A New Hierarchy of Research Evidence for Tumor Pathology: A Delphi Study to Define Levels of Evidence in Tumor Pathology.

The hierarchy of evidence is a fundamental concept in evidence-based medicine, but existing models can be challenging to apply in laboratory-based health care disciplines, such as pathology, where the types of evidence and contexts are significantly different from interventional medicine. This project aimed to define a comprehensive and complementary framework of new levels of evidence for evaluating research in tumor pathology-introducing a novel Hierarchy of Research Evidence for Tumor Pathology collaboratively designed by pathologists with help from epidemiologists, public health professionals, oncologists, and scientists, specifically tailored for use by pathologists-and to aid in the production of the World Health Organization Classification of Tumors (WCT) evidence gap maps. To achieve this, we adopted a modified Delphi approach, encompassing iterative online surveys, expert oversight, and external peer review, to establish the criteria for evidence in tumor pathology, determine the optimal structure for the new hierarchy, and ascertain the levels of confidence for each type of evidence. Over a span of 4 months and 3 survey rounds, we collected 1104 survey responses, culminating in a 3-day hybrid meeting in 2023, where a new hierarchy was unanimously agreed upon. The hierarchy is organized into 5 research theme groupings closely aligned with the subheadings of the WCT, and it consists of 5 levels of evidence-level P1 representing evidence types that merit the greatest level of confidence and level P5 reflecting the greatest risk of bias. For the first time, an international collaboration of pathology experts, supported by the International Agency for Research on Cancer, has successfully united to establish a standardized approach for evaluating evidence in tumor pathology. We intend to implement this novel Hierarchy of Research Evidence for Tumor Pathology to map the available evidence, thereby enriching and informing the WCT effectively.

Moving Forward on Tumor Pathology Research Reporting: A Guide for Pathologists From the World Health Organization Classification of Tumors Living Evidence Gap Map by Tumour Type Group.

Evidence-based medicine (EBM) can be an unfamiliar territory for those working in tumor pathology research, and there is a great deal of uncertainty about how to undertake an EBM approach to planning and reporting histopathology-based studies. In this article, reviewed and endorsed by the Word Health Organization International Agency for Research on Cancer's International Collaboration for Cancer Classification and Research, we aim to help pathologists and researchers understand the basics of planning an evidence-based tumor pathology research study, as well as our recommendations on how to report the findings from these. We introduce some basic EBM concepts, a framework for research questions, and thoughts on study design and emphasize the concept of reporting standards. There are many study-specific reporting guidelines available, and we provide an overview of these. However, existing reporting guidelines perhaps do not always fit tumor pathology research papers, and hence, here, we collate the key reporting data set together into one generic checklist that we think will simplify the task for pathologists. The article aims to complement our recent hierarchy of evidence for tumor pathology and glossary of evidence (study) types in tumor pathology. Together, these articles should help any researcher get to grips with the basics of EBM for planning and publishing research in tumor pathology, as well as encourage an improved standard of the reports available to us all in the literature.

Changes in the survival of patients with breast cancer: Poland, 2000-2019.

PURPOSE: The main aim of this study was to estimate breast cancer survival in Poland over the period from 2000 to 2019 in both sexes. METHODS: Data were obtained from the Polish National Cancer Registry. The presented metrics included age-standardized 5- and 10-year net survival (NS), median survival times, years of life lost (YLLs), and standardized mortality ratios (SMRs). RESULTS: Between 2000 and 2019, 315,278 patients (2353 men and 312,925 women; male-to-female ratio 1/100) were diagnosed with breast cancer in Poland. In this period, 721,987 YLLs were linked to breast cancer. Women presented a higher 5- and 10-year age-standardized NS than men (5-year NS: 77.33% for women and 65.47% for men, P < 0.001, common language effect size (CL) 1.00; 10-year NS: 68.75% for women and 49.50% for men, P < 0.001, CL 1.00). Between the earliest and latest studied period, namely 2000-2004 and 2015-2019, there was a statistically significant increase only in female survival (+ 7.32 pp, P < 0.001, CL 1.00). SMRs were significantly higher for women than for men (3.35 vs. 2.89, respectively). CONCLUSION: Over the last two decades, breast cancer survival in Poland has improved significantly. Nonetheless, special attention should be given to the disparities between sexes and the gap in overall improvement of survival rates compared with other European countries.

