Invasive and in situ squamous cell carcinoma of the skin: a nationwide study in Iceland.

BACKGROUND: The worldwide incidence of cutaneous squamous cell carcinoma (cSCC) is increasing. OBJECTIVES: To evaluate the tumour burden of in situ and invasive cSCC in Iceland, where the population is exposed to limited ultraviolet radiation. METHODS: This whole-population study used the Icelandic Cancer Registry, which contains records of all in situ and invasive cSCC cases from 1981 to 2017. Incidence of cSCC was evaluated according to age, anatomical location, residence and multiplicity, and trends were assessed using joinpoint analysis. Age-standardized rates (WSR) and age-specific incidence rates per 100 000 person-years were calculated, along with cumulative and lifetime risks. RESULTS: Between 1981 and 2017, in situ cSCC WSR increased from 1·2 to 19·1 for men and from 2·0 to 22·3 for women. Invasive cSCC WSR rose from 4·6 to 14 for men and from 0·3 to 13·2 for women. The average number of in situ cSCC lesions was 1·71 per woman and 1·39 per man. Women developed more in situ cSCCs than invasive cSCCs in almost all anatomical locations, whereas men developed more invasive cSCCs, mostly on the head and neck. The rates of in situ cSCC were higher in Reykjavik compared with rural areas. Furthermore, women more commonly developed multiple in situ lesions. For lip cSCCs, invasive lesions occurred more frequently than in situ lesions among both sexes. Joinpoint analysis showed that in situ cSCC in women exhibited the most rapid incidence increase. CONCLUSIONS: cSCC has become an increasingly significant public health problem in Iceland. Tanning bed use and travelling abroad may contribute to skin cancer development. Public health efforts are needed to stem the behaviours leading to this rapid rise in cSCC.

Basal cell carcinoma: an emerging epidemic in women in Iceland.

BACKGROUND: An epidemic of basal cell carcinoma (BCC) has led to a significant healthcare burden in white populations. OBJECTIVES: To provide an update on incidence rates and tumour burden in an unselected, geographically isolated population that is exposed to a low level of ultraviolet radiation. METHODS: This was a whole-population study using a cancer registry containing records of all cases of BCC in 1981-2017. We assessed BCC incidence according to age, residence and multiplicity and assessed trends using join-point analysis. Age-standardized and age-specific incidence rates were calculated along with cumulative and lifetime risks. RESULTS: During the study period, the age-standardized incidence rates increased from 25·7 to 59·9 for men, and from 22·2 to 83·1 for women (per 100 000). Compared with the single-tumour burden, the total tumour burden in the population was 1·72 times higher when accounting for multiplicity. At the beginning of the study period, the world-standardized rates in men and women were similar, but by the end of the study period the rates were 39% higher in women (83·1 per 100 000, 95% confidence interval 77·9-88·3) than in men (59·9 per 100 000, 95% confidence interval 55·6-64·2). This increase was most prominent in women on sites that are normally not exposed to ultraviolet radiation in Iceland: the trunk and legs. CONCLUSIONS: This is the only reported population in which the incidence of BCC is significantly higher in women than in men. The period of notable increase in BCC lesions correlates with the period of an increase in tanning beds and travel popularity. The high multiplicity rates suggest that the total tumour burden worldwide might be higher than previously thought. What is already known about this topic? Basal cell carcinoma (BCC) is becoming an increasing healthcare burden worldwide, especially in white populations. Recent population studies have reported a rapid increase in incidence among younger individuals, especially women. What does this study add? Iceland is the only reported population in which the incidence of BCC is significantly higher in women than in men, and there does not seem to be a clear relationship between latitude and BCC incidence in Europe. Men might be comparatively protected in the northern low-ultraviolet environment, with tanning beds and travel abroad likely playing important roles in the observed incidence increase, especially in women. The high multiplicity rates suggest that the total tumour burden worldwide might be higher than previously thought. Linked Comment: Pandeya. Br J Dermatol 2020; 183:799-800.

Investigations on the constituents of SagaPro tablets, a food supplement manufactured from Angelica archangelica leaf.

Saga Pro is a food supplement product manufactured in Iceland and marketed internationally. It is claimed to have anti-nocturia effect and the flavonoid isoquercitrin has been suggested to play a role in this assumed activity. The purpose of this study was to identify and quantify the main flavonoids and furanocoumarins in the SagaPro tablets and to evaluate the importance of their presence. Isoquercitrin was identified as a constituent in an amount of 158 µg/tablet. This is a p.o. dosage highly unlikely to have an effect on nocturia or any other pharmacologically significant effect in humans. The main furanocoumarins, xanthotoxin and imperatorin, were also identified and quantified to 280 and 2 µg/tablet, respectively.

