Oesophageal cancer: caregiver mental health and strain

Objective: To investigate strain and mental health among family caregivers of oesophageal cancer patients and possible factors associated with caregiver mental health and strain.

Methods: Patients with oesophageal adenocarcinoma in Ireland were recruited into the FINBAR study (the main aim of which was to investigate factors influencing the Barrett's adenocarcinoma relationship). Carers completed the 13-item Caregiver Strain Index and the General Health Questionnaire-30 (GHQ) in the context of a brief interview with trained research staff that was undertaken separately from the interview with each cancer patient.

Results: Two hundred and twenty-seven patients participated in the FINBAR study. A total of 39 patients did not have a family carer or the carer could not be identified. Fifty percent (94/188) of carers completed the questionnaires. Mean (SD) scores for strain (6.65, SD=3.63) and mental health status (10.21, SD=7.30) were high and 71% of carers scored >5 on the GHQ indicating psychological distress. There was a statistically significant positive relationship between level of strain experienced by caregivers and the severity of their mental health status and whether or not carers scored >5 on the GHQ. Relatives were 1.70 (95% CI 1.34-2.15) times more likely to be defined as high scorers with each unit increase in the CSI score.

Conclusions: A significant proportion of caregivers experienced high levels of strain and psychological distress. There is a need to provide appropriate support and services targeted specifically at reducing the considerable strain of caring for patients with oesophageal cancer, particularly for carers of patients from lower socioeconomic groups.

Antibody-Mediated Inhibition of Cathepsin S Blocks Colorectal Tumor Invasion and Angiogenesis

Purpose: Cathepsin S is a cysteine protease that promotes the invasion of tumor and endothelial cells during cancer progression. Here we investigated the potential to target cathepsin S using an antagonistic antibody, Fsn0503, to block these tumorigenic effects.
Experimental Design: A panel of monoclonal antibodies was raised to human cathepsin S. The effects of a selected antibody were subsequently determined using invasion and proteolysis assays. Endothelial cell tube formation and aorta sprouting assays were done to examine antiangiogenic effects. In vivo effects were also evaluated using HCT116 xenograft studies.
Results: A selected cathepsin S antibody, Fsn0503, significantly blocked invasion of a range of tumor cell lines, most significantly HCT116 colorectal carcinoma cells, through inhibition of extracellular cathepsin S–mediated proteolysis. We subsequently found enhanced expression of cathepsin S in colorectal adenocarcinoma biopsies when compared with normal colon tissue. Moreover, Fsn0503 blocked endothelial cell capillary tube formation and aortic microvascular sprouting. We further showed that administration of Fsn0503 resulted in inhibition of tumor growth and neovascularization of HCT116 xenograft tumors.
Conclusions: These results show that blocking the invasive and proangiogenic effects of cathepsin S with antibody inhibitors may have therapeutic utility upon further preclinical and clinical evaluation.

Stereotactic radiosurgery as a therapeutic strategy for intracranial metastatic prostate carcinoma.

Intracranial metastatic prostate carcinoma is rare. We sought to determine the clinical outcomes after Gamma Knife® stereotactic radiosurgery (GKSRS) for patients with intracranial prostate carcinoma metastases. We studied data from 10 patients who underwent radiosurgery for 15 intracranial metastases (9 dural-based and 6 parenchymal). Six patients had radiosurgery for solitary tumors and four had multiple tumors. The primary pathology was adenocarcinoma (eight patients) and small cell carcinoma (two patients). All patients received multimodality management for their primary tumor (including resection, radiation therapy, androgen deprivation therapy) and eight patients had evidence of systemic disease at time of radiosurgery. The mean tumor volume was 7.7 cm3 (range 1.1-17.2 cm3) and a median margin dose of 16 Gy was administered. Two patients had progressive intracranial disease in spite of fractionated partial brain radiation therapy (PBRT) prior to SRS. A local tumor control rate of 85% was achieved (including patients receiving boost, upfront and salvage SRS). New remote brain metastases developed in three patients (33%) and one patient had repeat SRS for tumor recurrence. The median survival after radiosurgery was 13 months and the 1-year survival rate was 60%. SRS was a well tolerated and effective therapy either alone or as a boost to fractionated radiation therapy in the management of patients with intracranial prostate carcinoma metastases. © 2009 Springer Science+Business Media, LLC.

