node metastases was not possible.

Pathological ultrastaging after routine hematoxylin and eosin staining in endometrial cancer patients has led to an increased detection rate of sentinel lymph node metastases. Different ultrastaging methods are used, with a preference for bread-loaf slicing. However, due to the large heterogeneity of the studies, assessing which ultrastaging method has the highest detection rate of sentinel lymph node metastases was not possible.

Burden of cancer mortality is often measured by death counts or mortality rates, but potential years of life lost (PYLL) and PYLL per death may be more useful to estimate the impact of cancer-related deaths occurring at younger ages.

We used U.S. national death certificate data. A total of 45 categories of common cancers were grouped for cancer-specific calculations of PYLL and PYLL per death. PYLL was defined as the sum of the total years of life lost prior to age 75 years.

The largest number of PYLL in 2017 was due to deaths from cancers of the lung/bronchus (891,313; 20.8%), colon/rectum (409,538; 9.6%), and breast (400,643; 9.4%). Cancers with the highest PYLLs generally also caused the largest number of deaths and had the highest mortality rates, with the exception of prostate cancer (5.1% of deaths, 2.0% of PYLL). In contrast, PYLLs per death were greatest for deaths due to cancers of testis (mean = 34.0 years), bones/joints (26.4), and other endocrine sites including thymus (25.2).

Although PYLLs generally reflect mortality rates, they more heavily weigh cancers that occur at younger ages. In contrast, PYLL per death, which is an average quantification of life years lost for individual patients with cancer, shows a different pattern.

Mortality rates, PYLL, and PYLL per death are complementary measures of the burden of deaths due to cancer that should be considered in tandem to prioritize public health interventions focused on preventing premature mortality.

Mortality rates, PYLL, and PYLL per death are complementary measures of the burden of deaths due to cancer that should be considered in tandem to prioritize public health interventions focused on preventing premature mortality.

Critically shortened telomeres contribute to chromosomal instability and neoplastic transformation and are associated with early death of patients with certain cancer types. Shorter leukocyte telomere length (LTL) has been associated with higher risk for pancreatic ductal adenocarcinoma (PDAC) and might be associated also with survival of patients with PDAC. We investigated the association between treatment-naïve LTL and overall survival of patients with incident PDAC.

The study included 642 consecutively enrolled PDAC patients in the Mayo Clinic Biospecimen Resource for Pancreas Research. Ataluren CFTR inhibitor Blood samples were obtained at the time of diagnosis, before the start of cancer treatment, from which LTL was assayed by qRT-PCR. LTL was first modeled as a continuous variable (per-interquartile range decrease in LTL) and then as a categorized variable (short, medium, long). Multivariable-adjusted HRs and 95% confidence intervals (CI) were calculated for overall mortality using Cox proportional hazard models.

Shorter treatment-naïve LTL was associated with higher mortality among patients with PDAC (HR

= 1.13, 95% CI 1.01-1.28,

= 0.03; HR

= 1.29, 95% CI 1.05-1.59,

= 0.01). There was a difference in the association between LTL and overall mortality by tumor stage at diagnosis; resectable tumors (HR

= 0.91; 95% CI 0.73-1.12), locally advanced tumors (HR

= 1.29; 95% CI 1.07-1.56), and metastatic tumors (HR

= 1.17; 95% CI 0.96-1.42),

= 0.04.

Shorter treatment-naïve LTL is associated with poorer overall survival of patients with incident PDAC.

Peripheral blood LTL might be a prognostic marker for PDAC.

Peripheral blood LTL might be a prognostic marker for PDAC.

Some countries have implemented stand-alone human papillomavirus (HPV) testing while others consider cotesting for cervical cancer screening. We compared both strategies within a population-based study.

The MARZY cohort study was conducted in Germany. Randomly selected women from population registries aged ≥30 years (

= 5,275) were invited to screening with Pap smear, liquid-based cytology (LBC, ThinPrep), and HPV testing (Hybrid Capture2, HC2). Screen-positive participants [ASC-US+ or high-risk HC2 (hrHC2)] and a random 5% sample of screen-negatives were referred to colposcopy.

HPV genotyping was conducted by GP5+/6+ PCR-EIA with reverse line blotting. Sensitivity, specificity (adjusted for verification bias), and potential harms, including number of colposcopies needed to detect 1 precancerous lesion (NNC), were calculated.

In 2,627 screened women, cytological sensitivities (Pap, LBC 47%) were lower than HC2 (95%) and PCR (79%) for CIN2+. Cotesting demonstrated higher sensitivities (HC2 cotesting 99%; PCR cotesting 84%), but at the cost of lower specificities (92%-95%) compared with HPV stand-alone (HC2 95%; PCR 94%) and cytology (97% or 99%). Cotesting versus HPV stand-alone showed equivalent relative sensitivity [HC2 1.06, 95% confidence interval (CI), 1.00-1.21; PCR 1.07, 95% CI, 1.00-1.27]. Relative specificity of Pap cotesting with either HPV test was inferior to stand-alone HPV. LBC cotesting demonstrated equivalent specificity (both tests 0.99, 95% CI, 0.99-1.00). NNC was highest for Pap cotesting.

Cotesting offers no benefit in detection over stand-alone HPV testing, resulting in more false positive results and colposcopy referrals.

HPV stand-alone screening offers a better balance of benefits and harms than cotesting.

.

HPV stand-alone screening offers a better balance of benefits and harms than cotesting.See related commentary by Wentzensen and Clarke, p. 432.

Past history of gallstones is associated with increased risk of gallbladder cancer in observational studies. We conducted complementary observational and Mendelian randomization (MR) analyses to determine whether history of gallstones is causally related to development of gallbladder cancer in an Indian population.

To investigate associations between history of gallstones and gallbladder cancer, we used questionnaire and imaging data from a gallbladder cancer case-control study conducted at Tata Memorial Hospital, Mumbai, Maharashtra, India (cases = 1,170; controls = 2,525). We then used 26 genetic variants identified in a genome-wide association study of 27,174 gallstone cases and 736,838 controls of European ancestry in an MR approach to assess causality. The association of these genetic variants with both gallstones and gallbladder cancer was examined in the gallbladder cancer case-control study. Various complementary MR approaches were used to evaluate the robustness of our results in the presence of pleiotropy and heterogeneity, and to consider the suitability of the selected SNPs as genetic instruments for gallstones in an Indian population.