Assessing the value of matrix metalloproteinase 9 (MMP9) in improving the appropriateness of referrals for colorectal cancer

Background:

A blood test may be an effective means of improving the appropriateness of referrals for symptomatic patients referred to specialist colorectal clinics. We evaluated the accuracy of a serum matrix metalloproteinase (MMP9) test in indicating colorectal cancer or its precursor conditions in a symptomatic population.

Methods:

Patients aged over 18, referred urgently or routinely to secondary care following primary care presentation with colorectal symptoms completed a questionnaire and provided a blood sample for serum MMP9 estimation. Univariate analysis and logistic regression modelling investigated the association between presenting symptoms, MMP9 measurements and the diagnostic outcome of patient investigations, in order to derive the combination of factors which best predicted a high risk of malignancy.

Results:

Data were analysed for 1002 patients. Forty-seven cases of neoplasia were identified. Age, male gender, absence of anal pain, diabetes, blood in stools, urgent referral, previous bowel polyps and previous bowel cancer were significantly associated with neoplasia. Matrix metalloproteinase 9 measurements were not found to be associated with significant colorectal pathology.

Conclusion:

This study, despite robust sampling protocols, showed no clear association between MMP9 and colorectal neoplasia. Matrix metalloproteinase 9 therefore appears to have little value as a tool to aid referral decisions in the symptomatic population.     

The epidemic of human papillomavirus and oropharyngeal cancer in a Canadian population

Background

Sexually transmitted infection with the human papillomavirus (hpv) is responsible for a significant burden of human cancers involving the cervix, anogenital tract, and oropharynx. Studies in the United States and Europe have demonstrated an alarming increase in the frequency of hpv-positive oropharyngeal cancer, but the same direct evidence does not exist in Canada.

Methods

Using the London Health Sciences Centre pathology database, we identified tonsillar cancers diagnosed between 1993 and 2011. Real-time polymerase chain reaction was then used on pre-treatment primary-site biopsy samples to test for dna from the high-risk hpv types 16 and 18. The study cohort was divided into three time periods: 1993–1999, 2000–2005, and 2006–2011.

Results

Of 160 tumour samples identified, 91 (57%) were positive for hpv 16. The total number of tonsillar cancers significantly increased from 1993–1999 to 2006–2011 (32 vs. 68), and the proportion of cases that were hpv-positive substantially increased (25% vs. 62%, p < 0.002). Those changes were associated with a marked improvement in 5-year overall survival (39% in 1993–1999 vs. 84% in 2006–2011, p < 0.001). When all factors were included in a multivariable model, only hpv status predicted treatment outcome.

Interpretation

The present study is the first to provide direct evidence that hpv-related oropharyngeal cancer is increasing in incidence in a Canadian population. Given the long lag time between hpv infection and clinically apparent malignancy, oropharyngeal cancer will be a significant clinical problem for the foreseeable future despite vaccination efforts.     

Favorable Changes in Serum Estrogens and Other Biologic Factors After Weight Loss in Breast Cancer Survivors Who are Overweight or Obese

BackgroundObesity is associated with an increased risk for recurrence and all-cause mortality in breast cancer survivors. Excess adiposity is associated with increased estrogen, insulin, and leptin, and with decreased sex hormone binding globulin (SHBG) concentrations, which may promote breast cancer progression and recurrence. This study aimed to assess the effects of weight loss on these factors.Patients and MethodsBreast cancer survivors who were overweight or obese (n = 220) and who were enrolled in a weight loss intervention study provided baseline and follow-up blood samples and weight data. Serum estrogens, SHBG, insulin, and leptin were measured at baseline, 6 months, and 18 months.ResultsWeight loss of ≥5% of initial weight decreased leptin and insulin compared with those who did not achieve that amount of weight loss (P < .0001). Weight loss also increased SHBG at 6 and 18 months (P < .01). Postmenopausal women who lost ≥5% of body weight at 6 months had lower estrone (P = .02), estradiol (P = .002), and bioavailable estradiol (P = .001) concentrations than women who did not lose at least 5% of body weight, and weight loss at 18 months was significantly related to a change in serum bioavailable estradiol concentration (P = .02).ConclusionsFavorable changes in estrogens, SHBG, insulin, and leptin were observed in association with weight loss in these women who were overweight or obese and who had been diagnosed and treated for breast cancer. Weight loss appears to have favorable effects on hormonal and biologic factors associated with increased risk for recurrence and poorer prognosis.     

