Unlocking Japan's cervical cancer prevention deadlock.

Cervical cancer prevention in Japan, which had nearly halted due to misinformation, is now recovering through HPV vaccination and screening efforts. While significant progress has been made, much work remains, yet the recent improvements are highly encouraging.

Resting energy expenditure, body composition, and metabolic alterations in breast cancer survivors vs. healthy controls: a cross-sectional study.

PURPOSE: This study aimed to investigate the difference in absolute and fat free mass (FFM)-adjusted resting energy expenditure (mREE) and body composition (body weight, fat mass (FM), FFM) between breast cancer survivors (BCs) and controls. Correlations with body composition were analyzed. We examined if survival year, or being metabolically dysfunctional were predictive variables. METHODS: A cross-sectional analysis was conducted on 32 BCs ≤5 years post treatment and 36 healthy controls. Indirect calorimetry measured absolute mREE. Body composition was determined by BOD POD. FFM-adjusted mREE was calculated (mREE/FFM). The Harris-Benedict equation was used to predict REE and determine hyper-/hypometabolism (mREE/pREE). The database of the multidisciplinary breast clinic of the University Hospital of Antwerp was consulted for survival year and metabolic dysfunctions. RESULTS: BCs have similar absolute mREE and greater FFM-adjusted mREE compared to controls. Absolute mREE and body composition between BCs differed; adjusted mREE was similar. FFM correlated significantly with absolute mREE in BCs. A significant interaction term was found between survival year and FM for absolute mREE. CONCLUSION: BCs have similar absolute mREE, but higher FFM-adjusted mREE. Differences in body composition between BCs are suggested to cause inter-individual variations. We suggest that increased FFM-adjusted mREE is caused by metabolic stress related to cancer/treatment. Accurate measurement of REE and body composition is advised when adapting nutritional strategies, especially in patients at risk for developing metabolic dysfunctions.

Urine biomarkers in cancer detection: A systematic review of preanalytical parameters and applied methods.

The aim of this review was to explore the status of urine sampling as a liquid biopsy for noninvasive cancer research by reviewing used preanalytical parameters and protocols. We searched two main health sciences databases, PubMed and Web of Science. From all eligible publications (2010-2022), information was extracted regarding: (a) study population characteristics, (b) cancer type, (c) urine preanalytics, (d) analyte class, (e) isolation method, (f) detection method, (g) comparator used, (h) biomarker type, (i) conclusion and (j) sensitivity and specificity. The search query identified 7835 records, of which 924 unique publications remained after screening the title, abstract and full text. Our analysis demonstrated that many publications did not report information about the preanalytical parameters of their urine samples, even though several other studies have shown the importance of standardization of sample handling. Interestingly, it was noted that urine is used for many cancer types and not just cancers originating from the urogenital tract. Many different types of relevant analytes have been shown to be found in urine. Additionally, future considerations and recommendations are discussed: (a) the heterogeneous nature of urine, (b) the need for standardized practice protocols and (c) the road toward the clinic. Urine is an emerging liquid biopsy with broad applicability in different analytes and several cancer types. However, standard practice protocols for sample handling and processing would help to elaborate the clinical utility of urine in cancer research, detection and disease monitoring.

Follow-up of humoral immune response after HPV vaccination using first-void urine: A longitudinal cohort study.

Assessment of humoral immune responses following human papillomavirus (HPV) vaccination currently relies on invasive blood sampling. This longitudinal cohort study explores the usability of first-void urine as a noninvasive alternative sample for antibody detection. In this study, 58 women receiving three doses of the 9vHPV vaccine within a Gardasil9 (9vHPV) Phase III randomized controlled trial were included. Participants provided paired first-void urine and blood samples before vaccination (M0), 1 month after the third dose (M7), and ~3 years after the third dose (M43). Type-specific antibody responses to the 9vHPV types were analyzed in 174 first-void urine and 172 serum samples using a virus-like particle-based IgG multiplex enzyme-linked immunosorbent assay. Additionally, total human IgG concentrations were determined using the BioPlex assay. At M7, 1 month after complete 9vHPV vaccination, 95%-100% of first-void urine and 100% of serum samples had detectable concentrations, varying by HPV type. At M43, 84%-100% of first-void urine and 98%-100% of serum samples had HPV-specific antibody concentrations. Results show significant Spearman rank correlations between type-specific HPV-antibody concentrations for paired first-void urine and serum at all time points. This study confirms the potential feasibility of utilizing first-void urine as a noninvasive immunological sample within HPV vaccine trials.

