Expression of cell adhesion molecules and prognosis in breast cancer.

BACKGROUND: Cell adhesion molecules (CAMs) play an important role in the process of metastasis. The prognostic value of tumour expression of N-cadherin, E-cadherin, carcinoembryonic antigen (CEA) and epithelial CAM (Ep-CAM) was evaluated in patients with breast cancer. METHODS: A tissue microarray of the patient cohort was stained immunohistochemically for all markers and analysed by microscopy. Expression was classified into two categories, with the median score as cut-off level. For CEA, the above-median category was further subdivided in two subgroups based on staining intensity (low or high intensity). RESULTS: The cohort consisted of 574 patients with breast cancer with a median follow-up of 19 years. Below-median expression of E-cadherin (P = 0·015), and above-median expression of N-cadherin (P = 0·004), Ep-CAM (P = 0·046) and CEA (P = 0·001) all resulted in a shorter relapse-free period. Multivariable analysis revealed E-cadherin and CEA to be independent prognostic variables. Combined analysis of CEA and E-cadherin expression showed a 3·6 times higher risk of relapse for patients with high-intensity expression of CEA, regardless of E-cadherin expression, compared with patients with below-median CEA and above-median E-cadherin tumour expression (hazard ratio 3·60, 95 per cent confidence interval 2·12 to 6·11; P < 0·001). An interaction was found between expression of these two CAMs (P < 0·001), suggesting a biological association. CONCLUSION: Combining E-cadherin and CEA tumour expression provides a prognostic parameter with high discriminative power that is a candidate tool for prediction of prognosis in breast cancer.

Vaccination uptake for pertussis and influenza vaccines in pregnancy among different practices at a single institution.

OBJECTIVE: The authors investigated tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) and influenza vaccination during pregnancy following Advisory Committee on Immunization Practices' (ACIP's) recommendation for antenatal pertussis vaccination. METHODS: A retrospective chart review was performed in 2019 of women receiving prenatal care at our institution between January 1, 2014 and December 31, 2018. Receipt of ACIP-recommended vaccines were examined using Current Procedural Terminology codes to identify initiation of prenatal care, then administration of Tdap and influenza vaccines. Data were examined by individual practice (university faculty, community physicians, obstetrics and gynecology (OBGYN) residents, and family medicine residents, practice staff composition, vaccination protocol use, and insurance status. Statistical analyses were performed using χ2 testing and χ2 testing of linear trend. RESULTS: Within our cohort (n = 17 973), highest vaccination uptake occurred in the university-based OBGYN faculty practice (Tdap = 58.2%, influenza = 56.5%) with lowest uptake in the OBGYN resident practice (Tdap = 28.6%, influenza = 18.5%). Higher uptake occurred in practices with standing orders, more advanced practice providers, lower provider to nursing ratios, and lower rates of Medicaid insurance. CONCLUSION: These data demonstrated higher vaccination uptake with standing orders, more advanced practice providers, and lower provider to nurse ratios. Future work optimizing practice staff composition and vaccination protocols may increase vaccine uptake.

Quality of life in relation to tamoxifen or exemestane treatment in postmenopausal breast cancer patients: a Tamoxifen Exemestane Adjuvant Multinational (TEAM) Trial side study.

Tamoxifen and aromatase inhibitors are associated with side effects which can significantly impact quality of life (QoL). We assessed QoL in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) Trial and compared these data with reported adverse events in the main database. 2,754 Dutch postmenopausal early breast cancer patients were randomized between 5 years of exemestane, or tamoxifen (2.5-3 years) followed by exemestane (2.5-2 years). 742 patients were invited to participate in the QoL side study and complete questionnaires at 1 (T1) and 2 (T2) years after start of endocrine treatment. Questionnaires comprised the EORTC QLQ-C30 and BR23 questionnaires, supplemented with FACT-ES questions. 543 patients completed questionnaires at T1 and 454 patients (84%) at T2. Overall QoL and most functioning scales improved over time. The only clinically relevant and statistically significant difference between treatment types concerned insomnia; exemestane-treated patients reported more insomnia than tamoxifen-treated patients. Discrepancy was observed between QoL issue scores reported by the patients and adverse events reported by physicians. Certain QoL issues are treatment- and/or time-specific and deserve attention by health care providers. There is a need for careful inquiry into QoL issues by those prescribing endocrine treatment to optimize QoL and treatment adherence.

