Will medical cause of death certifications data quality improve in the UK with the new medical examiner system?

OBJECTIVES: There are deficits in the completeness, accuracy and timeliness of death certification internationally. In April 2023, England implemented a statutory Medical Examiners system primarily aiming to improve the quality of certification of death data. We sought to assess the current quality of death certification among general practitioners and medical examiners. METHODS: An online survey was conducted with general practitioners and medical examiners in the Yorkshire region to determine how Medical Certifications of Cause of Death (MCCD) are completed and commonly experienced sources of errors (e.g., a lack of a reported time frame, absent or inadequate reporting of comorbidities, incorrect underlying cause-of-death, and an inaccurate sequence of events). RESULTS: The survey was completed by general practitioners (n = 95) and medical examiners (n = 9). Participant responses, including to a hypothetical case, confirmed the quality of the certification was less variable among MEs compared to GPs, but still below international standards. CONCLUSIONS: Efforts to enhance the quality of death certification require further consideration. Mandating a medical examiner system may not lead to intended improvements in the quality and cause of death data that form a critical component of mortality statistics that underpin health planning and monitoring.

Large volume "mammotome" biopsy may reduce the need for diagnostic surgery in papillary lesions of the breast.

BACKGROUND: There is currently debate as to whether all papillary lesions diagnosed on breast needle core biopsy (BNCB) require surgical excision. The development of large volume "mammotome" biopsy now permits non-operative removal. Few studies have assessed the usefulness of this approach. AIM: To review the pathological and radiological findings in a series of B3 and B4 papillary lesions identified on conventional BNCB with a view to assessing the usefulness of mammotome biopsy as a means of avoiding diagnostic surgery. METHODS: All BNCBs from 23 June 2005 to 14 August 2007 that contained a B3 or B4 papillary lesion were identified by searching the pathology department records. Follow-up histology and radiological details were obtained. RESULTS: 34 papillary BNCBs were included in this study: 21 from screen-detected lesions and 13 from patients presenting symptomatically. 31 were classified B3 and three were B4. Four cases included an atypical ductal epithelial proliferation (three B4, one B3). 14 patients had undergone open surgical biopsy, 15 had undergone mammotome excision, and five had had no subsequent procedure. All cases that had undergone mammotome biopsy had not shown atypia on the core, and 13 (87%) proved benign. In two cases the mammotome biopsy was either atypical or malignant, prompting surgery; the biopsy changes deriving from areas of ductal carcinoma in situ arising in the context of multiple intraduct papillomas and both were distinctive mammographically in presenting with large areas of segmental calcification. 11/14 cases that had undergone surgical excision had not shown atypia on the core, and proved benign. All three cases with atypia on the core proved malignant. CONCLUSION: In selected cases, mammotome biopsy may improve sampling of papillary lesions such that malignancy may be excluded without recourse to diagnostic surgery. Mammotome in such cases effectively acts as a therapeutic procedure. This has important implications for symptomatic and breast screening services.

Examination of breast needle core biopsy specimens performed for screen-detected microcalcification.

AIMS: To establish the number of histological levels necessary for the evaluation of breast needle core biopsy (NCB) specimens taken from areas of mammographic calcification in patients presenting via the UK National Health Service Breast Screening Programme. METHODS: Retrospective review of a series of breast NCB specimens initially examined routinely at nine levels. The presence of calcification within the histological sections in each of three sets of levels (levels 1-3, 4-6 and 7-9) and the (cumulative) diagnostic B category that would have pertained after each were assessed. RESULTS: Accurate diagnostic classification was possible after examination of three levels in 89% cases. Examination of a further three levels permitted accurate diagnosis in a further eight cases (total 97% cases). In only three cases were nine levels necessary for accurate classification. In only a single case (1%) was it likely that routine examination of six levels could have led to significant misclassification. In a significant group of patients (18%), nine levels were considered to provide additional useful information, although this information did not alter the diagnosis. CONCLUSIONS: NCBs for screen-detected mammographic calcification should be routinely examined at six levels. Further levels may be needed in occasional cases to identify more conclusively the associated pathological abnormality. Further levels may be of particular value when assessing atypical intraductal proliferative epithelial lesions.

