Aromatase inhibitors as solely treatment in postmenopausal breast cancer patients

Several studies evaluating the clinical effectiveness of endocrine therapy alone in breast cancer patients aged 70 years or older reported comparable survival rates to conventional surgical therapy, although the incidence of local recurrences was higher. Primary endocrine therapy is therefore only recommended as an alternative approach in elderly woman with estrogen receptor positive tumors who are deemed inoperable or who refuse surgery. We report our experience with aromatase inhibitors as primary endocrine therapy for estrogen receptor positive breast cancer in postmenopausal woman who are impaired by other diseases, refuse surgery or are of old age. Fifty-six patients with fifty-seven ER+ operable breast cancers who refused surgery, were judged ineligible for surgery because of comorbidity, or were of old age were treated with endocrine therapy using aromatase inhibitors only. Digital mammography and high-end breast ultrasound were used to assess tumor sizes. The mean age of the patients was 74 years (range 52-102 years). All patients suffered from breast cancer. The mean follow-up interval was 40 months (range 5-92 months). Seven patients (12%) achieved complete clinical remission, 31 (57%) partial response giving an overall objective response rate of 69%. In addition, seven (12%) patients showed stable disease, giving a clinical benefit rate (complete remission + partial response + stable disease rate) of 81%. Eleven patients (19%) progressed after an initial partial response or stable disease. Only one patient (2%) progressed on endocrine therapy within the first months. Eventually, 22 (39%) patients underwent surgery after informed consent to achieve better local tumor control. Primary endocrine therapy with aromatase inhibitors may offer an effective and safe alternative to surgery giving a high local control rate in postmenopausal women who refuse surgery, who are judged ineligible for surgery, or are of old age.     

Interleukin-7 levels in synovial fluid increase with age and MMP-1 levels decrease with progression of osteoarthritis

Background and purpose

Little is known about biochemical mediators that correlate with the initiation and progression of knee osteoarthritis (OA). We therefore valuated the roles of cytokines and metalloenzymes in knee OA in relation to OA grading, age, and BMI.

Patients and methods

A multiplex ELISA-based immunoassay (Luminex technology) was used to measure biochemical mediators in the synovial fluid (SF) of 82 patients undergoing knee surgery. All patients were classified according to age, BMI, and OA grade. 24 patients had no signs of OA (knee reconstruction surgeries). The mediators that were tested for included interleukins (IL-1Ra, IL-6, IL-7, and IL-18), chemokines (CCL2 (MCP-1), CCL3 (MIP-1a), and CXCL8 (IL-8)), growth factors (HGF and VEGF), and matrix metalloproteinases (MMP-1, MMP-2, MMP-9, and MMP-13).

Results

There was a correlation between IL-7 levels in SF and age (p < 0.01). The 11 highest IL-7 levels were seen in patients who were aged between 59 and 72 but had different OA grades. In contrast, all patients who had severe OA in all 3 knee compartments (pan-OA) had only low or medium IL-7 levels. There was a negative correlation between MMP-1 levels in synovial fluid and grade of OA (p < 0.001). Correlation studies between pairs of mediators revealed two groups of mediators that are important in OA progression, dominated by MCP-1 and IL-1Ra.

Interpretation

IL-7 levels in SF are elevated in elderly people suffering from OA of different grades, but they are depressed in patients with severe 3-compartment OA, possibly due to widely impaired chondrocytes embedded in the affected cartilage tissue. The observed decrease in MMP-1 levels in SF, which is dependent on the severity of OA, may be caused by deterioration of superficial cartilage layers during progression of OA.

