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Simple Summary: In recent years, artificial intelligence has been used increasingly in medical practice. Technological progress has made it possible to digitize the slides of histological preparations, allowing the use of image processing and AI technologies in surgical pathology. This potentially reduces variability and improves the uniformity of some histological evaluations, such as cellularity assessment in bone marrow biopsies, which is traditionally performed visually by expert human observers, resulting in inter-observer and intra-observer variability. In this work, we developed an accurate AI-based tool for the automated quantification of cellularity in BMB histology and compared its performances with cellularity estimates from five expert hematopathologists. Our results showed the robustness of our model across users and two different scanners for digitized image generation. The cellularity assessment in bone marrow biopsies (BMBs) for the diagnosis of Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) is a key diagnostic feature and is usually performed by the human eyes through an optical microscope with consequent inter-observer and intra-observer variability. Thus, the use of an automated tool may reduce variability, improving the uniformity of the evaluation. The aim of this work is to develop an accurate AI-based tool for the automated quantification of cellularity in BMB histology. A total of 55 BMB histological slides, diagnosed as Ph- MPN between January 2018 and June 2023 from the archives of the Pathology Unit of University "Luigi Vanvitelli" in Naples (Italy), were scanned on Ventana DP200 or Epredia P1000 and exported as whole-slide images (WSIs). Fifteen BMBs were randomly selected to obtain a training set of AI-based tools. An expert pathologist and a trained resident performed annotations of hematopoietic tissue and adipose tissue, and annotations were exported as.tiff images and.png labels with two colors (black for hematopoietic tissue and yellow for adipose tissue). Subsequently, we developed a semantic segmentation model for hematopoietic tissue and adipose tissue. The remaining 40 BMBs were used for model verification. The performance of our model was compared with an evaluation of the cellularity of five expert hematopathologists and three trainees; we obtained an optimal concordance between our model and the expert pathologists' evaluation, with poorer concordance for trainees. There were no significant differences in cellularity assessments between two different scanners. [ABSTRACT FROM AUTHOR]

Simple Summary: Public health is severely challenged by bladder cancer (BC). There are few known risk factors for BC, but among these, diet seems to have a potential role in its etiology. However, the effect of meat is yet to be determined. In this study, we reviewed the influence of meat consumption on BC incidence. Our results showed different associations between meat consumption and BC depending on the type of meat consumed, the cooking method and the temperature used. Consequently, the promotion of healthy lifestyle interventions based on dietary factors can halt BC onset and can ameliorate the treatment efficacy of BC patients. Bladder cancer (BC) represents the second most common genitourinary malignancy. The major risk factors for BC include age, gender, smoking, occupational exposure, and infections. The BC etiology and pathogenesis have not been fully defined yet. Since catabolites are excreted through the urinary tract, the diet may play a pivotal role in bladder carcinogenesis. Meat, conventionally classified as "red", "white" or "processed", represents a significant risk factor for chronic diseases like cardiovascular disease, obesity, type 2 diabetes, and cancer. In particular, red and processed meat consumption seems to increase the risk of BC onset. The most accepted mechanism proposed for explaining the correlation between meat intake and BC involves the generation of carcinogens, such as heterocyclic amines and polycyclic aromatic hydrocarbons by high-temperature cooking. This evidence claims the consumption limitation of meat. We reviewed the current literature on potential biological mechanisms underlying the impact of meat (red, white, and processed) intake on the increased risk of BC development and progression. Toward this purpose, we performed an online search on PubMed using the term "bladder cancer" in combination with "meat", "red meat", "white meat" or "processed meat". Although some studies did not report any association between BC and meat intake, several reports highlighted a positive correlation between red or processed meat intake, especially salami, pastrami, corned beef and bacon, and BC risk. We speculate that a reduction or rather a weighting of the consumption of red and processed meat can reduce the risk of developing BC. Obviously, this remark claims future indications regarding food education (type of meat to be preferred, quantity of red meat to be eaten and how to cook it) to reduce the risk of developing BC. Further well-designed prospective studies are needed to corroborate these findings. [ABSTRACT FROM AUTHOR]

