[Analysis of results of excerpts of generalized parametric indicators of facet classification of occupations in medicine, practical, industrial pharmacy, cosmetology and major of related occupations introduced to State classifiers 003:2010].

A comparative analysis of the content and the list of codified occupations (CO) of State classifiers (SC) of occupations SC 003-95 and SC 003:2010 (total 15 000 positions) is considered. Found that the number of corresponding CO in the SC 003-95 consist of 906 items including 57 of Vol. 78 "Care of public health", as well as in SC 003:2010 - 799 and 59 respectively.

Prevalence and nature of anaemia in a prospective, population-based sample of people with diabetes: Teesside anaemia in diabetes (TAD) study.

AIMS: Anaemia occurs in 25% of people attending hospital diabetes clinics, but this may not be representative of all people with diabetes. We aimed to determine the prevalence of anaemia in a prospective population-based sample stratified by estimated glomerular filtration rate (eGFR) using the 4-point Modification of Diet in Renal Disease (MDRD) formula. METHODS: All 7331 patients on our district register were stratified by eGFR. Seven hundred and thirty were approached by letter on two occasions. Two hundred and thirty-four (32%) returned questionnaires and blood samples. Responders (R), non-responders (NR) and the whole cohort (C) were similar: mean +/- sd age R 61.7 +/- 12.7 years; NR 61.3 +/- 15.1 years; C 61.8 +/- 14.2 years; diabetes duration R 8.8 +/- 8.6 years; NR 8.2 +/- 7.9 years; C 7.5 +/- 7.8 years, Type 1 diabetes R 10.1%, NR 10.8%, C 9.4%. Anaemia was defined using World Health Organization criteria: haemoglobin < 13 g/dl for men, < 12 g/dl for women. RESULTS: Previously undiagnosed anaemia was present in 15% of the whole group, 36% with eGFR < 60 ml/min per 1.73 m(2) and 9% of those with eGFR > 60 ml/min per 1.73 m(2). Anaemia was as a result of erythropoietin deficiency in 34%, abnormal haematinics in 40% and was unexplained in 26% of patients. Five per cent of the patients had anaemia below the treatment threshold of 11 g/dl. CONCLUSIONS: The prevalence of unrecognized anaemia in population-based cohorts is lower than that in hospital-based studies. Current clinical surveillance in the UK is failing to detect anaemia in stage 3-5 chronic kidney disease (eGFR < 60 ml/min per 1.73 m(2)) and current guidelines will not detect 9% of diabetic patients with anaemia and an eGFR > 60 ml/min per 1.73 m(2).

Quantitative mathematical modeling of clinical brain metastasis dynamics in non-small cell lung cancer.

Brain metastases (BMs) are associated with poor prognosis in non-small cell lung cancer (NSCLC), but are only visible when large enough. Therapeutic decisions such as whole brain radiation therapy would benefit from patient-specific predictions of radiologically undetectable BMs. Here, we propose a mathematical modeling approach and use it to analyze clinical data of BM from NSCLC. Primary tumor growth was best described by a gompertzian model for the pre-diagnosis history, followed by a tumor growth inhibition model during treatment. Growth parameters were estimated only from the size at diagnosis and histology, but predicted plausible individual estimates of the tumor age (2.1-5.3 years). Multiple metastatic models were further assessed from fitting either literature data of BM probability (n = 183 patients) or longitudinal measurements of visible BMs in two patients. Among the tested models, the one featuring dormancy was best able to describe the data. It predicted latency phases of 4.4-5.7 months and onset of BMs 14-19 months before diagnosis. This quantitative model paves the way for a computational tool of potential help during therapeutic management.

Immunocytochemistry and in situ hybridisation of epidermal growth factor receptor and relation to prognostic factors in breast cancer.

The breast tumour distribution of epidermal growth factor receptor (EGFR) was studied in 193 patients with primary breast cancer by immunocytochemistry on frozen sections. EGFR was correlated (P = 0.0009) with growth fraction assessed by Ki-67, and negatively correlated with oestrogen receptor (ER, P = 0.0001) and progesterone receptor (PR, P = 0.0001) status. In 47 patients, in-situ hybridisation for EGFR mRNA showed good agreement with the immunocytochemically assessed EGFR protein. There were, however, several tumours in which EGFR mRNA could be detected in the absence of EGFR protein and there were differences between the ER and PR status of those tumours in which translation of EGFR mRNA was not seen. The cause of these differences is unclear, but these findings may represent a clue as to the differential control of breast cancer cell receptors.

