Increased cancer risk in patients undergoing dialysis: a population-based cohort study in North-Eastern Italy

open116noBACKGROUND: In southern Europe, the risk of cancer in patients with end-stage kidney disease receiving dialysis has not been well quantified. The aim of this study was to assess the overall pattern of risk for de novo malignancies (DNMs) among dialysis patients in the Friuli Venezia Giulia region, north-eastern Italy. METHODS: A population-based cohort study among 3407 dialysis patients was conducted through a record linkage between local healthcare databases and the cancer registry (1998-2013). Person-years (PYs) were calculated from 30 days after the date of first dialysis to the date of DNM diagnosis, kidney transplant, death, last follow-up or December 31, 2013, whichever came first. The risk of DNM, as compared to the general population, was estimated using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). RESULTS: During 10,798 PYs, 357 DNMs were diagnosed in 330 dialysis patients. A higher than expected risk of 1.3-fold was found for all DNMs combined (95% CI: 1.15-1.43). The risk was particularly high in younger dialysis patients (SIR = 1.88, 95% CI: 1.42-2.45 for age 40-59 years), and it decreased with age. Moreover, significantly increased DNM risks emerged during the first 3 years since dialysis initiation, especially within the first year (SIR = 8.52, 95% CI: 6.89-10.41). Elevated excess risks were observed for kidney (SIR = 3.18; 95% CI: 2.06-4.69), skin non-melanoma (SIR = 1.81, 95% CI: 1.46-2.22), oral cavity (SIR = 2.42, 95% CI: 1.36-4.00), and Kaposi's sarcoma (SIR = 10.29, 95% CI: 1.25-37.16). CONCLUSIONS: The elevated risk for DNM herein documented suggest the need to implement a targeted approach to cancer prevention and control in dialysis patients.openTaborelli, Martina; Toffolutti, Federica; Del Zotto, Stefania; Clagnan, Elena; Furian, Lucrezia; Piselli, Pierluca; Citterio, Franco; Zanier, Loris; Boscutti, Giuliano; Serraino, Diego for the Italian Transplant & Cancer Cohort Study; Sarah Shalaby, Raffaella Petrara, Patrizia Burra, Giacomo Zanus, Stefano Zanini,Paolo Rigotti; Maria Rendina, AlfredoDi Leo, Francesco Paolo Schena, Giuseppe Grandaliano, Marco Fiorentino, Augusto Lauro, Antonio Daniele Pinna, PaoloDi Gioia, Sara Pellegrini, Chiara Zanfi, Maria Piera Scolari, Sergio Stefoni, PaolaTodeschini, Laura Panicali, Chiara Valentini, Umberto Baccarani, Andrea Risaliti, Gian Luigi Adani, Dario Lorenzin, Giuseppe Maria Ettorre, Giovanni Vennarecci,Marco Colasanti, Manuela Coco, Fabrizio Ettorre, Roberto Santoro, LuciaMiglioresi, Francesco Nudo, Massimo Rossi,Gianluca Mennini, Luca Toti, GiuseppeTisone, Annachiara Casella, Laura Fazzolari, Daniele Sforza, Giuseppe Iaria,Carlo Gazia, Chiara Belardi, ClaudiaCimaglia, Alessandro Agresta, Gianpiero D’Offizi, Ubaldo Visco Comandini,Raffaella Lionetti, Marzia Montalbano, Chiara Taibi, Giovanni Fantola, Fausto Zamboni, Gian Benedetto Piredda,Maria Benigna Michittu, Maria Gavina Murgia, Bruno Onano, Lucia Fratino, Luigino Dal Maso, Paolo De Paoli, Diana Verdirosi,Emanuela Vaccher, Francesco Pisani, Antonio Famulari, Federica