Risk factors for intrahepatic cholangiocarcinoma in a low-risk population: a nationwide case-control study

Recently, the incidence of intrahepatic cholangiocarcinoma (ICC) has been increasing in a number of developed (Western) countries. However, risk factors in these low-risk populations are poorly understood. In this nationwide population based case-control study in Denmark, we examined the relationship between selected medical conditions and subsequent ICC risk to provide additional clues to etiopathogenesis. All histologically confirmed ICC cases diagnosed in Denmark between 1978 and 1991 were identified from the Danish cancer registry. Population controls were selected from the central population registry and were matched 4:1 to cases on sex and year of birth. Cases and controls were linked to the Danish hospital discharge registry to obtain information on prior hospital diagnoses. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived using conditional logistic regression. A total of 764 ICC cases and 3,056 population controls were included in the study. Chronic liver diseases were significantly related to ICC: alcoholic liver disease (OR = 19.22, 95% CI = 5.55-66.54), unspecified cirrhosis (OR = 75.9, 95% CI 10.2-565.7). Bile duct diseases were also associated with risk: cholangitis (OR = 6.3, 95% CI = 2.3-17.5), choledocholithiasis (OR = 23.97, 95% CI = 2.9-198.9), cholecystolithiasis (OR = 4.0, 95% CI = 2.0-7.99), though gallbladder removal did not change risk (OR = 1.6, 95% CI = 0.65-3.7). Among other conditions, chronic inflammatory bowel disease (OR = 4.7, 95% CI = 1.65-13.9) was significantly associated with ICC. Diabetes was associated with risk in the year prior to diagnosis of ICC (OR = 3.02, 95% CI = 1.05-8.69). Obesity was unrelated to risk. These results confirm that prior bile duct diseases increase risk of ICC and suggest that alcoholic liver disease and diabetes may also increase risk.     

Congenital malformations and testicular germ cell tumors

Cryptorchidism is one of the few known risk factors for testicular germ cell tumors (TGCT). It has been postulated that other congenital malformations, in particular hypospadias, are also associated with increased risk; however, associations with birth defects have not been extensively studied. Using Swedish population‐based registries we evaluated the relationship between birth defects and risk of TGCT. TGCT cases (n = 6,593) diagnosed between 15 and 65 years of age were identified from the Swedish Cancer Registry between 1964 and 2008. Five controls per case were randomly selected from the population register and matched on birth year and birth county. Congenital malformations were identified via linkage with the Hospital Discharge Register. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each group of malformations and TGCT were estimated using conditional logistic regression. In addition to the expected association between cryptorchidism and TGCT risk [OR (95% CI): 3.18 (2.50–4.04)], hypospadias [2.41 (1.27–4.57)], inguinal hernia [1.37 (1.11–1.68)] and other genital malformations [2.19 (1.17–4.10)] were associated with an increased risk of TGCT. Mutual adjustment for cryptorchidism, hypospadias, inguinal hernia and other genital malformations did not appreciably change the associations (ORs: 3.16, 2.25, 1.30 and 1.90, respectively). The other (nongenital) malformations evaluated were not associated with TGCT. These data suggest that developmental urogenital abnormalities, specifically cryptorchidism, hypospadias and inguinal hernia, are associated with an increased risk of TGCT, further supporting the hypothesis that prenatal exposure(s) related to proper genital development are related to this tumor.     

Genetic variation in hormone metabolizing genes and risk of testicular germ cell tumors

Testicular germ cell tumors (TGCT) that arise in young men are composed of two histologic types, seminomas and nonseminomas. Risk patterns for the two types appear to be similar and may be related to either endogenous or exogenous hormonal exposures in utero. Why similar risk patterns would result in different histologic types is unclear, but could be related to varying genetic susceptibility profiles. Genetic variation in hormone metabolizing genes could potentially modify hormonal exposures, and thereby affect which histologic type a man develops. To examine this hypothesis, 33 single nucleotide polymorphisms (SNPs) in four hormone metabolism candidate genes (CYP1A1, CYP17A1, HSD17B1, HSD17B4) and the androgen receptor gene (AR) were genotyped. Associations with TGCT were evaluated among 577 TGCT cases (254 seminoma, 323 nonseminoma) and 707 controls from the US Servicemen’s Testicular Tumor Environmental and Endocrine Determinants (STEED) study. There were no significant associations with TGCT overall based on a test using an additive model. However, compared to homozygotes of the most common allele, two nonredundant SNPs in CYP1A1 were inversely associated with nonseminoma: CYP1A1 promoter SNP rs4886605 OR = 0.75 (95% CI = 0.54–1.04) among the heterozygotes and OR = 0.37, 95% CI = 0.12–1.11 among the homozygotes with a p-value for trend = 0.02; rs2606345 intron 1 SNP, OR = 0.69 (95% CI = 0.51–0.93) among heterozygotes and OR = 0.70 (95% CI = 0.42–1.17) among homozygotes, with a p-value for trend = 0.02. Caution in interpretation is warranted until findings are replicated in other studies; however, the results suggest that genetic variation in CYP1A1 may be associated with nonseminoma. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Pelvic Gliomatosis within Foci of Endometriosis