Recurrent myxoid liposarcoma of the buccal mucosa in a young boy: a case report and review of the literature

Liposarcomas are uncommon in the pediatric population. We present the case of a boy who had experienced multiple recurrences of liposarcoma in the buccal space before he reached the age of 13 years. We also provide a review of the literature and a discussion of adjuvant therapy, which are important to understanding the nature of this disease.     

Familial eosinophilic cellulitis, dysmorphic habitus, and mental retardation

Background: Eosinophilic cellulitis is a polymorphous, chronic disease characterized by eosinophil infiltration and granulomatous inflammation. Objective: Our purpose was to describe the clinical, histologic, and immunohistologic findings in three family members who have had eosinophilic cellulitis since childhood associated with mental retardation and abnormal body habitus. Methods: Family members were evaluated. Multiple skin biopsy specimens were obtained and examined after hematoxylin-and-eosin staining, by immunofluorescence and by electron microscopy. Blood specimens were analyzed by immunoassays for eosinophil granule proteins and eosinophil active cytokines. Results: Three short-statured, mentally retarded family members with abnormal body habitus in at least two generations had recurrent eosinophilic cellulitis. Peripheral blood and bone marrow eosinophilia was present. Plasma eosinophil granule major basic protein and eosinophil-derived neurotoxin levels were elevated with normal plasma eosinophil cationic protein levels. Eosinophil survival in culture was increased by patients’ plasma and was blocked with monoclonal interleukin-5 antibody. The level of plasma interleukin-5 was elevated. Lesional skin biopsy specimens showed massive staining for three eosinophil granule proteins. Electron microscopy showed eosinophil disruption. Conclusion: Eosinophilic cellulitis, mental retardation, and abnormal body habitus were likely inherited as a dominant syndrome in this family in which eosinophil involvement was striking. (J Am Acad Dermatol 1998;38:919-28.)     

Sustainability of a Curriculum-based Intervention on Dietary Behaviours and Physical Activity among Primary School Children in Trinidad and Tobago

Objectives:

Childhood obesity and poor lifestyle practices are emerging as major public health challenges in the Caribbean. Given the fact that a significant part of childhood is spent at school, curriculum-based interventions aimed at improving good dietary and physical activity patterns may provide a useful vehicle for mass inculcation of long-term healthy lifestyle practices. In this study, we evaluated the long-term impact of a brief curriculum based intervention on dietary behaviour, physical activity and knowledge level of primary schoolchildren.

Methods:

The study was a randomized, controlled, school-based nutrition education and physical activity intervention. One hundred students each were then randomly assigned to the intervention (IVG) and non-intervention (NIVG) groups and followed-up for 18 months. Participants in the IVG group were exposed to a curriculum consisting of six one-hour modules followed by school-based activities geared at fostering healthy behaviours. Students in the non-intervention group did not receive any modules and were subject to the information available at school on a regular basis.

Results:

In multivariate regression equations controlling for age, gender, body mass index (BMI) and baseline values, intervention was associated with lower intake of fried foods and sodas (p < 0.05) and higher knowledge scores (p < 0.01) 18 months later but not significantly associated with improved physical activity or lower BMI.

Conclusions:

In this study, participants in the intervention group reported significantly lower intakes of fried foods and sodas and higher knowledge scores than participants in the control group some 18 months post-intervention independent of age, gender, BMI, ethnicity and the intakes at baseline.