Worse histopathology and prognosis in women with breast cancer diagnosed during the second trimester of pregnancy.

BACKGROUND: Evidence suggests that women with breast cancer diagnosed during pregnancy (PrBC) and within 2 years of delivery (PPBC) have similar survival compared to women diagnosed not near pregnancy if adjusted for stage and subtype. To investigate whether this is true for all subtypes and for both pregnancy and post-delivery periods, we examined clinicopathologic features and survival in women with breast cancer by trimesters and 6-month post-delivery intervals. MATERIALS AND METHODS: Women diagnosed with invasive breast cancer during 1992-2018 at ages 18-44 years were identified in the Swedish Cancer Register, with information on childbirths from the Swedish Multi-Generation Register and clinical data from Breast Cancer Quality Registers. Each woman with PrBC or PPBC was matched 1 : 2 by age and year to comparators diagnosed with breast cancer not near pregnancy. Distributions of stage, grade, and surrogate subtypes were compared. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for breast cancer mortality were estimated using Cox regression. RESULTS: We identified 1430 women with PrBC and PPBC (181 during pregnancy, 499 during the first and 750 during the second year after delivery). Compared to 2860 comparators, women with PrBC and PPBC in the first year after delivery had a significantly higher proportion of luminal human epidermal growth factor receptor 2 (HER2)-positive, HER2-positive and triple-negative tumours, and more advanced stage at diagnosis. After adjustment for age, year, parity, country of birth, hospital region, subtype, and stage, women diagnosed during the second trimester had a worse prognosis than matched comparators (HR 1.8, 95% CI: 1.0-3.2). CONCLUSIONS: Women diagnosed during pregnancy or within the first year after delivery have a worse prognosis than women diagnosed not near pregnancy due to adverse tumour biology and advanced stage at diagnosis. A worse prognosis for women diagnosed during the second trimester remained after multivariable adjustment, possibly reflecting difficulties to provide optimal treatment during ongoing pregnancy.

A trans-diagnostic review of anxiety disorder comorbidity and the impact of multiple exclusion criteria on studying clinical outcomes in anxiety disorders.

Anxiety disorders are highly comorbid with each other and with other serious mental disorders. As our field progresses, we have the opportunity to pursue treatment study designs that consider these comorbidities. In this perspective review, we first characterized the prevalence of multiple anxiety disorder comorbidity by reanalyzing national survey data, then conducted an English-language PubMed search of studies analyzing the impact of exclusion criteria on treatment outcome data. In the prevalence data, 60% of people with an anxiety disorder had one or more additional anxiety or depression diagnosis. Because our commonly applied exclusion criteria focus on a single diagnosis and do not consider a multiple comorbidity profile, the impact of the criteria may be to exclude up to 92% of anxiety disorder treatment seekers. Moreover, the findings do not suggest a consistent relationship between the number of exclusion criteria and the effect size of treatment outcomes. Thus, future studies might consider a more trans-diagnostic rationale for determining exclusion criteria, one that is generalizable to real-world settings in which multiple diagnoses commonly co-occur. The findings also encourage a more systematic reporting of rationales for the choice of-and the implications of-each exclusion criterion.

Comparison of fully and semi-automated area-based methods for measuring mammographic density and predicting breast cancer risk.