Cancer-related neuropathic pain is a common adverse effect in the process of cancer development and treatment and has gradually attracted the attention of researchers. The purpose of this article is to systematically review the articles on cancer-related neuropathic pain published between 2012 and 2021 and visualize the data through CiteSpace and R software. The results show that in the past 10 years, a total of 5715 articles have been published, involving 118 categories, of which the most is Clinical Neurology, followed by Neurosciences, Pharmacology Pharmacy. The country with the most published articles is the United States, followed by China and Italy. A total of 22,228 authors were involved in the study of cancer-related neuropathic pain. These historical opinions about cancer-related neuropathic pain could be an important practical basis for further research into potential development trends. [ABSTRACT FROM AUTHOR]

Objective: The present study aims to explore post‐traumatic growth in cancer patients comparing the active phase, when patients undergo different treatments, and the remission phase, characterised by periodic follow‐ups and gradually return to lives outside the hospital world. Methods: 69 cancer patients (36 in active phase and 33 in remission phase) completed an online survey narrating their growth experience related to cancer disease. A modelling emergent theme analysis was implemented for narratives of both group by means of T‐Lab software. Results: Four themes emerged for narratives of active phase group: 'the time of illness and the time of life (saturating the 46% of words)', 'the meaning‐seeking' (21%), 'to find oneself in a battle (21%)' and 'to learn by battling' (12%). Remission phase group themes concerned 'the time of life' (40%), 'the seismic experience' (31%), 'to care for the Self and for others' (15%) and 'strength from vulnerability' (14%). Conclusions: Remission group narratives are close to PTG as defined in scientific literature, while patients in the active phase of disease narrated PTG as the attempt of including illness in their life trajectory and learning from the battle against cancer. Author suggests the definition of peritraumatic growth as a transformation process parallel to treatment phase. [ABSTRACT FROM AUTHOR]

Aim: In the last 5 years we have seen an increase in the number of women with breast cancer undergoing systemic therapy and reconstructive plastic surgery treatment, with a significant reduction in age <55 years. We have increased the use of new bioactive dressing technologies to improve the quality of care. Method: 51-year-old female, growing, bleeding skin lesion, extension 10x15, presented in the Emergency Department. Family history with familiarity, without specific risk factors. Time zero with TB bone scintigraphy, TB CT, mammography with histological examination, cardiological examination, medication and referral to the skin lesions specialist clinic. Set up a bi-weekly dressing plan with 16-layer gauze with oleic matrix releasing reactive oxygen species. Results / Discussion: Data relating to: - Percentage of lesion area reduction >80% in 2 months - Microbiological evaluation - Wound Bed Preparation -Customer satisfaction Conclusion: The oleic matrix technology with reactive oxygen species release represents an important opportunity allowing the maintenance of the technology even with different local conditions of the lesion. [ABSTRACT FROM AUTHOR]

Thyroid cancer (TC), the most common endocrine tumor, has steadily increased worldwide due to the increase of the papillary histotype. The reasons for this spread have not been established. In addition to more sensitive thyroid nodule screening, the effect of environ-mental factors cannot be excluded. Because high incidences of TC were found in volcanic areas (Hawaii and Iceland), a volcanic environment may play a role in the pathogenesis of TC. In January 2002, the Regional Register for TC was instituted in Sicily. With a population of approximately five million inhabitants with similar genetic and lifestyle features, the coexistence in Sicily of rural, urban, industrial, moderate-to-low iodine intake, and volcanic areas provides a conducive setting for assessing the environmental influences on the etiology of TC. In Sicily, between 2002 and 2004, 1,950 new cases of TC were identified, with an age-standardized rate (world) ASR(w)=17.8/105 in females and 3.7/105 in males and a high female/male ratio (4.3:1.0).The incidence ofTC was heterogeneous within Sicily. There were 2.3 times more cases in the Catania province (where most of the inhabitants live in the volcanic area of Mt. Etna): ASR(w)=31.7/105 in females and 6.4/105 in males vs. 14.1 in females and 3.0 in males in the rest of Sicily. Multivariate analysis documented that residents in the volcanic area of Mt. Etna had a higher risk of TC, compared to the residents in urban, industrial, and iodine deficient areas of Sicily. An abnormally high concentration of several chemicals was found in the drinking water of the Mt. Etna aquifer, which provides water to most of the residents in the Catania province. Our data suggest that environmental carcinogen(s) of volcanic origin may promote papillary TC. Additional analyses, including cancer biological and molecular features, will allow a better understanding of risk factors and etiopathogenetic mechanisms. [ABSTRACT FROM AUTHOR]

