Patterns of biomarker expression in patients treated with primary endocrine therapy - a unique insight using core needle biopsy tissue microarray.

PURPOSE: Prediction of response to primary endocrine therapy (PET) in older women is based on measurement of oestrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor (HER)-2. This study uses a unique method for construction of core needle biopsy (CNB) tissue microarray (TMA), to correlate expression of a panel of 17 biomarkers with clinical outcome, in patients receiving PET. METHODS: Over 37 years (1973-2010), 1758 older (≥ 70 years) women with operable primary breast cancer were managed in a single institution. Of these, 693 had sufficient good-quality CNB to construct TMA, of which 334 had ER-positive tumours treated by PET with a minimum of 6-month follow-up. A panel of biomarkers was measured by immunohistochemistry (ER, PgR, HER2, Ki-67, p53, CK5/6, CK 7/8, EGFR, BCL-2, MUC1, VEGF, LKB1, BRCA1, HER3, HER4, PTEN and AIB1). Expression of each biomarker was dichotomised into 'low' or 'high' based on breast cancer-specific survival (BCSS). RESULTS: From the panel of biomarkers, multivariate analysis showed: High ER (p = 0.003) and PgR (p = 0.002) were associated with clinical benefit of PET at 6 months, as opposed to progressive disease. High ER (p = 0.0023), PgR (p < 0.001) and BCL-2 (p = 0.043) and low LKB1 (p = 0.022) were associated with longer time to progression. High PgR (p < 0.001) and low MUC1 (p = 0.021) were associated with better BCSS. Expression of other biomarkers did not show any significant correlation. CONCLUSIONS: In addition to ER and PgR; MUC1, BCL-2 and LKB1 are important in determining the outcome of PET in this cohort.

Transarticular fusion for treatment of cystic lesion arising from an odontoid fracture.

INTRODUCTION: Odontoid fractures are the most common upper cervical spine fracture. There are two mechanisms in which odontoid fractures occur, most commonly hyperflexion of the neck resulting in displacement of the dens anteriorly and hyperextension resulting in posterior dens displacement. Type 2 fractures are the most common and are associated with significant non-union rates after treatment. One possible consequence of an odontoid fracture is a synovial cyst, resulting in spinal cord compression, presenting as myelopathy or radiculopathy. Synovial cysts as a result of spinal fracture, usually of the facet joint, are most common in the lumbar region, followed by the thoracic and then cervical region; cervical cysts are rare. Fracture and subsequent cyst formation is thought to be related to hyper-motion or trauma of the spine. This is reinforced by the appearance of spinal synovial cysts most commonly at the level of L4/5; this being the region with the biggest weight-bearing function. The most common site of cervical cyst formation is at the level of C7/T1; this is a transitional joint subjected to unique stress and mechanical forces not present at higher levels. Treatment of a cervical synovial cyst at the level of the odontoid is challenging with little information available in the literature. The majority of cases appear to implement posterior surgical resection of the cyst, with fusion of adjacent cervical vertebrae to stabilise the fracture, resulting in restricted range of movement. CASE PRESENTATION: We describe a case concerning a 39-year-old female who presented with uncertain cause of odontoid fracture, resulting in a cystic lesion compressing the upper cervical spinal cord. OUTCOME: Minimal invasive surgery of C1/C2 transarticular fusion was successfully performed resulting in significant improvement of neurological symptoms in this patient. At 1-year follow-up, the cyst had resolved without surgical removal and this was confirmed by radiological measures.

The impact of breast cancer surgery on functional status in older women - A systematic review of the literature.

Primary endocrine therapy as treatment of breast cancer is only recommended in older women with limited life expectancy. However, many older women opt for endocrine therapy due to concerns regarding frailty and potential decline in function after surgery. A decline in functional status after surgery is documented in some cancer types, such as colorectal, however, the full impact of breast cancer surgery is less understood. A systematic review was performed to examine the evidence for impact of breast cancer surgery on functional status in older women. PubMed and Embase databases were searched. Studies were eligible if performed within the last 10 years; included patients over the age of 65 years undergoing breast cancer surgery; included stratification of results by age; measured functional status pre-operatively and at least six months following surgery. A total of 11 studies including 12 030 women were appraised. Two studies represented level-II and nine level-IV evidence. Overall, physical activity level was negatively impacted by breast cancer surgery and this was compounded by the extent of surgery. Evidence for impact of breast cancer surgery on quality of life, fatigue and cognition, was conflicting. The possibility of decline in functional status after breast cancer surgery should be discussed in all older women considering surgery. A structured exercise program may improve the negative effects of surgery on physical activity. Further work is required in the areas of quality of life, fatigability and cognition.

Biology of primary breast cancer in older women beyond routine biomarkers.