Cutaneous melanoma in Iceland: changing Breslow's tumour thickness.

BACKGROUND: The incidence of cutaneous melanoma increased dramatically in Iceland during the last two decades of the 20th century. OBJECTIVE: The aim of this study was to investigate the trend in Breslow's tumour thickness during the years 1980-2009. METHODS: The population-based Icelandic Cancer Registry provided information on all cutaneous melanomas diagnosed in the country during the study period, a total of 854 cases. Incidence rates were stratified according to gender, age at diagnosis, year of diagnosis and Breslow's tumour thickness. RESULTS: When stratified by gender and age, the incidence of thin (≤1.0 mm) melanomas increased dramatically in all subgroups. The increase in thin (≤1.0 mm) melanomas was more apparent in women or 2.6 per 100,000 in 1980-1989 to 13.3 in 2000-2009 and especially in young (<50 years) women or from 1.6 to 12.2 per 100,000 during the same period compared to an increase from 0.2 to 3.4 per 100,000 for young (<50 years) men (P < 0.05). In intermediate thickness (1.01-4.0 mm) tumours, the incidence increased only in men over the age of 50 from 2.1 in 1980-1989 to 11.3 per 100,000 in 2000-2009 (P < 0.05). The incidence of thick melanomas (>4 mm) did not increase. The median Breslow's thickness declined from 2.15 mm in 1980-1989 to 0.9 mm in 2000-2009 in males and from 1.0 to 0.6 mm in females for the same period (P < 0.001). CONCLUSION: The rise in melanoma incidence in individuals under 50 years and in women over 50 years was confined to thin tumours. However, among older males there was also an increased incidence of tumours of an intermediate thickness. This could indicate that future melanoma educational campaigns in Iceland should be directed at older individuals, and that older men may need special attention regarding suspicious nevi.

Faecal calprotectin in HIV-infected, HAART-naïve Ugandan children.

OBJECTIVES: Calprotectin is a calcium- and zinc-binding protein and a marker in faeces of gastrointestinal inflammation. Reference values have been established in children older than 4 years. The aim of the present study was to determine the concentration of faecal calprotectin (FC) in human immunodeficiency virus (HIV)-infected, highly active antiretroviral therapy-naïve Ugandan children and compare it with the reference value. METHODS: We tested 193 HIV-infected children ages 0 to 12 years in a hospital-based survey for FC. A standardised interview with sociodemographic information and medical history was used to assess risk factors. A cluster of differentiation 4 (CD4) cell percentage was prevalent in all of the children. RESULTS: The median FC concentrations decreased with increasing age, as in healthy children. The median concentration was 208 mg/kg in infants 0 to 1 year, 171 mg/kg among toddlers 1 to 4 years, and 62 mg/kg for children 4 to 12 years. Children with advanced disease and a low CD4 cell percentage had significantly higher FC concentrations than those with a high CD4 cell percentage. Children older than 4 years with diarrhoea had significantly higher FC concentrations compared with those without diarrhoea. CONCLUSIONS: HIV-infected children older than 4 years had a median FC concentration above the reference value, and gut inflammation in the children with elevated values is likely. Children with more advanced disease had increased FC concentrations regardless of age.

The frequency of advanced adenoma in consulting patients: a nationwide survey in Iceland (2003-2006).

AIM: To assess the frequency of advanced colorectal adenomas in consulting patients in Iceland. METHOD: The histological configuration of colorectal adenomas (CRA) found in 3603 patients was classified into tubular (TA), villous (VA) and serrated (SA) and the degree of neoplastic severity into low-grade dysplasia (LGD), high-grade dysplasia (HGD), carcinoma in situ (CIS), intramucosal carcinoma (IMC) and submucosal carcinoma (SMC). Advanced CRA were those showing HGD, CIS, IMC and/or SMCs. In patients with two or more adenomas, the adenoma with the highest degree of epithelial neoplasia was selected to record cases. RESULTS: Between 2003 and 2006 a total of 19424 endoscopic examinations (13572 colonoscopies and 5852 sigmoidoscopies) were performed in Iceland (mean, 4856 endoscopies per year). At histology a mean of 759.3 CRA per year were found. Thus, CRA were found in 15.6% of the colorectal endoscopies performed per year. Out of the 3037 CRA studied, 67% were TA, 29% VA and the remaining 4% SA. LGD was present in 79%, HGD in 15%, CIS in 2.4%, IMC in 1.9% and SMC in 1.9%. Consequently, out of 3037 CRA investigated, 652 (21.5%) were advanced CRA; 71% of these showed HGD, 11% CIS, 9% IMC and 9% SMC. Two-thirds of the 652 advanced CRA were advanced VA, and more than three-quarters of 58 advanced CRA with SMC, were advanced VA. CONCLUSION: Advanced VA displaying intraepithelial neoplasia (HGD and CIS) showed a propensity to evolve into invasive carcinoma. Accordingly, VA displaying HGD and CIS might be regarded as biological markers for predicting colorectal cancer risk. This is the first study in which the frequency of CRA and advanced CRA detected in consulting patients is reported on a nationwide basis.