Delreno, Samuele Iesari, LindaDe Luca, Maurizio Iaria, Enzo Capocasale,Elena Cremaschi, Silvio Sandrini, Francesca Valerio,Valentina Mazzucotelli, Nicola Bossini, Gisella Setti, Massimiliano Veroux, Pierfrancesco Veroux, Giuseppe Giuffrida,Alessia Giaquinta, Domenico Zerbo, GhilBusnach, Laura Di Leo, Maria Luisa Perrino, Marialuisa Querques, ValerianaColombo, Maria Chiara Sghirlanzoni , Piergiorgio Messa, Antonio Leoni , Laura Galatioto, Salvatore Gruttadauria, Vito Sparacino, FlaviaCaputo, Barbara Buscemi ,Franco Cit-terio, Gionata Spagnoletti, Maria Paola Salerno, Evaldo Favi Giuseppe Paolo Segoloni, Luigi Biancone, AntonioLavacca, Maria Cristina Maresca, CarmeloCascone, Bice Virgilio, Donato Donati, Fiorella Dossi, Andrea Fontanella, Andrea Ambrosini, Marco Di CiccoTaborelli, Martina; Toffolutti, Federica; Del Zotto, Stefania; Clagnan, Elena; Furian, Lucrezia; Piselli, Pierluca; Citterio, Franco; Zanier, Loris; Boscutti, Giuliano; Serraino, Diego for the Italian Transplant & Cancer Cohort Study; Shalaby, Sarah; Petrara, MARIA RAFFAELLA; Burra, Patrizia; Zanus, Giacomo; Zanini, Stefano; Rigotti, Paolo; Maria, Rendina; Alfredodi, Leo; Francesco Paolo Schena, ; Giuseppe, Grandaliano; Marco, Fiorentino; Augusto, Lauro; Antonio Daniele Pinna, ; Paolodi, Gioia; Sara, Pellegrini; Chiara, Zanfi; Maria Piera Scolari, ; Sergio, Stefoni; Paolatodeschini, ; Laura, Panicali; Chiara, Valentini; Umberto, Baccarani; Andrea, Risaliti; Gian Luigi Adani, ; Dario, Lorenzin; Giuseppe Maria Ettorre, ; Giovanni, Vennarecci; Marco, Colasanti; Manuela, Coco; Fabrizio, Ettorre; Roberto, Santoro; Luciamiglioresi, ; Francesco, Nudo; Massimo, Rossi; Gianluca, Mennini; Luca, Toti; Giuseppetisone, ; Annachiara, Casella; Laura, Fazzolari; Daniele, Sforza; Giuseppe, Iaria; Carlo, Gazia; Chiara, Belardi; Claudiacimaglia, ; Alessandro, Agresta; Gianpiero, D’Offizi; Ubaldo Visco Comandini, ; Raffaella, Lionetti; Marzia, Montalbano; Chiara, Taibi; Giovanni, Fantola; Fausto, Zamboni; Gian Benedetto Piredda, ; Maria Benigna Michittu, ; Maria Gavina Murgia, ; Bruno, Onano; Lucia, Fratino; Luigino Dal Maso, ; Paolo De Paoli, ; Diana, Verdirosi; Emanuela, Vaccher; Francesco, Pisani; Antonio, Famulari; Federica, Delreno; Samuele, Iesari; Lindade, Luca; Maurizio, Iaria; Enzo, Capocasale; Elena, Cremaschi; Silvio, Sandrini; Francesca, Valerio; Valentina, Mazzucotelli; Nicola, Bossini; Gisella, Setti; Massimiliano, Veroux; Pierfrancesco, Veroux; Giuseppe, Giuffrida; Alessia, Giaquinta; Domenico, Zerbo; Ghilbusnach, ; Laura Di Leo, ; Maria Luisa Perrino, ; Marialuisa, Querques; Valerianacolombo, ; Maria Chiara Sghirlanzoni, ; Piergiorgio, Messa; Antonio, Leoni; Laura, Galatioto; Salvatore, Gruttadauria; Vito, Sparacino; Flaviacaputo, ; Barbara, Buscemi; Franco, Cit-terio; Gionata, Spagnoletti; Maria Paola Salerno, ; Evaldo Favi Giuseppe Paolo Segoloni, ; Luigi, Biancone; Antoniolavacca, ; Maria Cristina Maresca, ; Carmelocascone, ; Bice, Virgilio; Donato, Donati; Fiorella, Dossi; Andrea, Fontanella; Andrea, Ambrosini; Marco Di Cicco

Information and vaccine hesitancy: Evidence from the early stage of the vaccine roll-out in 28 European countries.