Evaluation of statin use and renal cell carcinoma risk identifies sex-specific associations with RCC subtypes.

Background: The association between statin use and risk of renal cell carcinoma (RCC) has been debated. We aimed to evaluate whether statin use is associated with RCC risk.Material and methods: We studied 100,195 women in the Nurses' Health Study (NHS) from 1994 to 2016; 91,427 women in the Nurses' Health Study II (NHS II) from 1999 to 2015; and 45,433 men in the Health Professionals Follow-up Study (HPFS) from 1990 to 2016. Statins and covariate data were collected at baseline and then biennially. Outcome was measured as incidence of total RCC and clinically relevant disease subgroups. Cox proportional hazards models estimated covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).Results: During follow-up, 661 participants developed RCC. There was no significant association between the use of statins and the risk of overall RCC, fatal RCC, or advanced or localized disease. Across cohorts, the adjusted HR for ever vs. never users was 0.97 (95% CI 0.81-1.16). Female ever users of statins were at increased risk of high-grade disease in the NHS only (HR 1.75, 95% CI 1.07-2.85). Among men only, ≥4 years of statin use was associated with an increased risk of clear cell RCC (HR 1.65, 95% CI 1.10-2.47).Conclusions: Statin use was not associated with the overall risk of RCC. However, it was associated with an increased risk of high-grade disease among women in the NHS cohort and an increased risk of clear cell RCC among men. The reasons for these inconsistent results by sex are unclear.

Tobacco products and electronic cigarettes' legislation violations - observational study in 31 European countries, 2005-2022.

BACKGROUND: European Union (EU) law regulates the manufacture, presentation, and sale of tobacco and related products in all member states. This study examined whether legislation non-compliant tobacco products and electronic cigarettes were available for sale in the European market. METHODS: We queried the EU Rapid Information System for dangerous non-food products, covering 28 current and former EU member states and 3 associated countries, also known as Rapex, for non-compliant tobacco and related products reported between 2005 and 2022. FINDINGS: During the operation of the Rapex system, 183 violations were reported (six on tobacco, three on traditional cigarettes, and 174 on e-cigarettes). Insufficient product safety information was found in 86% of the reports on e-cigarettes and 74% of the refills. Violations regarding the volume of the liquid container were observed in 26% of the e-cigarette reports and 20% of the refill reports. Approximately 15% of the reported e-cigarettes and 17% of refill liquids exceeded permissible nicotine levels. More serious standard violations were recorded for refills than for e-cigarettes. Approximately one-third of Rapex system countries submitted no notifications. INTERPRETATION: E-cigarettes were the most frequently reported items in the European market of tobacco and non-tobacco nicotine products. The most common concerns were inadequate product safety information, incorrect liquid container volume, and excessive nicotine concentration. Identifying the most recognized legal infringements did not require laboratory tests and was based only on packaging and the manufacturer's declaration analysis. Further studies are necessary to corroborate whether products available in countries where no violations have been reported meet EU safety standards.

Signet-Ring Cell/Histiocytoid Carcinoma: Report of Two Cases and Systematic Review of the Literature on the Epidemiology, Clinical Characteristics, and Pathological and Molecular Findings.

ABSTRACT: Signet-ring cell/histiocytoid carcinoma (SRCHC) is a rare appendageal tumor, mainly considering eyelids, more rarely axillae. This article describes 2 novel SRCHC cases of 71- and 66-year-old men and systematically reviews the literature on SRCHC. Of all cases reported in the literature, 73 (91.2%) were men and 7 (8.8%) were women. The median age at diagnosis was 71 years. Skin changes were located in the eyelids (68%) and axillae (32%). In all tested cases, SRCHC cells expressed CK7, CKAE1/AE3, EMA, CAM5.2, and AR and PIK3CA mutations. Future research should determine whether AR/PIK3CA-targeted therapies influence patients' survival.

Secretory carcinoma of major and minor salivary glands with ETV6-NTRK3 gene fusion: overcoming misdiagnosis in the era of tumour-agnostic therapy with TRK inhibitors.

