Epidemiology of basal and cutaneous squamous cell carcinoma in the U.K. 2013–15:a cohort study

BACKGROUND: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), together known as keratinocyte cancers (KCs), are the commonest cancer in white ethnic populations. Recent improvements to registry data collection in England has allowed more accurate analysis of the epidemiology of BCC and cSCC and for the first time we are able to provide an accurate (representative) tumour burden for KC in the U.K. OBJECTIVES: To estimate the incidence of BCC and cSCC in the U.K. METHODS: A cohort of patients with KCs between 2013 and 2015 were identified using linkage to diagnostic codes derived from pathology reports collected into the national cancer registry. Data from England's cancer registry were combined with data from Scotland, Northern Ireland and Wales. European age-standardized incidence rates (EASRs) of the first BCC and cSCC per patient per annum (PPPA) were calculated. RESULTS: In the U.K, the EASR of the first BCC and cSCC PPPA in 2013-15 were 285 and 77 per 100 000 person years, respectively (211 120 KCs total in 2015). The mean annual percentage increase was 5% between 2013 and 2015 for both BCC and cSCC. By counting the first KC PPPA, we include an additional 51% KCs compared with the previous reporting technique which counts only the first BCC and cSCC in a patient's lifetime, yet it represents a probable underestimation of 5-11% of the true tumour count. CONCLUSIONS: Based on an improved methodology, a more representative incidence of KC is presented, which is essential to healthcare planning and will lead to improved understanding of the epidemiology of KC. What's already known about this topic? Keratinocyte cancers (KCs) are the most common cancers affecting white ethnic populations. The incidence of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) is increasing worldwide including the U.K., most commonly in elderly male Caucasian patients. These cancers are traditionally substantially underreported and frequently excluded from national cancer statistics. What does this study add? Using improved data collection methods in England and validated tumour-reporting techniques, we report the most accurate BCC and cSCC incidence data for the U.K. ever published. Identifying the first BCC and cSCC per patient per annum, the incidence of BCC and cSCC in the U.K. (excluding Wales) was 285 and 77 per 100 000 person years, respectively, between 2013 and 2015, with more than 210 000 KCs in the U.K. in 2015

Objectives, design and main findings until 2020 from the Rotterdam Study

The Rotterdam Study is an ongoing prospective cohort study that started in 1990 in the city of Rotterdam, The Netherlands. The study aims to unravel etiology, preclinical course, natural history and potential targets for intervention for chronic diseases in mid-life and late-life. The study focuses on cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, otolaryngological, locomotor, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. Since 2016, the cohort is being expanded by persons aged 40 years and over. The findings of the Rotterdam Study have been presented in over 1700 research articles and reports. This article provides an update on the rationale and design of the study. It also presents a summary of the major findings from the preceding 3 years and outlines developments for the coming period

Pretransplant sequential hypo- and normothermic machine perfusion of suboptimal livers donated after circulatory death using a hemoglobin-based oxygen carrier perfusion solution

Ex situ dual hypothermic oxygenated machine perfusion (DHOPE) and normothermic machine perfusion (NMP) of donor livers may have a complementary effect when applied sequentially. While DHOPE resuscitates the mitochondria and increases hepatic adenosine triphosphate (ATP) content, NMP enables hepatobiliary viability assessment prior to transplantation. In contrast to DHOPE, NMP requires a perfusion solution with an oxygen carrier, for which red blood cells (RBC) have been used in most series. RBC, however, have limitations and cannot be used cold. We, therefore, established a protocol of sequential DHOPE, controlled oxygenated rewarming (COR), and NMP using a new hemoglobin-based oxygen carrier (HBOC)-based perfusion fluid (DHOPE-COR-NMP trial, NTR5972). Seven livers from donation after circulatory death (DCD) donors, which were initially declined for transplantation nationwide, underwent DHOPE-COR-NMP. Livers were considered transplantable if perfusate pH and lactate normalized, bile production was >= 10 mL and biliary pH > 7.45 within 150 minutes of NMP. Based on these criteria five livers were transplanted. The primary endpoint, 3-month graft survival, was a 100%. In conclusion, sequential DHOPE-COR-NMP using an HBOC-based perfusion fluid offers a novel method of liver machine perfusion for combined resuscitation and viability testing of suboptimal livers prior to transplantation

MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: A pooled-analysis from the M-SKIP project.