Risk factors analysis in bladder cancer should consider not only the clinical and pathological features of the tumor but also environmental and lifestyle factors. They may play, in fact, a relevant role not only in the pathogenesis but also in the biological behavior of the tumor. The association between cigarette smoking and bladder cancer has been consistently confirmed in several case-control and cohort studies. The risk of bladder cancer seems to increase with duration and intensity of smoking. Another environmental risk factor, although not definitively proved, is water supply. Chlorination or water pollution by pesticides and other chemical factors is considered a relevant risk factor. Familiarity and genetic predisposition, diet and individual risk factors should be taken into account. [ABSTRACT FROM AUTHOR]

Objective: Several studies have shown an inverse relation between vegetable and fruit intake and pancreatic cancer, but no specific beneficial component of such foods has been consistently identified. We considered the role of 15 selected vitamins and carotenoids and 6 minerals on pancreatic cancer risk in an Italian case–control study.Methods: Subjects were 326 patients with incident pancreatic cancer and 652 controls, admitted to the same hospitals as cases for acute conditions. Micronutrient computation was based on a validated and reproducible food-frequency questionnaire. We estimated the odds ratios (OR) and confidence intervals (CI) using conditional logistic regression models, adjusted for various confounding factors and for energy intake, according to the residual model.Results: Comparing the highest to the lowest quintile of intake, the OR were 0.60 (95% CI 0.36–0.98) for vitamin E, 0.44 (95% CI 0.27–0.73) for vitamin C, 0.56 (95% CI 0.34–0.93) for folate, and 0.57 (95% CI 0.35–0.92) for potassium. No significant inverse associations were observed for α-carotene (OR = 0.69, 95% CI 0.43–1.12), β-carotene (OR = 0.64, 95% CI 0.39–1.06), and β-cryptoxanthin (OR = 0.66, 95% CI 0.39–1.09). No relation was found for other micronutrients considered.Conclusion: Our findings support a favorable role of vitamins E and C, selected carotenoids, and folate on pancreatic carcinogenesis. [ABSTRACT FROM AUTHOR]

Background Malignant melanoma incidence has increased worldwide in recent decades. Cancer registry-derived epidemiologic data on malignant melanoma in Italy are available only in some northern regions of the country. Aim To report the number and characteristics of incident cases of cutaneous malignant melanoma in Abruzzo, a central-southern Italian region. Methods Screening of the archives of the pathology departments of regional hospitals from 2002 to 2005 was performed. For each patient, clinical and pathologic data were collected. Cases of metastatic, multiple, or relapsing melanoma were excluded. Results Six hundred and seventy-two cases of primary melanoma were recorded, with an incidence rate of 14.1 per 100,000 inhabitants per year. Differences related to gender (41.1% males and 58.9% females) and age (35% in the 50–70-year age group) were found. The trunk (30.7%) and lower limbs (25.94%) were the most frequent sites observed. The superficial spreading histiotype and thin melanoma (≤ 1.00 mm) were more often recorded (44.8% and 62%, respectively). Conclusions Despite the bias present in this study, linked to the nature and source of the data, we believe that the figures found in this report are comparable with those obtained in the international literature from other Mediterranean countries. [ABSTRACT FROM AUTHOR]