Introduction: Secretory carcinoma (SC) of the salivary gland is an extraordinarily rare tumour. Accurate diagnosis of SC is crucial for understanding the clinical course, prognosis, and selection of optimal therapy. The aim of this research was to analyse retrospectively the clinical and pathological characteristics of patients diagnosed with SC of the salivary gland from 2017 onwards, which aligns with its addition to the World Health Organization classification. Material and methods: We conducted a retrospective, single-centre, clinicopathological analysis of patients diagnosed with SC of the salivary gland between 2017 and 2022. The analysis included the evaluation of NTRK3 gene rearrangements and immunohistochemical (IHC) profiling. Results: The study included 6 patients, comprising 4 women and 2 men. The average age of the patients was 50 years (standard deviation 26). Three cases presented with tumours in the parotid gland, while one case each involved the submandibular gland, sinonasal tract, and buccal mucosa. Interestingly, despite the characteristic IHC profile, each case was initially diagnosed as a different type of salivary gland cancer. Next-generation sequencing analysis was performed in 3 cases, revealing the presence of the ETV6-NTRK3 fusion gene. This cohort notably features an intriguing case: the youngest patient documented in literature, distinguished by extended follow-up and delayed recurrence. Conclusions: In summary, emphasizing the risk of misdiagnosis is pivotal in the context of SC of the salivary gland, which can manifest across diverse glandular sites. Accurate diagnosis, underscored by the assessment of NTRK3 gene rearrangements, assumes a critical role in guiding effective management and treatment decisions.

Improved survival of Burkitt lymphoma/leukemia patients: observations from Poland, 1999-2020.

The aim of this study was to estimate the survival of Polish Burkitt lymphoma/leukemia (BL) patients diagnosed between 1999 and 2017, considering multiple covariates and periods, to reflect changes in BL treatment. We identified all BL patients registered in the Polish National Cancer Registry in 1999-2017. Observed survival (OS) was evaluated deploying the life table method. Univariate and multivariate Cox proportional hazards regression models were fit to generate hazard ratios (HR) and the corresponding 95% confidence intervals (95% CI), describing the association between exposures (sex, age at the diagnosis, year of diagnosis, and region of residence) and time-to-event (death). Two-sided log-rank test was applied to assess the significance of exposures. Overall, 937 BL cases were included in the study (654 men and 283 women). Between the periods 1999-2005 and 2015-2017, the 3-year OS changed from 56.0% (95% CI 50.4 to 62.2%) to 73.8% (68.1 to 80.0%; P < 0.001), and the 5-year OS increased from 53.8% (48.2 to 60.0%) to 73.0% (67.1 to 79.3%; P < 0.001). The death HR was significantly higher in adolescents and young adults' (AYA) and adults' groups than in pediatric patients (HR = 3.00, 95% CI 2.05 to 4.39, P < 0.001, for AYA; and HR = 7.30, 5.14 to 10.3, P < 0.001, for adults). During the last two decades, the survival of Polish BL patients has been systematically improving. The death hazard ratio is most significantly associated with the patients' age at diagnosis and year of diagnosis, and not associated with sex or region of residence.

Smoking-adjusted risk of kidney cancer by occupation: a population-based cohort study of Nordic men.

Background: Evidence suggests that among some occupational groups, there is an elevated risk of kidney cancer. This might, however, derive from a difference in smoking habits across occupational groups. The objective of this study was to determine smoking-adjusted occupational variation in the incidence of kidney cancer in Nordic males.Material and Methods: The source population for this study consisted of 7.4 million men from Denmark, Iceland, Finland, Norway, and Sweden. Data on occupation were obtained from national censuses conducted in the years 1960-1990. Data on cancer cases came from national cancer registries. A proxy for the occupation-specific smoking prevalence among all Nordic men was calculated based on the occupation-specific smoking prevalence and lung cancer incidence data for Finnish men. Smoking-adjusted standardized incidence ratio (SIRadj) with 95% confidence intervals (95%CI) were calculated for each occupational group.Results: The highest SIRadj estimates were observed in dentists (1.32, 95%CI 1.06-1.62), journalists (1.20, 95%CI 1.00-1.42), physicians (1.19, 95%CI 1.03-1.36), public safety workers (1.18, 95%CI 1.10-1.26), administrators (1.17, 95%CI 1.13-1.22), military personnel (1.16, 95%CI 1.05-1.28), and religious workers (1.17, 95%CI 1.09-1.26). The lowest SIRadj was observed among forestry workers (0.82, 95%CI 0.76-0.88).Conclusions: Tobacco smoking plays an important role in the occupational variation in the risk of kidney cancer. The smoking-adjusted incidence of kidney cancer was increased in dentists, physicians, journalists, administrators, and public safety workers.

