Posttransplant primary cutaneous T-cell lymphoma

A patient with posttransplant cutaneous lymphoma is described. Although most posttransplant lymphomas are of B-cell origin, this patient's lymphoma is a primary cutaneous lymphoma of T-cell origin. Another report exists of the first case of posttransplant primary cutaneous T-cell lymphoma localized to the lower extremities. Our patient's involvement was generalized with tumor nodules on the face and anterior chest. Reduced immune surveillance, chronic antigenic stimulation caused by transplant grafts, and the direct oncogenic effects of immunosuppressive drugs have all been suggested as mechanisms. Prompt recognition of this condition and initiation of appropriate therapy with reduction of high-dose immunosuppression can lead to better patient outcomes.     

Interest in genetic testing among first-degree relatives of colorectal cancer patients

PURPOSE: The present study examined colorectal cancer screening behaviors, risk perceptions, and willingness to receive genetic testing to determine colorectal cancer susceptibility. METHODS: We recruited 95 first-degree relatives of colorectal cancer patients, then conducted a brief telephone interview using a structured questionnaire that elicited information on sociodemographics, cancer screening behaviors, risk perceptions, and interest in genetic testing. RESULTS: Among these high-risk individuals who were aged 40 years or older, only 31% reported fecal occult blood testing within the past year and 59% reported undergoing sigmoidoscopy or colonoscopy within the past 5 years. The majority of participants believed their relative risk of colorectal cancer was increased (68%). Eighty-four percent of the participants indicated that they would have a genetic test if one were available. Participants who believed that <50% of colorectal cancers were caused by heredity were more likely to be interested in genetic testing than were participants who believed that 50% or more of colorectal cancers were caused by heredity. Referral source, sociodemographic factors, clinical factors, and perceived personal risk were not significantly associated with interest in genetic testing. CONCLUSION: Our results suggest that the demand for colorectal cancer susceptibility testing may be high among individuals with a family history of colorectal cancer. We also observed that a substantial number of first-degree relatives were not adhering to colorectal cancer screening guidelines. Accurate information on the genetic aspects of colorectal cancer and the benefits and limitations of genetic testing may help relatives of colorectal cancer patients make informed decisions about whether to undergo enhanced screening and genetic testing.     

Polymorphisms in the carcinogen detoxification genes CYB5A and CYB5R3 and breast cancer risk in African American women

Purpose

Cytochrome b ₅ (encoded by CYB5A) and NADH cytochrome b ₅ reductase (encoded by CYB5R3) detoxify aromatic and heterocyclic amine mammary carcinogens found in cigarette smoke. We hypothesized that CYB5A and CYB5R3 polymorphisms would be associated with breast cancer risk in women.

Methods

We characterized the prevalence of 18 CYB5A and CYB5R3 variants in genomic DNA from African American (AfrAm) and Caucasian (Cauc) women from the Carolina Breast Cancer Study population (1,946 cases and 1,747 controls) and determined their associations with breast cancer risk, with effect modification by smoking.

Results

A CYB5R3 variant, I1M+6T (rs8190370), was significantly more common in breast cancer cases (MAF 0.0238) compared with controls (0.0169, p = 0.039); this was attributable to a higher MAF in AfrAm cases (0.0611) compared with AfrAm controls (0.0441, p = 0.046; adjusted OR 1.41, CI 0.98–2.04; p = 0.062). When smoking was considered, I1M+6T was more strongly associated with breast cancer risk in AfrAm smokers (adjusted OR 2.10, 1.08–4.07; p = 0.028) compared with never smokers (OR = 1.21; 0.77–1.88; p for interaction = 0.176). I1M+6T and three additional CYB5R3 variants, -251T, I8-1676C, and *392C, as well as two CYB5A variants, 13G and I2-992T, were significantly more common in AfrAms compared with Caucs.

Conclusions

CYB5R3 I1M+6C>T should be considered in future molecular epidemiologic studies of breast cancer risk in AfrAms. Further, variants in CYB5A and CYB5R3 should be considered in the evaluation of other tumors in AfrAms that are associated with aromatic and heterocyclic amine exposures, to include prostate, bladder, and colon cancers.     

Assessment of recruit motivation and strength study: preaccession physical fitness assessment predicts early attrition

BACKGROUND: The Assessment of Recruit Motivation and Strength (ARMS) study was designed to pilot-test the use of a physical fitness screening tool for Army applicants before basic training. METHODS: The ARMS test consists of two components, namely, a 5-minute step test and push-ups. Attrition among 7,612 recruits who underwent preaccession ARMS testing and began service between May 2004 and December 2005 was studied. RESULTS: ARMS test performance was found to be significantly related to risk of attrition within 180 days; the hazard ratios for failing relative to passing the ARMS test were 2.27 (95% confidence interval, 1.70-3.04) among female subjects and 1.36 (95% confidence interval, 1.13-1.64) among male subjects. The attributable risk of attrition associated with failing the ARMS test was approximately 40% among female subjects and approximately 30% among male subjects. DISCUSSION: The ARMS study is the first prospective study conducted in the U.S. Army to assess physical fitness before accession. Physical fitness and motivation to serve were shown to correlate with attrition during initial entry training.     

