sara gandini

Follow-up is managed internally in 94% of centers and is programmed according to international guidelines in 52% of high-volume hospitals (>25 melanoma diagnoses per year); the remainder use internal guidelines; fewer low-volume centers (≤ 25 diagnoses per year) have internal guidelines (25%, p = 0.001). Instrumental examinations for stage III and IV disease are similar, while the examination interval changes from 3/4 months for stage III to 2/3 months for stage IV, and use of PET/CT increases from 44 to 54%. Overall, thoracic and abdominal CT is used most for follow-up in stage III (83%), while bone scintigraphy is used more commonly in low-volume centers (41 vs. 19%, p = 0.003), despite similar use of PET/CT (48 vs. 41%). Brain CT or MRI is more common in high-volume centers (63 vs. 39%, p > 0.0001), as is echography of draining lymph nodes (71 vs. 52%, p = 0.01). Hepatic/abdominal echography and thoracic radiography are used in about 50% of centers, regardless of type. In stage IV, use of bone scintigraphy is similar among groups (ca. 40%); brain CT/NMR use increases from 51 to 64% and is more common in high-volume centers (p = 0.03). Lymph node echography is more common in high-volume centers (56 vs. 39%, p = 0.03).

A case-control study to explore associations between retinoids, tocopherols, total and beta-carotenes and breast cancer was conducted by analysing concentrations of these biomarkers in adipose tissue, cheek cells and plasma. A total of 414 French-Canadians in Montreal with new diagnoses of breast cancer were age-matched to 429 population-based controls. Subjects were interviewed using a questionnaire, and biological samples from 287 cases and 112 controls were collected within 3 months of the diagnosis. Mean beta carotene concentrations in cheek cells were significantly lower among controls. Odds ratios (ORs) from logistic regression analysis were used to compare higher and lower tercile concentrations. Significant positive associations were observed in adipose tissue for retinoid [OR=2.11; 95% CI (1.09-4.08)] and beta carotene [OR=3.18; 95% CI (1.70-5.93)]; in cheek cells for beta carotene [OR=2.22; 95% CI (1.21-4.50)] and for total carotenes [OR=2.94; 95% CI (1.59-5.42)] and in plasma for beta carotene [OR=1.53; 95% CI (0.80-2.93)] and total carotenes [OR=1.04; 95% CI (0.53-2.05)]. Among the control groups, significant Pearson correlations were observed between cheek cells and adipose tissue for total carotenes (r=0.27; p=0.01) and cheek cells and plasma (r=0.22; p=0.04). In contrast to previous works, this study shows that high concentrations of retinoids and carotenes in adipose tissue and cheek cells are associated with increased risk of breast cancer. However, all these studies are limited by small sample size. Although our study tested a limited number of controls, important associations were observed. These results suggest that the effect of disease on biomarkers is fundamental to the interpretation of epidemiological data. We suggest either that the high levels of these biomarkers found in cancer patients in this study may be due to the disease process that affects the pharmacokinetics of the biomarker or that the disease causes a change in dietary habits. In addition, in studies involving the application of biomarkers to cancer epidemiology it is imperative that a typical biomarker concentration is not associated with breast cancer risk before further examination of the methodological limitations of epidemiological studies investigating this relationship. Therefore, sample size, selection bias, information bias, and confounding should be considered in the design of studies investigating the aetiological relationship between biomarkers and breast cancer.

Epidemiologic evidence supported a role for vitamin D and vitamin D receptor (VDR) polymorphisms in cancer risk. Beyond VDR, the biologic effects of vitamin D are mediated by the vitamin D-binding protein (DBP), a key protein in vitamin D metabolism. Furthermore, the gene encoding the DBP (GC, group-specific component) has an important role in the vitamin D pathway. Several studies investigated DBP serologic levels and GC polymorphisms in association with cancer risk with controversial results. Thus, we carried out a meta-analysis to investigate these associations. We included 28 independent studies concerning the following tumors: basal cell carcinoma, bladder, breast, colon-rectum, endometrium, liver, esophagus, stomach, melanoma, pancreas, prostate, and kidney. Through random-effect models, we calculated the summary odds ratios (SOR) for serum DBP and the GC polymorphisms rs2282679, rs12512631, rs7041, rs4588, rs17467825, rs1155563, and rs1352844. We found a borderline decrease i...