Sarcomas following radiation therapy for breast cancer: a report of three cases and a review of the literature.

PURPOSE: First to describe clinical and pathologic features of sarcomas arising after radiation therapy for breast cancer and to report three cases of sarcoma arising 7, 15, and 20 years following radiation therapy for breast cancer. Second, to review the literature on this treatment complication. METHODS AND MATERIALS: Medline literature search. RESULTS: The most frequent histology is osteosarcoma and bone is affected more commonly than soft tissue at a median latency of 11 years. The scapula is the most frequently affected bone. The most frequently affected soft tissue site is now the conserved breast with a median latency of 5.5 years. The aetiologic factors relating to these sarcomas are not fully defined with factors of beam energy, radiation dose, chemotherapy and regional edema being inconsistently reported. CONCLUSION: The frequency of radiation-induced sarcoma at 10 years of follow-up is approximately 0.2%. This is an overestimate by an unknown factor because of the description of sarcomas arising metachromously in breast cancer patients, in nonirradiated areas.

Fat necrosis of the breast following lumpectomy and radiation therapy for early breast cancer.

Between January 1980 and December 1985, 121 patients with early breast cancer were treated in the Department of Radiation Oncology at Westmead Hospital by external beam irradiation and an iridium wire boost following "lumpectomy". After a median follow-up of 26 months, 14 patients have developed recurrent masses in the treated breast. In four, recurrent carcinoma was strongly suspected and subsequently confirmed by fine needle aspiration biopsy, but in only two was a subsequent salvage mastectomy possible. The remaining 10 patients developed a nodule which was usually tender. With three exceptions, the nodule was at the primary tumour site and developed 4-43 months after treatment. In seven, tumour recurrence was suspected but not confirmed by biopsy and the other three were accepted as having post-treatment "radiation fibrosis". Excision biopsy was undertaken in eight of the 10 patients. Another patient underwent partial mastectomy for presumed local recurrence. The histological appearance in all cases was similar, with areas of fat necrosis and fibrosis with atypical stromal fibroblasts. Suture material was present microscopically in eight patients and was noted macroscopically (that is, by mammogram) in the one patient who did not undergo surgery. This complication is most likely caused by a combination of surgical and radiation factors. The difficulty in management is differentiation between tumour recurrence and a benign condition.

Excess iodine induces the expression of thyroid solid cell nests in lymphocytic thyroiditis-prone BB/W rats.

Previous epidemiological studies have suggested that lymphocytic thyroiditis and/or an increased iodine intake may be risk factors for the development of thyroid cancer. We previously reported that excess iodine accelerated the development of thyroid lymphocytic infiltration (LI) in the autoimmune BB/W rat model. We also found that excess iodine increased thyroid cell proliferation in a disordered manner. The present study was designed to further explore these observations and to address the question as to whether excess iodine under certain conditions predisposes the thyroid gland to neoplasia. To test this hypothesis, the lymphocytic thyroiditis-prone BB/W rat was exposed to excess iodine in drinking water. Ten BB/W rats at 4 weeks of age were given iodine water (NaI 0.05%) for 10 weeks, whilst another 10 BB/W rats were given tap water and served as controls. Eighteen normal Wistar rats were also divided into excess iodine and control groups, served as a comparison to the BB/W rats. We found that an excess iodine intake accelerated the development of LI in the BB/W rat. Severe LI was usually accompanied by prominent thyroid cell proliferation, evident as numerous microfollicles and cell masses, not forming normal thyroid follicles. Numerous lymphocytes and plasma cells often encroached on these areas of increased cellular proliferation. The surprising feature, and a possible indicator of activated thyroid cell proliferation, was the high incidence of thyroid solid cell nest-like lesions (SCN) in the iodine treated BB/W rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Is centralized histopathology review necessary for screen-detected breast lesions?

To address quality requirements for breast pathology in the Australian screening programme, one breast cancer Screening and Assessment Service initiated a process of central pathologic review of all lesions detected through the service. The aim of this study was to measure concordance between the initial and review pathology, and to assess the merit of routine review. Concordance was measured by observed agreement and the kappa statistic for 267 women with 273 lesions. Concordance was excellent for the four classification schemes examined, good for the identification of benign lesions and hyperplasia, and excellent for the identification of DCIS or invasive carcinoma. For the sub-categorization of hyperplasias and invasive carcinomas concordance was good, but was poor for the sub-typing of DCIS. Initial and review concordance was acceptable, suggesting that disagreement among pathologists may not present a major impediment to the provision of dependable diagnoses. Full case review is unnecessary for benign lesions or invasive carcinoma, but should be maintained for DCIS and hyperplasias.

