Lynch syndrome-associated breast cancers do not overexpress chromosome 11-encoded mucins.

Mismatch repair-deficient breast cancers may be identified in Lynch syndrome mutation carriers, and have clinicopathological features in common with mismatch repair-deficient colorectal and endometrial cancers such as tumour-infiltrating lymphocytes and poor differentiation. Mismatch repair-deficient colorectal cancers frequently show mucinous differentiation associated with upregulation of chromosome 11 mucins. The aim of this study was to compare the protein expression of these mucins in mismatch repair-deficient and -proficient breast cancers.

Risk of metachronous colon cancer following surgery for rectal cancer in mismatch repair gene mutation carriers.

Background: Despite regular surveillance colonoscopy, the metachronous colorectal cancer risk for mismatch repair (MMR) gene mutation carriers after segmental resection for colon cancer is high and total or subtotal colectomy is the preferred option. However, if the index cancer is in the rectum, management decisions are complicated by considerations of impaired bowel function. We aimed to estimate the risk of metachronous colon cancer for MMR gene mutation carriers who underwent a proctectomy for index rectal cancer.

Colorectal carcinomas with KRAS mutation are associated with distinctive morphological and molecular features.

KRAS-mutated carcinomas comprise 35-40% of all colorectal carcinomas but little is known about their characteristics. The aim of this study was to examine the pathological and molecular features of KRAS-mutated colorectal carcinomas and to compare them with other carcinoma subgroups. KRAS mutation testing was performed in 776 incident tumors from the Melbourne Collaborative Cohort Study.

Muir-Torre syndrome-associated pleomorphic liposarcoma arising in a previous radiation field.

Muir-Torre syndrome is a variant of Lynch syndrome, characterised by sebaceous neoplasia and/or keratoacanthomas associated with visceral malignancies. Muir-Torre syndrome is caused by germline mutations of one of the mismatch repair genes, frequently MSH2 and less frequently MLH1 and MSH6. Visceral malignancies associated with Muir-Torre syndrome and Lynch syndrome include colorectal, endometrial and other gastrointestinal, urological and gynaecological malignancies.

Cancer risks for MLH1 and MSH2 mutation carriers.

We studied 17,576 members of 166 MLH1 and 224 MSH2 mutation-carrying families from the Colon Cancer Family Registry. Average cumulative risks of colorectal cancer (CRC), endometrial cancer (EC), and other cancers for carriers were estimated using modified segregation analysis conditioned on ascertainment criteria. Heterogeneity in risks was investigated using a polygenic risk modifier.

Can transabdominal ultrasound be used as a screening test for short cervical length?

Objective: Universal transvaginal cervical length screening can be associated with a significant logistical burden. We hypothesized that there is a threshold cervical length measured by transabdominal ultrasound above which risk for short transvaginal cervical length is extremely low.

Study Design: This prospective cohort study evaluated a consecutive series of women offered universal transvaginal cervical length screening during anatomy ultrasound.

Multiplicity and molecular heterogeneity of colorectal carcinomas in individuals with serrated polyposis.

Serrated polyposis (SP) is a clinically defined syndrome characterized by the occurrence of multiple serrated polyps in the large intestine. Individuals with SP and their relatives are at increased risk of colorectal carcinoma (CRC). We aimed to determine the pathologic and molecular profiles of CRCs in individuals fulfilling World Health Organization criteria for SP.

Effects of increased fetuin-A in human trophoblast cells and associated pregnancy outcomes.

Objective: The purpose of this study was to determine whether fetuin-A affects trophoblast viability and invasion, whether growth factors that bind receptors that activate tyrosine kinase are impaired by fetuin-A, and whether elevated maternal serum fetuin-A levels are associated with adverse pregnancy outcomes.

Study Design: We studied viability and invasion in first-trimester extravillous trophoblast cells that were exposed to fetuin-A, insulin-like growth factor, and placental growth factor. Insulin receptor substrates expression was assessed.

Becoming an effective learner.

The teaching of medicine and the expectations of trainees has changed enormously over the past two decades in parallel to changes in medical technology, advances in information technology and the provision of healthcare. With a shortened time in medical training efficient learning is ever more crucial and the skills with which to optimise and enhance our learning opportunities are discussed.

An anatomically comprehensive atlas of the adult human brain transcriptome.

Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ∼900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals.

Early rehabilitation in critical care (eRiCC): functional electrical stimulation with cycling protocol for a randomised controlled trial.

Introduction: Intensive care-acquired weakness is a common problem, leads to significant impairment in physical functioning and muscle strength, and is prevalent in individuals with sepsis. Early rehabilitation has been shown to be safe and feasible; however, commencement is often delayed due to a patient's inability to co-operate. An intervention that begins early in an intensive care unit (ICU) admission without the need for patient volition may be beneficial in attenuating muscle wasting.

Longitudinal evaluation of predictive value for preeclampsia of circulating angiogenic factors through pregnancy.

Objective: The purpose of this study was to examine whether longitudinally sampled maternal angiogenic concentrations predict preeclampsia.

Study Design: Plasma sFlt-1 and placental growth factor (PlGF) concentrations in healthy pregnant women were quantified at 10, 17, 25, and 35 weeks' gestation. Preeclampsia was diagnosed with criteria from the American College of Obstetricians and Gynecologists.

Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome.

Background: Lynch syndrome is a highly penetrant cancer predisposition syndrome caused by germline mutations in DNA mismatch repair (MMR) genes. We estimated the risks of primary cancers other than colorectal cancer following a diagnosis of colorectal cancer in mutation carriers.