Maintenance of physical activity and body weight in relation to subsequent quality of life in postmenopausal breast cancer patients.

BACKGROUND: We prospectively examined the association between physical activity, body weight and quality of life in Dutch postmenopausal early breast cancer patients treated with adjuvant endocrine therapy. PATIENTS AND METHODS: In this side study of a large clinical trial, lifestyle and quality-of-life questionnaires were filled out 1 and 2 years after the start of endocrine therapy (T1 and T2, respectively) and included a pre-diagnosis lifestyle assessment (T0). A total of 435 breast cancer patients returned both questionnaires. RESULTS: Individuals with a physical activity level above the median who maintained this level from T0 to T1 reported the best global quality of life and physical functioning and the least fatigue at T2, as compared with individuals with low levels of physical activity which further decreased after diagnosis (difference of +16, +14, and -22 points on a 0-100 quality-of-life scale, respectively; P < 0.01). Overweight or obese women who gained body weight after diagnosis reported worst quality of life and most fatigue as compared with women who maintained a stable body weight (difference of -8, -10 and +2 points, respectively; P < 0.01). CONCLUSION: Maintaining high pre-diagnosis physical activity levels and a healthy body weight is associated with better quality of life after breast cancer.

Patterns of care in Dutch postmenopausal patients with hormone-sensitive early breast cancer participating in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial.

BACKGROUND: The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial investigates the efficacy and safety of adjuvant exemestane alone and in sequence after tamoxifen in postmenopausal women with hormone-sensitive early breast cancer. As there was a nationwide participation in The Netherlands, we studied the variations in patterns of care in the Comprehensive Cancer Centre Regions (CCCRs) and compliance with national guidelines. METHODS: Clinicopathological characteristics, carried out local treatment strategies and adjuvant chemotherapy data were collected. RESULTS: From 2001 to January 2006, 2754 Dutch patients were randomised to the study. Mean age of patients was 65 years (standard deviation 9). Tumours were < or =2 cm in 46% (within CCCRs 39%-50%), node-negative disease varied from 25% to 45%, and PgR status was determined in 75%-100% of patients. Mastectomy was carried out in 55% (45%-70%), sentinel lymph node procedure in 68% (42%-79%) and axillary lymph node dissections in 77% (67%-83%) of patients, all different between CCCRs (P < 0.0001). Adjuvant chemotherapy was given in 15%-70% of eligible patients (P < 0.001). DISCUSSION: In spite of national guidelines, breast cancer treatment on specific issues widely varied between the various Dutch regions. These data provide valuable information for breast cancer organisations indicating (lack of) guideline adherence and areas for breast cancer care improvement.

Variations in locoregional therapy in postmenopausal patients with early breast cancer treated in different countries.

BACKGROUND: The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial is an international randomized trial evaluating the efficacy and safety of exemestane, alone or following tamoxifen. The large number of patients already recruited offered the opportunity to explore locoregional treatment practices between countries. METHODS: Patients were enrolled in Belgium, France, Germany, Greece, Ireland, Japan, the Netherlands, the UK and the USA. The core protocol had minor differences in eligibility criteria between countries, reflecting variations in national guidelines and practice regarding adjuvant endocrine therapy. RESULTS: Between 2001 and 2006, 9779 patients of mean(s.d.) age 64(9) years were randomized. Some 58.4 per cent had T1 tumours (range between countries 36.8-75.9 per cent; P < 0.001) and 47.3 per cent were axillary node positive (range 25.9-84.6 per cent; P < 0.001). Independent factors for type of breast surgery were country, age, tumour status and calendar year of surgery. After breast-conserving surgery, radiotherapy was given to 93.2 per cent of patients, 86.0 per cent in the USA and 100 per cent in France. Axillary lymph node dissection was performed in 82.0 (range 74.6-99.1) per cent. CONCLUSION: Despite international consensus guidelines, wide global variations were observed in treatment practices of early breast cancer. There should be further efforts to optimize locoregional treatment for breast cancer worldwide.

Validation study of the prognostic value of cyclin-dependent kinase (CDK)-based risk in Caucasian breast cancer patients.