Unlabelled: To investigate the role of genetic and environmental factors in the pathogenesis of type 1 diabetes mellitus (T1D), we carried out a study in Germany aimed at comparing the prevalence and incidence of T1D among children of migrant Italians from high-risk (Sardinia) and low-risk (continental Italy) regions versus German children. Children from Italy were identified by the "Baden-Wuerttemberg (BW) Diabetes Incidence Registry", which registered 4017 newly diagnosed T1D patients, aged 0-14 years, between 1987 and 2003. Data relating to T1D children from Sardinia were elicited from more than 2000 questionnaires. Our findings were: (1) T1D is more frequent among German children than among children of Italian migrants [incidence rate (IR) 14.8/100,000/year, 95% confidence interval (CI) 14.4-15.4 vs. IR 10.8/100,000/year, 95% CI 8.2-13.6); (2) the incidence of T1D among Italian children residing in Germany is similar to that of Italian children in the home country (IR 10.8/100,000/year, 95% CI 8.2-13.6 vs. 8.4/100,000/year, 95% CI 7.9-8.9); (3) the prevalence of T1D among Sardinian children is higher than that among German children (0.11%, 95% CI 0.11-0.12) independent of the place where the Sardinian children are living (Sardinian children in Germany 2.3%, 95% CI 0.5-6.5 vs. Sardinian children in Sardinia 0.30%, 95% CI 0.27-0.32).Conclusion: Children from high- and low-risk areas of Italy have incidence rates of T1D that are closer to those of their native regions than to those of German children, indicating that genetic factors play a predominant role in the pathogenesis of T1D. [ABSTRACT FROM AUTHOR]

Background: Although the diagnostic criteria and pathogenesis of gastrointestinal stromal tumors (GIST) have recently been elucidated, knowledge of the epidemiology of this malignancy is still limited. This study examined the incidence of GIST in the province of Modena, including pathologic features and clinical outcome. Methods: Gastrointestinal mesenchymal tumors identified by the Modena Cancer Registry between 1991 and 2004 were analyzed with an immunohistochemical panel that included staining for CD-117 and PDGFRα. Size, mitotic rate, and other pathologic parameters were recorded. Each tumor was categorized into National Institutes of Health risk categories (very low, low, intermediate, and high risk). Results: One hundred twenty-four cases were classified as GIST. The age-adjusted incidence rate was 6.6 per million. Seventy-five percent of patients were symptomatic; 34% had a previous or concomitant history of cancer. High-risk features were present in 47% of cases. Seventy-eight percent were submitted to radical surgery. After complete resection, the 5-year disease-free survival rates were 94%, 92%, 100%, and 40% for patients at very low, low, intermediate, and high risk, respectively. In multivariate analysis, high risk was the main predictor of recurrence. Conclusion: This population-based study shows that the incidence of GIST in Northern Italy is comparable to that reported in other European countries. Survival was favorable in lower risk categories and in most of the resected cases. In our study, resected patients at very low, low, and intermediate risk had a similar outcome. Our data support the need to consider high-risk patients after complete surgical resection for treatment with the best available approach. [ABSTRACT FROM AUTHOR]

The bulk depositions of seven carcinogenic PAHs were investigated by collecting two monthly samples at seven sites. Deposition rates of individual PAHs ranged 2–89 ng/m 2 /d (BaP, 2–7 ng/m 2 /d), in agreement with the few available rates previously measured at background European sites. On six days, air samples were also collected at three sites and resulted in mean particle-bound BaP ranging 0.01–0.04 ng/m 3 . The ratios between the concentrations of each PAH and BaP in the deposition samples were significantly higher than those in the air samples. To investigate if an on-sampler BaP degradation during a 1-month sampling period could generate a measurable artefact, a test was carried out by two co-located samplers collecting, respectively, one continuous 5-week sample and five weekly samples. No difference in PAH profiles was found among the samples collected by the two samplers. The occurrence of PAH profiles different from those commonly found in air may affect the validity of the BaP-marker approach in risk assessment for deposition samples. [ABSTRACT FROM AUTHOR]