The incidence of esophageal cancer and high-grade dysplasia in Barrett's esophagus: A systematic review and meta-analysis

Barrett's esophagus is a well-recognized precursor of esophageal adenocarcinoma. Surveillance of Barrett's esophagus patients is recommended to detect high-grade dysplasia (HGD) or early cancer. Because of wide variation in the published cancer incidence in Barrett's esophagus, the authors undertook a systematic review and meta-analysis of cancer and HGD incidence in Barrett's esophagus. Ovid Medline (Ovid Technologies, Inc., New York, New York) and EMBASE (Elsevier, Amsterdam, the Netherlands) databases were searched for papers published between 1950 and 2006 that reported the cancer/HGD risk in Barrett's esophagus. Where possible, early incident cancers/HGD were excluded, as were patients with HGD at baseline. Forty-seven studies were included in the main analysis, and the pooled estimate for cancer incidence in Barrett's esophagus was 6.1/1,000 person-years, 5.3/1,000 person-years when early incident cancers were excluded, and 4.1/1,000 person-years when both early incident cancer and HGD at baseline were excluded. Corresponding figures for combined HGD/cancer incidence were 10.0 person-years, 9.3 person-years, and 9.1/1,000 person-years. Compared with women, men progressed to cancer at twice the rate. Cancer or HGD/cancer incidences were lower when only high-quality studies were analyzed (3.9/1,000 person-years and 7.7/1,000 person-years, respectively). The pooled estimates of cancer and HGD incidence were low, suggesting that the cost-effectiveness of surveillance is questionable unless it can be targeted to those with the highest cancer risk.

The death of massive stars - I. Observational constraints on the progenitors of Type II-P supernovae

We present the results of a 10.5-yr, volume-limited (28-Mpc) search for supernova (SN) progenitor stars. In doing so we compile all SNe discovered within this volume (132, of which 27 per cent are Type Ia) and determine the relative rates of each subtype from literature studies. The core-collapse SNe break down into 59 per cent II-P and 29 per cent Ib/c, with the remainder being IIb (5 per cent), IIn (4 per cent) and II-L (3 per cent). There have been 20 II-P SNe with high-quality optical or near-infrared pre-explosion images that allow a meaningful search for the progenitor stars. In five cases they are clearly red supergiants, one case is unconstrained, two fall on compact coeval star clusters and the other twelve have no progenitor detected. We review and update all the available data for the host galaxies and SN environments (distance, metallicity and extinction) and determine masses and upper mass estimates for these 20 progenitor stars using the STARS stellar evolutionary code and a single consistent homogeneous method. A maximum likelihood calculation suggests that the minimum stellar mass for a Type II-P to form is m(min) = 8.5(-1.5)(+1) M-circle dot and the maximum mass for II-P progenitors is m(max) = 16.5 +/- 1.5 M-circle dot, assuming a Salpeter initial mass function holds for the progenitor population (in the range Gamma = -1.35(-0.7)(+0.3)). The minimum mass is consistent with current estimates for the upper limit to white dwarf progenitor masses, but the maximum mass does not appear consistent with massive star populations in Local Group galaxies. Red supergiants in the Local Group have masses up to 25 M-circle dot and the minimum mass to produce a Wolf-Rayet star in single star evolution (between solar and LMC metallicity) is similarly 25-30 M-circle dot. The reason we have not detected any high-mass red supergiant progenitors above 17 M-circle dot is unclear, but we estimate that it is statistically significant at 2.4 sigma confidence. Two simple reasons for this could be that we have systematically underestimated the progenitor masses due to dust extinction or that stars between 17-25 M-circle dot produce other kinds of SNe which are not II-P. We discuss these possibilities and find that neither provides a satisfactory solution. We term this discrepancy the 'red supergiant problem' and speculate that these stars could have core masses high enough to form black holes and SNe which are too faint to have been detected. We compare the Ni-56 masses ejected in the SNe to the progenitor mass estimates and find that low-luminosity SNe with low Ni-56 production are most likely to arise from explosions of low-mass progenitors near the mass threshold that can produce a core-collapse.

Metastatic testicular carcinoma from the colon with clinical, immunophenotypical, and molecular characterization: Report of a case

We report a case of testicular metastasis from a colonic adenocarcinoma. The presentation of testicular metastasis, diagnosis, management, and possible modes of spread are reported. In addition to conventional investigations and histopathologic techniques, a molecular study of the testicular metastasis and colon primary, using microsatellite analysis, was performed to confirm the primary origin. Its potential uses are discussed.

Risk of Malignant Progression in Barrett’s Esophagus Patients: Results from a Large Population-Based Study

Background: Barrett's esophagus (BE) is a premalignant lesion that predisposes to esophageal adenocarcinoma. However, the reported incidence of esophageal adenocarcinoma in patients with BE varies widely. We examined the risk of malignant progression in patients with BE using data from the Northern Ireland Barrett's esophagus Register (NIBR), one of the largest population-based registries of BE worldwide, which includes every adult diagnosed with BE in Northern Ireland between 1993 and 2005.