Increased claudin‐4 expression is associated with poor prognosis and high tumour grade in breast cancer

The role of intercellular tight junctions in breast epithelial cells is traditionally thought to be in maintaining polarity and barrier function. However, claudin‐4, a tight junction protein, is overexpressed in breast tumour cells compared to normal epithelial cells, which generally corresponds to a loss in polarity. The aim of this study was to investigate the distribution and potential clinical value of claudin‐4 in breast cancer, and to evaluate its usefulness as a prognostic and predictive biomarker. Expression of claudin‐4 was initially examined by Western blot analysis in a cohort of 88 breast tumours, and was found to correlate positively with tumour grade and negatively with ER. Claudin‐4 expression was then evaluated by immunohistochemistry in a larger cohort of 299 tumours represented on a tissue microarray. Claudin‐4 expression correlated positively with tumour grade and Her2, and negatively with ER. High claudin‐4 expression was also associated with worse breast cancer‐specific survival (p = 0.003), recurrence‐free survival (p = 0.025) and overall survival (p = 0.034). Multivariate analysis revealed that claudin‐4 independently predicted survival in the entire cohort (HR 1.95; 95%CI 1.01–3.79; p = 0.047) and in the ER positive subgroup treated with adjuvant tamoxifen (HR 4.34; 95%CI 1.14–16.53; p = 0.032). This relationship between increased claudin‐4 expression and adverse outcome was validated at the mRNA level in a DNA microarray dataset of 295 breast tumours. We conclude that high levels of claudin‐4 protein are associated with adverse outcome in breast cancer patients, including the subgroup of patients treated with adjuvant tamoxifen. © 2008 Wiley‐Liss, Inc.     

Development and implementation of a science training course for breast cancer activists: Project LEAD (leadership, education and advocacy development)

Objective  To develop and implement Project LEAD (leadership, education, and advocacy development), a science course for breast cancer activists.
Population  Students were breast cancer activists and other consumers, mainly affiliated with advocacy organizations in the United States of America.
Setting  Project LEAD is offered by the National Breast Cancer Coalition; the course takes place over 5 days and is offered 4 times a year, in various cities in the United States of America.
Results  The Project LEAD curriculum has developed over 5 years to include lectures, problem-based study groups, case studies, interactive critical appraisal sessions, a seminar by an 'expert' scientist, role play, and homework components. A core faculty has been valuable for evaluating and revising the course and has proved necessary to provide consistent high quality teaching. Course evaluations indicated that students gained critical appraisal skills, enhanced their knowledge and developed confidence in selected areas of basic science and epidemiology.
Conclusions  Project LEAD comprises a unique curriculum for training breast cancer activists in science and critical appraisal. Course evaluations indicate that students gain confidence and skills from the course.     

Activities of the hepatic enzymes of vitamin B6 metabolism for patients with cirrhosis

Patients with cirrhosis and other hepatic diseases frequently exhibit lower concentrations of plasma pyridoxal 5'-phosphate (PLP), which is derived primarily from liver. To determine the biochemical basis for this abnormality, the enzymes of vitamin B6 metabolism--pyridoxal kinase, pyridoxine (pyridoxamine) 5'-phosphate oxidase, PLP phosphatase(s), and pyridoxal oxidase(s)--were analyzed in liver. The activities of the two biosynthetic enzymes, pyridoxal kinase and pyridoxine (pyridoxamine) 5'-phosphate oxidase were similar for both. The phosphatase activities were significantly higher (mean +/- SD of 9.55 +/- 8.03 versus 3.97 +/- 2.36 nmol X min X mg protein, p less than 0.05) for cirrhotics. Pyridoxal oxidase activities appeared slightly lower for cirrhotics. There was considerable variation in many indices of liver function, which suggests that the defects contributing to altered vitamin B6 metabolism may be complex and individualistic. These analyses have shown that cirrhotics are capable of apparently normal PLP synthesis and that increased hepatic dephosphorylation may be responsible for low levels of plasma PLP.     

Beta-2-microglobulin as a marker of malignant epithelial tumors of the skin

Twenty-seven formalin-fixed, paraffin-embedded skin samples were examined to determine the usefulness of the loss of beta-2-microglobulin (B2m) in determining the malignancy of the epithelial cells of skin tumors. Our results confirm that there is loss of B2m from the cell surface in certain malignant lesions whereas the cells in the clearly benign lesions retain B2m on their cell membrane. Variable staining in the low-grade malignant and premalignant lesions renders B2m as an unreliable cell surface marker for differentiating borderline lesions.     

Noncirrhotic portal vein thrombosis. Physiology before and after shunts.

Controversy exists concerning the proper therapy for bleeding gastroesophageal varices secondary to noncirrhotic portal vein thrombosis. Disparity of opinion exists regarding the significance of hepatic portal blood flow and the consequences of total portal-systemic shunts in this condition. One patient is presented who developed severe, crippling encephalopathy 20 years after a central splenorenal shunt. This was associated with loss of portal flow to the liver and marked nitrogen intolerance. Closure of the shunt resulted in restoration of hepatic portal flow via collateral veins (HPI 0.36), clearance of encephalopathy and return to near normal protein tolerance. An additional patient was studied with hyperammonemia and early suggestive signs of encephalopathy eight years following a mesocaval shunt. Four patients were evaluated before and after selective distal splenorenal shunts. All had "cavernous transformation" of the portal vein with angiographic evidence of portal flow to the liver. Postoperative angiograms revealed continued hepatic portal perfusion and a patent shunt in each patient. Radionuclide imaging postoperatively gave an estimated portal fraction of total hepatic blood flow (HPI) of .39 and .60 in two of the four patients. We conclude that 1) there is significant hepatic portal perfusion in noncirrhotic portal vein thrombosis (cavernous transformation), 2) loss of this hepatic portal flow following total shunts can lead to severe encephalopathy, 3) the selective distal splenorenal shunt maintains hepatic portal perfusion and is the procedure of choice when there is a patent splenic vein and surgical intervention is indicated.