In a Japanese study, cyclin-dependent kinase (CDK) based risk determined by CDK 1 and 2 activities was associated with risk of distance recurrence in early breast cancer patients. The aim of our study was to validate this risk categorization in European early breast cancer patients. We retrospectively analyzed frozen breast cancer specimens of 352 Dutch patients with histologically confirmed primary invasive early breast cancer. CDK-based risk was determined in tumour tissues by calculating a risk score (RS) according to kinases activity and protein mass concentration assay without the knowledge of outcome. Determination of CDK-based risk was feasible in 184 out of 352 (52%) tumours. Median follow-up of these patients was 15 years. In patients not receiving systemic treatment, the proportions of risk categories were 44% low, 16% intermediate, and 40% high CDK-based risk. These groups remained significant after univariate and multivariate Cox-regression analysis. Factors associated with a shorter distant recurrence-free period were positive lymph nodes, mastectomy with radiotherapy, and high CDK-based risk. There was no significant correlation with overall survival (OS). CDK-based risk is a prognostic marker of distance recurrence of patients with early breast cancer. More validation would be warranted to use of CDK-based risk into clinical practice.

Catecholamine excretion profiles identify clinical subgroups of neuroblastoma patients.

INTRODUCTION: Analysis of urinary catecholamine metabolites is one of the primary modalities to diagnose patients with neuroblastoma. Although catecholamine excretion patterns have been recognised in the past, their biological rationale and clinical relevance remain largely unknown. Therefore, this study was designed to identify unique catecholamine excretion patterns and elucidate their underlying biology and clinical relevance. PATIENTS AND METHODS: A panel of 25 neuroblastoma cell lines was screened for catecholamine excretion. Detection of the catecholamine enzymes was performed using Western blot. Based on catecholamine enzymes presence and excreted catecholamine metabolites, excretion profiles were defined. The prevalence of these profiles was investigated in vivo using diagnostic urines from 301 patients with neuroblastoma and immunohistochemistry on primary tumours. The clinical relevance of the profiles was determined by linking the profiles to clinical characteristics and outcome of patients with neuroblastoma. RESULTS: Four excretion profiles (A-D) were identified in vitro, which correlated with the relative protein expression of the catecholamine enzymes. These profiles were also identified in urine samples from patients with neuroblastoma and correlated with the presence of the catecholamine enzymes in the tumour. Strikingly, in 66% of the patients, homovanillic acid and vanillylmandelic acid excretions were discordant with the catecholamine profiles. Clinical characteristics and outcome gradually improved from patients with profile A (predominantly high risk) towards profile D (predominantly observation), with 5-years overall survival of 35% and 93%, respectively. CONCLUSIONS: Catecholamine profiles in vitro and in vivo reflect, to a large extent, the presence of the individual catecholamine enzymes and represent distinct subgroups of patients with neuroblastoma.

[The advantages of preoperative systemic therapy in breast cancer]. / De voordelen van preoperatieve systemische therapie bij borstkanker.

Neoadjuvant systemic therapy is administered preoperatively in order to provide a better preparation for surgery by down sizing the tumour. A recent meta-analysis comparing neoadjuvant and adjuvant chemotherapy demonstrated a 17% (95% CI: 15.1-18.1) increase in breast-conserving operations with equal survival rates and maintenance of local control providing adequate surgery was performed. Comparable results have been reported with neoadjuvant hormonal therapy. However, in the case of hormonal therapy the tumour-shrinking effects persisted when treatment was sustained. Research has shown that the sentinel lymph node procedure continues to be reliable after neoadjuvant therapy. Therefore, axillary lymph node dissection is not necessary if the lymph node metastases have disappeared as a result of the neoadjuvant therapy: down staging. However, further research is needed to confirm the safety of this treatment approach. Assessment oftumour sensitivity during neoadjuvant therapy facilitates analysis of the prognostic value of tumour markers. The aim of this translational research is to provide better selection criteria to identify patients in which the systemic treatment will be beneficial.

The preferred treatment for young women with breast cancer--mastectomy versus breast conservation.

