Correction to: Clinicopathological predictors of recurrence in nodular and superficial spreading cutaneous melanoma: a multivariate analysis of 214 cases.

In the original version of this article [1], published on 7 November 2017, affiliation 18 has been incorrectly assigned to the authors Serena Magi and Laura Mazzoni. They are only affiliated to the Skin Cancer Unit, Istituto Tumori Romagna (IRST), Meldola, Italy (affiliation 5).

Health-related quality of life after BCG or MMC induction for non-muscle invasive bladder cancer.

INTRODUCTION: To evaluate health-related quality of life (HRQoL) in patients with non-muscle invasive bladder cancer (NMIBC) during the induction phase of intravesical instillations with BCG or MMC. MATERIALS AND METHODS: HRQoL was measured by two questionnaires from EORTC (QLQ-C30 and QLQ-BLS24), stratifying results by gender, age and therapy at the start of the therapy (T0), at last instillation (T1) and at 3 months after T1 (T2). The persistence of QoL-related side effects after 3 months from the end of the induction cycle was evaluated. RESULTS: We enrolled 108 naïve patients and 103 patients self-completed the questionnaires. Treatment was well tolerated in both groups. Side effects were reported by 46.6% of patients at T1 and 47.5% of patients at T2. QoL dropped at T1, returning to the baseline at T2. Drop of QoL was greater in the physical, role, emotional and social functioning domains and in some clinical domains as pain, fatigue and insomnia. Our stratified analysis showed that patients > 70 years have a worsening of QoL, a higher incidence of patient-reported side effects or symptoms in the BCG arm as compared to MMC arm. CONCLUSIONS: Our study shows that intravesical instillations of BCG or MMC during the induction phase might have a relevant effect on HRQoL.

Health-Related Quality of Life after Radical Cystectomy for Bladder Cancer in Elderly Patients with Ileal Orthotopic Neobladder or Ileal Conduit: Results from a Multicentre Cross-Sectional Study Using Validated Questionnaires.

OBJECTIVE: To evaluate health-related quality of life (HR-QoL) outcomes in elderly patients with different type of urinary diversion (UD), ileal conduit (IC) and ileal orthotopic neobladder (IONB), after radical cystectomy (RC) for bladder cancer, by using validated self-reported cancer-specific instruments. PATIENTS AND METHODS: We retrospectively reviewed 77 patients who received an IC or an IONB after RC. HR-QoL was assessed with specific and validated disease questionnaires, administered at last follow-up. RESULT: At univariate analysis, at a mean follow-up of 60.91 ± 5.63 months, IONB results were favourable with regard to the following HR-QoL aspects: nausea and vomiting (p = 0.045), pain (p = 0.049), appetite loss (p = 0.03), constipation (p = 0.000), financial impact (p = 0.012) and cognitive functioning (p = 0.000). This last functional aspect was significantly worse in female patients (p = 0.029). Emotional functioning was significantly better in patients without long-term complications (p = 0.016). At multivariate analysis, male gender and IONB were independent predictors of better cognitive functioning, while long-term complications negatively affected emotional functioning. CONCLUSIONS: Obtained results suggest that an IONB can also be suitable for elderly patients compared with an IC with few and selected advantages in favour of the former UD. Preoperative patient's selection, counselling, education and active participation in the decision-making process lead to a more suitable choice of treatment.

Clinicopathological predictors of recurrence in nodular and superficial spreading cutaneous melanoma: a multivariate analysis of 214 cases.