Comparison of energy expenditure measurements by a new basic respiratory room vs. classical ventilated hood.

BACKGROUND: Nutritional support is often based on predicted resting energy expenditure (REE). In patients, predictions seem invalid. Indirect calorimetry is the gold standard for measuring EE. For assessments over longer periods (up to days), room calorimeters are used. Their design makes their use cumbersome, and warrants improvements to increase utility. Current study aims to compare data on momentary EE, obtained by a basic respiration room vs. classical ventilated hood. The objective is to compare results of the basic room and to determine its 1)reliability for measuring EE and 2)sensitivity for minute changes in activity. METHODS: Two protocols (P1; P2)(n = 62; 25 men/37 women) were applied. When measured by hood, participants in both protocols were in complete rest (supine position). When assessed by room, participants in P1 were instructed to stay half-seated while performing light desk work; in P2 participants were in complete rest mimicking hood conditions. The Omnical calorimeter operated both modalities. Following data were collected/calculated: Oxygen uptake ([Formula: see text] O2(ml/min)), carbon dioxide production ([Formula: see text] CO2ml/min), 24h_EE (kcal/min), and respiratory exchange ratio (RER). Statistical analyses were done between modalities and between protocols. The agreement between 24h_EE, [Formula: see text] O2 and [Formula: see text] CO2 obtained by both modalities was investigated by linear regression. Reliability analysis on 24h_EE determined ICC. RESULTS: No significant differences were found for 24h_EE and [Formula: see text] O2. [Formula: see text] CO2 significantly differed in P1 + P2, and P2 (hood > room). RER was significantly different (hood > room) for P1 + P2 and both protocols individually. Reliability of 24h_EE between modalities was high. Modality-specific results were not different between protocols. DISCUSSION/CONCLUSION: The room is valid for assessing momentary EE. Minute changes in activity lead to a non-significant increase in EE and significant increase in RER. The significant difference in [Formula: see text] CO2 for hood might be related to perceived comfort. More research is necessary on determinants of RER, type (intensity) of activity, and restlessness. The design of the room facilitates metabolic measurements in research, with promising results for future clinical use.

The evolution of breast reconstructions with free flaps: a historical overview.

BACKGROUND: Breast cancer is the most frequent cancer among women and is responsible for the highest number of cancer-related deaths. Approximately 40% of the patients with breast cancer will undergo a mastectomy. Breast amputation is a lifesaving but mutilating procedure. Therefore a good quality of life and a good cosmetic outcome is mandatory after breast cancer treatment. Reconstructive breast surgery aims to recreate a natural looking breast that is warm, soft and feels natural. The chosen reconstruction technique depends on the physiognomy of the patient, technical skills of the surgeon and most important the expectations of the patient. RESULTS: The idea of 'like-by-like' replacement refers to reconstruction of a natural-looking, warm, soft and ptotic breast that matches the contralateral side. Autologous breast-reconstruction matches these expectations. Autologous breast reconstructions with free flaps evolved from prolonged and laborious procedures with only limited free flaps available, to routine surgeries with a widespread availability of flaps to use. The first publication of free tissue transfer for breast reconstruction was in 1976 by Fujino. Two years later Holmström was the first to use the abdominal pannus for breast reconstruction. Over the next four decades multiple free flaps have been described. The possible options for donor site are the abdomen, the gluteal region, the thigh and the lower back. During this evolution the reduction of donor site morbidity became more important. CONCLUSION: Present article gives an overview of the evolution of free tissue transfer in breast reconstruction, highlighting the most important milestones.

Skin Cancer Detection Using Infrared Thermography: Measurement Setup, Procedure and Equipment.

Infrared thermography technology has improved dramatically in recent years and is gaining renewed interest in the medical community for applications in skin tissue identification applications. However, there is still a need for an optimized measurement setup and protocol to obtain the most appropriate images for decision making and further processing. Nowadays, various cooling methods, measurement setups and cameras are used, but a general optimized cooling and measurement protocol has not been defined yet. In this literature review, an overview of different measurement setups, thermal excitation techniques and infrared camera equipment is given. It is possible to improve thermal images of skin lesions by choosing an appropriate cooling method, infrared camera and optimized measurement setup.