The article presents the meeting report from the EMBO Workshop on Notch Signaling in Development and Cancer held between 22 and 25 April 2005 in Rome, Italy. This meeting brought together a diverse group of researchers whose interests span invertebrate and vertebrate development, structural biology, biochemistry, cell signaling, immunology and tumor biology. In this report, after a brief introduction to the Notch signaling pathway, we summarize the presentations that covered different aspects of Notch signaling, including the pathway itself, development, hematopoiesis and cancer.

Risk evaluation for human health was carried out using PCB and PAH concentrations measured in seven fish species from Lake Iseo (Italy) and comparing the experimental data with legal levels and the two new approaches proposed by the US FDA and the US EPA to protect local populations with different food habits. We verified that none of the persistent organic compounds analyzed exceeded the legal limits set by the US FDA, since no specific limit has yet been proposed by the European Union. The two other approaches have pointed out that the acute and chronic effects do not represent any risk for human health, while a possible carcinogenic risk for the local population can arise when 4 and 8 monthly meals are consumed, based on PCB and PAH content in the edible part of fish, respectively. [Copyright &y& Elsevier]

Acrylamide (AA) is a neo-formed toxic compound that develops in foods during cooking at temperatures above 120 °C. AA shows in vivo neurotoxic and carcinogenic effects, and it is potentially carcinogenic for humans. Its occurrence is common in baked food, such as bread and similar products. This study set out to analyze bread and sweets from the Italian market to evaluate the effects of the benchmark thresholds set by EU Regulation 2017/2158 and to ascertain the exposure of the Italian population to AA, across three age groups, through the consumption of baked products, according to the margin of exposure (MOE) approach. Two hundred samples were tested, and the content of AA ranged from 31 to 454 µg/kg for bread and products thereof and from 204 to 400 µg/kg for the sweets category. The exposure data did not show any neurotoxic health concern, whereas the MOE related to the carcinogenic endpoint is well below the minimum safety value of 10,000.

We analyzed the impact of alloHSCT in a single center cohort of 89 newly diagnosed NPM1mut AML patients, consecutively treated according to the Northern Italy Leukemia Group protocol 02/06 [NCT00495287]. After two consolidation cycles, the detection of measurable residual disease (MRD) by RQ-PCR was strongly associated with an inferior three-year overall survival (OS, 45% versus 84%, p = 0.001) and disease-free survival (DFS, 44% versus 76%, p = 0.006). In MRD-negative patients, post-remissional consolidation with alloHSCT did not provide a significant additional benefit over a conventional chemotherapy in terms of overall survival [OS, 89% (95% CI 71–100%) versus 81% (95% CI 64–100%), p = 0.59] and disease-free survival [DFS, 80% (95% CI 59–100%) versus 75% (95% CI 56–99%), p = 0.87]. On the contrary, in patients with persistent MRD positivity, the three-year OS and DFS were improved in patients receiving an alloHSCT compared to those allocated to conventional chemotherapy (OS, 52% versus 31%, p = 0.45 and DFS, 50% versus 17%, p = 0.31, respectively). However, in this group of patients, the benefit of alloHSCT was still hampered by a high incidence of leukemia relapse during the first year after transplantation (43%, 95% CI 25–60%). Consolidative alloHSCT improves outcomes compared to standard chemotherapy in patients with persistent NPM1mut MRD positivity, but in these high-risk patients, the significant incidence of leukemia relapse must be tackled by post-transplant preemptive treatments. [ABSTRACT FROM AUTHOR]