BACKGROUND: Nodular melanoma (NM) accounts for most thick melanomas and because of their frequent association with ulceration, fast growth rate and high mitotic rate, contribute substantially to melanoma-related mortality. In a multicentric series of 214 primary melanomas including 96 NM and 118 superficial spreading melanoma (SSM), histopathological features were examined with the aim to identify clinicopathological predictors of recurrence. METHODS: All consecutive cases of histopathologically diagnosed primary invasive SSM and NM during the period 2005-2010, were retrieved from the 12 participating Italian Melanoma Intergroup (IMI) centers. Each center provided clinico-pathological data such as gender, age at diagnosis, anatomical site, histopathological conventional parameters, date of excision and first melanoma recurrence. RESULTS: Results showed that NM subtype was significantly associated with Breslow thickness (BT) at multivariate analysis: [BT 1.01-2 mm (OR 7.22; 95% CI 2.73-19.05), BT 2.01-4 mm (OR 7.04; 95% CI 2.54-19.56), and BT > 4 mm (OR 51.78; 95% CI 5.65-474.86) (p < 0.0001)]. Furthermore, mitotic rate (MR) was significantly correlated with NM histotype: [(MR 3-5 mitoses/mm2 (OR 2.62; 95% CI 1.01-6.83) and MR > 5 mitoses/mm2 (OR 4.87; 95% CI 1.77-13.40) (p = 0.002)]. The risk of recurrence was not significantly associated with NM histotype while BT [BT 1.01-2.00 mm (HR 1.55; 95% CI 0.51-4.71), BT 2.01-4.00 mm (HR 2.42; 95% CI 0.89-6.54), BT > 4.00 mm. (HR 3.13; 95% CI 0.95-10.28) (p = 0.05)], mitotic rate [MR > 2 mitoses/mm2 (HR 2.34; 95% CI, 1.11-4.97) (p = 0.03)] and the positivity of lymph node sentinel biopsy (SNLB) (HR 2.60; 95% CI 1.19-5.68) (p = 0.007) were significantly associated with an increased risk of recurrence at multivariate analysis. CONCLUSIONS: We found that NM subtype was significantly associated with higher BT and MR but it was not a prognostic factor since it did not significantly correlate with melanoma recurrence rate. Conversely, increased BT and MR as well as SNLB positivity were significantly associated with a higher risk of melanoma recurrence.

Dietary Acrylamide and the Risk of Endometrial Cancer: An Italian Case-Control.

The role of dietary acrylamide on the risk of hormone-related, and specifically endometrial, cancers is debated. Epidemiological data are scanty. Thus, we examined the relation between acrylamide intake and endometrial cancer risk in a case-control study conducted between 1992 and 2006 in 3 Italian areas. Cases were 454 women with incident, histologically confirmed endometrial cancer. Controls were 908 age-matched women admitted to the same network of hospitals of cases for acute, non-neoplastic conditions. We calculated multivariate odds ratios (OR) and 95% confidence intervals (CI) using logistic regression models. The OR of endometrial cancer for increasing quintiles of dietary acrylamide, as compared to the lowest one, were 1.02 (95% CI: 0.67-1.54), 1.20 (95% CI: 0.80-1.80), 1.00 (95% CI: 0.65-1.54) and 1.17 (95% CI: 0.73-1.85). The OR for an increase of 10 µg/day of dietary acrylamide was 1.00 (95% CI: 0.91-1.10). In subgroup analyses, the ORs for high vs. low acrylamide intake were 1.28 (95% CI: 0.73-2.25) in never smokers and 1.14 (95% CI: 0.45-2.90) in ever smokers. Our data do not support an association between dietary acrylamide intake and endometrial cancer.

Postoperative Quality of Life in Patients with Ileal Neobladder at Short-, Intermediate- and Long-Term Follow-Up.