The MC1R gene is a key regulator of skin pigmentation. We aimed to evaluate the association between MC1R variants and the risk of sporadic cutaneous melanoma (CM) within the M-SKIP project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. Data included 5,160 cases and 12,119 controls from 17 studies. We calculated a summary odds ratio (SOR) for the association of each of the nine most studied MC1R variants and of variants combined with CM by using random-effects models. Stratified analysis by phenotypic characteristics were also performed. Melanoma risk increased with presence of any of the main MC1R variants: the SOR for each variant ranged from 1.47 (95%CI: 1.17\u20131.84) for V60L to 2.74 (1.53\u20134.89) for D84E. Carriers of any MC1R variant had a 66% higher risk of developing melanoma compared with wild-type subjects (SOR; 95%CI: 1.66; 1.41\u20131.96) and the risk attributable to MC1R variants was 28%. When taking into account phenotypic characteristics, we found that MC1R-associated melanoma risk increased only for darker-pigmented Caucasians: SOR (95%CI) was 3.14 (2.06\u20134.80) for subjects with no freckles, no red hair and skin Type III/IV. Our study documents the important role of all the main MC1R variants in sporadic CM and suggests that they have a direct effect on melanoma risk, independently on the phenotypic characteristics of carriers. This is of particular importance for assessing preventive strategies, which may be directed to darker-pigmented Caucasians with MC1R variants as well as to lightly pigmented, fair-skinned subjects

Identifying the best predictive diagnostic criteria for psoriasis in children (< 18 years): a UK multicentre case-control diagnostic accuracy study (DIPSOC study).

BACKGROUND: In children, psoriasis can be challenging to diagnose. Difficulties arise from differences in the clinical presentation compared with adults. OBJECTIVES: To test the diagnostic accuracy of previously agreed consensus criteria and to develop a shortlist of the best predictive diagnostic criteria for childhood psoriasis. METHODS: A case-control diagnostic accuracy study in 12 UK dermatology departments (2017-2019) assessed 18 clinical criteria using blinded trained investigators. Children (< 18 years) with dermatologist-diagnosed psoriasis (cases, N = 170) or a different scaly inflammatory rash (controls, N = 160) were recruited. The best predictive criteria were identified using backward logistic regression, and internal validation was conducted using bootstrapping. RESULTS: The sensitivity of the consensus-agreed criteria and consensus scoring algorithm was 84·6%, the specificity was 65·1% and the area under the curve (AUC) was 0·75. The seven diagnostic criteria that performed best were: (i) scale and erythema in the scalp involving the hairline, (ii) scaly erythema inside the external auditory meatus, (iii) persistent well-demarcated erythematous rash anywhere on the body, (iv) persistent erythema in the umbilicus, (v) scaly erythematous plaques on the extensor surfaces of the elbows and/or knees, (vi) well-demarcated erythematous rash in the napkin area involving the crural fold and (vii) family history of psoriasis. The sensitivity of the best predictive model was 76·8%, with specificity 72·7% and AUC 0·84. The c-statistic optimism-adjusted shrinkage factor was 0·012. CONCLUSIONS: This study provides examination- and history-based data on the clinical features of psoriasis in children and proposes seven diagnostic criteria with good discriminatory ability in secondary-care patients. External validation is now needed

Definition of treatment goals for moderate to severe psoriasis: a European consensus