Individual risk assessment and information technology to optimise screening frequency for diabetic retinopathy.

AIMS/HYPOTHESIS: The aim of this study was to reduce the frequency of diabetic eye-screening visits, while maintaining safety, by using information technology and individualised risk assessment to determine screening intervals. METHODS: A mathematical algorithm was created based on epidemiological data on risk factors for diabetic retinopathy. Through a website, www.risk.is , the algorithm receives clinical data, including type and duration of diabetes, HbA(1c) or mean blood glucose, blood pressure and the presence and grade of retinopathy. These data are used to calculate risk for sight-threatening retinopathy for each individual's worse eye over time. A risk margin is defined and the algorithm recommends the screening interval for each patient with standardised risk of developing sight-threatening retinopathy (STR) within the screening interval. We set the risk margin so that the same number of patients develop STR within the screening interval with either fixed annual screening or our individualised screening system. The database for diabetic retinopathy at the Department of Ophthalmology, Aarhus University Hospital, Denmark, was used to empirically test the efficacy of the algorithm. Clinical data exist for 5,199 patients for 20 years and this allows testing of the algorithm in a prospective manner. RESULTS: In the Danish diabetes database, the algorithm recommends screening intervals ranging from 6 to 60 months with a mean of 29 months. This is 59% fewer visits than with fixed annual screening. This amounts to 41 annual visits per 100 patients. CONCLUSION: Information technology based on epidemiological data may facilitate individualised determination of screening intervals for diabetic eye disease. Empirical testing suggests that this approach may be less expensive than conventional annual screening, while not compromising safety. The algorithm determines individual risk and the screening interval is individually determined based on each person's risk profile. The algorithm has potential to save on healthcare resources and patients' working hours by reducing the number of screening visits for an ever increasing number of diabetic patients in the world.

The interaction of adiposity with the CRP gene affects CRP levels: age, gene/environment susceptibilty-Reykjavik study.

OBJECTIVE: Common diseases often have an inflammatory component reflected by associated markers such as serum C-reactive protein (CRP) levels. Circulating CRP levels have also been associated with adipose tissue as well as with specific CRP genotypes. We examined the interaction between measures of body mass index (BMI), waist circumference and fat percent (total fat measured by bioimpedance) with genotypes of the CRP gene in the determination of CRP levels. METHODS: The first 2296 participants (mean age 76+/-6 years, 42% men) in the Age, Gene/Environment Susceptibility-Reykjavik Study, a multidisciplinary epidemiological study to determine risk factors in aging, were genotyped for 10 single nucleotide polymorphisms (SNPs) in the CRP gene. General linear models with age and terms for interaction of CRP genotypes with BMI, waist circumference and percent fat were used to evaluate the association of genotypes to CRP levels (high-sensitivity method, range 0-10 mg l(-1)) in men and women separately. RESULTS: We focused on the SNP rs1205 that represents the allele that captures the strongest effects of the gene on CRP levels. Carriers of the rs1205 G allele had significantly higher CRP levels than noncarriers in a dose-dependent manner. Compared to the AA genotype, the slope of the increase in CRP with increasing BMI (P=0.045) and waist circumference (P=0.014) was different for the G allele carriers and of similar magnitude in both men and women. The rs1205 interactions were not significant for fat mass percent, suggesting a possible association with fat localization. CONCLUSIONS: This study further illuminates the known association between measures of adiposity and CRP levels and is shown to be dependent on variation in the rs1205 SNP of the CRP gene. The correlated increase in CRP levels with adiposity is accentuated by presence of the G allele.

In vitro and in vivo immunomodulating effects of traditionally prepared extract and purified compounds from Cetraria islandica.