BACKGROUND: To evaluate the difference at different steps of follow-up of the postoperative quality of life (QoL) in patients who had undergone radical cystectomy and ileal orthotopic neobladder derivation. PATIENTS AND METHODS: A multicentric, cross-qualitative study was performed in 5 Italian centers of reference for the treatment of bladder cancer. One hundred seventy one patients who underwent radical cystectomy and creation of ileal orthotopic neobladder according to 'Vescica Ileale Padovana' between 2006 and 2011 have been analyzed. The validated and dedicated questionnaires EORTC QLQ-C30, IOB-PRO and EORTC QLQ-BLM30 were used. RESULTS: All data gathered were then processed, specifically means ± SD were included for comparison during 4 periods of follow-up (quartile): the first ranging from 1 to 18 months; the second ranging from 19 to 36 months; the third from 37 to 72 months and the fourth >72 months. Cancer-specific and health-related factors were analyzed separately, and the change was determined during follow-up. CONCLUSIONS: The global QoL, highlighted by validated cancer-specific and health-related questionnaires, is certainly on a satisfactory level. Thus, the education of the patient, the exploration of the pros and cons of an orthotopic neobladder and the active participation in treatment decision seem to be the keys to better improve the post-operative QoL during the follow-up period.

Folate intake and the risk of oral cavity and pharyngeal cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology Consortium.

There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPCs), but most studies are limited in sample size, with only few reporting information on the source of dietary folate. Our study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual-level data from ten case-control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest vs. the lowest quintile was 0.65, 95% CI: 0.43-0.99), with a stronger association for oral cavity (OR = 0.57, 95% CI: 0.43-0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only in oral cavity cancer (OR = 0.64, 95% CI: 0.45-0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR = 4.05, 95% CI: 3.43-4.79); the attributable proportion (AP) owing to interaction was 11.1% (95% CI: 1.4-20.8%). Lastly, we reported an OR of 2.73 (95% CI:2.34-3.19) for those ever tobacco users with low folate intake, compared with nevere tobacco users and high folate intake (AP of interaction =10.6%, 95% CI: 0.41-20.8%). Our project of a large pool of case-control studies supports a protective effect of total folate intake on OPC risk.

Mediterranean diet and hepatocellular carcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) has a very poor prognosis and any effort to identify additional risk factors, besides those already established, would be important for the prevention of the disease. Data on the role of diet on HCC risk are still controversial. METHODS: We have evaluated the association of adherence to the Mediterranean diet with HCC risk, as well as the interaction of this dietary pattern with chronic hepatitis infection, by combining two case-control studies undertaken in Italy and Greece, including overall 518 cases of HCC and 772 controls. Adherence to the traditional Mediterranean diet was assessed through the Mediterranean diet score (MDS), which ranges between 0 (lowest adherence) and 9 (highest adherence). Odds ratios (OR) for HCC were obtained through multiple logistic regression models, controlling for potentially confounding factors, including chronic infection with hepatitis B/C viruses. RESULTS: Compared to MDS of 0-3, the ORs for HCC were 0.66 (95% confidence interval (CI), 0.41-1.04) for MDS equal to 4 and 0.51 (95% CI, 0.34-0.75) for MDS ⩾ 5, with a significant trend (p<0.001). The detrimental effect of poor adherence to Mediterranean diet on HCC risk was disproportionally high among those chronically infected with hepatitis B and/or C viruses, with a suggestion of super-additive interaction, albeit statistically non-significant. CONCLUSIONS: Closer adherence to the Mediterranean diet appears to be protective against HCC. Our results also point to potential benefits from adhering to a Mediterranean dietary pattern for patients chronically infected with hepatitis viruses.

Nutrient-based dietary patterns and prostate cancer risk: a case-control study from Italy.