Subjects and Methods: We followed 8522 patients with BE, defined as columnar lined epithelium of the esophagus with or without specialized intestinal metaplasia (SIM), until the end of 2008. Patients with incident adenocarcinomas of the esophagus or gastric cardia or with high-grade dysplasia of the esophagus were identified by matching the NIBR with the Northern Ireland Cancer Registry, and deaths were identified by matching with records from the Registrar General's Office. Incidence of cancer outcomes or high-grade dysplasia was calculated as events per 100 person-years (% per year) of follow-up, and Cox proportional hazard models were used to determine incidence by age, sex, length of BE segment, presence of SIM, macroscopic BE, or low-grade dysplasia. All P values were from two-sided tests.

Results: After a mean of 7.0 years of follow-up, 79 patients were diagnosed with esophageal cancer, 16 with cancer of the gastric cardia, and 36 with high-grade dysplasia. In the entire cohort, incidence of esophageal or gastric cardia cancer or high-grade dysplasia combined was 0.22% per year (95% confidence interval [CI] = 0.19% to 0.26%). SIM was found in 46.0% of patients. In patients with SIM, the combined incidence was 0.38% per year (95% CI = 0.31 to 0.46%). The risk of cancer was statistically significantly elevated in patients with vs without SIM at index biopsy (0.38% per year vs 0.07% per year; hazard ratio [HR] = 3.54, 95% CI = 2.09 to 6.00, P <. 001), in men compared with women (0.28% per year vs 0.13% per year; HR = 2.11, 95% CI = 1.41 to 3.16, P <. 001), and in patients with low-grade dysplasia compared with no dysplasia (1.40% per year vs 0.17% per year; HR = 5.67, 95% CI = 3.77 to 8.53, P <. 001).

Conclusion: We found the risk of malignant progression among patients with BE to be lower than previously reported, suggesting that currently recommended surveillance strategies may not be cost-effective. © The Author 2011. Published by Oxford University Press. All rights reserved.

Increasing incidence of Barrett's oesophagus: a population-based study

Oesophageal adenocarcinoma, a highly fatal cancer, has risen in incidence in Western societies, but it is unclear whether this is due to increasing incidence of its pre-cursor condition, Barrett's oesophagus (BO) or whether the proportion of BO patients undergoing malignant progression has increased in the face of unchanged BO incidence. Data from population-based studies of BO incidence is limited, with equivocal results to date difficult to distinguish from changes in endoscopic practices. The aim of this study was to assess population trends in Barrett's oesophagus (BO) diagnoses in relation to endoscopy and biopsy rates over a 13 year period. The Northern Ireland Barrett's oesophagus Register (NIBR) is a population-based register of all 9,329 adults diagnosed with columnar epithelium of the oesophagus in Northern Ireland between 1993 and 2005, of whom 58.3% were male. European age-standardised annual BO incidence rates were calculated per 100,000 of the population, per 100 endoscopies and per 100 endoscopies including an oesophageal biopsy. Average annual BO incidence rates rose by 159% during the study period, increasing from 23.9/100,000 during 1993-1997 to 62.0/100,000 during 2002-2005. This elevation far exceeded corresponding increases in rates of endoscopies and oesophageal biopsies being conducted. BO incidence increased most markedly in individuals aged <60 years, and most notably amongst males aged <40 years. This study points towards a true increase in the incidence of BO which would appear to be most marked in young males. These findings have significant implications for future rates of oesophageal adenocarcinoma and surveillance programmes. © 2011 Springer Science+Business Media B.V.

Spatial Mobility Intentions, the Labour Market and Incapacity Benefit Claimants Evidence from Northern Ireland

The paper analyses the work-related spatial mobility intentions of incapacity benefit (IB) claimants in Northern Ireland using a new survey dataset. Greater understanding of the prospective mobility of benefit claimants contributes to debates about employability, inclusion in the labour market and arguments about spatial mismatch. The analysis finds that IB claimants are not markedly less mobile than other population groups; that mobility is shaped by age, level of qualification, illness type, ability to drive and motivation; and that geography is important in several ways. The paper concludes by arguing that limited spatial mobility is a good indicator of disadvantage and that spatial mobility should be placed nearer the centre of the design and delivery of labour market policy

SN 2009jf: a slow-evolving stripped-envelope core-collapse supernova

We present an extensive set of photometric and spectroscopic data for SN 2009jf, a nearby Type Ib supernova (SN), spanning from ˜20 d before B-band maximum to 1 yr after maximum. We show that SN 2009jf is a slowly evolving and energetic stripped-envelope SN and is likely from a massive progenitor (25-30 Msun). The large progenitor's mass allows us to explain the complete hydrogen plus helium stripping without invoking the presence of a binary companion. The SN occurred close to a young cluster, in a crowded environment with ongoing star formation. The spectroscopic similarity with the He-poor Type Ic SN 2007gr suggests a common progenitor for some SNe Ib and Ic. The nebular spectra of SN 2009jf are consistent with an asymmetric explosion, with an off-centre dense core. We also find evidence that He-rich Ib SNe have a rise time longer than other stripped-envelope SNe, however confirmation of this result and further observations are needed. This paper is based on observations with several telescopes, including NTT(184.D-1151), VLT-UT1(085.D-0750,386.D-0126), NOT, WHT, TNG, PROMPT, Ekar, Calar Alto and Liverpool Telescope.