Clinical and analytical evaluation of the RealTime High Risk HPV assay in Colli-Pee collected first-void urine using the VALHUDES protocol.

OBJECTIVE: Urine self-sampling has gained increasing interest for cervical cancer screening. In contrast to analytical performance, little information is available regarding the clinical accuracy for high-risk Human Papillomavirus (hrHPV) testing on urine. METHODS: VALHUDES is a diagnostic test accuracy study comparing clinical accuracy to detect high-grade cervical precancer (CIN2+) of HPV testing on self-collected compared to clinician-collected samples (NCT03064087). Disease outcome was assessed by colposcopy and histology. The Abbott RealTime High Risk HPV assay performance was evaluated on Colli-Pee collected first-void urine with cervical outcomes as comparator. RESULTS: As no assay cut-off for urine has been clinically validated, we used the predefined cut-off for cervical samples (CN ≤ 32). Using this cut-off, hrHPV testing was similarly sensitive (relative sensitivity 0.95; 95% CI: 0.88-1.01) and specific (relative specificity 1.03; 95% CI: 0.95-1.13) for detection of CIN2+ compared to testing cervical samples. In the subgroup of women of 30 years and older, similar relative sensitivity (0.97; 95% CI: 0.89-1.05) and specificity (1.02; 95% CI: 0.93-1.12) was found. Additionally, an exploratory cut-off (CN ≤ 33.86) was defined which further improved sensitivity and analytical test performance. CONCLUSION: HrHPV-DNA based PCR testing on home-collected first-void urine has similar accuracy for detecting CIN2+ compared to cervical samples taken by a clinician.

Breast cancer-related lymphedema and its treatment: how big is the financial impact?

PURPOSE: Decongestive lymphatic treatment (DLT) is still the gold standard for treatment of breast cancer-related lymphedema (BCRL). With up to 17% of the patients treated for breast cancer developing BCRL, this morbidity imposes a tremendous financial burden for patients and society. Knowledge about this economic burden related to BCRL and its conservative treatment in a European setting is lacking. The aim of this prospective, longitudinal cohort study was to estimate the direct healthcare costs related to BCRL and its treatment in a European setting. METHODS: Patients with BCRL were treated with DLT consisting of an intensive treatment phase of 3 weeks, followed by a maintenance treatment phase of 6 months. Additionally, the follow-up period comprised 6 months. During these 3 weeks and 12 months, all direct costs associated with the treatment of BCRL and its sequelae were documented through billing prices and a self-developed questionnaire which was administered after the intensive treatment phase, and subsequently 3-monthly during the entire period. RESULTS: A total of 194 patients were enrolled in this study. Of these, 17% (n = 32) showed lymphedema stage I, 56% (n = 109) had lymphedema stage IIa, and 27% (n = 53) had lymphedema stage IIb. Total direct healthcare costs per patient were €2248.93 on average during the entire period of 3 weeks of intensive treatments and 12 months of maintenance decongestive therapy. Within these mean direct costs, €1803.35 (80%) was accounted for statutory health insurances, and €445.58 (20%) was out-of-pocket expenses for patients. CONCLUSION: This study is one of the first standardized high-quality health economic analyses of BRCL treatment in Europe. The present study indicates that the price tag of BCRL treatment in Belgium is high not only for the health insurance but also for the patients Clinical trial registration number The study makes part of a double-blind, multi-center, randomized controlled trial (EFforT-BCRL trial), which is registered in clinicaltrials.gov (NCT02609724). CME reference S58689, EudraCT Number 2015-004822-33.

Comparison of a VLP-based and GST-L1-based multiplex immunoassay to detect vaccine-induced HPV-specific antibodies in first-void urine.