Background and objectives: Non-melanoma skin cancers (NMSCs) represent the most frequently encountered malignancy in organ transplant recipients and their incidence increases proportionally to the duration of immunosuppression. Furthermore, patients of this group often develop multiple and more aggressive cancers and, to date, risk factors for the development of multiple NMSCs have not been yet established. The present study aimed to identify risk factors for multiple NMSCs in a cohort of Italian kidney transplant recipients (KTRs). Materials and Methods: We consecutively included all KTRs referring to two post-transplant outpatient clinics of North-Western Italy between 2001 and 2017. In this cohort, we evaluated different clinical (endogenous and exogenous) risk factors in order to establish their correlation with NMSCs. Results: 518 KTRs were included, of which 148 (28.6%) developed keratinocyte cancers, with a single tumor in 77 subjects, two skin cancers in 31 patients, 3 in 21 patients, whereas at least 4 NMSCs developed in 19 KTRs. We observed an increased risk of the development of cutaneous neoplasms for the male gender, old age at transplantation (>50 years), light phototype, solar lentigo, history of sunburns, or chronic actinic damage. Considering patients affected by multiple keratinocyte neoplasms, we observed a significant association of actinic damage and solar lentigo with an increased risk of NMSCs; their significance was confirmed even at the multivariable model. Conclusions: Our results confirm the role played by chronic cutaneous actinic damage in carcinogenesis on KTRs and highlight the significance of individualized periodic dermatological screening.

BAP1 germline mutations predispose to a cancer predisposition syndrome that includes mesothelioma, cutaneous melanoma, uveal melanoma and other cancers. This co-occurrence suggests that these tumors share a common carcinogenic pathway. To evaluate this hypothesis, we studied 40 Italian families with mesothelioma and/or melanoma. The probands were sequenced for BAP1 and for the most common melanoma predisposition genes (i.e. CDKN2A, CDK4, TERT, MITF and POT1) to investigate if these genes may also confer susceptibility to mesothelioma. In two out of six families with both mesothelioma and melanoma we identified either a germline nonsense mutation (c.1153C > T, p.Arg385*) in BAP1 or a recurrent pathogenic germline mutation (c.301G > T, p.Gly101Trp) in CDKN2A. Our study suggests that CDKN2A, in addition to BAP1, could be involved in the melanoma and mesothelioma susceptibility, leading to the rare familial cancer syndromes. It also suggests that these tumors share key steps that drive carcinogenesis and that other genes may be involved in inherited predisposition to malignant mesothelioma and melanoma., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The crosstalk between microRNAs (miRNAs) and other epigenetic factors may lead to novel hypotheses about carcinogenesis identifying new targets for research. Because a single miRNA can regulate multiple downstream target genes, its altered expression may potentially be a sensitive biomarker to detect early malignant transformation and improve diagnosis and prognosis. In the current study, we tested the hypothesis that altered methylation of miRNA encoding genes, associated with deregulated mature miRNA expression, may be related to dietary and lifestyle factors and may contribute to cancer development. In a case-control study nested in a prospective cohort (EPIC-Italy), we analysed DNA methylation levels of miRNA encoding genes (2191 CpG probes related to 517 genes) that are present in the Infinium Human Methylation450 BeadChip array in prediagnostic peripheral white blood cells of subjects who developed colorectal cancer (CRC, n = 159) or breast cancer (BC, n = 166) and matched subjects who remained clinically healthy. In the whole cohort, several differentially methylated miRNA genes were observed in association with age, sex, smoking habits and physical activity. Interestingly, in the case-control study, eight differentially methylated miRNAs were identified in subjects who went on to develop BC (miR-328, miR-675, miR-1307, miR-1286, miR-1275, miR-1910, miR-24-1 and miR-548a-1; all Bonferroni-adjusted P < 0.05). No significant associations were found with CRC. Assuming that altered methylation of miRNAs detectable in blood may be present before diagnosis, it may represent a biomarker for early detection or risk of cancer and may help to understand the cascade of events preceding tumour onset., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)