Steroid hormone receptor expression in male breast cancer.

AIMS: To investigate expression of the steroid hormone receptors estrogen receptor (ER)-alpha and -beta, progesterone receptor (PR) and androgen receptor (AR) in male breast cancer. METHODS: Specimens from 16 male breast cancers were immunostained for ERalpha, ERbeta, PR and AR. FINDINGS: Eighty-seven percent of tumours expressed ERalpha, 93% PR, 87% ERbeta and 87% AR. Staining for ERalpha and PR was confined exclusively to the nuclei of epithelial cells with some heterogeneity. Nuclear immunoreactivity was also observed with AR. Again this was restricted to epithelial cells but tended to be more uniform. ERbeta was seen in the nuclei of epithelial cells and also in stromal fibroblasts and lymphocytes. Analysis of serial sections revealed a similar pattern of staining with ERbeta and AR in epithelial cells. CONCLUSIONS: In addition to expression of the better known steroid receptors, ERalpha, PR and AR, we have demonstrated a high rate of expression of ERbeta in male breast cancer. This is in keeping with the generally high steroid receptor expression seen in males. However, the abundance of ERbeta expressed in this small series of male breast cancer is in contrast to female breast cancer where ERbeta expression is often reduced.

Needle core biopsy can reliably distinguish between benign and malignant papillary lesions of the breast.

AIMS: To review 21 screen-detected papillary lesions in which the core biopsy findings suggested a papillary lesion and to correlate pathological and radiological findings in order to assess the risks of associated malignancy and the need for surgical intervention. The appropriate management of non-malignant papillary breast lesions detected on needle core biopsy (NCB) is currently uncertain. METHODS AND RESULTS: Forty-seven papillary breast lesions with a histological diagnosis of papilloma, papilloma with atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS), multiple papillomas, 'papillomatosis' or papillary carcinoma (invasive or in situ) were identified from records at the Leeds Breast Screening and Assessment Unit. The cases were diagnosed between between May 1995 and May 2002. In 21 cases the previous NCB contained a papillary proliferation which had been categorized as either 'B2', benign, 'B3', of uncertain malignant potential, or 'B4', suspicious of malignancy. All of the 19 'B3' or 'B4' cases and one of the two 'B2' lesions had undergone open surgical biopsy. All cases with a previous 'B4' were malignant on subsequent excision. All excised cases with a previous 'B3' or 'B2' were found benign, although four of the 'B3's derived from papillomata associated with an atypical proliferation amounting to ADH. In three of these four (75%) the papillary proliferation had been associated with epithelial hyperplasia of usual type (HUT) on the core and the radiological features were of a mass lesion detected on incident round screen which had increased in size. CONCLUSION: Our results confirm the accuracy of NCB in the diagnosis of screen-detected papillary lesions of the breast. Surgical excision may not always be necessary following a 'B3' core biopsy.

Expression of prostate specific antigen in male breast cancer.

Male breast cancer is uncommon, accounting for less than 1% of all breast cancers. Carcinoma metastatic to the male breast is also unusual, with metastatic prostatic carcinoma being among the most common primary sites from which such tumours derive. Metastatic prostatic cancer and primary breast cancer may be histologically indistinguishable without immunohistochemistry because both often infiltrate with a cribriform architecture. Distinguishing between primary and metastatic disease within the breast is important because the treatment options for each are radically different. Following a case in which metastatic prostatic disease was initially wrongly diagnosed as primary breast cancer, a small series of male breast cancers was examined for expression of prostate specific antigen (PSA) and prostatic acid phosphatase to assess the usefulness of these markers in making this distinction. Focal expression of PSA was found in one of 11 cases of male breast cancer. These results indicate that PSA should be used with caution in this context.

Surgical excision is warranted following a core biopsy diagnosis of mucocoele-like lesion of the breast.

