Follow-up of basal cell carcinomas: an audit of current practice

BACKGROUND: Follow-up of patients after treatment of basal cell carcinoma (BCC) allows for monitoring of recurrence and detection of new tumours, but adds a significant burden to outpatient clinics. At the skin tumour clinic in the dermatology department, the Royal Hospitals, Belfast, all patients are reviewed for 2 years after surgical excision of a low-risk primary BCC. OBJECTIVES: An audit was undertaken to determine the quality of data set recorded relating to prognostic factors for BCCs to determine the rate of recurrence and number of new primary tumours detected and to determine the completeness of follow-up by patients. METHOD: Patients who had primary BCCs treated by excision were identified from a database held at the clinic. Medical charts were reviewed to determine data recorded about lesions, the number of recurrent BCCs and new tumours detected, and the number of patients completing follow-up. RESULTS: Between January 1999 and December 2000, 114 patients had 121 primary BCCs excised. BCC location and size were recorded in 100% and 35% of cases, respectively. Histological type was stated for morphoeic or multifocal lesions. Two years of follow-up was completed by 53% of patients and 1 year by 78% of patients. The rate of recurrence was low, with 2 BCC recurring within 2 years of excision. The risk of developing a new BCC was 11.6% in the first year and 6.3% in the second year. CONCLUSIONS: Follow-up of patients after excision of a low-risk BCC at the clinic has been reduced to 1 year. A proforma has been developed to encourage documentation of prognostic factors.     

Locus-specific databases and recommendations to strengthen their contribution to the classification of variants in cancer susceptibility genes

Locus-specific databases (LSDBs) are curated collections of sequence variants in genes associated with disease. LSDBs of cancer-related genes often serve as a critical resource to researchers, diagnostic laboratories, clinicians, and others in the cancer genetics community. LSDBs are poised to play an important role in disseminating clinical classification of variants. The IARC Working Group on Unclassified Genetic Variants has proposed a new system of five classes of variants in cancer susceptibility genes. However, standards are lacking for reporting and analyzing the multiple data types that assist in classifying variants. By adhering to standards of transparency and consistency in the curation and annotation of data, LSDBs can be critical for organizing our understanding of how genetic variation relates to disease. In this article we discuss how LSDBs can accomplish these goals, using existing databases for BRCA1, BRCA2, MSH2, MLH1, TP53, and CDKN2A to illustrate the progress and remaining challenges in this field. We recommend that: 1) LSDBs should only report a conclusion related to pathogenicity if a consensus has been reached by an expert panel. 2) The system used to classify variants should be standardized. The Working Group encourages use of the five class system described in this issue by Plon and colleagues. 3) Evidence that supports a conclusion should be reported in the database, including sources and criteria used for assignment. 4) Variants should only be classified as pathogenic if more than one type of evidence has been considered. 5) All instances of all variants should be recorded.     

High-field MR surface-coil imaging of the hand and wrist. Part I. Normal anatomy

High-resolution magnetic resonance (MR) images of the hands and wrists of six healthy volunteers were obtained at 1.5 T with a surface coil. Additionally, the hands and wrists of two fresh cadavers were imaged and were subsequently sectioned for anatomic correlation. High contrast when depicting soft-tissue, coupled with impressive spatial resolution and multiplanar capabilities, enabled delineation of fine structures including nerves, tendons, and blood vessels. Osseous and cartilaginous structures were also well depicted. MR imaging gives anatomic definition of the hand and wrist unmatched by other diagnostic imaging methods.     

Benign Cystic Mesothelioma of the Peritoneum

Benign cystic mesothelioma of the peritoneum is a well-defined but rare entity. A total of 35 instances have been reported, almost all in adults, the majority females. Cystic mesotheliomas have, until recently, been labeled cystic lymphangiomas or lymphohemangiomas. We report the case of a 14-year-old boy who, despite only subtotal resection of his abdominal mass, is well and recurrence free 9 months after surgery. The role of immunohistochemistry and electron microscopy in diagnosis is emphasized.     