Occupation and risk of cancer of the renal pelvis in Nordic countries.

OBJECTIVES: To evaluate occupational variation in the incidence of the malignant neoplasm of the renal pelvis in the population of the Nordic countries: Denmark, Iceland, Finland, Norway and Sweden. MATERIALS AND METHODS: The study cohort comprised 14.9 million individuals. Data on occupational history were obtained from national censuses. Standardized incidence ratios (SIRs) were calculated for each occupation. RESULTS: The highest SIRs were found in seamen (1.51, 95% confidence interval [CI] 1.23-1.82), printers (1.39, 95% CI 1.11-1.71), welders (1.37, 95% CI 1.03-1.78), and public safety workers (1.35, 95% CI 1.12-1.62). The lowest SIRs were observed in forestry workers (0.47, 95% CI 0.35-0.62), gardeners (0.72, 95% CI 0.62-0.83) and woodworkers (0.81, 95% CI 0.72-0.91). CONCLUSIONS: The study suggests that there is an association between profession and risk of malignancy of the renal pelvis. The possible associations between exposure to asbestos, heavy metals and welding fumes, and risk of developing the disease should be studied further.

Heavy metals, welding fumes, and other occupational exposures, and the risk of kidney cancer: A population-based nested case-control study in three Nordic countries.

OBJECTIVES: To determine whether occupational exposure to heavy metals (chromium (VI), iron, nickel, lead) and welding fumes is associated with the risk of kidney cancer and to describe whether other occupational exposures included in the Job Exposure Matrix of the Nordic Occupational Cancer (NOCCA) study are associated with the risk. MATERIALS AND METHODS: Nested case-control study among individuals registered in population censuses in Finland, Iceland, and Sweden in 1960-1990. A total of 59,778 kidney cancer cases, and 298,890 controls matched on sex, age, and country. Cumulative occupational exposures to metals (chromium (VI), iron, nickel, lead), welding fumes, and 24 other occupational exposure covariates, lagged 0, 10, and 20 years. RESULTS: Overall, there was no or very little association between kidney cancer and exposures studied. The risk was elevated in individuals with high exposure to asbestos (OR 1.19, 95%CI 1.08-1.31). The risk was significantly decreased for individuals characterized with high perceived physical workload (OR 0.86, 95%CI 0.82-0.91), high exposure to ultraviolet radiation (OR 0.85, 95%CI 0.79-0.92), and high exposure to wood dust (OR 0.82, 95%CI 0.71-0.94). The risk of kidney cancer under the age of 59 was elevated in individuals with high exposure to nickel (OR 1.49, 95%CI 1.03-2.17). The risk of kidney cancer in age 59-74 years was elevated for individuals with high exposure to iron (OR 1.41, 95%CI 1.07-1.85), and high exposure to welding fumes (OR 1.43, 95%CI 1.09-1.89). CONCLUSIONS: The only markedly elevated risks of kidney cancer were seen for the highest exposures of nickel and iron/welding fumes in specific age strata.

A systematic review of global legal regulations on the permissible level of heavy metals in cosmetics with particular emphasis on skin lightening products.

BACKGROUND: There is an urgent need to address the safety problems caused by the use of skin lightening cosmetics. Evidence suggests that some of them may contain heavy metals. OBJECTIVES: We conducted a systematic review of global legal regulations regarding the permissible level of mercury, lead, arsenic, and cadmium in cosmetic products, with particular emphasis on skin lightening preparations. METHODS: The systematic search of documents was a two-stage process. First, official websites of 17 regional organizations and subsequently regulations for countries with a population over 100 million were searched. RESULTS: Fifteen legislative acts, encompassing more than 67·2% of the global population were reviewed. Regulations were identified for 44/59 high income countries, 16/55 upper middle income countries, 9/45 lower income countries, 0/34 low income countries. The median adult literacy rate was 91·4% and 64·2% in countries with and without regulations, respectively. The use of mercury, lead, arsenic, and cadmium has been banned in 67, 67, 65, and 65 out of 69 countries, respectively. CONCLUSIONS: While regulations exist in most of the high income countries, in low income countries there is a lack of similar standards. In most countries for which these legal regulations have been identified, restrictions on the permissible level of heavy metals are strict. There is a need for enforcement of existing rules, and rigorous assessment of the effectiveness of these regulations.