Cetraria islandica (Iceland moss) has been used for centuries in folk medicine in many countries against a number of conditions, including inflammatory conditions, mainly as an aqueous extract. C. islandica contains many compounds, such as polysaccharides and secondary metabolites, some of which have established biological activity. However, very little is known about their effect on the immune system. Human monocyte-derived immature dendritic cells were cultured with an aqueous extract from C. islandica quantified with regard to the polysaccharides lichenan and isolichenan and secondary metabolites protolichesterinic and fumarprotocetraric acids. The purified compounds were also tested individually. Their effect on the maturation of the dendritic cells was assessed by measuring secretion of IL-10 and IL-12p40 and expression of surface molecules. In addition, the effect of the aqueous extract on antigen-induced arthritis in rats was investigated. The aqueous extract caused upregulated secretion of both IL-10 and IL-12p40, with IL-10 secretion being more prominent. Lichenan had similar effects, whereas isolichenan and the secondary metabolites were inactive, suggesting that the effect observed by the aqueous extract was mainly mediated by lichenan. Significantly less arthritis was observed for rats treated by the aqueous extract, administered subcutaneously, compared with rats treated with saline alone. These results suggest that the aqueous extract of C. islandica has anti-inflammatory effect, possibly by changing the cytokine secretion bias from IL-12p40 towards IL-10.

Cyanohydrin glycosides with unusual sugar residues: revised structure of passitrifasciatin.

The cyclopentanoid cyanohydrin glycoside passitrifasciatin was reisolated, and shown to be (1S,4R)-1-(beta-D-gluopyranosyloxy)-4-(6-deoxy-beta-D-allopyran osyloxy)-2-cyclopentene-1-carbonitrile, using one- and two dimensional NMR spectroscopy, selective acid-catalysed cleavage of the glycosidic linkage of 6-deoxy-D-allose, and optical rotation data.

Activated protein C resistance in young adults with central retinal vein occlusion.

BACKGROUND: Central retinal vein occlusion is a disease that is most common in old people. While the disease in old people often is associated with atherosclerosis, hypertension, diabetes, or glaucoma, this is much less evident in young people. However, a new defect in the anticoagulant system has recently been discovered, activated protein C resistance. This hereditary defect may well be associated with central retinal vein occlusion, and so this factor was analysed in patients younger than 50 years with a history of central retinal vein occlusion. METHODS: Blood samples were obtained from 31 patients younger than 50 years with a history of central retinal vein occlusion, and analysed for activated protein C resistance with standard clinical laboratory methods. RESULTS: In this material 26% of all the patients and 36% of the patients younger than 45 years were resistant to activated protein C. The normal incidence of activated protein C resistance is 2-7%. CONCLUSION: Activated protein C resistance seems to be the most common known cause of central retinal vein occlusion in young people.

Quality status of serum cholesterol analysis in Iceland.

Eight laboratories participated in the first Icelandic quality assessment survey of serum cholesterol analysis in 1989. Quality control material, lyophilized animal serum and frozen human serum, was distributed three times over a period of one year and analyzed each time over 10 consecutive days. After two distributions of control material the laboratories were advised to start using a common calibrator from the U.S. National Bureau of Standards, and six months later the third lot of control material was analyzed. All laboratories use the same enzymatic methods for estimating serum cholesterol. Average total imprecision within and between laboratories improved throughout the survey, but did not reach the quality goal of the U.S. National Cholesterol Education Panel of +/- 3% for imprecision and +/- 3% for bias leaving scope for further improvement.

A Nordic reference serum suitable for use as trueness control in the clinical routine laboratory.

The described reference serum is characterized by: liquid human serum at "normal" level stored in frozen state at -80 degrees C; minimum damage of proteins; aseptic preparation; cryoprecipitate and excess fibrin removed; serum cleared by ultracentrifugation; pH at 7.2-7.6; available in sealed glass ampoules with inert gas (one ml serum in each); specified components among most frequently analyzed analytes; homogeneity assured and stability monitored; produced under strict rules for good manufacturing practices (GMP). The assigned values are traceable to reference measurement procedures and reference materials of highest achievable metrological level; according to the present proposal the maximum allowable uncertainty of the assigned value is based on biological variation (shared common reference intervals); the uncertainty should ideally not exceed 1/5 of the maximum allowable bias of results obtained on patients samples (even 1/2 would theoretically be acceptable and, for a practical guide approximately < 1% may suffice). The present document provides some guidance of how the reference serum could be established in practice. The document also indicates the use of the material and further extension of the concept. The present work is done as a NORDKEM project.

Gastro-oesophageal reflux and chronic respiratory disease in infants and children: treatment with cisapride.