Patients with moderate to severe psoriasis are undertreated. To solve this persistent problem, the consensus programme was performed to define goals for treatment of plaque psoriasis with systemic therapy and to improve patient care. An expert consensus meeting and a collaborative Delphi procedure were carried out. Nineteen dermatologists from different European countries met for a face-to-face discussion and defined items through a four-round Delphi process. Severity of plaque psoriasis was graded into mild and moderate to severe disease. Mild disease was defined as body surface area (BSA) ≤10 and psoriasis area and severity index (PASI) ≤10 and dermatology life quality index (DLQI) ≤10 and moderate to severe psoriasis as (BSA > 10 or PASI > 10) and DLQI > 10. Special clinical situations may change mild psoriasis to moderate to severe including involvement of visible areas or severe nail involvement. For systemic therapy of plaque psoriasis two treatment phases were defined: (1) induction phase as the treatment period until week 16; however, depending on the type of drug and dose regimen used, this phase may be extended until week 24 and (2) maintenance phase for all drugs was defined as the treatment period after the induction phase. For the definition of treatment goals in plaque psoriasis, the change of PASI from baseline until the time of evaluation (ΔPASI) and the absolute DLQI were used. After induction and during maintenance therapy, treatment can be continued if reduction in PASI is ≥75%. The treatment regimen should be modified if improvement of PASI is <50%. In a situation where the therapeutic response improved ≥50% but <75%, as assessed by PASI, therapy should be modified if the DLQI is >5 but can be continued if the DLQI is ≤5. This programme defines the severity of plaque psoriasis for the first time using a formal consensus of 19 European experts. In addition, treatment goals for moderate to severe disease were established. Implementation of treatment goals in the daily management of psoriasis will improve patient care and mitigate the problem of undertreatment. It is planned to evaluate the implementation of these treatment goals in a subsequent programme involving patients and physicians

Extended Esophagectomy in Elderly Patients with Esophageal Cancer: Minor Effect of Age Alone in Determining the Postoperative Course and Survival

Elderly patients who undergo esophagectomy for cancer often have a high prevalence of coexisting diseases, which may adversely affect their postoperative course. We determined the relationship of advanced age (i.e., a parts per thousand yen70 years) with outcome and evaluated age as a selection criterion for surgery. Between January 1991 and January 2007, we performed a curative-intent extended transthoracic esophagectomy in 234 patients with cancer of the esophagus. Patients were divided into two age groups: <70 years (group I; 170 patients) and a parts per thousand yen70 years (group II; 64 patients). Both groups were comparable regarding comorbidity (American Society of Anesthesiologists classification), and tumor and surgical characteristics. The overall in-hospital mortality rate was 6.2% (group I, 5%, vs. group II, 11%, P = 0.09). Advanced age was not a prognostic factor for developing postoperative complications (odds ratio, 1.578; 95% confidence interval, 0.857-2.904; P = 0.143). The overall number of complications was equal with 58% in group I vs. 69% in group II (P = 0.142). Moreover, the occurrence of complications in elderly patients did not influence survival (P = 0.174). Recurrences developed more in patients <70 years (58% vs. 42%, P = 0.028). The overall 5-year survival was 35%, and, when included, postoperative mortality was 33% in both groups (P = 0.676).The presence of comorbidity was an independent prognostic factor for survival (P = 0.002). Advanced age (a parts per thousand yen70 years) has minor influence on postoperative course, recurrent disease, and survival in patients who underwent an extended esophagectomy. Age alone is not a prognostic indicator for survival. We propose that a radical resection should not be withheld in elderly patients with limited frailty and comorbidity

Ethnicity and Cutaneous Melanoma in the City of Sao Paulo, Brazil: A Case-Control Study

