Changes in body composition during and after adjuvant or neo-adjuvant chemotherapy in women with breast cancer stage I-IIIB compared with changes over a similar timeframe in women without cancer.

PURPOSE: Body weight and body composition may change during and after adjuvant or neo-adjuvant chemotherapy for breast cancer. However, most studies did not include a comparison group of women without cancer, thus could not assess whether observed changes differed from age-related fluctuations in body weight and body composition over time. We assessed changes in body composition during and after chemotherapy in breast cancer patients compared with age-matched women not diagnosed with cancer. METHODS: We recruited 181 patients with stage I-IIIb breast cancer and 180 women without cancer. In patients, we assessed body composition using a dual-energy X-ray scan before start of chemotherapy (T1), shortly after chemotherapy (T2), and 6 months after chemotherapy (T3); for the comparison group, the corresponding time points were recruitment (T1) and 6 (T2) and 12 (T3) months. RESULTS: Fifteen percent of patients and 8% of the comparison group gained at least 5% in body weight between T1 and T3. Among the comparison group, no statistically significant changes in body weight, or body composition were observed over time. Body weight of patients significantly increased from baseline (72.1 kg ± 0.4 kg) to T2 (73.3 kg ± 0.4 kg), but decreased to 73.0 kg ± 0.4 kg after chemotherapy (T3). Lean mass of patients significantly increased from 43.1 kg ± 0.5 kg at baseline to 44.0 kg ± 0.5 kg at T2, but returned to 43.1 kg ± 0.5 kg at T3. There were no differential changes in fat mass over time between patients and the comparison group. CONCLUSIONS: Changes in body weight and body composition during and after chemotherapy for early stage breast cancer were modest, and did not differ substantially from changes in body weight and body composition among women without cancer.

A longitudinal mixed methods study on changes in body weight, body composition, and lifestyle in breast cancer patients during chemotherapy and in a comparison group of women without cancer: study protocol.

BACKGROUND: More than 60% of women diagnosed with early stage breast cancer receive (neo)adjuvant chemotherapy. Breast cancer patients receiving chemotherapy often experience symptoms such as nausea, vomiting and loss of appetite that potentially affect body weight and body composition. Changes in body weight and body composition may detrimentally affect their quality of life, and could potentially increase the risk of disease recurrence, cardiovascular disease and diabetes. To date, from existing single method (quantitative or qualitative) studies is not clear whether changes in body weight and body composition in breast cancer patients are treatment related because previous studies have not included a control group of women without breast cancer. METHODS: We therefore developed the COBRA-study (Change Of Body composition in BReast cancer: All-in Assessment-study) to assess changes in body weight, body composition and related lifestyle factors such as changes in physical activity, dietary intake and other behaviours. Important and unique features of the COBRA-study is that it used I) a "Mixed Methods Design", in order to quantitatively assess changes in body weight, body composition and lifestyle factors and, to qualitatively assess how perceptions of women may have influenced these measured changes pre-, during and post-chemotherapy, and II) a control group of non-cancer women for comparison. Descriptive statistics on individual quantitative data were combined with results from a thematic analysis on the interviews- and focus group data to understand patients' experiences before, during and after chemotherapy. DISCUSSION: The findings of our mixed methods study, on chemotherapy treated cancer patients and a comparison group, can enable healthcare researchers and professionals to develop tailored intervention schemes to help breast cancer patients prevent or handle the physical and mental changes they experience as a result of their chemotherapy. This will ultimately improve their quality of life and could potentially reduce their risk for other co-morbidity health issues such as cardiovascular disease and diabetes.

Perceptions of Dutch health care professionals on weight gain during chemotherapy in women with breast cancer.