Possible evidence of asymmetry in SN 2007rt, a type IIn supernova

An optical photometric and spectroscopic analysis of the slowly-evolving type IIn SN 2007rt is presented, covering a duration of 481 days after discovery. Its earliest spectrum, taken approximately 100 days after the explosion epoch, indicates the presence of a dense circumstellar medium, with which the supernova ejecta is interacting. This is supported by the slowly-evolving light curve. A notable feature in the spectrum of SN 2007rt is the presence of a broad He i 5875 line, not usually detected in type IIn supernovae. This may imply that the progenitor star has a high He/H ratio, having shed a significant portion of its hydrogen shell via mass-loss. An intermediate resolution spectrum reveals a narrow Ha P-Cygni profile, the absorption component of which has a width of 128 km s-1. This slow velocity suggests that the progenitor of SN 2007rt recently underwent mass-loss with wind speeds comparable to the lower limits of those detected in luminous blue variables. Asymmetries in the line profiles of H and He at early phases bears some resemblance to double-peaked features observed in a number of Ib/c spectra. These asymmetries may be indicative of an asymmetric or bipolar outflow or alternatively dust formation in the fast expanding ejecta. In addition, the late time spectrum, at over 240 days post-explosion, shows clear evidence for the presence of newly formed dust.

Implications for Powering Biomarker Discovery Studies

This study examined variations in gene expression between FFPE blocks within tumors of individual patients. Microarray data were used to measure tumor heterogeneity within and between patients and disease states. Data were used to determine the number of samples needed to power biomarker discovery studies. Bias and variation in gene expression were assessed at the intrapatient and interpatient levels and between adenocarcinoma and squamous samples. A mixed-model analysis of variance was fitted to gene expression data and model signatures to assess the statistical significance of observed variations within and between samples and disease states. Sample size analysis, adjusted for sample heterogeneity, was used to determine the number of samples required to support biomarker discovery studies. Variation in gene expression was observed between blocks taken from a single patient. However, this variation was considerably less than differences between histological characteristics. This degree of block-to-block variation still permits biomarker discovery using either macrodissected tumors or whole FFPE sections, provided that intratumor heterogeneity is taken into account. Failure to consider intratumor heterogeneity may result in underpowered biomarker studies that may result in either the generation of longer gene signatures or the inability to identify a viable biomarker. Moreover, the results of this study indicate that a single biopsy sample is suitable for applying a biomarker in nonsmall-cell lung cancer. © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology.

Tobacco smoking increases the risk of high-grade dysplasia and cancer among patients with Barrett's esophagus

Background & Aims: Esophageal adenocarcinoma arises from Barrett's esophagus (BE); patients with this cancer have a poor prognosis. Identification of modifiable lifestyle factors that affect the risk of progression from BE to esophageal adenocarcinoma might prevent its development. We investigated associations among body size, smoking, and alcohol use with progression of BE to neoplasia. Methods: We analyzed data from patients with BE identified from the population-based Northern Ireland BE register, diagnosed between 1993 and 2005 with specialized intestinal metaplasia (n = 3167). Data on clinical, demographic, and lifestyle factors related to diagnosis of BE were collected from hospital case notes. We used the Northern Ireland Cancer Registry to identify which of these patients later developed esophageal adenocarcinoma, adenocarcinomas of the gastric cardia, or esophageal high-grade dysplasia. Cox proportional hazards models were used to associate lifestyle factors with risk of progression.
Results: By December 31, 2008, 117 of the patients with BE developed esophageal high-grade dysplasia or adenocarcinomas of the esophagus or gastric cardia. Current tobacco smoking was significantly associated with an increased risk of progression (hazard ratio = 2.03; 95% confidence interval, 1.29-3.17) compared with never smoking, and across all strata of smoking intensity. Alcohol consumption was not related to risk of progression. Measures of body size were infrequently reported in endoscopy reports, and body size was not associated with risk of progression.
Conclusions: Smoking tobacco increases the risk of progression to cancer or high-grade dysplasia 2-fold among patients with BE, compared with patients with BE that have never smoked. Smoking cessation strategies should be considered for patients with BE.