AIMS: Mucocoele-like lesions (MLLs) of the breast are unusual lesions in which mucin-filled ducts or cysts are accompanied by extrusion of mucin into surrounding stroma. A possible diagnosis of MLL may be suggested by the finding of mucin-filled ducts or cysts and/or stromal mucin in a core biopsy sample. Whether such findings should prompt immediate open diagnostic biopsy to exclude malignancy is currently uncertain, although this represents current practice in our institution. In this study we have reviewed 11 cases of possible MLL on core biopsy correlating both pathological and radiological findings in order to determine the risks of associated malignancy and whether excision is the most appropriate management option. METHODS AND RESULTS: Eleven cases of possible MLL presenting via the Breast Screening and Assessment Unit in Leeds since April 1999 were identified by review of pathological records. Histological slides, mammograms and ultrasound images were reviewed. Ten of the 11 had undergone open surgical biopsy for diagnosis. Three of the 10 (30%) proved to derive from malignant lesions. Two were ductal carcinoma in situ (DCIS) and one was an invasive mucinous carcinoma. All three cases had an associated atypical epithelial proliferation which, in a surgical excision, would be classified as atypical ductal hyperplasia (ADH) at least, as well as mucin in the core biopsy sample. The majority of possible MLLs presented radiologically as coarse calcification, but two of four (50%) which had a radiological mass subsequently proved malignant. Seven cases were without atypia on the core and all subsequently proved benign. Three of these, however, were associated with ADH on the excision biopsy. CONCLUSION: Surgical excision is warranted following a core biopsy suggestion of possible MLL when mucin-filled ducts or cysts and stromal mucin have been seen. The risk of malignancy is high when the core biopsy also contains an atypical epithelial proliferation (100% in our series) and also when there is an associated radiological mass lesion. In cases without atypia on the core a significant proportion of cases (43%) are associated with ADH on excision.

Negotiating medications: patient perceptions of long-term medication use.

OBJECTIVE: To investigate how adults with one of several chronic illnesses (bipolar disorder, multiple sclerosis, rheumatoid arthritis, schizophrenia/schizoaffective disorder, or systemic lupus erythematosus) perceive their need to take medications during the course of their illness. METHOD: Eighty-three adults, aged 18-64 years, all members of a health maintenance organization, were interviewed. Each participant completed an ethnographic interview that was transcribed verbatim and analysed using grounded theory techniques. RESULTS: Participants described two forms of ongoing efforts to negotiate their need for medications, internal and external. The former category includes struggles over self-identify (e.g. worries about becoming dependent on drugs, feeling like a 'guinea pig'). The latter includes negotiations with health care providers over the type, route, and frequency of medication use. Dimensions of both negotiation types include acceptance and resistance. Specifically, patients with chronic illness must manage not only drug regimens, but also renegotiate their self-identities as formerly well persons. During this dynamic process, patients may accept and/or resist taking prescribed medications. CONCLUSION: Practitioners should recognize that patients experience not only physical, but emotional side effects of medications, and that resistance might be part of a negotiation process rather than a final stance.

Will the spectrum of lesions prompting a "B3" breast core biopsy increase the benign biopsy rate?

AIM: To audit the benign surgical biopsies in women screened, assessed, and referred by the Leeds/Wakefield Breast Screening Unit for the year 1999-2000 with a view to determining any association with a preoperative B3 core biopsy categorisation. METHODS: The results of all preoperative diagnostic procedures in all patients who underwent surgical excision for a lesion proving benign in the year 1999-2000 were reviewed. Cases were categorised according to whether the preoperative fine needle aspirate cytology (FNAC) or core biopsy had been equivocal or of uncertain malignant potential (C3/B3), inadequate or unrepresentative (C1/B1), or benign (C2/B2). In those cases with a C3/B3 FNAC or core biopsy result, reasons for the uncertainty were determined by examination of the report and, where necessary, slides. In cases with C1/B1 or C2/B2 investigations and in those without a preoperative procedure, the reasons for surgical referral were determined from the screening records. Case records of all patients with a B3 core biopsy categorisation who subsequently proved to have malignancy were also reviewed. RESULTS: Thirty six women had benign surgical biopsies in the 1999-2000 screening year. In 13 of the 36 patients, referral for diagnostic biopsy rested on radiological and/or pathological suspicion of radial scar. The core biopsy category was B3 in all but one, which was in the B1 category. In a further 10 patients, referral was based primarily on a pathological B3 categorisation. The reasons for this were as follows: papillary lesion (two), fibroepithelial lesion (two), atypical intraductal epithelial proliferation (two), stromal mucin (two), atypical lobular hyperplasia (one), and an unusual vascular lesion (one). Two cases with a C3 on FNAC also derived from papillary lesions. In the remaining nine patients, the radiological features were sufficiently suspicious to prompt referral in the presence of either inadequate/unrepresentative (C1/B1) or benign (B2) preoperative pathological findings. Two women had no preoperative needle biopsy. CONCLUSIONS: In 22 of 36 benign biopsies, the initial core biopsy categorisation was B3. According to the current system of core biopsy categorisation, a diversity of lesions must be designated as of "uncertain malignant potential" (B3) because the technique provides insufficient tissue for full histological assessment. The use of this category may increase the number of benign biopsies if all such cases are referred for surgery. An increase in the benign biopsy rate may be averted if larger amounts of tissue can be obtained using newer vacuum assisted techniques such as the Mammotome.