Paradigms on breast cancer influence surgical treatment policies. Randomised trials that compared mastectomy with breast-conserving therapy (BCT) with adequate radiotherapy showed no difference in overall survival. However, after a long follow-up, BCT was associated with a higher local recurrence rate (up to four times higher). The EBCTCG meta-analysis of 2005 concluded that one breast cancer death can be avoided for four local recurrences avoided. A minority of breast cancer patients are younger than 40 years (6.5%). When confronted with the diagnosis of breast cancer, they potentially have a long lifespan. Therefore, it is crucial to avoid local recurrences. The following factors have a positive impact on local control: mastectomy (in stead of BCT), negative surgical margins and adjuvant treatment (radiotherapy and chemotherapy). In order to provide optimal local and systemic treatment for young patients, breast cancer requires a multidisciplinary approach and the patient has to be involved in the proper treatment decision. A predictive model is needed for doctors and patients to facilitate this process.

[Optimal adjuvant hormone therapy in postmenopausal women with hormone-sensitive mammary carcinoma: tamoxifen and the aromatase inhibitors anastrozole, exemestane and letrozole]. / Optimale adjuvante hormonale therapie bij postmenopauzale vrouwen met een hormoongevoelig mammacarcinoom: tamoxifen en de aromataseremmers anastrozol, exemestaan en letrozol.

Postmenopausal patients with hormone-sensitive breast cancer may be eligible for adjuvant hormone therapy. - For years, tamoxifen was the treatment of choice. - However, the side effects associated with tamoxifen, such as endometrial cancer and thromboembolic disorders, and the search for more effective agents have led to the introduction of new hormonal therapies. - The results of randomised trials with the third-generation aromatase inhibitors anastrozole, exemestane and letrozole demonstrate improved efficacy compared to tamoxifen. - Using aromatase inhibitors, the disease-free survival is prolonged and recent data from some studies also show a benefit in overall survival. - Aromatase inhibitors are associated with specific side effects consisting of osteoporosis/increased incidence of fractures and myalgia/arthralgia.

[Cerebellar cortical degeneration in an American Staffordshire terrier]. / Cerebellaire corticale degeneratie bij een Amerikaanse Staffordshire terriër.

Most diseases affecting the cerebellum are congenital and three groups can be distinguished on pathogenetic grounds. In the first group, diseases are caused by intrauterine or neonatal viral infections, in the second group by malformations of genetic or unknown origin, and in the third group by degenerative disease, or abiotrophies. Familial late-onset cerebellar abiotrophy has been reported in the Gordon Setter the Old English Sheepdog, the Brittany Spaniel and more recently the American Staffordshire Terrier. This case report describes the clinical, diagnostic and pathological changes in an American Staffordshire Terrier with cerebellar cortical degeneration. This is the first case diagnosed in the Netherlands.

[Acute sialoadenitis of the parotid gland]. / Acute sialoadenitis van de glandula parotidea.

An 88-year-old diabetic women was hospitalized because of a pheripheral vascular disorder. During her hospitalization she developed a right-sided facial swelling which was not limited by anatomical structures in this area. Ultrasound and computertomographic scanning supported the clinical diagnosis acute sialoadenitis of the parotid gland. The swelling resolved shortly after starting antibiotic therapy.

[The multidisciplinary breast cancer care team: promoting better care]. / Het multidisciplinair mammateam: bevordering van goede zorg.

Breast cancer is the most commonly diagnosed form of cancer in women in the Western world. Various sorts of therapies are available and treatment plans are becoming more and more complex. The treatment of breast cancer is based on several prognostic and predictive factors, of which the TNM-classification is the best known. However, several new factors have been discovered and implemented over the past decade. As well as these, economic factors and doctor- and patient-related factors are also important. As a consequence of the multitude of factors and the ensuing complexity of treatment, it has become impossible for a single doctor to coordinate the complete treatment of a patient. Therefore, it seems obvious that patients with breast cancer should be managed by a breast cancer care team. Specialists and nurses from different disciplines are represented within this team, with the advanced practice nurse as the primary contact person. This type of team helps to lower mortality, improve quality of care and lower associated costs.

[Diagnostic image (236). A woman with acute unilateral swelling of the face]. / Diagnose in beeld (236). Een vrouw met acute enkelzijdige zwelling van het gelaat.

An 88-year-old woman developed right-sided facial swelling due to acute sialoadenitis of the parotid and submandibular glands.