BACKGROUND: Mammographic density is a strong risk factor for breast cancer but the lack of valid fully automated methods for quantifying it has precluded its use in clinical and screening settings. We compared the performance of a recently developed automated approach, based on the public domain ImageJ programme, to the well-established semi-automated Cumulus method. METHODS: We undertook a case-control study within the intervention arm of the Age Trial, in which ∼54,000 British women were offered annual mammography at ages 40-49 years. A total of 299 breast cancer cases diagnosed during follow-up and 422 matched (on screening centre, date of birth and dates of screenings) controls were included. Medio-lateral oblique (MLO) images taken closest to age 41 and at least one year before the index case's diagnosis were digitised for each participant. Cumulus readings were performed in the left MLO and ImageJ-based readings in both left and right MLOs. Conditional logistic regression was used to examine density-breast cancer associations. RESULTS: The association between density readings taken from one single MLO and breast cancer risk was weaker for the ImageJ-based method than for Cumulus (age-body mass index-adjusted odds ratio (OR) per one s.d. increase in percent density (95% CI): 1.52 (1.24-1.86) and 1.61 (1.33-1.94), respectively). The ImageJ-based density-cancer association strengthened when the mean of left-right MLO readings was used: OR=1.61 (1.31-1.98). CONCLUSIONS: The mean of left-right MLO readings yielded by the ImageJ-based method was as strong a predictor of risk as Cumulus readings from a single MLO image. The ImageJ-based method, using the mean of two measurements, is a valid automated alternative to Cumulus for measuring density in analogue films.

Common genetic variability in ESR1 and EGF in relation to endometrial cancer risk and survival.

We investigated common genetic variation in the entire ESR1 and EGF genes in relation to endometrial cancer risk, myometrial invasion and endometrial cancer survival. We genotyped a dense set of single-nucleotide polymorphisms (SNPs) in both genes and selected haplotype tagging SNPs (tagSNPs). The tagSNPs were genotyped in 713 Swedish endometrial cancer cases and 1567 population controls and the results incorporated into logistic regression and Cox proportional hazards models. We found five adjacent tagSNPs covering a region of 15 kb at the 5' end of ESR1 that decreased the endometrial cancer risk. The ESR1 variants did not, however, seem to affect myometrial invasion or endometrial cancer survival. For the EGF gene, no association emerged between common genetic variants and endometrial cancer risk or myometrial invasion, but we found a five-tagSNP region that covered 51 kb at the 5' end of the gene where all five tagSNPs seemed to decrease the risk of dying from endometrial cancer. One of the five tagSNPs in this region was in strong linkage disequilibrium (LD) with the untranslated A61G (rs4444903) EGF variant, earlier shown to be associated with risk for other forms of cancer.

Post traumatic intra-abdominal pseudo-aneurysms in children.

Pseudoaneurysms are uncommon following blunt abdominal trauma. A review of the literature has shown that such cases are usually managed aggressively. We report our experience of two cases of post traumatic intra-abdominal pseudoaneurysms which were managed conservatively.

Gene expression profiling for prognosis using Cox regression.

Given the promise of rich biological information in microarray data we will expect an increasing demand for a robust, practical and well-tested methodology to provide patient prognosis based on gene expression data. In standard settings, with few clinical predictors, such a methodology has been provided by the Cox proportional hazard model, but no corresponding methodology is available to deal with the full set of genes in microarray data. Furthermore, we want the procedure to be able to deal with the general survival data that include censored information. Conceptually such a procedure can be constructed quite easily, but its implementation will never be straightforward due to computational problems. We have developed an approach that relies on an extension of the Cox proportional likelihood that allows random effects parameters. In this approach, we use the full set of genes in the analysis and deal with survival data in the most general way. We describe the development of the model and the steps in the implementation, including a fast computational formula based on a subsampling of the risk set and the singular value decomposition. Finally, we illustrate the methodology using a data set obtained from a cohort of breast cancer patients.

Medical applications of terahertz imaging: a review of current technology and potential applications in biomedical engineering.

Terahertz (THz) imaging is in its early stages of development but already the potential clinical impact of this new imaging modality is clear. From cancer research to DNA analysis THz technology is improving or even making possible imaging of hitherto inaccessible phenomena. In this paper we present a short review of THz imaging from the point of view of biomedical engineering. We discuss the current state of the art in terms of THz imaging systems; describe current applications, future potential and our own approaches to harnessing this novel technology. We draw attention to open problems in the area with respect to the limitations of the technology before concluding with descriptions of our future work in the area.

Whole gut lavage fluid analysis : a minimally invasive method for study of mucosal immunity and inflammation.