List of abbreviations

BMI

body mass index

CCL

chemokine (C-C motif) ligand

CXCL

chemokine (C-X-C motif) ligand

HGF

hepatocyte growth factor

ICRS

International Cartilage Repair Society

IL

interleukin

IL-1Ra

IL-1 receptor antagonist

MCP

monocyte chemoattractant protein

MIP

macrophage inflammatory protein

MMP

matrix metalloproteinase

OA

osteoarthritis

SF

synovial fluid

VEGF

vascular endothelial growth factor

Progression of knee OA is often driven by biomechanical forces (Englund 2010), whereas the etiology of OA in other joints is less affected by mechanical stress. Biochemical mediators such as cytokines, growth factors, and matrix metalloproteinases—acting individually or in networks—profoundly influence cellular responses in joint tissues, modifying both catabolic and anabolic activities involved in the pathogenesis of OA (Goldring and Goldring 2007). Ageing is the most prominent risk factor for OA, and chondrocyte senescence and aging-related changes in the matrix, such as articular surface fibrillation and proteoglycan changes, are most likely to contribute to joint ageing (Martin and Buckwalter 2002, Shane Anderson and Loeser 2010). However, despite intensive research efforts, little is known about biochemical factors whose levels may correlate with the severity of knee OA (Belo et al. 2007). Also, age-related changes in cytokine production in body fluids have not been investigated completely (Gardner and Murasko 2002).Biochemical mediators found in synovial fluid (SF) that affect the cellular functions of tissues of the knee joint include interleukins (ILs), chemokines, growth factors, and matrix metalloproteinases (MMPs). Interleukins, both pro- and anti-inflammatory, have a pivotal role in arthritic diseases and are potential targets of OA therapy. Chemokines, which are small, chemoattractant cytokines, have key roles in the accumulation of inflammatory cells at the site of inflammation. Growth factors produced by chondrocytes and subchondral bone regulate the growth of blood vessels in the joint. Some recent studies have supported the notion that inhibition of abnormal angiogenesis will provide effective therapeutic strategies for treatment of OA (Ashraf and Walsh 2008). MMPs and pro-inflammatory cytokines are involved in a collagen II-dependent feed-forward mechanism of matrix degradation in human articular cartilage (Klatt et al. 2009).To improve our understanding of the molecular and cellular processes involved in joint ageing and in the initiation and progression of OA, we wanted to determine the levels of biochemical mediators that correlate with the severity of knee OA or patient age.     

Better Walking Performance in Older Children With Cerebral Palsy

Background  

Children with cerebral palsy (CP) often walk with a slower speed and a higher energy cost. Their walking performance and choice of mobility method may vary in different environments. Independent mobility is important for activity and participation.     

A Swedish consensus on the surgical treatment of concomitant atrial fibrillation

Atrial fibrillation (AF) is a common arrhythmia among patients scheduled for open heart surgery and is associated with increased morbidity and mortality. According to international guidelines, symptomatic and selected asymptomatic patients should be offered concomitant surgical AF ablation in conjunction with valvular or coronary surgery. The gold standard in AF surgery is the Cox Maze III ("cut-and-sew") procedure, with surgical incisions in both atria according to a specified pattern, in order to prevent AF reentry circuits from developing. Over 90% of patients treated with the Cox Maze III procedure are free of AF after 1 year. Recent developments in ablation technology have introduced several energy sources capable of creating nonconducting atrial wall lesions. In addition, simplified lesion patterns have been suggested, but results with these techniques have been unsatisfactory. There is a clear need for standardization in AF surgery. The Swedish Arrhythmia Surgery Group, represented by surgeons from all Swedish units for cardiothoracic surgery, has therefore reached a consensus on surgical treatment of concomitant AF. This consensus emphasizes adherence to the lesion pattern in the Cox Maze III procedure and the use of biatrial lesions in nonparoxysmal AF.     

Neurofunctional and behavioral correlates of phonetic and temporal categorization in musically trained and untrained subjects

The perception of rapidly changing verbal and nonverbal auditory patterns is a fundamental prerequisite for speech and music processing. Previously, the left planum temporale (PT) has been consistently shown to support the discrimination of fast changing verbal and nonverbal sounds. Furthermore, it has been repeatedly shown that the functional and structural architecture of this supratemporal brain region differs as a function of musical training. In the present study, we used the functional magnetic resonance imaging technique, in a sample of professional musicians and nonmusicians, in order to examine the functional contribution of the left PT to the categorization of consonant-vowel syllables and their reduced-spectrum analogues. In line with our hypothesis, the musicians showed enhanced brain responses in the left PT and superior discrimination abilities in the reduced-spectrum condition. Moreover, we found a positive correlation between the responsiveness of the left PT and the performance in the reduced-spectrum condition across all subjects irrespective of musical expertise. These results have implications for our understanding of musical expertise in relation to segmental speech processing.     