Skin lightening products' violations in Europe: An analysis of the rapid alert system for dangerous non-food products 2005-2018.

BACKGROUND: Skin lightening products containing dangerous levels of chemicals pose a serious health concern for consumers. However, to date, the extent of these products in Europe has not been extensively studied. The aim of this study was to determine whether harmful skin lightening products are available for sale in Europe and what violations exist regarding their composition. MATERIALS AND METHODS: We queried the Rapex database, which is the Rapid Alert System for dangerous non-food products among 31 European countries, to identify skin lightening cosmetics reported between 2005 and 2018, and presented a detailed summary of these notifications. RESULTS: In the years 2005-2018, of all violations regarding cosmetics, 26.3% concerned skin lightening products. In the database, 266 reports on skin lightening products were identified. Most of the notifications came from Germany (17.29%), France (17.29%), Portugal (15.41%), and the United Kingdom (11.65%). The majority of the registered products originated from non-European countries, mainly the Côte d'Ivoire (29.70%). The major reason for the violation was the content of hydroquinone, mercury, or clobetasol propionate. CONCLUSIONS: Hazardous skin lightening products that are not in line with European cosmetics legislation are available on the European market. Most of the products are imported. The main risk associated with these products is the content of hydroquinone, mercury, and clobetasol propionate. It is important to bear in mind that this study focuses on the Rapex system and other sources of information may exist. Based on our findings, a more comprehensive evaluation by international authorities is justified.

Peptides stimulating synthesis of extracellular matrix used in anti-ageing cosmetics: Are they clinically tested? A systematic review of the literature.

Peptides stimulating synthesis of extracellular matrix are now commonly used in the production of anti-ageing cosmetics. However, much uncertainty still exists about the methodology of their clinical assessment. The aim of the study was to review the literature for clinical study designs assessing the efficacy of these peptides. The authors searched systematically publications indexed in PubMed, Scope and Web of Science, according to the PRISMA protocol. Altogether 12 scientific papers, reporting results of 15 independent studies were identified. Out of these 15 studies, only six used a placebo control. Double-blinding was applied in five out of 15 studies. Nine studies were based on female-only populations. For the product performance evaluation, most of the studies (10 out of the 15) used image-based methods. The literature on the topic is sparse. The studies carried out so far have many methodological limitations. Most of the clinical experiments hitherto conducted were non-double-blind and used no placebo control. There is a need for better planned and controlled clinical trials in this area.

National launch of human papillomavirus (HPV) immunization program in Poland, 2023.

Poland launched a nationwide Human Papillomavirus (HPV) immunization program in June 2023, transitioning from a recommended to publicly funded approach. Targeting mainly 12 to 13-year-olds, the program offers universal and cost-free vaccinations with Cervarix and Gardasil 9. The initiative, aligned with the National Oncology Strategy, involves 4945 healthcare facilities, ensuring accessibility across regions. The streamlined process, empowering parents to choose, includes diverse healthcare professionals.

Unveiling the silent crisis: global burden of suicide-related deaths among children aged 10-14 years.