Tamoxifen administered at 20 mg/d has been shown to decrease breast cancer incidence in at-risk women by 50%, but toxicity may limit its broad use, particularly in postmenopausal women. Because toxicity may be dose-dependent, we studied the biologic activity of low concentrations of tamoxifen to determine the plausibility of a dose reduction. We measured the blood concentrations of tamoxifen and its main metabolites in a dose titration study in 105 healthy women (placebo, tamoxifen 10 mg on alternate days, tamoxifen 10 mg/d, and tamoxifen 20 mg/d). Drug levels measured after 2 months of treatment were correlated with the changes in surrogate biomarkers of different diseases, including lipid profile, blood cell count, fibrinogen, antithrombin III, osteocalcin, and insulin-like growth factor I, a promising surrogate biomarker of breast cancer. The means (+/- SD) for tamoxifen and N-desmethyltamoxifen (metabolite X) concentrations (ng/mL) were dose-related, being, respectively, 0 and 0 with placebo, 26.8 +/- 15.1 and 43.7 +/- 22.5 with 10 mg every other day, 51.2 +/- 24.1 and 90.7 +/- 48.0 with 10 mg/d, and 136.0 +/- 52.7 and 230.6 +/- 75.0 with 20 mg/d of tamoxifen. At variance, the biomarker changes were of comparable magnitude at any drug concentration except for platelet count and triglycerides levels, the latter showing a trend to an increase with increasing tamoxifen concentrations. An 80% reduction in blood concentrations does not seem to affect the activity of tamoxifen on biomarkers of cardiovascular or breast cancer risk and may in fact have a more favorable safety profile. Additional studies are warranted to determine the most appropriate dose of this agent.

ABSTRACT Abstract e20634 Background: Axillary lymph node dissection is an inevitable part of breast cancer surgery in certain cases. Definitive data regarding the incidence of postoperative winged scapula remains inconsistent. Ignorance of its diagnosis may lead to under-treatment and result in physical morbidity. Methods: All breast cancer patients who underwent axillary lymph node dissection procedures were recruited. In the early postoperative period, within 24 hours after surgery, the physiotherapy staff performed physical examinations to evaluate and identify the physical signs of long thoracic nerve injury by means of two specific orthopedic evaluation tests. The factors that may relate to winged scapula were recorded and analyzed. Results: From July to October 2012, 51 out of 187 patients were diagnosed with winged scapula (27.2%). The median age was 49.0 years old. 130 patients had undergone mastectomy and 100 cases had immediate breast reconstruction. Age, BMI, history of shoulder joint morbidity and previous breast surgery were not significantly associated with winged scapula. Administration of neoadjuvant treatment, mastectomy or breast conservative surgery, immediate reconstruction and its type, tumor size and nodal involvement also did not show any correlation. Conclusions: The winged scapula is not an infrequent sequela after axillary lymph node dissection in the breast cancer patient. It is usually underestimated and overlooked. There is no association between age, BMI, neoadjuvant treatment, type of breast surgery, tumor size or nodal stage. As breast reconstruction plats an ever-increasing role in current breast surgery practice it is interesting to note that reconstruction with prosthesis, even with serratus muscle dissection does not increase the incidence of winged scapula. Post reconstruction morbidity could interfere with the physical evaluation and outcome, but the result of our subgroup analysis showed no significant correlation among them. In our clinical experience, this sequela is not irreversible, being a transitory problem. Our series show only immediate 24 hr result that lack of long term follow-up and still need physical therapy proctocols to evaluate the recovery.

Silybin-phosphatidylcholine is an orally bioavailable complex of silybin, a polyphenolic flavonolignan derived from milk thistle, endowed with potential anti-cancer activity in preclinical models. The purpose of this window of opportunity trial was to determine, for the first time in early breast cancer (BC) patients, the breast tissue distribution of silybin. Twelve BC patients received silybin-phosphatidylcholine, 2.8 g daily for 4 weeks prior to surgery. Silybin levels were measured before (SIL) and after (TOT-SIL) enzymatic hydrolysis by HPLC-MS/MS in biological samples (plasma, urine, BC and surrounding normal tissue). Fasting blood samples were taken at baseline, before the last administration and 2 hours later. All patients were fully compliant and completed the treatment program. No toxicity was observed. SIL and TOT-SIL were undetectable in baseline samples. Despite a high between-subject variability, repeated administration of Siliphos achieved levels of TOT-SIL of 31121 t...