PURPOSE: There are numerous biomarkers which may have potential predictive and prognostic significance in breast cancer. This is extremely important in older adults, who may opt for less aggressive therapy. This work outlines the literature on biological assessment outside of standard biomarkers (defined as ER, PgR, HER2, Ki67) in women ≥ 65 years with primary operable invasive breast cancer, to determine which additional biomarkers are relevant to outcome in older women. METHODS: Medline and Embase databases were searched. Studies were eligible if included ≥ 50 patients aged ≥ 65 years; stratified results by age; measured a biomarker outside of standard assay and reported patient data. RESULTS: A total of 12 studies were appraised involving 5000 patients, measuring 28 biomarkers. The studies were extremely varied in methodology and outcome but three themes emerged: 1. Differences in biomarker expression between younger and older women, indicating that breast cancer in older women is generally less aggressive compared to younger women; 2. Relationship of biomarker expression with survival, suggesting biomarkers which may exclusively predict response to primary treatment in older women; 3. Association of biomarker with chemotherapy, suggesting that older patients should not be declined chemotherapy based on age alone. CONCLUSION: There is evidence to support further investigation of B-cell lymphoma (BCL2), liver kinase (LK)B1, epidermal growth factor receptor (EGFR), cytoplasmic cyclin-E, mucin (MUC)1 and cytokeratins (CKs) as potential predictive or prognostic markers in older women with breast cancer undergoing surgery. Studies exploring these biomarkers in larger cohorts and in women undergoing non-operative therapies are required.

Axillary reverse mapping in N0 patients requiring sentinel lymph node biopsy - A systematic review of the literature and necessity of a randomised study.

OBJECTIVES: Axillary reverse mapping (ARM) is a technique to map and preserve arm lymphatics which may be damaged during surgery, resulting in lymphoedema. This work systematically reviews the incidence of lymphoedema following sentinel lymph node biopsy (SLNB) + ARM, compared to SLNB alone, for clinically node negative disease, as well as recurrence rate, other morbidity and the feasibility and difficulties of ARM. MATERIALS AND METHODS: The following databases were searched: PubMed, Embase, Cochrane Library. Abstracts submitted to recognised societies dedicated to research in oncology were included. Studies were eligible if performed within the last 10 years; ARM was used in any form; ARM performed during SLNB ± axillary lymph node dissection (ALND). Studies were analysed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: No studies were found meeting the initial inclusion criteria. Therefore, studies reporting use of SLNB + ARM (i.e. no comparison to SLNB) were reviewed. A second search was performed to identify studies reporting outcome following SLNB alone. Twelve studies reported data on patients undergoing SLNB + ARM and 23 studies on patients undergoing SLNB. Incidence of lymphoedema following SLNB + ARM was quoted between 0-4% and 0-63.4% following SLNB. Few studies commented on recurrence rate. Studies included were of mainly low level of evidence. CONCLUSION: Evidence is beginning to emerge for the use of ARM in order to reduce lymphoedema following axillary surgery. However, data regarding oncological safety of ARM is not clear and randomised controlled trials, with adequate follow-up, need to be performed to determine this.

Biomechanics and technique analysis of classic and freestyle Nordic skiing.

The author takes an in-depth look at classical and freestyle Nordic skiing techniques. Specific biomechanical principles and techniques to enhance performance are analyzed. Equipment design and lower extremity injuries are discussed.

Parental reactions to the birth of a handicapped child.

Study of the theories of crisis reaction and grief and mourning therapy provide an enlightened understanding of parental reactions to the birth of a handicapped child. This article explores ways in which the hospital social worker can assist parents in meeting this crisis and in dealing with the issues this reality presents.

Complications with the use of bioabsorbable pins in the foot.

The authors present a brief history and overview of the usage of bioabsorbable pins in Podiatric Surgery. A retrospective study of 49 patients who had been implanted with Biofix pins is presented. The number of patients who displayed reactions to the pin sufficient to require subsequent surgical intervention was found to be 10.2%. Three specific cases are presented in detail. All of the patients who displayed reactions were over 40 years of age and the majority were between 55 and 60 years of age. A discussion of these facts is presented with the authors' views on why bioabsorbable pin reactions may be expected to occur in older age groups.

Use of gonozyme on urine sediment for diagnosis of gonorrhea in males.

We compared enzyme immunoassay (Gonozyme; Abbott Laboratories, North Chicago, Ill.) for detection of gonococcal antigen in urine sediments with urethral swab culture for diagnosis of gonorrhea in men attending a venereal disease clinic. The prevalence of infection was 14% by culture (27/196). The sensitivity of enzyme immunoassay was 93% (25/27) compared with the culture method, and the specificity was 99% (167/169). The ability to detect gonococcal antigen in urine sediment may provide the basis for a noninvasive method of screening for gonococcal infection.

Enzyme immunoassay for diagnosis of gonorrhea.

An enzyme immunoassay (EIA; Gonozyme [Abbott Laboratories]) for gonococcal antigen was assessed for the rapid diagnosis of gonorrhea. Patients attending two sexually transmitted disease clinics were tested by EIA and culture on Thayer-Martin medium. EIA was highly effective in detecting gonococcal infection among symptomatic men, with 70 of 75 (93.3%) culture-positive men having positive tests and no false-positive reactions. The performance of the test was not as good in detecting cervical gonorrhea; the best result obtained was a sensitivity of 87% (33 of 38) for EIA compared with culture. EIA false-positives occurred at a relatively low rate for women, with the test having a specificity of ca. 97%. The test clearly is capable of detecting gonococcal antigen in cervical and urethral specimens, but its role in routine diagnosis is not clear. Its performance seems equal to that of the Gram stain for men, but it seems to be less sensitive than culture for cervical gonorrhea--a drawback in high-risk populations. The low false-positive rate could be an important issue in screening low-prevalence populations.