Predicting the HER2 status of breast cancer from basic histopathology data: an analysis of 1500 breast cancers as part of the HER2000 International Study.

The tests that are currently available for the measurement of overexpression of the human epidermal growth factor-2 (HER2) in breast cancer have shown considerable problems in accuracy and interlaboratory reproducibility. Although these problems are partly alleviated by the use of validated, standardised 'kits', there may be considerable cost involved in their use. Prior to testing it may therefore be an advantage to be able to predict from basic pathology data whether a cancer is likely to overexpress HER2. In this study, we have correlated pathology features of cancers with the frequency of HER2 overexpression assessed by immunohistochemistry (IHC) using HercepTest (Dako). In addition, fluorescence in situ hybridisation (FISH) has been used to re-test the equivocal cancers and interobserver variation in assessing HER2 overexpression has been examined by a slide circulation scheme. Of the 1536 cancers, 1144 (74.5%) did not overexpress HER2. Unequivocal overexpression (3+ by IHC) was seen in 186 cancers (12%) and an equivocal result (2+ by IHC ) was seen in 206 cancers (13%). Of the 156 IHC 3+ cancers for which complete data was available, 149 (95.5%) were ductal NST and 152 (97%) were histological grade 2 or 3. Only 1 of 124 infiltrating lobular carcinomas (0.8%) showed HER2 overexpression. None of the 49 'special types' of carcinoma showed HER2 overexpression. Re-testing by FISH of a proportion of the IHC 2+ cancers showed that only 25 (23%) of those assessable exhibited HER2 gene amplification, but 46 of the 47 IHC 3+ cancers (98%) were confirmed as showing gene amplification. Circulating slides for the assessment of HER2 score showed a moderate level of agreement between pathologists (kappa 0.4). As a result of this study we would advocate consideration of a triage approach to HER2 testing. Infiltrating lobular and special types of carcinoma may not need to be routinely tested at presentation nor may grade 1 NST carcinomas in which only 1.4% have been shown to overexpress HER2. Testing of these carcinomas may be performed when HER2 status is required to assist in therapeutic or other clinical/prognostic decision-making. The highest yield of HER2 overexpressing carcinomas is seen in the grade 3 NST subgroup in which 24% are positive by IHC.

HER2 testing recommendations in Australia.

HER2 is the target of a new treatment for metastatic breast cancer using the humanised monoclonal antibody trastuzumab (Herceptin). Since only around 20% of breast cancers carry the overexpressed HER2 receptor protein to which this treatment is directed, patient selection is very important in determining eligibility for the drug. Currently, immunohistochemistry and fluorescence in situ hybridisation are the main tests used for HER2 detection, and these testing recommendations have been developed based on national and international data.

Adequacy of histopathology reports for breast cancer in New South Wales.

To assess the adequacy of diagnostic histopathology reports for breast cancer in New South Wales (NSW) and the Australian Capital Territory (ACT), a cross-sectional survey of diagnostic histopathology reports was carried out on a random sample (n = 1000) of NSW and ACT women diagnosed with breast cancer in 1992 and notified to the NSW Central Cancer Registry. A single pathologist with expertise in breast cancer reviewed the reports, from laboratories in public and private sectors, against a checklist enumerating basic features considered useful for decision making by surgeons and/or medical and radiation oncologists. While information was provided by almost all reports on histological classification (94%), size of tumor (93%) and involvement of lymph nodes (99.8%), this was not so for tumor resection/biopsy margin (77%), histological grade (69%), nuclear grade (23%), mitotic rate (11%) and the presence or absence of lymphatic (34%) or vascular (24%) invasion. Pathologists from teaching hospitals and those who reported on more than 10 cases in the sample were more likely to provide relevant information. Many diagnostic histopathology reports for breast cancer did not fulfil the requirements for a satisfactory report, established prognostic and predictive features frequently being omitted. The uniform use by pathologists of a carefully designed checklist could ensure that standard information is provided for every breast cancer, thereby facilitating choice of therapy for all patients.

Complex sclerosing lesion: the lesion is complex, the management is straightforward.