PURPOSE: Dutch Health care professionals (HCPs) provide little information concerning health risks associated with weight gain during chemotherapy for breast cancer. Women with breast cancer have specified the need for more information on nutrition and physical activity to deal with weight gain. The aims of this study were to assess the perceptions of Dutch HCPs on weight gain during chemotherapy and in addition evaluate whether and what kind of information on dietary intake and physical activity HCPs provide to prevent/treat weight gain during (neo)adjuvant chemotherapy. METHODS: A qualitative study was conducted using semi-structured interviews with 34 HCPs involved in breast cancer care: general practitioners, oncologists, specialized nurses, and dieticians. RESULTS: To date, little information about nutrition, physical activity, and weight gain is given during chemotherapy because it is not part of most HCPs' training, it is not included in the guidelines and it is not the best time to bring up information in the opinion of HCPs. Weight gain was perceived as just a matter of a few kilos and not an important health issue during treatment. All HCPs felt it is better that women themselves addressed their weight gain after chemotherapy. CONCLUSION: More knowledge about health risks associated with chemotherapy-induced weight gain and how to combat these issues needs to be made readily available to the HCPs and should become part of their training. Existing patient guidelines should include information on how to prevent and/or reduce weight gain through self-management of nutrition intake and physical activity during and post chemotherapy.

The randomised uterine septum transsection trial (TRUST): design and protocol.

BACKGROUND: A septate uterus is a uterine anomaly that may affect reproductive outcome, and is associated with an increased risk for miscarriage, subfertility and preterm birth. Resection of the septum is subject of debate. There is no convincing evidence concerning its effectiveness and safety. This study aims to assess whether hysteroscopic septum resection improves reproductive outcome in women with a septate uterus. METHODS/DESIGN: A multi-centre randomised controlled trial comparing hysteroscopic septum resection and expectant management in women with recurrent miscarriage or subfertility and diagnosed with a septate uterus. The primary outcome is live birth, defined as the birth of a living foetus beyond 24 weeks of gestational age. Secondary outcomes are ongoing pregnancy, clinical pregnancy, miscarriage and complications following hysteroscopic septum resection. The analysis will be performed according to the intention to treat principle. Kaplan-Meier curves will be constructed, estimating the cumulative probability of conception leading to live birth rate over time. Based on retrospective studies, we anticipate an improvement of the live birth rate from 35% without surgery to 70% with surgery. To demonstrate this difference, 68 women need to be randomised. DISCUSSION: Hysteroscopic septum resection is worldwide considered as a standard procedure in women with a septate uterus. Solid evidence for this recommendation is lacking and data from randomised trials is urgently needed. TRIAL REGISTRATION: Dutch trial registry ( NTR1676 , 18th of February 2009).

Taste and smell perception and quality of life during and after systemic therapy for breast cancer.

PURPOSE: The purpose of the study was to assess self-reported taste and smell perception after chemotherapy in breast cancer patients compared with women without cancer, and to assess whether taste and smell perception is associated with quality of life after the end of chemotherapy. METHODS: We included 135 newly diagnosed breast cancer patients who completed chemotherapy and 114 women without cancer. Questionnaires on taste, smell, and quality of life were completed shortly after and 6 months after chemotherapy (patients) or at two moments with 6 months' time window in between (comparisons). RESULTS: Self-reported taste and smell perception were significantly lower in patients shortly after chemotherapy compared to the comparison group. Most patients recovered 6 months after chemotherapy, although patients who were still receiving trastuzumab then reported a lower taste and smell perception compared to patients who were not. A lower self-reported taste and smell were statistically significantly associated with a worse quality of life, social, emotional, and role functioning shortly after chemotherapy. Six months after chemotherapy, taste and smell were statistically significantly associated with quality of life, social and role functioning, but only in patients receiving trastuzumab. CONCLUSIONS: Most taste and smell alterations recovered within 6 months after the end of chemotherapy for breast cancer, but not for patients receiving trastuzumab. These results highlight the importance of monitoring taste and smell alterations during and after treatment with chemotherapy and trastuzumab, as they may impact quality of life.

The Burden of ADHD in Older Adults: A Qualitative Study.

OBJECTIVE: To explore how ADHD may have affected the lives of older adults who meet the diagnostic criteria of ADHD, but are unaware of their diagnosis. Our second aim was to examine whether the reported symptoms change over the life span. METHOD: A qualitative study was conducted. Seventeen Dutch older people (>65 years) diagnosed in this study with ADHD participated in in-depth interviews. Data were analyzed according to techniques of thematic approach. RESULTS: Seven themes emerged from the analyses. Four themes correspond to ADHD symptoms: "being active," "being impulsive," "attention problems," and "mental restlessness." In addition, the themes "low self-esteem," "overstepping boundaries," and "feeling misunderstood" emerged. The impact of ADHD symptoms seems to have declined with age. CONCLUSION: ADHD has a negative impact on late life, and older adults with the disorder may benefit from treatment. Moreover, this study's findings call for early detection and treatment of ADHD in children and adults.