Background: Over the last century the incidence of cutaneous melanoma has increased worldwide, a trend that has also been observed in Brazil. The identified risk factors for melanoma include the pattern of sun exposure, family history, and certain phenotypic features. In addition, the incidence of melanoma might be influenced by ethnicity. Like many countries, Brazil has high immigration rates and consequently a heterogenous population. However, Brazil is unique among such countries in that the ethnic heterogeneity of its population is primarily attributable to admixture. This study aimed to evaluate the contribution of European ethnicity to the risk of cutaneous melanoma in Brazil. Methodology/Principal Findings: We carried out a hospital-based case-control study in the metropolitan area of Sao Paulo, Brazil. We evaluated 424 hospitalized patients (202 melanoma patients and 222 control patients) regarding phenotypic features, sun exposure, and number of grandparents born in Europe. Through multivariate logistic regression analysis, we found the following variables to be independently associated with melanoma: grandparents born in Europe-Spain (OR = 3.01, 95% CI: 1.03-8.77), Italy (OR = 3.47, 95% CI: 1.41-8.57), a Germanic/Slavic country (OR = 3.06, 95% CI: 1.05-8.93), or &gt;= 2 European countries (OR = 2.82, 95% CI: 1.06-7.47); eye color-light brown (OR = 1.99, 95% CI: 1.14-3.84) and green/blue (OR = 4.62; 95% CI 2.22-9.58); pigmented lesion removal (OR = 3.78; 95% CI: 2.21-6.49); no lifetime sunscreen use (OR = 3.08; 95% CI: 1.03-9.22); and lifetime severe sunburn (OR = 1.81; 95% CI: 1.03-3.19). Conclusions: Our results indicate that European ancestry is a risk factor for cutaneous melanoma. Such risk appears to be related not only to skin type, eye color, and tanning capacity but also to others specific characteristics of European populations introduced in the New World by European immigrants.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESP [06-52041-9, 5-56069-2]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico - Brasil (National Counsel of Technological and Scientific Development - Brazil) - CNPq [478239/03-3]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico Brasil (National Counsel of Technological and Scientific Development Brazil) CNP

Quality of Reporting and Study Design of CKD Cohort Studies Assessing Mortality in the Elderly Before and After STROBE:A Systematic Review

BACKGROUND:The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement was published in October 2007 to improve quality of reporting of observational studies. The aim of this review was to assess the impact of the STROBE statement on observational study reporting and study design quality in the nephrology literature. STUDY DESIGN:Systematic literature review. SETTING & POPULATION:European and North American, Pre-dialysis Chronic Kidney Disease (CKD) cohort studies. SELECTION CRITERIA FOR STUDIES:Studies assessing the association between CKD and mortality in the elderly (>65 years) published from 1st January 2002 to 31st December 2013 were included, following systematic searching of MEDLINE & EMBASE. PREDICTOR:Time period before and after the publication of the STROBE statement. OUTCOME:Quality of study reporting using the STROBE statement and quality of study design using the Newcastle Ottawa Scale (NOS), Scottish Intercollegiate Guidelines Network (SIGN) and Critical Appraisal Skills Programme (CASP) tools. RESULTS:37 papers (11 Pre & 26 Post STROBE) were identified from 3621 potential articles. Only four of the 22 STROBE items and their sub-criteria (objectives reporting, choice of quantitative groups and description of and carrying out sensitivity analysis) showed improvements, with the majority of items showing little change between the period before and after publication of the STROBE statement. Pre- and post-period analysis revealed a Manuscript STROBE score increase (median score 77.8% (Inter-quartile range [IQR], 64.7-82.0) vs 83% (IQR, 78.4-84.9, p = 0.05). There was no change in quality of study design with identical median scores in the two periods for NOS (Manuscript NOS score 88.9), SIGN (Manuscript SIGN score 83.3) and CASP (Manuscript CASP score 91.7) tools. LIMITATIONS:Only 37 Studies from Europe and North America were included from one medical specialty. Assessment of study design largely reliant on good reporting. CONCLUSIONS:This study highlights continuing deficiencies in the reporting of STROBE items and their sub-criteria in cohort studies in nephrology. There was weak evidence of improvement in the overall reporting quality, with no improvement in methodological quality of CKD cohort studies between the period before and after publication of the STROBE statement