The third reported case of pelvic gliomatosis found within foci of endometriosis is documented 16 years after the removal of a benign cystic teratoma. Grossly at laparoscopy the lesions appear as typical deep fibrotic endometriotic implants.     

Defining and measuring quality of care: a perspective from US researchers.

The modern quality field in medicine is about one-third of a century old. The purpose of this paper is to summarize what we know about quality of care and indicate what we can do to improve quality of care in the next century. We assert that quality can be measured, that quality of care varies enormously, that improving quality of care is difficult, that financial incentives directed at the health system level have little effect on quality, and that we lack a publicly available tool kit to assess quality. To improve quality of care we will need adequate data and that will require patients to provide information about what happened to them and to allow people to abstract their medical records. It also will require that physicians provide patient information when asked. We also need a strategy to measure quality and then report the results and we need to place in the public domain tool kits that can be used by physicians, administrators, and patient groups to assess and improve quality. Each country should have a national quality report, based on standardized comprehensive and scientifically valid measures, which describes the country's progress in improving quality of care. We can act now. For the 70-100 procedures that dominate what physicians do, we should have a computer-based, prospective system to ensure that physicians ask patients the questions required to decide whether to do the procedure. The patient should verify the responses. Answers from patients should be combined with test results and other information obtained from the patient's physician to produce an assessment of the procedure's appropriateness and necessity. Advanced tools to assess quality, based on data from the patient and medical records, are also currently being developed. These tools could be used to comprehensively assess the quality of primary care across multiple conditions at the country, regional, and medical group level.     

The derivation and application of a risk related value of the spend for saving a statistical life.

The concept of a risk related value of the spend for saving a statistical life (VSSSL) is advanced for use in cost-benefit studies across the power generation sector, and the nuclear industry in particular. For illustrative purposes, a best estimate VSSSL is set based on HSE guidance at 2 M pounds. Above a risk of 10(-3) y(-1) it is assumed that the VSSSL may approach this maximum sustainable value. As the risk reduces so does the VSSSL. At a risk level of 10(-6) y(-1) a VSSSL of 0.5 M pounds is applied. For risks below 10(-9) y(-1) the value of further risk reduction approaches zero, although a nominal VSSSL of 10 k pounds is applied as a pragmatic way forward in this study. The implications of adopting this concept as an aid to decision making in determining the spend on radiological dose reduction measures are illustrated through a worked example with a banded approach to estimating collective dose.     

Dairy Consumption and Risk of Testicular Cancer: A Systematic Review

Dairy consumption has been studied extensively in terms of its relationship with testicular cancer (TC), yet this relationship remains unclear. In this systematic review, we aimed to answer whether TC development is associated with (a) high amounts of dairy product consumption, (b) the type of dairy product consumed, (c) increasing levels of dairy product consumption, and (d) dairy consumption during certain periods during the lifecourse. Following a systematic review of the literature, eight studies (all case-control studies) were included in our review. The included studies varied in terms of the dairy product(s) investigated (milk, cheese, cream, butter, and yoghurt) as well as the type of exposure to dairy consumption (e.g., high vs. low exposure, dose-response, and timing during lifecourse). We found that there was no strong evidence that high levels of dairy consumption are associated with risk of TC, conflicting evidence of a dose–response relationship, inconsistent evidence on whether certain types of dairy are more strongly associated with TC than others, and conflicting evidence that exposure during certain life-course periods affects TC risk more than other periods. There is no consistent evidence to support the premise that dairy product consumption is associated with the risk of TC development.