In 2003, a skin cancer screening campaign based on total body skin examination was launched in the federal state of Schleswig-Holstein, Germany. 20% of adults aged 20 and over were screened. In 2008, a 48% decline in melanoma mortality was reported. In the same year, skin screening was extended to the rest of Germany. We evaluated whether melanoma mortality trends decreased in Germany as compared with surrounding countries where skin screening is uncommon. We also evaluated whether the initial decreasing mortality trend observed in Schleswig-Holstein was maintained with a longer follow-up. Regional and national melanoma mortality data from 1995 to 2013 were extracted from the GEKID database and the Federal Statistical Office. Mortality data for Germany and surrounding countries from 1980 to 2012 were extracted from the WHO mortality database. Age-adjusted (European Standard Population) mortality rates were computed and joinpoint analysis performed for Schleswig-Holstein, Germany and surrounding countries. In Schleswig-Holstein, melanoma mortality rates declined by 48% from 2003 to 2008, and from 2009 to 2013 returned to levels observed before screening initiation. During the 5 years of the national programme (2008-2012), melanoma mortality rates increased by 2.6% (95% CI -0.1 to 5.2) in men and 0.02% (95% CI -1.8 to 1.8) in women. No inflexion point in trends was identified after 2008 that could have suggested a decreasing melanoma mortality. Trends of cutaneous melanoma mortality in Germany from 1980 to 2012 did not differ from those observed in surrounding countries. The transient decrease mortality in Schleswig-Holstein followed by return to pre-screening levels could reflect a temporal modification in the reporting of death causes. An in-depth evaluation of the screening programme is required.

Use of mouthwash and an increased risk of oral cancer has been a source of controversy for decades. A meta-analysis of epidemiological studies of mouthwash and oral cancer and, specifically, mouthwash containing >25% alcohol, was undertaken. Summary estimates were obtained with maximum likelihood estimates from random effects models. Sensitivity analyses were conducted to evaluate the influence of various inclusion. Eighteen studies were included in the meta-analysis. There was no statistically significant associations found between regular use of mouthwash and risk of oral cancer (RR=1.13; 95% CI (0.95-1.35)). There was no significant trend in risk of oral cancer associated with increased daily usage of mouthwash (p=0.11). There was no association between reported use of mouthwash specifically containing alcohol and risk of oral cancer (RR=1.16; 95% CI (0.44, 3.08)). This quantitative analysis of mouthwash use and oral malignancy revealed no statistically significant association...

Vitamin D plays a significant role in our health, including cancer incidence and mortality. Vitamin D receptor (VDR) single-nucleotide polymorphisms (SNPs) may affect its activity, influencing the risk of cancer. Several studies have investigated VDR SNPs, but the association with the risk of cancer is controversial. Here, we present a meta-analysis to assess the association of TaqI, ApaI, and Cdx2 SNPs with the risk of cancer. A systematic literature search was performed following a predefined protocol and using validated search strategies. This meta-analysis shows the summary odd ratio (SOR) overall, by cancer sites and by ethnicity. Up to January 2014, we identified 73 independent studies with 35 525 cases and 38 675 controls. The meta-analysis of Cdx2 gg versus GG showed a significant 12% increased risk for all cancers [SOR=1.12; 95% confidence interval (CI): 1.00-1.25]. The other SNPs analyzed did not show an overall significant association with the risk of cancer: SOR=0.98 (95% CI: 0.90-1.07) and 1.06 (95% CI: 0.95-1.19) for TaqI tt versus TT and ApaI aa versus AA, respectively. TaqI shows a significant 43% increased risk for colorectal cancer (SOR=1.43; 95% CI: 1.30-1.58 for tt vs. TT). Strong frequency variations are present among different ethnic groups. This meta-analysis showed an overall increased risk of cancer associated with Cdx2 SNP and a specific higher risk of colorectal cancer associated with the TaqI polymorphism. The VDR genotype might become more relevant when clustered in a specific haplotype, associated with other SNPs of genes involved in vitamin D metabolism, or for specific tumors and/or patient characteristics.

This review highlights the role of vitamins and natural compounds in breast cancer prevention, with a particular focus on Vitamin D. In the last decades, both encouraging and discouraging results about the association between antioxidant supplementation and cancer have been reported to public and scientific community. Their safe and favorable toxicity profile makes them suitable to be investigated in a preventive setting. However, a recent large meta-analysis showed that treatment with beta carotene, vitamin A, and vitamin E may increase mortality, whereas the potential roles of vitamin C and selenium on mortality need further study. Likewise, folate levels were not associated with reduced breast cancer risk in a recent meta-analysis. Several studies have shown that a high proportion of women at-risk for breast cancer or affected by the disease have deficient vitamin D levels, i.e., 250 H-D <20 ng/ml or 50 nmol/L. While the association between Vitamin D levels and breast cancer risk/prognosis is still controversial, the U-shaped relationship between 250 H-D levels observed in different studies suggests the need to avoid both deficient and too high levels. Further trials using an optimal dose range are needed to assess the preventive and therapeutic effect of vitamin D. Finally, Fenretinide, a pro-apoptotic and pro-oxidant vitamin A derivative, has shown promise in several trials and its preventive potential is being assessed in young women at very high risk for breast cancer.