PURPOSE: The role of various foods and nutrients, and their combinations, on prostate cancer risk remains largely undefined. We addressed therefore the issue of complex dietary patterns. METHODS: We analyzed data from an Italian case-control study, including 1,294 men with prostate cancer and 1,451 hospital controls. We carried out an exploratory principal component factor analysis on 28 selected nutrients in order to identify dietary patterns. We estimated odds ratios (ORs) and corresponding confidence intervals (CIs) using logistic regression models on quintiles of factor scores, adjusting for major confounding variables. RESULTS: We identified five dietary patterns, labeled "Animal Products," "Vitamins and Fiber," "Starch-rich," "Vegetable Unsaturated Fatty Acids (VUFA)," and "Animal Unsaturated Fatty Acids (AUFA)." We found positive associations between prostate cancer and "Animal Products" (OR for the highest vs. the lowest score quintile: 1.51, 95 % CI 1.16-1.96), "Starch-rich" (OR 1.50, 95 % CI 1.16 1.93), and "AUFA" (OR 1.32, 95 % CI 1.02-1.70) patterns. No significant associations emerged with "Vitamins and Fiber" (OR 0.93) and "VUFA" (OR 1.16) patterns. CONCLUSIONS: Our findings suggest that a diet rich in animal products, including several types of meat and dairy products, as well as of (refined) cereals and sugars has an unfavorable role on prostate cancer.

Duration and intensity of tobacco smoking and the risk of papillary and non-papillary transitional cell carcinoma of the bladder.

PURPOSE: To evaluate the impact of tobacco smoking on specific histological subtypes of transitional cell carcinoma of the bladder (TCC). METHODS: Between 2003 and 2009, we conducted a hospital-based case-control study in Italy, enrolling 531 incident TCC cases and 524 cancer-free matched patients. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were estimated through multiple logistic regression models. RESULTS: Compared to never smokers, TCC risk was threefold higher in former smokers (95% CI 2.07-4.18) and more than sixfold higher in current smokers (95% CI 4.54-9.85). TCC risk steadily increased with increasing intensity (OR for ≥25 cigarettes/day 8.75; 95% CI 3.40-22.55) and duration of smoking (OR for ≥50 years 5.46; 95% CI 2.60-11.49). No heterogeneity emerged between papillary and non-papillary TCCs for smoking intensity and duration, but the risk for those who had smoked for ≥50 years was twice for non-papillary TCC (OR 10.88) compared with papillary one (OR 4.76). Among current smokers, the risk for a 10-year increase in duration grew across strata of intensity (p-trend = 0.046). Conversely, the risk for a 5-cigarette/day increase in smoking intensity was quite steady across strata of duration (p-trend = 0.18). CONCLUSIONS: Study results suggested that duration of smoking outweighs intensity in determining TCC risk, with limited differences across histological subtypes. Elimination of tobacco smoking may prevent about 65 % of TCCs.

Anthracycline-free neoadjuvant therapy induces pathological complete responses by exploiting immune proficiency in HER2+ breast cancer patients.

BACKGROUND: Neoadjuvant Chemotherapy (NC) including trastuzumab induces a high rate of pathological Complete Responses (pCR) in patients with locally advanced HER2-overexpressing Breast Cancer (BC), but is penalized by a severe cardiotoxicity when combined with anthracyclines. A phase II study was designed to assess whether an anthracycline-free NC regimen based on the early addition of trastuzumab to paclitaxel may increase the pCR rate without inducing severe cardiotoxicity in patients with locally advanced HER2-overexpressing BC. Immunomonitoring was performed to assess the contribution of patients' immunological background to the induction of clinical responses. METHODS: Stage II-III HER2-positive BC patients received 24 weeks paclitaxel and trastuzumab NC, followed by 1 year adjuvant trastuzumab ± hormonal and/or radio-therapy. Assessment of pCR rate was the primary endpoint. A group of HER2-negative BC patients treated with neoadjuvant taxanes and anthracyclines was included. Serum levels of 10 cytokines and the efficiency of trastuzumab-mediated antibody-dependent cell cytotoxicity (ADCC) were monitored in vitro every 3 months. RESULTS: From July 2006 to February 2013, we enrolled 109 patients including 46 evaluable HER2-positive cases. A pCR rate of 50% was reached and no severe cardiotoxicity occurred. Serum cytokine profiling revealed only an IL-10 decrease (P = 0.02) in patients achieving a partial response, while HER2-negative patients disclosed marked cytokines changes. Compared to the unfavourable F/F genotype, patients carrying the V allele in the FcγRIIIa-158 polymorphism showed a higher efficacy of trastuzumab-ADCC throughout treatment (P ≤0.05). CONCLUSIONS: In the absence of anthracyclines, trastuzumab and paclitaxel induced a high rate of pCR, exploiting the synergy between the immunomodulating properties of these drugs and the retained immunological proficiency of patients with HER2-overexpressing BC. TRIAL REGISTRATION: Trial registration number: NCT02307227, registered on ClinicalTrials.gov (http://www.clinicaltrials.gov, November 26, 2014).

