Red orange: experimental models and epidemiological evidence of its benefits on human health.

In recent years, there has been increasing public interest in plant antioxidants, thanks to the potential anticarcinogenic and cardioprotective actions mediated by their biochemical properties. The red (or blood) orange (Citrus sinensis (L.) Osbeck) is a pigmented sweet orange variety typical of eastern Sicily (southern Italy), California, and Spain. In this paper, we discuss the main health-related properties of the red orange that include anticancer, anti-inflammatory, and cardiovascular protection activities. Moreover, the effects on health of its main constituents (namely, flavonoids, carotenoids, ascorbic acid, hydroxycinnamic acids, and anthocyanins) are described. The red orange juice demonstrates an important antioxidant activity by modulating many antioxidant enzyme systems that efficiently counteract the oxidative damage which may play an important role in the etiology of numerous diseases, such as atherosclerosis, diabetes, and cancer. The beneficial effects of this fruit may be mediated by the synergic effects of its compounds. Thus, the supply of natural antioxidant compounds through a balanced diet rich in red oranges might provide protection against oxidative damage under differing conditions and could be more effective than, the supplementation of an individual antioxidant.

Intraoperative avidination for radionuclide treatment as a radiotherapy boost in breast cancer: results of a phase II study with (90)Y-labeled biotin.

PURPOSE: External beam radiotherapy (EBRT) after conservative surgery for early breast cancer requires 5-7 weeks. For elderly patients and those distant from an RT center, attending for EBRT may be difficult or impossible. We investigated local toxicity, cosmetic outcomes, and quality of life in a new breast irradiation technique-intraoperative avidination for radionuclide therapy (IART)-in which avidin is administered to the tumor bed and (90)Y-labelled biotin later administered intravenously to bind the avidin and provide irradiation. Reduced duration EBRT (40 Gy) is given subsequently. METHODS: After surgery, 50 (ten patients), 100 (15 patients) or 150 mg (ten patients) of avidin was injected into the tumor bed. After 12-24 h, 3.7 GBq (90)Y-biotin (beta source for therapeutic effect) plus 185 MBq (111)In-biotin (gamma source for imaging and dosimetry) was infused slowly. Whole-body scintigraphy and SPECT/CT images were taken for up to 30 h. Shortened EBRT started 4 weeks later. Local toxicity was assessed by RTOG scale; quality of life was assessed by EORTC QOL-30. RESULTS: Of 35 patients recruited (mean age 63 years; range 42-74) 32 received IART plus EBRT. 100 mg avidin provided 19.5 +/- 4.0 Gy to the tumor bed and was considered the optimum dose. No side-effects of avidin or (90)Y-biotin occurred, with no hematological or local toxicity. Local G3 toxicity occurred in 3/32 patients during EBRT. IART plus EBRT was well accepted, with good cosmetic outcomes and maintained quality of life. CONCLUSIONS: IART plus reduced EBRT can accelerate irradiation after conservative breast surgery.

Analysis of the presence of cutaneous and mucosal papillomavirus types in ductal lavage fluid, milk and colostrum to evaluate its role in breast carcinogenesis.

Several independent studies have presented evidence for the involvement of human papillomaviruses (HPV) in the aetiology of human breast cancer, while others have reported the opposite findings. Here, we have analysed by a high sensitive multiplex PCR-based method the prevalence of alpha mucosal and beta cutaneous HPV DNA in 90 ductal lavages, colostrum and milk. Ten of the 70 DLs analyzed (14%) contained a single or multiple beta HPV types, while DNA from mucosal high-risk HPV types was detected in only one sample (1/70). A strong reduction of HPV positivity in DL fluids was observed in 45 specimens collected after removal of the superficial layers of the nipple epidermis. All DLs were negative for the mucosal low-risk HPV types 6 and 11. Finally, HPV positivity was low in colostrum and milk. Our data show that DNA of alpha mucosa and beta cutaneous HPV types are rarely present in the breast fluids and suggest that a direct role of HPV in breast carcinogenesis is unlikely.