Weight change during chemotherapy in breast cancer patients: a meta-analysis.

BACKGROUND: Weight gain during chemotherapy in women with breast cancer is commonly reported. However, there are important differences between studies that examined weight change during chemotherapy; e.g. type of chemotherapy, menopausal status, time between body weight measurements and sample size. The purpose of this meta-analysis was to quantify changes in body weight during chemotherapy for women with breast cancer, taking these differences into account. METHODS: We identified relevant studies using PubMed, Scopus and Embase databases. The search was limited to human studies published in English up to and including December 2015. Only studies among women with early stage breast cancer treated with chemotherapy, with reported body weight before and after chemotherapy and type of chemotherapy were included. Random-effect models were used, and heterogeneity between studies was explored through stratified analyses and meta-regression. Sensitivity analyses were done to explore whether a specific study markedly affected the results. RESULTS: In total 25 papers were found, including data from 2620 women. Overall, body weight increased during chemotherapy: 2.7 kg (95% CI 2.0, 7.5) with a high degree of heterogeneity (I2 = 94.2%). Stratified analyses showed weight gain in all strata, but did not substantially reduce heterogeneity. Univariate meta-regression showed less weight gain in prospective studies compared to chart review studies (-2.0, 95% CI: -3.1, -0.8). Studies including cyclophosphamide, methotrexate and 5-fluorouracil (CMF) regimes showed a greater weight gain compared to those that did not (2.2, 95% CI: 1.1, 3.3); and papers published until the year 2000 showed a greater weight gain compared to those published after 2000 (1.9, 95% CI:-0.8, 3.1). In the multivariate models only studies including CMF regimes and studies published until 2000 were associated with significant weight gain of respectively 1.3 and 1.4 kg. CONCLUSION: Despite the high heterogeneity, this meta-analysis shows significant weight gain during chemotherapy for women with breast cancer. Weight gain was more pronounced in papers published until 2000 and women receiving CMF as chemotherapy regime. Although weight gain after chemotherapy has decreased over the course of time, weight gain is still substantial and deserves clinical attention.

Differences in dietary intake during chemotherapy in breast cancer patients compared to women without cancer.

PURPOSE: Breast cancer patients receiving chemotherapy often experience symptoms such as nausea, vomiting and loss of appetite that potentially affect dietary habits. This study assessed the intake of energy, macronutrients and food groups before and during chemotherapy in breast cancer patients compared with women without cancer, and determined the association between symptoms and energy and macronutrient intake. METHODS: This study included 117 newly diagnosed breast cancer patients scheduled for chemotherapy and 88 women without cancer. Habitual intake before chemotherapy was assessed with a food frequency questionnaire. Two 24-h dietary recalls were completed on random days for each participant during the whole chemotherapy treatment for patients and within 6 months after recruitment for women without cancer. Shortly, after the dietary recall, participants filled out questionnaires on symptoms. RESULTS: Before chemotherapy, habitual energy and macronutrient intake was similar for breast cancer patients and women without cancer. During chemotherapy, breast cancer patients reported a significantly lower total energy, fat, protein and alcohol intake than women without cancer, as shown by a lower intake of pastry and biscuits, cheese, legumes and meat products. A decline in subjective taste perception, appetite and hunger and experiencing a dry mouth, difficulty chewing, lack of energy and nausea were associated with a lower energy intake. CONCLUSIONS: Symptoms induced by chemotherapy are associated with lower dietary intake and manifested by a lower intake of specific food groups. To ensure an optimal dietary intake during chemotherapy, it is important to monitor nutritional status and symptom burden during chemotherapy in breast cancer patients.

[Thoracic endometriosis with aspecific manifestation]. / Thoracale endometriose met een aspecifieke uiting.