Adult height and head and neck cancer: a pooled analysis within the INHANCE Consortium.

Several epidemiological studies have shown a positive association between adult height and cancer incidence. The only study conducted among women on mouth and pharynx cancer risk, however, reported an inverse association. This study aims to investigate the association between height and the risk of head and neck cancer (HNC) within a large international consortium of HNC. We analyzed pooled individual-level data from 24 case-control studies participating in the International Head and Neck Cancer Epidemiology Consortium. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated separately for men and women for associations between height and HNC risk. Educational level, tobacco smoking, and alcohol consumption were included in all regression models. Stratified analyses by HNC subsites were performed. This project included 17,666 cases and 28,198 controls. We found an inverse association between height and HNC (adjusted OR per 10 cm height = 0.91, 95% CI 0.86-0.95 for men; adjusted OR = 0.86, 95% CI 0.79-0.93 for women). In men, the estimated OR did vary by educational level, smoking status, geographic area, and control source. No differences by subsites were detected. Adult height is inversely associated with HNC risk. As height can be considered a marker of childhood illness and low energy intake, the inverse association is consistent with prior studies showing that HNC occur more frequently among deprived individuals. Further studies designed to elucidate the mechanism of such association would be warranted.

Development of a questionnaire specifically for patients with Ileal Orthotopic Neobladder (IONB).

BACKGROUND: The ileal orthotopic neobladder (IONB) is often used in patients undergoing radical cystectomy. The IONB allows to void avoiding the disadvantages of the external urinary diversion.In IONB patients the quality of life (QoL) appears compromised by the need to urinate voluntarily. The patients need to wake up at night interrupting the sleep-wake rhythm with consequences on social and emotional life.At present the QoL in IONB patients is evaluated by generic questionnaires. These are useful when IONB patients are compared with patients with different urinary diversions but they are less effective when only IONB patients are evaluated. To address this problem a specific questionnaire-the IONB-PRO-was developed. METHODS: A) Based on a conceptual framework, narrative-based interviews were conducted on 35 IONB patients. A basic pool of 43 items was produced and organized throughout two clinical and four QoL dimensions. An additional 15 IONB patients were interviewed for face validity testing.B) Psychometric testing was conducted on 145 IONB patients. Both classic test strategy and Rasch analysis were applied. Psychometric properties of the resulting scales were comparatively tested against other QoL-validated scales. RESULTS: The IONB-PRO questionnaire includes two sections: one on the QoL and a second section on the capability of the patient to manage the IONB. For evaluation of the QoL, three versions were delivered: 1) a basic 23-item QoL version (3 domains 23-items; alpha 0.86÷ 9.69), 2) a short-form 12-item QoL scale (alpha = 0.947), and 3) a short-form 15-item Rasch QoL scale (alpha = 0.967). Correlations of the long version scales with the corresponding dimensions of the EORTC-QLQ C30 and the EORTC-BLM30 were significant. The short forms exhibited significant correlations with the global health dimension of the EORTC-QLQ and with the urinary subscales of the EORTC-BLM30. The effect size was approximately 1.00 between patients at the 1-year follow-up period and those with 3, 5, and > 5-year follow-up periods for all scales. No relevant differences were observed between the 12-item short-form and the Rasch scale. CONCLUSIONS: The IONB-PRO long and short-forms demonstrated a high level of internal consistency and reliability with an excellent discriminanting validity.