Vaccine-induced human papillomavirus (HPV) antibodies originating from cervicovaginal secretions were recently shown to be detectable in first-void (FV) urine. This presents a novel opportunity for noninvasive sampling to monitor HPV antibody status in women participating in large epidemiological studies and HPV vaccine trials. With a view towards method optimization, this study compared the measurement of HPV antibodies in FV urine using a multiplex L1/L2 virus-like particles (VLP)-based ELISA (M4ELISA) with previously reported results using a glutathione S-transferase (GST)-L1-based immunoassay (GST-L1-MIA). We tested 53 paired FV urine and serum samples from 19- to 26-year-old healthy women, unvaccinated (n = 17) or vaccinated with either the bivalent or quadrivalent HPV-vaccine during adolescence (n = 36). HPV6/11/16/18 antibodies were measured using M4ELISA and compared with GST-L1-MIA results. Inter-assay and inter-specimen correlations were examined using the Spearman's rank test (rs). As expected, lower HPV antibody concentrations were found in FV urine than in serum. Vaccinated women had significantly higher HPV6/11/16/18 antibody levels in both FV urine and serum compared with those unvaccinated (M4ELISA; FV urine P = .0003; serum P ≤ .0001). HPV antibody levels in FV urine and serum showed a significant positive correlation (M4ELISA anti-HPV6/11/16/18, rs = 0.85/0.86/0.91/0.79, P ≤ .001). Despite assay differences, there was moderate to good correlation between M4ELISA and GST-L1-MIA (FV urine anti-HPV6/11/16/18, rs = 0.86/0.83/0.89/0.53, P ≤ .0001; serum anti-HPV6/11/16/18, rs = 0.93/0.89/0.94/0.75, P ≤ .0001). FV urine HPV antibody detection is comparable with both assays, further supporting this noninvasive sampling method as a possible option for HPV vaccine assessment. Approaches to improve the sensitivity and larger studies are warranted to determine the feasibility of FV urine for vaccine-induced HPV antibody detection.

What are the economic burden and costs associated with the treatment of breast cancer-related lymphoedema? A systematic review.

OBJECTIVES: To provide an overview of costs associated with the treatment of breast cancer-related lymphoedema (BCRL) and its possible sequelae, borne by patients or by society. DATA SOURCES: According to the PRISMA guideline, a systematic literature search was carried out in four electronic databases: PubMed, Web of Science, Cochrane Clinical Trials and EMBASE. Searches were performed on October 1, 2018. STUDY SELECTION: Eligibility criteria: (1) expenses of adults (age > 18 years), (2) concerning patients with BCRL, (3) overview of (in)direct costs associated with BCRL, (4) expenses in which at least one type of conservative treatment modality for lymphoedema is included and/or costs for hospital admissions due to infections. Reviews and meta-analyses were excluded. DATA EXTRACTION: After assessing the risk of bias and level of evidence, quantitative data on (in)direct costs for BCRL treatment during a well-mentioned timeframe were extracted. DATA SYNTHESIS: Eight studies were included. Three studies reported on patient-borne costs related to BCRL. Mean direct costs per year borne by patients ranged between USD$2306 and USD$2574. Indirect costs borne by patients ranged between USD$3325 and USD$5545 per year. Five studies estimated society-borne costs related to BCRL from claims data, billing prices and providers' services during 12 to 24 months of follow-up. Mean direct treatment costs after 1 year of decongestive lymphatic therapy (DLT) ranged between €799 (= USD$1126.60) and USD$3165. CONCLUSION: This systematic review revealed that BCRL imposes a substantial economic burden on patients and society. However, more standardized high-quality health economic analyses among this field are required. Recent economic analyses related to BCRL treatment in Europe, Asia, Africa and South America are lacking. Worldwide, further scrutiny of the economic impact of DLT for BCRL in clinical settings is needed. CLINICAL TRIAL REGISTRATION NUMBER: The review makes part of a double-blind, multi-center, randomized controlled trial (EFforT-BCRL trial), which is registered in clinicaltrials.gov (NCT02609724). CME reference S58689, EudraCT Number 2015-004822-33.

Physical activity level and age contribute to functioning problems in patients with breast cancer-related lymphedema: a multicentre cross-sectional study.