BACKGROUND: Complex sclerosing lesion (CSL) and its smaller counterpart, the radial scar (RS), are frequently seen pathological entities. They are clinically asymptomatic and, prior to the implementation of mammographic screening, were most commonly found incidentally during pathological examination of other biopsied lesions. Complex sclerosing lesions are being detected regularly on mammograms due to widespread screening; many of their features resemble those of malignancy. Management varies and has been controversial. METHODS: Twenty-three cases of CSL detected during the first prevalent round of screening at BreastScreen Western Sydney (from February 1993 until June 1995) are presented and reviewed. Assessment was by a combination of radiological, clinical and cytological work-up prior to surgical biopsy. In addition, 126 spiculated carcinomas detected in the same period were reviewed and compared. RESULTS: Fourteen RS/CSL (62%) had lucent centres and nine (38%) had a central mass; three had been diagnosed provisionally as RS/CSL. Spicule lengths ranged from 25 to 90 mm; central masses ranged from 5 to 50 mm; and mass:spicule length ratio ranged from 1.2:1 to 1:10. Calcification (benign or indeterminate) was present in six cases (29%). No RS/CSL contained 'suspicious' calcifications, whereas 120 of 126 carcinomas (95%) had a central mass and six (5%) had a lucent centre (spicule lengths: 10-90 mm; central mass: 5-40 mm; and mass:spicule length ratio: 1.1:1-1:10). Twenty-one spiculated carcinomas (17%) contained microcalcifications (14 benign or indeterminate; seven suspicious). Provisional radiological diagnosis (PRD) after mammogram, with or without ultrasound, for histologically confirmed RS/CSL, was RS/CSL in 18 cases (78%), carcinoma in four cases (17%) and equivocal in one case (5%). For eight (6.5%) spiculate carcinomas the PRD was RS/CSL prior to histological diagnosis. The RS/CSL were detected with equal frequency in right and left breasts, and 22 (96%) lesions occurred in the upper breast. Seven RS/CSL (31%) and 83 spiculated carcinomas (65%) had been described as 'palpable' but most were subtle. Twelve fine-needle aspiration biopsies were performed (six 'palpable' lesions (no radiological guidance); four with ultrasound guidance and two with stereotactic guidance), and five (62.5%) of eight adequate lesions were reported as benign, two (25%) were reported as atypical, and one (12.5%) was reported as suspicious. CONCLUSIONS: Definitive mammographic and sonographic differentiation of RS/CSL and stellate-type carcinoma is impossible. For screen-detected lesions that may be RS/CSL, the appropriate surgical procedure is a small but adequate biopsy using guidewire or other localization methods with optimal cosmetic incision.

Orofacial sensitivity reactions and the role of dietary components. Case reports.

Dietary components have proven to be important aetiological factors in orofacial sensitivity reactions such as plasma cell gingivitis and orofacial granulomatosis. The use of elimination diets to identify these dietary antigens can be instrumental in both diagnosis and effective treatment for these disorders.

Universal screening to identify gestational diabetes: a multi-centre study in the North of England.

We conducted an audit of treatment and outcomes in 116 women with gestational diabetes. These women received intense monitoring and high levels of medical and obstetric intervention. 24% would not have been identified by risk factor based screening. Cost effective strategies to identify all women with gestational diabetes are needed.

A quality assurance exercise to evaluate the accuracy and reproducibility of chromogenic in situ hybridisation for HER2 analysis in breast cancer.

BACKGROUND: Chromogenic in situ hybridisation (CISH) is an alternative to immunohistochemistry or FISH for the assessment of HER2 oncogene status in breast cancer. Although CISH is being used increasingly in routine diagnostics, there are no established inter-laboratory quality assurance programmes for this test. METHODS: The reproducibility of HER2 CISH analysis was assessed when performed by seven different centres that use the test routinely in diagnostic service. RESULTS: The results from 28 cases showed overall concordance of 98.5% (192/195 tests; kappa coefficient 0.91). One of the discrepancies was due to the invasive carcinoma having been cut out in the sections received by two of the centres, and the other two were in the non-amplified/equivocal/low-amplified category. CONCLUSION: This is believed to be the first report of a quality assurance study assessing laboratories that use HER2 CISH routinely in clinical diagnostics. The results show that CISH is a robust technique providing a suitable assay for the frontline testing of HER2 status in breast cancer.

Borderline breast core needle histology: predictive values for malignancy in lesions of uncertain malignant potential (B3).