Behavioural profile and human adaptation of survivors after radical cystectomy and ileal conduit.

BACKGROUND: There is a lack of good data in the literature evaluating the Health-Related Quality of Life (HR- QoL) in patients with urinary diversions. The aim of this study was to examine the changes in expectation and needs in terms of human adaptation and behavioural profiles in patients with ileal conduit (IC) after radical cystectomy (RC) for bladder cancer (BC). MATERIALS AND METHODS: A qualitative, multicenter cross-sectional study using a "narrative based" approach was planned. We proceed with a sampling reasoned choice (purposive), selecting groups of patients with follow-up from one up to more than 7 years after surgery. Data were collected through individual interviews. RESULTS: Thirty patients participated in the study. The processing of the interviews allowed us to identify 2 major profiles: positive and negative. Patients with a positive profile resumed normal daily activities with no or limited restrictions both on the personal and the social level. This profile reflects a good HR-QoL. The negative profile reflects the patients for whom the ostomy has meant a worsening of HR-QoL. A positive profile was statistically more frequent in older patients (p = 0.023), with a longer follow-up (p = 0.042) and less complications rates (p = 0.0002). According to the length of follow-up and the occurrence of complitations, we identified further 5 intermediate profiles. CONCLUSIONS: Patients' satisfaction is related to the degree of adaptation to their new life with an urinary stoma and its correct management. Live "with urinary diversion" represents a new phase of life and not a deterioration.

A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25.

Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 x 10(-10)). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 x 10(-20) overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines, and they bind to N'-nitrosonornicotine and potential lung carcinogens. A non-synonymous variant of CHRNA5 that induces an amino acid substitution (D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets.

Negative pigment network and shiny white streaks: a dermoscopic-pathological correlation study.

It has been suggested that both negative pigment network (NPN) and shiny white streaks (SWS) were related to an increase of dermal collagen. To study precisely the dermoscopic-histopathologic correlation of NPN and SWS, we have performed a dermoscopic-pathological correlation study. A total of 25 skin lesions dermoscopically characterized by the presence of NPN and/or SWS, including histopathologically confirmed dermatofibroma (2), Spitz nevus (3), compound nevus (6), dysplastic nevus (7), and melanoma (7), were evaluated for the presence of NPN, SWS, and blue-white veil. The histopathologic features such as orthokeratosis, orthokeratosis plus nests of pigmented melanocytes at the junction, hypergranulosis, hypergranulosis plus nests of pigmented melanocytes at the junction, epidermal invagination plus orthokeratosis, fibrosis, lamellar fibrosis, and elongation and bridging of rete ridges were evaluated. We found a disagreement in 80% of skin lesions between NPN and fibrosis (P = 0.02). For SWS, a significant agreement emerged with hypergranulosis (76%; P = 0.01), and the same occurred with fibrosis (80%; P = 0.01). Moreover, blue-white veil also displayed a significant agreement with hypergranulosis (68%; P = 0.04). Our findings confirm the correlation of SWS with fibrosis, whereas a clear-cut histopathologic substrate of NPN could not be established.

Natural history of atypical and equivocal melanocytic lesions in children: an observational study of 19 cases.