BACKGROUND: Endometriosis is a common disease, especially in subfertile women. The most common location is in the pelvis, but extragenital locations are also possible. This far less common condition has been described in almost all tissues in the body. Symptoms occurring cyclically are characteristic of endometriosis. CASE DESCRIPTION: A 37-year-old woman was discovered by chance to have ascites and pleural effusion. She had no symptoms of this. Thoracoscopy showed an image consistent with thoracic endometriosis. After initial drug therapy was unsuccessful, surgical intervention was performed. CONCLUSION: Thoracic endometriosis is a rare disease, in which the cyclical nature of the symptoms often leads to correct diagnosis. Drug therapy is the preferred treatment for patients.

[Mission statements of Dutch mental health institutions; the quality of communication with stakeholders]. / Mission statements van Nederlandse ggz-instellingen; de kwaliteit van communicatie met belanghebbenden.

BACKGROUND: As a result of recent reforms in Dutch health care, healthcare providers are having to operate more and more like commercial organisations and adopt some of the rules prevailing in the profit sector. Because missions statements can be an efficient means of useful communication with internal and external stakeholders they can make a useful contribution to the way healthcare institutions are managed and to their status and reputation. Research shows that in view of this the quality of the messages conveyed via mission statements is important. AIM: To ascertain which stakeholders are mentioned in the mission statements of Dutch mental healthcare providers and to quantify the quality of the messages conveyed to them via mission statements. METHOD: We examined the mission statements of 34 mental health providers to find out which stakeholders were included. The message conveyed to the stakeholders was quantified by means of a validated measuring instrument devised specifically for this purpose. RESULTS: Patients were referred to in all mission statements and the quality of the messages conveyed was of higher quality than the messages conveyed to other stakeholders. Other important stakeholders on whom the institutions depended were referred to much less frequently and the quality of sections of text referring to them was definitely inferior. CONCLUSION: Mission statements frequently serve as management tool for Dutch mental healthcare providers. The potential benefits that these statements could bestow on the providers are not being fully exploited because the standard of communication with several internal and external stakeholders is of poor quality.

Metroplasty versus expectant management for women with recurrent miscarriage and a septate uterus.

BACKGROUND: The prevalence of recurrent miscarriage in women with a septate uterus has increased. Restoration of the morphology of the uterus can hypothetically increase live birth rate and subsequent pregnancies in women with a septate uterus and recurrent miscarriage. OBJECTIVES: To determine whether hysteroscopic metroplasty in women with a septate uterus and two or more preceding miscarriages improves pregnancy outcomes. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register (inception to August 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (inception to August 2010),  MEDLINE (1950 to August 2010), EMBASE (1980 to August 2010). PSYCHINFO (1806 to August 2010). In addition we searched trial registers for ongoing and registered trials, conference abstracts and OpenSigle and sources of Grey literature. SELECTION CRITERIA: Only randomised controlled trials (RCTs) that assess the effect on reproductive outcome of hysteroscopic metroplasty in women with a history of two or more preceding miscarriages and a septate uterus were eligible for inclusion. DATA COLLECTION AND ANALYSIS: If there had been data to include, two authors would have independently assessed trial quality and extracted data. They would have also contacted study authors for additional information. We collected adverse effects information from the trials. MAIN RESULTS: No randomised controlled trials were identified for inclusion. AUTHORS' CONCLUSIONS: Hysteroscopic metroplasty in women with recurrent miscarriage and a septate uterus is being performed in many countries to improve reproductive outcomes in women.This treatment has been assessed in non-controlled studies, which suggested a positive effect on pregnancy outcomes. However, these studies are biased due to the fact that the participants with recurrent miscarriage treated by hysteroscopic metroplasty served as their own controls. Until now, the effectiveness and possible complications of hysteroscopic metroplasty have never been considered in a randomised controlled trial.Taking this into account there is insufficient evidence to support this treatment in these women. A randomised controlled trial is urgently needed and currently underway (www.studies-obsgyn.nl/trust NTR 1676).

Laparoscopic subtotal hysterectomy versus laparoscopic total hysterectomy: a decade of experience.