Studies of intestinal mucosal immunity and inflammation are limited by the relative inaccessibility of most of the small intestine. Any new method of studying mucosal immunity and inflammation in patients should be minimally invasive, cost-effective, and provide information not readily available using current methods. Gaspari et al. (1) described gut lavage with 3 to 4 L of nonabsorbable, commercially available polyethylene glycol (PEG)-based bowel cleansing fluid as a method for analyzing human intestinal secretions for antibody content. Peroral gastrointestinal (GI) lavage is widely used to cleanse the GI tract prior to colonoscopy, barium enema examination, or colonic surgery. Whole gut lavage fluid (WGLF) therefore often becomes available without subjecting a patient to any additional investigation. This method is also often more acceptable to healthy volunteers than almost any other method of studying small intestinal secretions. Over the past decade, we have found that WGLFs from patients (both adults and children) suffering from a variety of intestinal diseases contain immunoglobulins (Igs) and antibodies, hemoglobin, plasma-derived proteins, cytokines, inflammatory cells, and their granule-derived proteins and growth factors (2,3). In this chapter, we describe our experience of the use of WGLF to study mucosal immunity and inflammation.

Preoperative esophageal transit studies are a useful predictor of dysphagia after fundoplication.

Fundoplication performed for gastroesophageal reflux disease may be complicated by postoperative dysphagia despite successful reduction in reflux symptoms. This is more likely in those patients with reflux who have concurrent esophageal dysmotility. The aim of this study was to establish whether esophageal transit studies using a technetium-99m jello bolus (jello esophageal transit) could detect the presence of motility disorders preoperatively and hence predict surgical outcome. Transit studies in 33 healthy volunteers yielded a normal range of 2 to 24 seconds using ninety-fifth percentile distribution. In the second phase of the study, 26 patients accepted for laparoscopic fundoplication were enrolled: jello esophageal transit, manometry, and endoscopy were attempted preoperatively in all subjects. A clinical dysphagia score was assigned from a questionnaire. Six months after surgery, five patients had dysphagia and of these four were found to have abnormal preoperative jello esophageal transit, for a sensitivity of 80%. Of the 21 patients who had no dysphagia after surgery, 20 patients had normal preoperative jello esophageal transit, showing a specificity of 95%. This esophageal transit study is noninvasive, reliable, and sensitive. When performed prior to fundoplication, it appears to be of significant value in detecting a subtle functional motility disorder that predisposes to postoperative dysphagia. Jello esophageal transit may assist the surgeon in planning treatment of gastroesophageal reflux disease.

Do enhanced friendship networks and active coping mediate the effect of self-help groups on substance abuse?

Self-help groups are the most commonly sought source of help for substance abuse problems, but few studies have evaluated the mechanisms through which they exert their effects on members. The present project evaluates mediators of the effects of self-help groups in a sample of 2,337 male veterans who were treated for substance abuse. The majority of participants became involved in self-help groups after inpatient treatment, and this involvement predicted reduced substance use at 1-year follow-up. Both enhanced friendship networks and increased active coping responses appeared to mediate these effects. Implications for self-help groups and professional treatments are discussed.

Detection of insulin-like growth factor-I and transforming growth factor-beta in whole gut lavage fluid: a novel method of studying intestinal fibrosis.

BACKGROUND: Insulin-like growth factor-I (IGF-I) and/or transforming growth factor-beta (IGF-beta), may be involved in gut fibrous strictures. METHODS: Concentrations of these two peptides have been measured by enzyme-linked immunosorbent assays (ELISAs) in whole gut lavage fluid from 57 patients, of whom 14 had strictures of the small intestine or colon associated with Crohn's disease, irradiation injury, ischaemia or diverticulitis. RESULTS: IGF-I was detected in fluid from 11 of 14 patients with strictures, and 5 of 43 others (P < 0.01). TGF-beta was detectable in all 57 samples and concentrations were unrelated to the presence or absence of strictures. CONCLUSION: Clinical studies of growth factors in intestinal fluid should facilitate research on intestinal fibrogenesis, and the diagnosis of fibrous stricturing in Crohn's disease.