Incidence,Risk Factors,and Obstetrical Outcomes of Women with Breast Cancer in Pregnancy

Abstract: Breast cancer in pregnancy is a rare condition. The objective of our study was to describe the incidence, risk factors, and obstetrical outcomes of breast cancer in pregnancy. We conducted a population‐based cohort study on 8.8 million births using data from the Healthcare Cost and Utilization Project – Nationwide Inpatient Sample from 1999–2008. The incidence of breast cancer was calculated and logistic regression analysis was used to evaluate the independent effects of demographic determinants on the diagnosis of breast cancer and to estimate the adjusted effect of breast cancer on obstetrical outcomes. There were 8,826,137 births in our cohort of which 573 cases of breast cancer were identified for an overall 10‐year incidence of 6.5 cases per 100,000 births with the incidence slightly increasing over the 10‐year period. Breast cancer appeared to be more common among women >35 years of age, odds ratio (OR) = 3.36 (2.84–3.97); women with private insurance plans, OR = 1.39 (1.10–1.76); and women who delivered in an urban teaching hospital, OR = 2.10 (1.44–3.06). After adjusting for baseline characteristics, women with pregnancy‐associated breast cancer were more likely to have an induction of labor, OR = 2.25 (1.88, 2.70), but similar rates of gestational diabetes, preeclampsia, instrumental deliveries, and placental abruption. The incidence of breast cancer in pregnancy appears higher than previously reported with women over 35 being at greatest risk. Aside from an increased risk for induction of labor, women with breast cancer in pregnancy have similar obstetrical outcomes.     

Extent of Primary Breast Cancer Surgery: Standards and Individualized Concepts

Surgery is still a main therapeutic option in breast cancer treatment. Nowadays, methods of resection and reconstruction vary according to different tumors and patients. This review presents and discusses standards of care and arising questions on how radical primary breast cancer surgery should be according to different clinical situations. In most early breast cancer patients, breast conservation is the method of choice. The discussion on resection margins is still controversial as different studies show conflicting results. Modified radical mastectomy is the standard in locally advanced breast cancer patients, although there are different promising approaches to spare skin or even the nipple-areola complex. A sentinel node biopsy is the standard of care in clinically node-negative invasive breast cancer patients, whereas the significance of axillary lymphonodectomy seems to be questioned through a number of different findings. Although there are interesting findings to modify surgical approaches in very young or elderly breast cancer patients, it will always be an individualized approach if we do not adhere to current guidelines. Up to date, there are no special surgical procedures in BRCA mutation carriers or patients of high-risk families.     

Male breast cancer

Male breast cancer is rare, and many patients and health care providers are not familiar with this entity. Although the underlying causes are not well understood, certain populations are at higher risk, including certain gene mutation carriers, men with Klinefelter syndrome, and certain ethnic groups. Male breast cancer typically presents at a later stage than female breast cancer. A palpable mass is the most common presentation, but nipple discharge or other nipple changes may be seen. Because the number of affected individuals is small, prospective trials have not been conducted; thus, treatment recommendations are typically taken from large trials involving female breast cancer populations. Although outcomes in male breast cancer were previously thought to be worse than female breast cancer outcomes, it appears that they are similar. Questions regarding the most effective surgical and adjuvant therapies remain. Mastectomy with axillary lymph node evaluation, adjuvant hormonal therapy, and chemotherapy are commonly used. Providers of health care to male patients must be aware of the possibility of breast cancer and appropriately evaluate any suspicious changes.     

Spinal anaesthesia

Spinal anaesthesia is the injection of local anaesthetic into the subarachnoid space. It is a simple technique that can be used to provide surgical anaesthesia for procedures involving the abdomen, pelvis and lower limbs. To perform the technique safely it is important to understand the physiology of the block and the pharmacology of the drugs commonly used. Although serious complications are rare, they must be recognized and managed quickly.     

Spicae aetheroleum in uncomplicated acute bronchitis: a double-blind,randomised clinical trial

Wiener Medizinische Wochenschrift - The trial aimed to evaluate the efficacy and safety of Spicae aetheroleum (Spicae ae.), a&nbsp;phytomedicine obtained by steam distillation of the flowering...