Adipokines are linked to obesity and insulin sensitivity and have recently been related to breast cancer risk and prognosis. We investigated the associations of plasma leptin and adiponectin with mammographic density and disease status and assessed their prognostic effect on recurrence-free survival in premenopausal women at risk for breast cancer.

The purpose of this review is to present the preclinical, epidemiological and clinical data relevant to the association between β-blockers and melanoma progression. Preclinical studies have shown that β-adrenergic receptor (β-AR) signaling can inhibit multiple cellular processes involved in melanoma progression and metastasis. These observations have suggested the possibility that drugs originally intended for the treatment of cardiovascular disease, the β-AR blockers, may provide new therapeutic opportunities for the control of tumor progression. A large number of observational studies demonstrated the protective effect of β-blockers in breast cancer but, more recently, similar findings were also reported in other cancers such as prostate cancer and melanoma. With regard to melanoma, two recently published studies demonstrated a great reduction in the risk of disease progression for each year of treatment with β-blockers. The results from these studies have suggested a potential role for targeting the β-AR pathway in melanoma patients. Questions regarding the type of β-blocker or tumor characteristics, appropriate treatment paradigms and, most importantly, efficacy must be answered in randomized clinical studies before β-blockers can be considered a therapeutic option for patients with melanoma.

Primary lymphoma of the lung is a rare entity. Clinical features, optimal treatment, role of surgery and outcomes are not well defined, and the follow-up is variable in published data. Clinical data of 205 patients who were confirmed to have bronchus mucosa-associated lymphoid tissue lymphoma from December 1986 to December 2011 in 17 different centres worldwide were evaluated. Fifty-five per cent of the patients were female. The median age at diagnosis was 62 (range 28-88) years. Only 9% had a history of exposure to toxic substances, while about 45% of the patients had a history of smoking. Ten per cent of the patients had autoimmune disease at presentation, and 19% patients had a reported preexisting lung disease. Treatment modalities included surgery alone in 63 patients (30%), radiotherapy in 3 (2%), antibiotics in 1 (1%) and systemic treatment in 128 (62%). Patients receiving a local approach, mainly surgical resection, experienced significantly improved progression-free survival (p = 0.003) versus those receiving a systemic treatment. There were no other significant differences among treatment modalities. The survival data confirm the indolent nature of the disease. Local therapy (surgery or radiotherapy) results in long-term disease-free survival for patients with localized disease. Systemic treatment, including alkylating-containing regimens, can be reserved to patients in relapse after incomplete surgical excision or for patients with advanced disease. Copyright © 2015 John Wiley & Sons, Ltd.

Melanoma is the most deadly form of skin cancer and its incidence is increasing worldwide. In 2009, the International Agency for Research on Cancer classified the entire UV spectrum as carcinogenic. In many countries, including Italy, the use of tanning equipment by minors and individuals with high risk phenotypes has been banned. This study assessed tan-seeking behaviour in a Mediterranean population with a relatively high melanoma incidence, where a considerable time is spent tanning outdoors. Subjects spending the most time in the sun were typically young single men, who use significantly less sunscreen and sunglasses. The overall prevalence of sunbed use was 22% in youth (≤35 years old) and 18% of them used sunbeds throughout the year. Sunbed use in youth was greater for phenotypes at risk. In Italy, 3.8% of melanoma cases are attributable to sunbed use, more in women (4.2% vs 3.1%, for women and men respectively) and much more in the young (17%). Of 8013 new melanoma cases in 2...

Factors linked to glucose metabolism play an important role in the development of cancers, and both glycemic index (GI) and glycemic load (GL) have been investigated as potential etiologic factors. A meta-analysis was performed to explore the association between GI and GL and cancer risk from published studies. A comprehensive, systematic bibliographic search of the medical literature was conducted to identify relevant studies. Case-control and cohort studies published before October 2007 that reported cancer risk estimates for GI and GL were included. Pooled relative risks (RRs) were estimated for breast, colorectal, endometrial, and pancreatic cancer. Thirty-nine studies were included in the meta-analysis. The interquantile ranges of GL were significantly wider in case-control studies, most of which were conducted in European countries, than in cohort studies. Cohort studies that presented lower ranges of GL also reported lower risk estimates. Overall, both GL and GI were signific...