BACKGROUND: The rise in suicides among children aged 10-14 years demands urgent attention globally. This study aims to assess the global burden of suicide-related deaths in this age group from 1990 to 2019, considering factors such as sex, geography, and sociodemographics, to inform prevention strategies and interventions. METHODS: The data from Global Burden of Disease 2019, encompassing 204 countries and territories, were analyzed to investigate deaths and years of life lost (YLLs) due to suicide among children aged 10-14 years. Statistical analyses, including mortality rates, YLLs, and the sociodemographic index (SDI), were conducted using standardized tools. RESULTS: In 2019, a total of 8327 [95% uncertainty interval (UI) = 7073-9685] children aged 10-14 years died globally due to suicide, with a mortality rate of 1.30 (95% UI = 1.10-1.51) per 100,000. The rates varied across countries/territories ranging between 0.05 (95% UI = 0.02-0.10) in South Africa and 7.49 (95% UI = 5.13-10.57) in Greenland. The contribution of suicide-related deaths to all-cause mortality ranged from 0.07% (95% UI = 0.04%-0.15%) in South Africa to 33.02% (95% UI = 24.36%-41.53%) in Greenland. Worldwide, there were approximately 636,196 (95% UI = 540,383-740,009) YLLs due to suicide, with a rate of 99.07 (95% UI = 84.15-115.23) per 100,000. The association between SDI and suicide-related deaths was evident, with higher contributions observed in countries with higher SDI. CONCLUSIONS: This study reveals a concerning global burden of suicide-related deaths among children aged 10-14 years. Despite progress in reducing mortality rates, suicide remains a significant issue. While overall rates have declined, the percentage of deaths caused by suicide in this age group is increasing.

Decrease in the number of new cancer diagnoses during the first year of the COVID-19 pandemic - cohort study of 3.5 million individuals in western Poland.

Introduction: The COVID-19 pandemic has considerably affected healthcare systems worldwide and is expected to influence cancer incidence, mortality, stage at diagnosis, and survival. This study aimed to assess COVID-19-related changes in cancer incidence observed in 2020 in the Greater Poland region. Materials and methods: Data from the Greater Poland Cancer Registry on cancer patients diagnosed between 2010 and 2020 were analysed. To quantify the change in the number of incident cancer cases during the COVID-19 pandemic, we calculated the standardized incidence ratio (SIR) and the incidence rate difference (IRD) to assume the pandemic-attributable gap in cancer incidence. Results: In 2020, in Greater Poland, the expected number of new cancer cases was 18 154 (9 226 among males and 8 927 among females), while the observed number was 14 770 (7 336 among males and 7 434 among females). The registered number of cancer cases decreased in 2020 by 20% (SIR 0·80, 95% CI 0·78 to 0·81) and 17% (SIR 0·83, 95% CI 0·81 to 0·85) in males and females, respectively. Among men, the most significant difference was reported for myeloma (SIR 0·59, 95% CI 0·45 to 0·77), among women for bone cancer (SIR 0·47, 95% CI 0·20 to 0·93). In females the observed incidence was higher than expected for cancer of an unspecified site (SIR 1·19, 95% CI 1·01 to 1·38). In our study, the decrease in new cancer cases was greater in males than in females. Discussion: The observed incidence was affected in most cancer sites, with the most significant deviation from the expected number in the case of myeloma. An increase in the observed incidence was reported only in women diagnosed with cancer of an unspecified site, which might reflect shortages in access to oncological diagnostics.

Survival of patients with cancers of the female genital organs in Poland, 2000-2019.

The purpose of this study was to estimate cancer survival in Poland between 2000 and 2019 for malignant neoplasms of female genital organs (FGO). We calculated survival in cancer of vulva, vagina, cervix uteri, corpus uteri, ovary, and other unspecified female genital organs. Data were obtained from the Polish National Cancer Registry. We estimated age-standardized 5- and 10-year net survival (NS) with the life table method and the Pohar-Perme estimator using the International Cancer Survival Standard weights. Overall, 231,925 FGO cancer cases were included in the study. The overall FGO age-standardized 5-year NS was 58.2% (95% confidence interval (CI) 57.9-58.5%) and the 10-year NS 51.5% (51.5-52.3%). Between 2000 and 2004 and 2015-2018, the highest statistically significant increase in age-standardized 5-year survival was noted for ovarian cancer at + 5.6% (P < 0.001). The FGO cancer median survival time was 8.8 years (8.6-8.9 years), with a standardized mortality rate of 6.1 (6.0-6.1), and with cause-specific years of life lost at 7.8 years (7.7-7.8 years). Hazard ratios (HR) increased with age at diagnosis (HR = 1.02, 95% CI 1.01-1.03, P = 0.001). Although FGO cancer survivorship has been consistently improving during the last twenty years, additional efforts need to be undertaken to improve survivorship in several FGO cancers.