Gastro-oesophageal reflux (GOR) has been implicated in such clinical phenomena as aspiration pneumonia, bronchospasm or wheezing, apnea, stridor, and hoarseness. Various tests have been used as an aid to diagnosing patients with chronic respiratory disease where GOR is a causal factor. Different forms of conservative treatment have been tried for GOR, including cisapride. Several studies have evaluated its effect on the pH profile and respiratory symptoms in patients with chronic respiratory disease and have demonstrated improvement of nocturnal wheezing, cough, and irritability. Our experience with cisapride is positive in children with GOR. Patients refractory to medical treatment have been surgically treated with good results.

Structural characterisation of a complex heteroglycan from the cyanobacterium Nostoc commune.

An alkali-extractable O-methylated ribofuranose-containing heteroglycan, Nc-5-s, was isolated from wild-growing field colonies of the cyanobacterium Nostoc commune collected in Iceland, using ethanol fractionation and anion-exchange chromatography. The average molecular weight was estimated to be 1500 kDa. Structural characterisation of the heteroglycan was performed by high-field NMR spectroscopy (1D proton, 2D-COSY, 2D-NOESY, 2D-TOCSY, (1)H (13)C-HSQC, HMBC, H2BC and HSQC-NOESY) as well as monosaccharide analysis after methanolysis by GC and supported by linkage analysis by GC-MS. According to the data obtained, the structure of Nc-5-s is composed of repeating units of 1, 1a, 1b and 2 and 2a in approximate molar ratio of (10:25:50:5:10).

Biennial eye screening in patients with diabetes without retinopathy: 10-year experience.

AIMS: To evaluate the safety of every-other-year eye screening for patients with diabetes without retinopathy. METHODS: Since 1994, patients with diabetes without retinopathy in Iceland have received eye screening every other year. 296 patients with diabetes who had no diabetic retinopathy in 1994/95 were followed with biennial eye examinations until they had developed retinopathy. The 10-year experience of this approach is reviewed. RESULTS: Out of the 296 diabetic individuals, 172 did not develop diabetic retinopathy during the 10-year observation period. 96 patients developed mild non-proliferative retinopathy, six developed clinically significant diabetic macular oedema, 23 developed preproliferative retinopathy, and four developed proliferative diabetic retinopathy during the 10-year observation period. All the patients who developed macular oedema or proliferative retinopathy had already been diagnosed as having mild nonproliferative retinopathy and entered an annual screening protocol before the sight-threatening retinopathy developed. No patient had any undue delay in treatment. CONCLUSION: Every other year screening for diabetic eye disease seems to be safe and effective in diabetics without retinopathy. Such an approach will reduce the number of screening visits more than 25%. This reduces health costs and strain on resources considerably and relieves the patients with diabetes from unnecessary clinic visits and examinations.

Adenocarcinoma of the prostate in Iceland: a population-based study of stage, Gleason grade, treatment and long-term survival in males diagnosed between 1983 and 1987.

OBJECTIVE: To investigate adenocarcinoma of the prostate in a single population with an extended follow-up period. MATERIAL AND METHODS: Using the Icelandic Cancer Registry, we identified all Icelandic men diagnosed with prostate cancer between 1983 and 1987. Disease stage, initial treatment and follow-up information were obtained from hospital records and death certificates. A critical evaluation was made of the accuracy of the death certificates regarding prostate cancer. All available histology information was reviewed and graded according to the Gleason grading system. RESULTS: A total of 414 men were diagnosed with adenocarcinoma of the prostate. Of these, 370 were alive at the time of diagnosis and stage could be determined. Four stage groups were defined: focal incidental (n=50); localized (n=164); local advanced (n=32); and metastatic disease (n=124). The mean age at diagnosis was 74.4 years (range 53-94 years). The combined Gleason score was 2-5 in 89, 6-7 in 117, 8-10 in 117 and unknown in 47 cases. The median follow-up period for the group was 6.15 years (range 0.3-19.8 years). Thirty men received treatment with curative intent: radiation therapy, n=20; and radical prostatectomy, n=10. A total of 334 patients died during the follow-up period, of whom 168 (50%) died of prostate cancer. Prostate cancer-specific survival at 10 and 15 years was 100% and 90.6%, respectively for focal incidental cancer; 73.1% and 60.8% for men with localized disease; 23.4% and 11.7% for local advanced disease; and 6.81% and 5.45% for metastatic disease. A Cox multivariate analysis showed age, stage and Gleason score to be independent predictors of prostate cancer death. A total of 104 patients with localized disease and a Gleason score of