Methods: We obtained data from the Colon Cancer Family Registry for 764 carriers of an MMR gene mutation (316 MLH1, 357 MSH2, 49 MSH6, and 42 PMS2), who had a previous diagnosis of colorectal cancer.

Salivary duct carcinomas can be classified into luminal androgen receptor-positive, HER2 and basal-like phenotypes.

Aims: The aim of this study was to devise a molecular classification for salivary duct carcinomas (SDCs) based on the similarities between SDCs and breast carcinomas and on characteristics of the microarray-based gene expression profiling-defined molecular subtypes of breast cancer.

Methods And Results: Forty-two pure salivary duct carcinomas, 35 of which contained an in-situ component as defined by histological review and/or immunohistochemical analysis, were stained with antibodies for oestrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR) and cytokeratin (CK) 5/6. Based on these markers, tumours were classified into HER2, luminal androgen receptor-positive, basal-like, luminal and indeterminate phenotype.

Can vibroacoustic stimulation improve the efficiency of a tertiary care antenatal testing unit?

Objective: Our primary objective was to determine whether vibroacoustic stimulation (VAS) decreases time to fetal reactivity in the antenatal testing unit (ATU) of a tertiary care center.

Methods: We performed a prospective, quality assurance initiative to determine whether VAS could increase the efficiency of our ATU. On pre-specified "VAS days," VAS was applied for 3 s, if the non-stress test was non-reactive in the first 10 min.

Aggressive -negative peptic ulceration as the initial manifestation of Crohn's disease.

Peptic ulceration is a recognised feature of Crohn's disease, but the characteristics of this manifestation are rather poorly described. Furthermore, most reports in the literature relate to ulcer disease in cases of established Crohn's disease. The authors report a series of four cases in which the diagnosis of Crohn's disease was preceded by peptic ulceration.

Colonoscopy requirements of population screening for colorectal cancer in New Zealand.

Aim: To estimate the colonoscopy burden of introducing population screening for colorectal cancer in New Zealand.

Methods: Screening for colorectal cancer using biennial immunochemical faecal occult blood tests offered to people aged 50-74 years of age was modelled using population estimates from Statistics New Zealand for 2011-2031. Modelling to determine colonoscopy requirements was based on participation and test positivity rates from published results of screening programmes.

Serrated lesions of the colorectum: review and recommendations from an expert panel.

Serrated lesions of the colorectum are the precursors of perhaps one-third of colorectal cancers (CRCs). Cancers arising in serrated lesions are usually in the proximal colon, and account for a disproportionate fraction of cancer identified after colonoscopy. We sought to provide guidance for the clinical management of serrated colorectal lesions based on current evidence and expert opinion regarding definitions, classification, and significance of serrated lesions.

Examining the correlation between placental and serum placenta growth factor in preeclampsia.

Objective: Decreased levels of serum placenta growth factor (PlGF) are associated with preeclampsia. We sought to determine whether serum and placental levels of PlGF (sPlGF and pPlGF) are associated with preeclampsia and whether there is a correlation between serum and placental PlGF levels.

Study Design: These analyses were part of a larger, prospective, case-control study.

Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22.

A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e.

Universal maternal cervical length screening during the second trimester: pros and cons of a strategy to identify women at risk of spontaneous preterm delivery.

Three large randomized controlled trials investigating the efficacy of universal cervical length screening and treatment with vaginal progesterone or cervical cerclage to prevent preterm delivery have been published over the past several years. None of these trials demonstrate proven efficacy for universal cervical length screening and cerclage placement in women with short cervical length. However, universal cervical length screening and treatment with daily vaginal progesterone in women with short cervical length reduces the risk of preterm birth, but large numbers of women must be screened to prevent a relatively small number of preterm deliveries.

Cancer risks for relatives of patients with serrated polyposis.

Objectives: Serrated polyposis (hyperplastic polyposis) is characterized by multiple polyps with serrated architecture in the colorectum. Although patients with serrated polyposis are known to be at increased risk of colorectal cancer (CRC) and possibly extracolonic cancers, cancer risk for their relatives has not been widely explored. The aim of this study was to estimate the risks of CRC and extracolonic cancers for relatives of patients with serrated polyposis.

Phenotype and polyp landscape in serrated polyposis syndrome: a series of 100 patients from genetics clinics.

Serrated polyposis syndrome (SPS), also known as hyperplastic polyposis, is a syndrome of unknown genetic basis defined by the occurrence of multiple serrated polyps in the large intestine and associated with an increased risk of colorectal cancer (CRC). There are a variety of SPS presentations, which may encompass a continuum of phenotypes modified by environmental and genetic factors. To explore the phenotype of SPS, we recorded the histologic and molecular characteristics of multiple colorectal polyps in patients with SPS recruited between 2000 and 2010 from genetics clinics in Australia, New Zealand, Canada, and the United States.

Two-dimensional sonographic placental measurements in the prediction of small-for-gestational-age infants.

Objectives: To determine the utility of two-dimensional (2D) sonographic placental measurements in the prediction of small-for-gestational-age (SGA) infants.

Methods: The maximal diameter along the fetal surface of the placenta and the maximal placental thickness were measured at 18-24 weeks' gestation, and the measurements repeated in the orthogonal plane. 'Biometric lags' were calculated as the difference between sonographic gestational age, estimated using each of a number of fetal biometric measurements, and actual gestational age.