[The 4th large meta-analysis of all trials of the treatment of operable breast cancer: increased survival after a longer follow-up]. / De 4e grote meta-analyse op het gebied van operabel mammacarcinoom: meer overlevingswinst na langere follow-up.

The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) was founded in 1983. The EBCTCG coordinates the quinquennial worldwide meta-analyses of centrally located data on women in all randomised trials of early breast cancer. This 4th meta-analysis, with a follow-up of 15 years, showed an increased survival after the use of adjuvant hormonal or chemotherapy. The EBCTCG analyses have been responsible for major changes in the treatment of breast cancer in the past. However, we do not need another meta-analysis before implementing, for example, the improvement of chemotherapy with taxoids and the improvement of hormonal treatment with aromatase inhibitors. Nowadays, new treatments are implemented before the 5-year follow-up and are aimed more specifically at certain tumour characteristics.

Sensory neuronopathy in dogs: a study of four cases.

A neurological disease which selectively affects the primary sensory pathways was observed in 4 dogs. Clinical signs were dominated by ataxia due to impaired position sense. Deficient or abnormal pain sensation was also observed. Difficulty in eating probably arose from oral and lingual sensory deficit. The lesions were characterized by degeneration and loss of central and peripheral primary sensory axons, with a predilection for large myelinated fibres. The concept of a sensory neuronopathy was supported by the finding of neuronal degeneration and loss in dorsal root ganglia seen in 2 dogs. The cause of the disease is not known. The presence of mononuclear inflammatory cells in acute lesions suggests an infectious or autoimmune disease. Toxic and genetic factors are also to be considered.

Electrophysiological evaluation of traumatic forelimb paralysis of the dog.

The results of clinical neurological, electromyographic and electroneurographic examinations in 26 dogs with traumatic forelimb paralysis are presented. The results of neurological examination varied considerably among the cases. Electromyographic evidence of denervation in the epaxial muscles was observed in 22 dogs. A post ganglionic dorsal root lesion was diagnosed in 14 cases by the presence of an evoked sensory nerve action potential in association with loss of conscious pain perception in the appropriate area. Motor nerve studies in the ulnar nerve were not helpful in discriminating root lesions from spinal nerve involvement. It was concluded that electromyographic examination of the ipsilateral epaxial muscles under general anaesthesia is essential for the detection of root involvement. Sensory conduction studies in the radial nerve are indicated if conscious pain perception is absent in the fifth digit. Motor and sensory conduction studies of the ulnar nerve system seldom provide additional diagnostic information seldom provide additional diagnostic information. The absence of electrophysiological signs of root involvement does not exclude a post ganglionic dorsal root lesion.

Electroneurographic examination of the ulnar and radial nerves in the dog: reference values, biological variation and reproducibility.

The radial and ulnar nerves were examined electrophysiologically in 90 normal dogs. In 66 of these dogs, aged between one and eight years, the reference values were established for 27 variables. Multicomponent sensory nerve action potentials were encountered at the proximal recording site in the ulnar nerve in 68 per cent of the dogs in the reference group and in the radial nerve in 26 per cent. Differences between the sexes were not significant, nor were differences between two breeds of similar body size. There were no significant age related differences between the ages of one and eight years. Limb length, measured as the distance between sensory stimulation site (digits) and proximal recording site (elbow), was found to have a significant effect on the velocity, amplitude, number of positive peaks and duration of the nerve action potentials. The variation in results of repeated measurements of velocities ranged from 0 to 11 per cent. The relative error in velocities due to errors in measurement of distance and latency ranged from 1 to 12 per cent.

Electrophysiological evidence of peripheral nerve dysfunction in six dogs with botulism type C.

In six dogs with botulism type C electrophysiological examinations showed: fibrillation potentials and prolonged insertional activity; low amplitude of the evoked muscle action potential; decrease in amplitude of the compound muscle action potential with slow repetitive stimulation; slowing of motor and sensory velocities in the peripheral nerve; and restoration of velocity and amplitude corresponding to clinical improvement. These findings indicate peripheral nerve dysfunction which cannot be explained adequately by current knowledge of the action of botulinum toxin on cholinergic nerve endings. It is therefore suggested that botulinum toxin also interferes with peripheral nerve conduction.