The success of mass vaccination programs against SARS-CoV-2 hinges on the public's acceptance of the vaccines. During a vaccine roll-out, individuals have limited information about the potential side-effects and benefits. Given the public health concern of the COVID pandemic, providing appropriate information fast matters for the success of the campaign. In this paper, time-trends in vaccine hesitancy were examined using a sample of 35,390 respondents from the Eurofound's Living, Working and COVID-19 (LWC) data collected between 12 February and 28 March 2021 across 28 European countries. The data cover the initial stage of the vaccine roll-out. We exploit the fact that during this period, news about rare cases of blood clots with low blood platelets were potentially linked to the Oxford/AstraZeneca vaccine (or Vaxzeveria). Multivariate regression models were used to analyze i) vaccine hesitancy trends, and whether any trend-change was associated with the link between the AstraZeneca vaccine ii) and blood clots (AstraZeneca controversy), and iii) the suspension among several European countries. Our estimates show that vaccine hesitancy increased over the early stage of the vaccine roll-out (0·002, 95% CI: [0·002 to 0·003]), a positive shift took place in the likelihood of hesitancy following the controversy (0·230, 95% CI: [0·157 to 0·302]), with the trend subsequently turning negative (-0·007, 95% CI: [-0·010 to -0·005]). Countries deciding to suspend the AstraZeneca vaccine experienced an increase in vaccine hesitancy after the suspensions (0·068, 95% CI: [0·04 to 0·095]). Trust in institutions is negatively associated with vaccine hesitancy. The results suggest that SARS-CoV-2 vaccine hesitancy increased steadily since the beginning of the vaccine roll-out and the AstraZeneca controversy and its suspension, made modest (though significant) contributions to increased hesitancy

The SHOX gene and the short stature. Roundtable on diagnosis and treatment of short stature due to SHOX haploinsufficiency: How genetics, radiology and anthropometry can help the pediatrician in the diagnostic process padova (April 20th, 2011)

The growth of the human body depends from a complex interaction between nutritional, environmental and hormonal factors and by a large number of different genes. One of these genes, short stature homeobox (SHOX), is believed to play a major role in growth. SHOX haploinsufficiency is associated with a wide spectrum of conditions, all characterized growth failure such as Leri-Weill dyschondrosteosis , Turner syndrome, short stature with subtle auxological and radiological findings and the so called “idiopathic short stature” (short stature with no specific findings other than growth failure). The document was prepared by a multidisciplinary team (paediatric endocrinologists, paediatrician, radiologist, geneticist and epidemiologist) to focus on the investigation of children with suspected SHOX- deficiency (SHOX-D) for an early identification and a correct diagnostic work - up of this genetic disorder. On the basis of a number of screening studies, SHOX-D appears to be a relatively frequent cause of short stature. The following recommendations were suggested by our multidisciplinary team: (i) a careful family history, measurements of body proportions and detection of any dysmorphic features are important for the suspect of a genetic disorder ,(ii)the presence of any combination of the following physical findings, such as reduced arm span/ height ratio, increased sitting height/height ratio, above average BMI, Madelung deformity, cubitus valgus, short or bowed forearm, dislocation of the ulna at the elbow, or the appearance of muscular hypertrophy, should prompt the clinician to obtain a molecular analysis of the SHOX region, (iii) it is of practical importance to recognise early or mild signs of Madelung deformity on hand and wrist radiographs, (iv) growth hormone ,after stimulation test, is usually normal . However, treatment with rhGH may improve final adult height; the efficacy of treatment is similar to that observed in those treated for Turner syndrome

Amelanotic/hypomelanotic lentigo maligna: Dermoscopic and confocal features predicting diagnosis