Breast core needle biopsy (CNB) is an accurate test but may result in borderline histology (lesions of uncertain malignant potential or B3). This is an evaluation of the largest series (to date) of B3 histology, which focuses on estimating positive predictive values (PPV) for malignancy. We identified all B3 CNBs over a 10-year period in a single institution (N=372) from a series of 4035 consecutive needle biopsies. We describe the imaging findings, and report excision histology outcomes (N=279) and category-specific PPV for B3 lesions using two approaches including estimates based on subjects who had either excision or follow-up (N=328). B3 represented 9.2% of all CNB results. Excision histology was benign in 181 (64.9%) and malignant in 98 (35.1%) subjects (61 ductal carcinoma in situ, 37 invasive carcinoma). Positive predictive value for malignancy (based on excision histology) was 35.1% (95% CI: 29.5-40.7) and PPV (based on excision or review) was 29.9% (95% CI: 24.9-34.8). Lesion-specific PPV (estimates in parentheses for excision or follow-up) was atypical ductal hyperplasia 44.7% (40.6%); lobular intraepithelial neoplasia 60.9% (58.3%); papillary lesion 22.7% (15.9%); radial scar 16.7% (12.3%); phyllodes tumour 12.5% (12.5%); and B3 not specified 20.0%. Approximately one-third of CNB results classified as B3 are malignant on excision, and the likelihood of malignancy varies substantially between specific lesion groups. Whereas cases may be selectively managed without surgery, the majority warrant excision biopsy based on our estimates. Research is needed to improve differentiation between malignant and benign diseases in B3 lesions using diagnostic or predictive methods.

A risk index for early node-negative breast cancer.

BACKGROUND: This study compared the application of the St Gallen 2001 classification with a risk index developed at the New South Wales Breast Cancer Institute (BCI Index) for women with node-negative breast cancer treated without adjuvant systemic therapy. METHODS: The BCI risk categories were constructed by identifying combinations of prognostic indicators that produced homogeneous low-, intermediate- and high-risk groups using the same variables as in the St Gallen classification. RESULTS: The BCI low-risk category consisted of women aged 35 years or more with a grade 1 oestrogen receptor (ER)-positive tumour 20 mm or less in diameter, or with a grade 2 ER-positive tumour of 15 mm or less. This category constituted 40.1 per cent of patients, with a 10-year distant relapse-free survival (DRFS) rate of 97.2 per cent. The BCI intermediate-risk category included women aged 35 years or more with a grade 2 ER-positive tumour of diameter 16-20 mm, or a grade 1 or 2 ER-negative tumour measuring 15 mm or less, and comprised 12.1 per cent of the women, with a 10-year DRFS rate of 88 per cent. The high-risk category comprised 47.7 per cent of women, with a 10-year DRFS rate of 68.4 per cent. CONCLUSION: If confirmed in other data sets, the BCI Index may be used to identify women at low risk of distant relapse (2.8 per cent at 10 years) who are unlikely to benefit from adjuvant systemic therapy, and women at intermediate risk of distant relapse (12 per cent at 10 years) in whom the benefit of adjuvant systemic therapy is small.

Effect of an omental wrap on the healing and vascularity of compromised intestinal anastomoses.

Adult Wistar rats were used to investigate the ability of an omental wrap to limit leakage from compromised intestinal anastomoses. Under ketamine anesthesia, a section of small bowel was divided and then reanastomosed using a "control" anastomosis, a "deficient" anastomosis, or an "ischemic" anastomosis, plus or minus the addition of a wrap of omentum. Initially 10 rats were randomly assigned to each group. Nineteen of the 20 rats with unwrapped compromised anastomoses died within six weeks, compared with five deaths in the rats protected by an omental wrap (Fisher's exact test; P less than 0.01). The experiment was then repeated with a sample of rats from each anastomotic group being sacrificed for histologic examination on days 2 to 7, 10, 14, and 42. At the time of sacrifice a dye was injected into the omental vasculature to determine its contribution to the healing anastomosis. An anastomosis could be demonstrated between omental and bowel wall vessels by the third postoperative day. At one week the infarcted bowel edges were being resorbed and the omentum formed a fibrotic cylinder aligning the separated ends of bowel wall. At six weeks the scar became more contracted and the bowel mucosa had started to grow onto its luminal surface. It is concluded from this study that the omental wrap is protective to a compromised anastomosis by providing a biologically viable plug to prevent early leakage and a source of granulation tissue and neovasculature for later wound repair.