At present, there are only few data on the surgical outcomes of laparoscopic hysterectomy (LH). Up till now, it has been unclear whether there is a difference in number of complications among the subcategories of laparoscopic total hysterectomy and laparoscopic subtotal hysterectomy (LSH). Therefore, we have performed a retrospective analysis to evaluate the peri- and postoperative outcomes in women undergoing LSH versus LH. This multi-centre retrospective cohort study (Canadian Task Force classification II-2) was conducted in multi-centres (two teaching hospitals and one university medical centre) in the Netherlands, all experienced in minimally invasive gynaecology. In a multi-centre retrospective cohort study we compared the long-term outcomes of laparoscopic subtotal hysterectomy and laparoscopic total hysterectomy (including laparoscopic assisted vaginal hysterectomy, laparoscopic hysterectomy and total laparoscopic hysterectomy). All laparoscopic hysterectomies from the last 10 years (January 1998 till December 2007) were included. Patient characteristics, intra- and postoperative complications, operating time and duration of hospital stay were recorded. The minimum follow-up was 6 months. A total of 390 cases of laparoscopic hysterectomies were included in the analysis: 192 laparoscopic subtotal hysterectomies and 198 laparoscopic total hysterectomies. Patient characteristics such as age and parity were equal in the groups. The overall number of short-term and long-term complications was comparable in both groups: 17% and 15%. Short-term complications (bleeding, fever) were 3% in the LSH group and 12% in the LH group. Long-term complications were (tubal prolapse and cervical stump reoperations) 15% in the LSH group and 3% in the LH group. Laparoscopic subtotal hysterectomy as compared with the different types of laparoscopic total hysterectomy is associated with more long-term postoperative complications, whereas laparoscopic total hysterectomy is associated with more short-term complications.

Case report: retroperitoneoscopic tumor nephrectomy during pregnancy.

When considering laparoscopic tumor nephrectomy during pregnancy, questions will arise about the consequences of the increased abdominal pressure (IAP) for uterine-placental perfusion and the impact of carbondioxide insufflation on the fetus. These considerations should be weighed against the advantages for the mother, in term of shorter convalescence and decreased wound problems. This situation presents the urologists with a dilemma. At 16 weeks of gestation, a 30-year-old woman underwent a retroperitoneoscopic tumor nephrectomy. This case report and the following discussion highlight the key issues involved in laparoscopic surgery during pregnancy. In theory, laparoscopy in pregnancy carries some specific hazards, which may influence fetal outcome. First, the elevation of IAP may lead to alterations in placental perfusion, and second, CO2 insufflation may disturb the acid-base balance. However, in a study covering more than 2 million pregnancies, no difference was found in fetal mortality or malformations after laparoscopic surgery for non-obstetric reasons compared with open surgery. Animal experiments have demonstrated an IAP of 15 mm Hg or less to cause almost no reduction in the uterine-placental blood flow. According to our limited experience and with the support of the literature, pneumo(retro)peritoneum during pregnancy seems to be safe.

An algorithm for the clinical assessment of nutritional status in hospitalized patients.

Upon admission to hospital, 30-50 % of patients either are or become malnourished. There is no generally accepted definition of malnutrition or guidelines on the best way to establish nutritional status. We consider it self-evident that the nursing staff have an important role in screening patients at risk of malnutrition on admission and thereafter at regular times. This is why we developed the nursing nutritional screening form (NNSF). The NNSF was tested by nurses, dietitians and clinicians, in pairs, to establish the extent of agreement in two phases on sixty-nine and forty patients. Later, the form was used in practice by nursing staff on five wards (334 patients). Based on the results of the NNSF, patients were referred to a dietitian. The dietitian established whether the patient was indeed at risk, or was actually malnourished, using a complete nutritional history. The degree of concurrence within pairs was reasonable to good. The same applied to the concurrence between nursing staff and dietitians, but concurrence between clinicians and nursing staff was less. In total, 334 patients were screened and sixty-nine of them were referred to the dietitian. It was established that 86 % of the referred patients were potentially at risk of malnutrition or were malnourished. Without the NNSF, 39 % (n 27) of the patients referred to the dietitian would not have been referred, or would have been referred much later. The NNSF makes it possible for nurses to detect malnourished patients or patients at risk of malnutrition at an early stage of their hospitalization.