Treatment of metastatic breast cancer with liver transplantation.

Resection of liver metastases is accepted as an appropriate treatment for colorectal metastases in suitable patients. Liver transplant is not often used for malignant disease as there is a high incidence of undetectable micrometastases elsewhere and recurrence is likely. The effects of immunosuppression may also enhance the growth of malignant cells at other sites. We report a case where a young patient with undiagnosed breast cancer with axillary and liver metastases underwent liver transplantation and is effectively leading a normal life 33 months after transplant.

Evaluation of seven oestrogen receptor beta antibodies for immunohistochemistry, western blotting, and flow cytometry in human breast tissue.

Two oestrogen receptors, ER alpha and ER beta, exist. While much is known about ER alpha, the role of ER beta is still undefined, especially at the protein level. The aim of this study was to determine the utility of seven ER beta antibodies (14C8, 8D5, PAI313, PPG5/10, N19, 9.88, and D7N) raised against different domains of ER beta in three commonly used laboratory applications, namely immunohistochemistry, western blot, and flow cytometry, using human breast material. For immunohistochemical analysis of frozen material, PAI313 and D7N gave stronger and more specific signals than 14C8, 8D5, and PPG5/10. In paraffin sections, 14C8, closely followed by PPG5/10, gave by far the most superior nuclear immunoreactivity, compared with the other antibodies tested. In general, flow cytometry results mirrored the immunohistochemistry data for paraffin sections, with antibodies ranked 14C8 > 8D5> or = PAI-313 > PPG5/10 >D7N. For western blotting, 8D5 and D7N yielded the strongest and most consistent bands, with weaker bands seen with the others. It is concluded that ER beta protein can be detected using specific antibodies. However, there is considerable variation between the specificity and application of these antibodies, highlighting the fact that careful optimization is required when selecting an antibody for use in a particular laboratory technique.

Distinct expression patterns of ER alpha and ER beta in normal human mammary gland.

AIM: Two oestrogen receptors (ERs) have been identified to date-the "classic" ER alpha and the more recently described ER beta. Although much is known about ER alpha at the mRNA and protein levels, our knowledge of the expression and distribution of ER beta protein is much more limited. The aim of this study was to compare the cellular distribution of ER alpha and ER beta in normal human mammary gland. METHODS: Formalin fixed, paraffin wax embedded material was obtained from reduction mammoplasty specimens, normal tissue adjacent to breast tumour, or fibroadenoma. Sections were immunohistochemically stained for ER alpha, ER beta, and the progesterone receptor. The staining pattern for each antibody was evaluated and compared. RESULTS: ER alpha was restricted to the cell nuclei of epithelial cells lining ducts and lobules. Although ER beta was also seen in these cells, additional strong staining was detected specifically in the cell nuclei of myoepithelial cells. Occasional staining was seen in surrounding stromal and endothelial cell nuclei and in lymphocytes. CONCLUSIONS: ER subtypes have distinct distribution patterns in the normal mammary gland. The widespread distribution of ER beta suggests that it may be the dominant ER in the mammary gland where it may be acting as a natural suppressor.