Background: Amelanotic/hypomelanotic lentigo maligna and lentigo maligna melanoma (AHLM/LMM) may be very difficult to diagnose at an early stage. Objectives: To quantify the predictive value of dermoscopic and reflectance confocal microscopy (RCM) features for AHLM/LMM. Methods: Dermoscopic and RCM images of histopathologically diagnosed AHLM/LMM, amelanotic/hypomelanotic benign lesions (AHBL), and amelanotic/hypomelanotic basal and squamous cell carcinomas (AHBCC/AHSCC) of the head and neck from consecutive patients were retrospectively collected and blindly evaluated by three observers to assess presence or absence of dermoscopic and RCM criteria. Results: Overall, 224 lesions in 216 patients including LM/LMM (n = 55, 24.6%), AHBL (n = 107, 47.8%) and AHBCC/AHSCC (n = 62, 27.7%) were analysed. Multivariable analysis showed that milky-red areas (OR = 5.46; 95% CI: 1.51–19.75), peripheral light brown structureless areas (OR = 19.10; 4.45–81.96), linear irregular vessels (OR = 5.44; 1.45–20.40), and asymmetric pigmented follicles (OR = 14.45; 2.77–75.44) at dermoscopy, and ≥3 atypical cells in five fields (OR = 10.12; 3.00–34.12) and focal follicular localization of atypical cells at dermo-epidermal junction (DEJ) (OR = 10.48; 1.10–99.81) at RCM were significantly independent diagnostic factors for AHLM/LMM vs. AHBL. In comparison with AHBCC/AHSCC, peripheral light brown structureless area (OR = 7.11; 1.53–32.96), pseudonetwork around hair follicles (OR = 16.69; 2.73–102.07), and annular granular structures (OR = 42.36; 3.51–511.16) at dermoscopy and large dendritic (OR = 6.86; 3.15–38.28) and round pagetoid cells (OR = 26.78; 3.15–227.98) at RCM led to a significantly increased risk of diagnosing AHLM/LMM. Conclusions: Amelanotic/hypomelanotic lentigo maligna and lentigo maligna melanoma may have the same dermoscopic features of AHM on other body sites, such as milky red areas, peripheral light brown structureless areas and linear irregular vessels. These features, asymmetric pigmented follicles and at RCM ≥ 3 atypical cells in five fields and focal follicular extension of atypical cells at DEJ may help in recognizing AHLM/LMM even when LM conventional features (e.g., obliteration of hair follicles under dermoscopy and large pagetoid cells under RCM) are absent or present only in very small areas of the lesion

The SHOX Gene and The Short Stature. Roundtable On Diagnosis and Treatment of Short Stature Due To SHOX Haploinsufficiency: How Genetics, Radiology And Anthropometry Can Help The Pediatrician in The Diagnostic Process Padova

SHOX haploinsufficiency is associated with a wide spectrum of conditions, all characterized growth failure. The document was prepared by a multidisciplinary team (paediatric endocrinologists, paediatrician, radiologist, geneticist and epidemiologist) to focus on the investigation of children with suspected SHOX- deficiency (SHOX-D) for an early identification and a correct diagnostic work - up of this genetic disorder

CDKN1B mutation and copy number variation are associated with tumor aggressiveness in luminal breast cancer

The CDKN1B gene, encoding for the CDK inhibitor p27kip1, is mutated in defined human cancer subtypes, including breast, prostate carcinomas and small intestine neuroendocrine tumors. Lessons learned from small intestine neuroendocrine tumors suggest that CDKN1B mutations could be subclonal, raising the question of whether a deeper sequencing approach could lead to the identification of higher numbers of patients with mutations. Here, we addressed this question and analyzed human cancer biopsies from breast (n = 396), ovarian (n = 110) and head and neck squamous carcinoma (n = 202) patients, using an ultra-deep sequencing approach. Notwithstanding this effort, the mutation rate of CDKN1B remained substantially aligned with values from the literature, showing that essentially only hormone receptor-positive breast cancer displayed CDKN1B mutations in a relevant number of cases (3%). However, the analysis of copy number variation showed that another fraction of luminal breast cancer displayed loss (8%) or gain (6%) of the CDKN1B gene, further reinforcing the idea that the function of p27kip1 is important in this type of tumor. Intriguingly, an enrichment for CDKN1B alterations was found in samples from premenopausal luminal breast cancer patients (n = 227, 4%) and in circulating cell-free DNA from metastatic luminal breast cancer patients (n = 59, 8.5%), suggesting that CDKN1B alterations could correlate with tumor aggressiveness and/or occur later during disease progression. Notably, many of the identified somatic mutations resulted in p27kip1 protein truncation, leading to loss of most of the protein or of its C-terminal domain. Using a gene-editing approach in a luminal breast cancer cell line, MCF-7, we observed that the expression of p27kip1 truncating mutants that lose the C-terminal domains failed to rescue most of the phenotypes induced by CDKN1B gene knockout, indicating that the functions retained by the C-terminal portion are critical for its role as an oncosuppressor, at least in luminal breast cancer. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland

Risk of thyroid as a first or second primary cancer. A population-based study in Italy, 1998–2012

Background: The number of patients living after a cancer diagnosis is increasing, especially after thyroid cancer (TC). This study aims at evaluating both the risk of a second primary cancer (SPC) in TC patients and the risk of TC as a SPC. Methods: We analyzed two population-based cohorts of individuals with TC or other neoplasms diagnosed between 1998 and 2012, in 28 Italian areas covered by population-based cancer registries. Standardized incidence ratios (SIRs) of SPC were stratified by sex, age, and time since first cancer. Results: A total of 38,535 TC patients and 1,329,624 patients with other primary cancers were included. The overall SIR was 1.16 (95% CI: 1.12–1.21) for SPC in TC patients, though no increase was shown for people with follicular (1.06) and medullary (0.95) TC. SPC with significantly increased SIRs was bone/soft tissue (2.0), breast (1.2), prostate (1.4), kidney (2.2), and hemolymphopoietic (1.4) cancers. The overall SIR for TC as a SPC was 1.49 (95% CI: 1.42–1.55), similar for all TC subtypes, and it was significantly increased for people diagnosed with head and neck (2.1), colon–rectum (1.4), lung (1.8), melanoma (2.0), bone/soft tissue (2.8), breast (1.3), corpus uteri (1.4), prostate (1.5), kidney (3.2), central nervous system (2.3), and hemolymphopoietic (1.8) cancers. Conclusions: The increased risk of TC after many other neoplasms and of few SPC after TC questions the best way to follow-up cancer patients, avoiding overdiagnosis and overtreatment for TC and, possibly, for other malignancies

Real Life Clinical Management and Survival in Advanced Cutaneous Melanoma: The Italian Clinical National Melanoma Registry Experience

Background: Cutaneous melanoma (CM) is one of the most aggressive types of skin cancer. Currently, innovative approaches such as target therapies and immunotherapies have been introduced in clinical practice. Data of clinical trials and real life studies that evaluate the outcomes of these therapeutic associations are necessary to establish their clinical utility. The aim of this study is to investigate the types of oncological treatments employed in the real-life clinical management of patients with advanced CM in several Italian centers, which are part of the Clinical National Melanoma Registry (CNMR). Methods: Melanoma-specific survival and overall survival were calculated. Multivariate Cox regression models were used to estimate the hazard ratios adjusting for confounders and other prognostic factors. Results: The median follow-up time was 36 months (range 1.2-185.1). 787 CM were included in the analysis with completed information about therapies. All types of immunotherapy showed a significant improved survival compared with all other therapies (p=0.001). 75% was the highest reduction of death reached by anti-PD-1 (HR=0.25), globally immunotherapy was significantly associated with improved survival, either for anti-CTLA4 monotherapy or combined with anti-PD-1 (HR=0.47 and 0.26, respectively) and BRAFI+MEKI (HR=0.62). Conclusions: The nivolumab/pembrolizumab in combination of ipilimumab and the addition of ant-MEK to the BRAFi can be considered the best therapies to improve survival in a real-world-population. The CNMR can complement clinical registries with the intent of improving cancer management and standardizing cancer treatment

Running economy during a 60-km Race

[no abstract available