles, as follows: spiritual faith, rationale faith, anxiety, apathy, and accusation behavior. RESULTS: Tumor response rate was significantly higher in patients treated by chemotherapy plus MLT than in those treated by chemotherapy alone (21/50 vs. 24/100, p < 0.001). However, the percentage of objective tumor regressions obtained in patients with spiritual faith was significantly higher than that found in the overall other patients concomitantly treated by chemotherapy plus MLT (6/8 vs. 15/42, p < 0.01). CONCLUSIONS: In conclusion, the efficacy of chemotherapy may be enhanced by the pineal hormone MLT, by representing a new promising biochemotherapeutic combination; also despite its objective ability to enhance chemotherapy efficacy, the activity of MLT is depending at least in part on the psychospiritual status of cancer patients, and it is maximal in the presence of a real spiritual faith.

Andreano A.,University of Milan Bicocca | Meneghel E.,Bassini Hospital | Bovo G.,San Gerardo Hospital | Ippolito D.,University of Milan Bicocca | And 4 more authors.
Journal of Ultrasound | Year: 2010

Introduction: Liver metastases often exhibit a hypervascular halo during the arterial phase of contrast-enhanced ultrasonography (CEUS). This finding has no correlates on baseline gray-scale imaging, and it has never been characterized. The aim of this study was to identify the features of this halo and determine whether it should be included in the ablation volume during thermal ablation procedures. Materials and methods: We prospectively enrolled 25 patients referred to our department for thermal ablation of liver metastases. Before treatment all patients underwent CEUS, and the maximum diameter of the metastatic lesion was measured before administration of the ultrasound contrast agent and during the arterial and portal venous phases of the contrast contrast-enhanced study. Maximum diameters in the different vascular phases were compared with the Turkey-Kramer test. Two biopsies were obtained from each lesion with a 21-gauge needle: 1) one from the center of the metastasis to confirm the diagnosis and 2) one from the hypervascular peripheral halo identified in the arterial phase at CEUS. Results: The mean (±standard deviation) maximum lesion diameter was 2.67 ± 1.2 cm before contrast agent injection, 3.50 ± 1.4 cm during the arterial phase, and 2.71 ± 1.2 cm during the venous phase. The difference between maximum diameters measured before contrast enhancement and in the arterial phase was highly significant (mean: 0.84 ± 0.45 cm, p < 0.0001). Histological examination of halo specimens revealed inflammatory infiltrates with no evidence of tumor infiltration in 24/25 (96%) cases and normal hepatic parenchymal tissue in the 25th specimen. Discussion: The hypervascular halo surrounding liver metastases during the arterial phase of CEUS represents a chronic inflammatory infiltrate, not tumor infiltration. However, since chronic inflammation appears to promote neovascularization and the production of tumoral growth factors, it seems wise to include the hypervascular halo in the intended-to-treat volume when planning the ablation procedure. © 2010 Elsevier Srl.

Nespoli L.,University of Milan Bicocca | Uggeri F.,University of Milan Bicocca | Romano F.,University of Milan Bicocca | Nespoli A.,University of Milan Bicocca | And 4 more authors.
Anticancer Research | Year: 2012

Interactions between host and malignant tumor is currently under intensive investigation. The immune system seems to have a key role in cancer development and spread. Novel strategies to actively modulate the immune system have been proposed to improve the outcome of disease in patients with neoplasms. Our experience with systemic immunomodulation by interleukin-2 (IL-2) focused on both systemic and local immunity in surgical gastrointestinal cancer. Preoperative IL-2 subcutaneous injection was effective in counteracting postoperative immunosuppression, with a reduction of serum levels of IL-6 and the maintenance of preoperative levels of IL-12, a higher number of circulating total lymphocytes, and CD3 + and CD4 + T-cells, and a smaller decrease in circulating mature and immature dendritic cells (DCs), as well as a reduction in postoperative serum levels of vascular endothelial growth factor. At the intestinal level, in patients with colorectal cancer, preoperative administration of IL-2 affected both phenotype and function of resident dendritic cells and T-cells, skewing local immunity toward a more immunogenic one. Our data showed that immunomodulation by IL-2 was effective in counteracting the systemic postoperative immune suppression related to surgical stress. IL-2 was also active at a local level on intestinal immunity, affecting both phenotype and function of resident T-cells and DCs. Future studies will encompass the possibility of reaching more adequate intratumoral IL-2 concentrations by direct intralesional injection to maximize immunostimulatory effects and minimize adverse effects.

Vigore L.,Laboratory of Immunomicrobiology | Messina G.,Polyclinic Hospital | Brivio F.,Bassini Hospital | Fumagalli L.,Bassini Hospital | And 3 more authors.
In Vivo | Year: 2010

Background: At present, it is known that cancer-related immunosuppression would mainly depend on an immunosuppressive action mediated by a subtype of CD4+ lymphocytes, the so-called regulatory T lymphocytes (T-reg), which are identified as CD4+CD25+ cells. Moreover, it has been shown that anticancer immunity is under psychoneuroendocrine regulation, mainly mediated by the pineal hormone melatonin (MLT). This study was performed to investigate the in vivo and in vitro effects of MLT on T-reg generation. Materials and Methods: We evaluated the in vivo effects of MLT (20 mg/daily orally in the evening) in 20 patients with untreatable metastatic solid tumor and the in vitro effects of MLT incubation (at 10 and 100 pg/ml) of pure lymphocyte cultures on T-reg cell count. Results: MLT induced a statistically significant decline in mean T-reg cell numbers in patients who achieved disease control, whereas no effect was seen in those who had progressed. In contrast, no in vitro effect of MLT incubation was apparent. Conclusion: This preliminary study would suggest that MLT may exert in vivo an inhibitory action on T-reg cell generation in cancer patients which is associated with a control of the neoplastic progression, whereas no direct effect was seen in vitro on lymphocyte differentiation. This finding would suggest that MLT may counteract T-reg cell generation in vivo by inhibiting macrophage activity which is involved in stimulating T-reg cell production.

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