Digital dermoscopy follow-up helps to identify patterns of change typical of common atypical nevi and early melanoma and improves the follow-up of patients with atypical nevi. We report the morphologic changes observed over time in 19 atypical or equivocal acquired melanocytic nevi that underwent dermoscopic follow-up. Two observers retrospectively examined digitalized dermoscopic images of 19 atypical melanocytic nevi from 15 children and young adults (median age 12 years, range 3-26 years). The images were assessed for global dermoscopic patterns at baseline and after a median 25-month (range 6-138 mos) follow-up. Ten (52.6%) nevi changed and nine (47.4%) retained a stable dermoscopic pattern. Of the 10 changing lesions, 2 of 4 homogeneous nevi evolved into a reticular pattern and 2 into a mixed pattern; 1 of 2 nevi with a mixed pattern evolved into a homogeneous nevus and 1 into a regressing nevus; 1 of 2 nevi with "other" patterns, such as negative pigment network and peppering throughout the lesion, evolved into a mixed nevus and 1 into a regressing nevus; 1 globular nevus evolved into a mixed pattern; and 1 starburst nevus evolved into a homogeneous nevus. The most striking results of our study were that atypical nevi can evolve into common nevi or they can regress, as documented by long-term dermoscopic follow-up. In children and young adults, dermoscopic follow-up of atypical nevi might be a valid alternative to surgical excision and enables us to achieve new insights into the natural history of these nevi.

A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻7). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10⁻8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻8); rs1229984-ADH1B, p = 7 × 10⁻9; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

Short-term effects of bowel function on global health quality of life after radical cystectomy.

BACKGROUND: Radical cystectomy (RC) shows an important impact on quality of life (QoL), for various clinical aspects. The aim of our study was to evaluate the short-term bowel function in patients that underwent RC. METHODS: Two hundred and six patients with MIBC underwent RC with ONB or IC urinary diversion. QoL was measured using the EORTC QLQ C30 and the Short-Form SF-36 questionnaires before surgery and at 12 months postoperatively. Baseline characteristics, including demographic profile, BMI, Charlson Comorbidity Index (CCI), modified Frailty Index (m-FI), pathological tumor stage, Clavien-Dindo grade, and neo-adjuvant chemotherapy were recorded and compared. RESULTS: The uni-variate and multivariate analysis (OR) were performed for constipation, diarrhea and m-FI of patients underwent RC for localized MIBC according to global health status score (poor/good vs. very good). Multivariate analysis showed that constipation medium/high was significant associated with global health status poor/good (OR=2.39; 95% CI: 1.22-4.71; P=0.01); Diarrhea medium/high was associated with global health status poor/good (OR=2.85; 95% CI:1.18-6.92; P=0.02), and m-FI ≥2 score (OR=2.13; 95% CI: 0.99-4.57; P=0.05). CONCLUSIONS: Diarrhea and constipation are associated with a lower QoL in cystectomized patients, both with ONB or IC urinary diversion; such association is especially significant in more fragile patients (Frailty Index ≥2).

Smoking addiction and the risk of upper-aerodigestive-tract cancer in a multicenter case-control study.

Although previous studies on tobacco and alcohol and the risk of upper-aerodigestive-tract (UADT) cancers have clearly shown dose-response relations with the frequency and duration of tobacco and alcohol, studies on addiction to tobacco smoking itself as a risk factor for UADT cancer have not been published, to our knowledge. The aim of this report is to assess whether smoking addiction is an independent risk factor or a refinement to smoking variables (intensity and duration) for UADT squamous cell carcinoma (SCC) risk in the multicenter case-control study (ARCAGE) in Western Europe. The analyses included 1,586 ever smoking UADT SCC cases and 1,260 ever smoking controls. Addiction was measured by a modified Fagerström score (first cigarette after waking up, difficulty refraining from smoking in places where it is forbidden and cigarettes per day). Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for UADT cancers with addiction variables were estimated with unconditional logistic regression. Among current smokers, the participants who smoked their first cigarette within 5 min of waking up were two times more likely to develop UADT SCC than those who smoked 60 min after waking up. Greater tobacco smoking addiction was associated with an increased risk of UADT SCC among current smokers (OR = 3.83, 95% CI: 2.56-5.73 for score of 3-7 vs. 0) but not among former smokers. These results may be consistent with a residual effect of smoking that was not captured by the questionnaire responses (smoking intensity and smoking duration) alone, suggesting addiction a refinement to smoking variables.