FACTORS GOVERNING INSULIN AND GLUCAGON RESPONSES DURING NORMAL MEALS

An experimental model is described which can be used to study substrate and hormone responses to normal meals administered in very near normal circumstances. After 500, 300 and 125 calorie meals, the relative proportion of fat or protein content did not influence the plasma glucose except for minor differences between the high protein-high fat meals. The insulin response to such meals was correlated positively with the increment in glucose but reduction of protein content below 8 g caused a significant reduction in the increment in plasma insulin per unit increase in plasma glucose. Alterations in protein content above 8 g made no difference. Fat content of the meal did not significantly alter the insulin response. No evidence was obtained for a major component of insulin release attributable to either bulk or pre-absorption phenomena such as sight or smell. It is concluded that a significant accentuation of the insulin response to meals is dependent on a minimum amount of protein and that this is probably mediated by one of the gastro-intestinal hormones. Glucagon release is dependent on protein and carbohydrate content of the meal and is independent of the fat content. There may also be an early stimulation of glucagon release, regardless of content, which may also be hormonally mediated.     

Hormone-induced refractoriness to mammary carcinogenesis in Wistar- Furth rats

One of the most consistent results in the epidemiology of human breast cancer is the inverse relationship of risk and early full-term parity. The goal of this study was to investigate the molecular mechanisms through which early full-term pregnancy protects the breast from cancer development. We used Wistar-Furth (WF) rats as our experimental system and mimicked pregnancy using estrogen and progesterone (E/P). Sexually mature female rats were treated with steroid hormones for 21 days and after 28 days of gland involution, the rats were administered MNU. Rats that received a high dose of 20 microg E and 20 mg P exhibited an 82% reduction in the incidence of mammary adenocarcinomas as compared to the rats receiving only blank pellets. Decreasing doses of E/P were partially protective suggesting that complete differentiation of the gland was not required for refractoriness. We measured the RNA expression levels of several target genes involved in the regulation of mammary cell proliferation and/or differentiation including estrogen receptor (ER) and progesterone receptor (PR), cyclins D1 and D2, the cell cycle inhibitors p16, p21 and p27, and the tumor suppressor p53. At the time of MNU treatment we found no significant differences in the expression of these genes, with the possible exception of p21, indicating that hormone treatment did not result in constitutive changes in expression levels. The numbers of apoptotic cells were low and comparable in the hormone exposed and age-matched virgin gland (AMV) at the time of carcinogen challenge and remained low for 8 days after MNU treatment. The number of BrdU-labeled cells at the time of carcinogen challenge were also low in both the AMV (1.8%) and hormone exposed (0.8%) animals. In contrast, cell proliferation in the AMV (5.7%) was significantly different from both the parous involuted (1.2%) and the E/P-treated involuted (1.5%) animals 8 days after MNU treatment. We interpret these data to indicate that hormone treatment results in mammary epithelial cells that have persistent alterations in intracellular pathways governing proliferation responses to carcinogens.      

BRCA1 and BRCA2 Mutations in Breast and Ovarian Cancer Syndrome: Reflection on the Creighton University Historical Series of High Risk Families

Over the last four decades, Henry Lynch has collected pedigrees and samples from high risk breast and/or ovarian cancer families, generating a unique resource for the study of breast cancer susceptibility. These families have made a major contribution to increasing our knowledge in the cancer genetic susceptibility field, allowing the discovery of a genetic association between breast and ovarian cancer predisposition, contributing to the mapping of the BRCA1 and BRCA2 genes, advancing the idea of the existence of other breast cancer susceptibility genes, allowing the evaluation of BRCA-associated cancer risks and psychosocial aspects of BRCA testing and so on. Ten years after the cloning of BRCA1 and BRCA2, we report the current status of these families and compare the observed BRCA1/2 mutation detection rate with the estimations obtained by linkage analysis of the Breast Cancer Linkage Consortium families.