Intraoperative avidination for radionuclide therapy: a prospective new development to accelerate radiotherapy in breast cancer.

PURPOSE: In a continuous effort to seek for anticancer treatments with minimal side effects, we aim at proving the feasibility of the Intraoperative Avidination for Radionuclide Therapy, a new procedure for partial breast irradiation. EXPERIMENTAL DESIGN: To assess doses of 90Y-DOTA-biotin to target (i.e., breast tumor bed) and nontarget organs, we did simulation studies with 111In-DOTA-biotin in 10 candidates for conservative breast surgery. Immediately after quadrantectomy, patients were injected with 100-mg avidin in the tumor bed. On the following day, patients were given 111In-DOTA-biotin (approximately 111 MBq) i.v. after appropriate chase of biotinylated albumin (20 mg) to remove circulating avidin. Biokinetic studies were done by measuring radioactivity in scheduled blood samples, 48-h urine collection, and through scintigraphic images. The medical internal radiation dose formalism (OLINDA code) enabled dosimetry assessment in target and nontarget organs. RESULTS: Images showed early and long-lasting radioactive biotin uptake in the operated breast. Rapid blood clearance (<1% at 12 h) and urine excretion (>75% at 24 h) were observed. Absorbed doses, expressed as mean+/-SD in Gy/GBq, were as low as 0.15+/-0.05 in lungs, 0.10+/-0.02 in heart, 0.06+/-0.02 in red marrow, 1.30+/-0.50 in kidneys, 1.50+/-0.30 in urinary bladder, and 0.06+/-0.02 in total body, whereas in the targeted area, they increased to 5.5+/-1.1 Gy/GBq (50% ISOROI) and 4.8+/-1.0 Gy/GBq (30% ISOROI). CONCLUSION: Our preliminary results suggest that Intraoperative Avidination for Radionuclide Therapy is a simple and feasible procedure that may improve breast cancer patients' postsurgical management by shortening radiotherapy duration.

IART: intraoperative avidination for radionuclide treatment. A new way of partial breast irradiation.

A new procedure, known as Intraoperative Avidination for Radionuclide Therapy (IART), is described in breast cancer patients. In this paper, we provide proof of the principle that intraoperative injection of avidin in the tumour bed after quadrantectomy allows homing in of intravenously (IV) administered radioactive biotin to the target site. This approach of targeted therapy consists of two steps: (i) "avidination" of the anatomical area of the tumour with avidin injected by the surgeon, into and around the tumour bed; (ii) targeting the anatomical area of the tumour by IV injection of radiolabelled biotin. The scintigraphic images demonstrated fast and stable uptake of labelled biotin at the site of operated breast. The radiation dose released to the index quadrant was more than 5 Gy/GBq, consistent with a boost of 20 Gy for an activity of 3.7 GBq 90Y-biotin (100mCi). A further large clinical trial facing IART in combination with reduced external-beam radiotherapy is, in our opinion, fully justified.

Full-dose intraoperative radiotherapy with electrons in breast surgery: broadening the indications.

HYPOTHESIS: Although postoperative fractionated radiotherapy (PFR) remains the standard method for conservative treatment of breast carcinomas, widespread experience in the use of full-dose intraoperative radiotherapy with electrons (ELIOT) merits its application in novel clinical situations, although long-term results of ongoing clinical trials have not been fully reported. DESIGN: Retrospective case series. SETTING: Division of breast surgery in a comprehensive cancer center. PATIENTS: From June 1999 to September 2003 ELIOT was used as the sole radiotherapy in 355 patients with unifocal invasive carcinoma who were candidates for breast-conserving surgery and most of whom were participating in an ongoing institutional trial. In a group of patients in whom PFR was not considered safe or feasible (because of previous mantle field irradiation for Hodgkin disease, cosmetic breast augmentation, severe cardiopathy, large hypertrophic scarring from skin burns, vitiligo, and geographic or social obstacles), ELIOT was performed outside of the ongoing trial. RESULTS: No particular adverse effects, unusual acute reactions, late sequelae, and local or systemic events were noted in these patients after a mean follow-up of 27.3 months. CONCLUSIONS: In appropriated selected patients, when it is critical to perform PFR after breast-conserving therapy, a single dose of ELIOT may be considered to avoid mastectomy, reduce potential treatment toxicity, improve quality of life, and resolve logistic problems. The long-term results of ongoing clinical trials will further delineate patients in whom ELIOT may replace PFR.

Axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast.

HYPOTHESIS: A sentinel lymph node (SLN) biopsy should not be considered a standard procedure in the treatment of all patients with ductal carcinoma in situ (DCIS) of the breast if the lesion is completely excised by radical surgery and there are free margins of resection. DESIGN: Prospective case series. SETTING: Department of breast surgery of a comprehensive cancer center. PATIENTS: From January 1, 1998, to December 1, 2001, 223 unselected consecutive patients affected by pure DCIS of the breast underwent an SLN biopsy. RESULTS: Metastases in the SLN were detected in 7 (3.1%) of the 223 patients, and complete axillary dissection was subsequently performed in all these patients but 1. Of these 7 patients, 5 had only micrometastases in the SLNs; and in the 6 patients treated with complete axillary dissection, the SLN was the only positive node. CONCLUSIONS: Because of the low prevalence of metastases, an SLN biopsy should not be considered a standard procedure in all patients with DCIS. In patients with pure DCIS in whom the lesion is completely excised by radical surgery, an SLN biopsy could be avoided. It could be considered in patients with DCIS undergoing mastectomy, in whom there exists a higher risk of harboring an invasive component using definitive histologic features, like large solid tumors or diffuse or multicentric microcalcifications; in these patients, an SLN biopsy cannot be performed at a later operation. Complete axillary dissection may not be mandatory if the SLN is micrometastatic.

Sentinel lymph node biopsy performed with local anesthesia in patients with early-stage breast carcinoma.

HYPOTHESIS: Sentinel lymph node (SN) biopsy performed with local anesthesia has a positive effect on patients' quality of life and on treatment management for early-stage breast carcinoma. This method represents an interesting development in breast-conserving surgery. DESIGN: We performed SN biopsy with local anesthesia in selected patients to test the feasibility of the technique and its impact on our organization and on patients' quality of life. PATIENTS AND METHODS: From September 2000 to December 2001, we studied 115 patients with a palpable breast tumor (maximum diameter, 2.5 cm). The axilla was clinically negative for metastasis in all cases. RESULTS: Forty-eight patients (41.7%) had SNs that were positive for metastasis. In 20 cases (17.4%), the SN was macrometastatic and in 28 cases (24.3%), it was micrometastatic (diameter <2 mm). The SN was negative for metastasis in 66 cases (57.4%). In 1 case, the histologic examination revealed the presence of a non-Hodgkin B-cell lymphoma. The complete axillary dissection performed in the subgroup of patients with macrometastatic SNs showed that in 9 cases (45%), the SN was the only positive node. In another 9 cases (45%), patients had fewer than 4 positive axillary lymph nodes; more than 4 axillary nodes were metastatic in 2 cases (10%). Among the 28 patients with SN micrometastasis, 21 received complete axillary dissection: 15 patients (53.6%) had no other metastasis to the axillary nodes and 6 patients (21.4%) had cancer cells in other axillary nodes. In case of micrometastasis, we suggested that patients enter the International Breast Cancer Study Group 2301 trial (15 of them accepted and signed the informed consent), which compared completion of axillary dissection with no further surgical treatment of the axilla. Based on randomization, 7 patients (25%) in the group with micrometastasis to the SN received no axillary dissection. Patients' tolerance to this kind of treatment was excellent. CONCLUSION: Our experience indicates that SN biopsy performed with local anesthesia can be a suitable alternative to standard intraoperative evaluation with general anesthesia in patients with unifocal, early-stage breast carcinoma.