Monitoring of neutrophil priming in whole blood by antibodies isolated from a synthetic phage antibody library.

Neutrophil activation is a multistep process. In vitro activation of neutrophils with semiphysiological activators is optimal only after preactivation or priming with cytokines, chemotaxins, and/or bacterial products. Until now, no antibodies have been developed that can distinguish between resting and (cytokine) primed neutrophils with a sufficient dynamic range necessary for screening clinical samples. We have isolated two human phage antibodies, designated MoPhab A17 and A27, from a synthetic bacteriophage antibody library. These phage antibodies recognize epitopes that are upregulated on neutrophils present in whole blood treated with low priming concentrations of cytokines, such as GM-CSF and TNF-alpha. This induction was time- and concentration-dependent and optimal at concentrations that are sufficient for priming functional responses in neutrophils: GM-CSF (10 pM) and TNF-alpha (100 IU/ml). PMNs, isolated from the peripheral blood of chronic obstructive pulmonary disease (COPD) patients with a clinical exacerbation, exhibited a partial in vivo primed phenotype. These antibodies promise to be an ideal tool to monitor disease activity in whole blood of patients with inflammatory diseases.

[Fibroids and fertility]. / Myomen en vruchtbaarheid.

Fibroids are the most common benign uterine tumours. A relation between fibroids and infertility is suggested. Successful implantation depends on a normal, receptive endometrium. Fibroids can change the normal appearance of the uterine cavity and can adversely affect the endometrium. It seems that treatment of fibroids in infertility patients is useful but this is not yet proven scientifically. It is advised to refrain from extirpation of fibroids in patients with fertility problems.

Limitations of the semisynthetic library approach for obtaining human monoclonal autoantibodies to the thyrotropin receptor of Graves' disease.

Graves' disease (GD) is characterized by the presence of autoantibodies against the TSH-receptor (TSH-R) which are pathogenic and, upon binding to the receptor, trigger intracellular signal transduction. The autoantibodies are oligoclonal and as they are responsible for disease activity, their characterization would lead to a better understanding of the development of GD. Attempts to isolate anti-TSH-R antibodies from patients have proved to be difficult due to the exceedingly low serum levels due to rarity of these B cells, together with difficulties in obtaining purified TSH-R capable of interacting with patients autoantibodies. We employed phage antibody display technology and performed selection with a previously characterized semisynthetic antibody library on the purified extracellular ectodomain of the TSH-R. We report the isolation of six different anti-TSH-R monoclonal phage antibodies (moPhabs) from this library. All the moPhabs recognized TSH-R and its recombinant fragments by Western blotting, but failed to recognize the native TSH-R by flow cytometry. Consequently, the moPhabs did not lead to TSH-R activation. As these were the first moPhabs to TSH-R, they were analysed in terms of nucleotide and amino acid sequence and epitope specificity on the receptor. The moPhabs used immunoglobulin VH1 and VH3 germ line genes, all associated with Vlambda3 genes. Interestingly, the CDR3 regions of all moPhabs were remarkably similar, though not identical. In light of the common CDR3 usage, the epitopes recognized on TSH-R appeared to be restricted to amino acids residues 405-411 and 357-364. In summary, our results show that semisynthetic libraries may be limited in isolating human monoclonal antibodies that resemble pathogenic antithyrotropin receptor autoantibodies present in patients with GD. It is likely that until preparations of purified TSH-R that can be recognized by patients autoantibodies become available, similar to the recently described glycosylphosphatidylinositol (GPI) anchored TSH-R ectodomain, monoclonal antibodies from phage antibody display to TSH-R will be limited for isolating the rare, pathogenic antibodies of GD.

A recombinant, fully human monoclonal antibody with antitumor activity constructed from phage-displayed antibody fragments.

A single-chain Fv antibody fragment specific for the tumor-associated Ep-CAM molecule was isolated from a semisynthetic phage display library and converted into an intact, fully human IgG1 monoclonal antibody (huMab). The purified huMab had an affinity of 5 nM and effectively mediated tumor cell killing in in vitro and in vivo assays. These experiments show that nonimmunized phage antibody display libraries can be used to obtain high-affinity, functional, and clinically applicable huMabs directed against a tumor-associated antigen.