PURPOSE: Breast cancer survivors face a high risk of developing breast cancer-related lymphedema (BCRL). Besides physical symptoms such as swelling, BCRL can have a psychosocial impact and lead to problems in daily functioning. Understanding contributing variables to problems in functioning yields possibilities to improve treatment modalities and consequently patients' quality of life. Therefore, the aim of this study was to explore the association between patient-, lymphedema-, and cancer treatment-related variables with problems in functioning in patients with BCRL. METHODS: A cross-sectional study was performed in 185 patients with BCRL. Problems in daily functioning (dependent variable) were evaluated with the Lymph-ICF-UL questionnaire. Following independent variables were analysed by bi-variate and multivariable analyses, including a stepwise regression analysis: patient-related variables (age, BMI, physical activity level, education), lymphedema-related variables (excessive arm volume, duration of lymphedema, total pitting score, presence of hand edema, hardness of the tissue, lymphedema stage), and cancer treatment-related variables (type of surgery, surgery at the dominant side, radiotherapy, chemotherapy, hormone therapy, immunotherapy, TNM-classification). RESULTS: The Lymph-ICF-UL mean total score was 38% (± 21), representing a moderate amount of problems in general functioning. Multivariable regression analyses revealed that lower physical activity level and lower age are contributing factors to more problems in daily functioning. Stepwise regression analysis indicated that up to 8% of the variance in problems in functioning could be explained by physical activity level and age of patients with BCRL. CONCLUSION: Especially patients with low physical activity level and younger patients experience more problems in functioning. For the determination of certain causal interactions, future longitudinal studies including other independent variables that might explain a higher amount of problems in functioning in this population, are warranted. TRIAL REGISTRATION: The study makes part of a double-blind, multi-center, randomized controlled trial (EFforT-BCRL trial), which is registered in clinicaltrials.gov (NCT02609724). CME reference S58689, EudraCT Number 2015-004822-33.

Development and clinimetric properties of the Dutch Breast Edema Questionnaire (BrEQ-Dutch version) to diagnose the presence of breast edema in breast cancer patients.

PURPOSE: To develop a diagnostic tool, the Breast Edema Questionnaire (BrEQ) and to determine its clinimetric properties. METHODS: The BrEQ was developed based on information from literature, experts and breast edema patients. Content validity, construct validity, test-retest reliability, internal consistency and cut-off point were investigated in a group of breast cancer patients. Construct validity made up two parts; convergent and known-groups validity. Convergent validity was tested by correlating the BrEQ with skin thickness measured with ultrasound (US). RESULTS: In part 1 of the BrEQ, symptoms of breast edema were scored from 0 to 10: pain, heaviness, swelling, tensed skin, redness, pitting sign, enlarged skin pores and hardness. Taking into account the International Classification of Functioning, Disability and Health, several activity limitations and participation restrictions were scored from 0 to 10 in part 2. Clinimetric properties of part 1 were examined in 55 patients. US showed that 35 women had breast edema. Content validity was good. Regarding convergent validity, all breast symptoms correlated moderately with skin thickness. The total symptom score had a strong correlation with skin thickness. Concerning known-groups validity, patients with breast edema had a higher total symptom score. Test-retest reliability ranged between moderate and strong. The internal consistency was good for all items and the total symptom score. We identified that a score cut-off point of ≥ 8.5 discriminates between patients with breast edema and those without. CONCLUSION: Part 1 of the BrEQ-Dutch version is a valid and reliable tool for assessing clinical indicators of breast edema.

DIEP flap breast reconstructions: thermographic assistance as a possibility for perforator mapping and improvement of DIEP flap quality.

In the modern world, one-third or more of breast cancer patients still undergo uni- or bilateral mastectomy. Breast cancer patients, in general, have a good prognosis and long-term survival. Therefore, the treatment must not only focus on survival but also on the quality of life. Breast reconstruction with an autologous free deep inferior epigastric artery perforator (DIEP) flap is one of the preferred options after mastectomy. A challenging step in this procedure is the selection of a suitable perforator that provides sufficient blood supply for the flap to prevent necrosis after anastomosis. In this pilot study, the possibilities for dynamic infrared thermography (DIRT) are investigated to select the best suitable perforator. The measurements are done with external cooling in the preoperative stage to accurately predict the location of the dominant perforators. During the surgery, in the peroperative stage, measurements are done for mapping the influence of a specific perforator on the perfused areas of the abdominal flap. Perforators are sequentially closed and opened again to map the influence of that perforator on the vascularization of the flap, visualized with the help of the thermographic camera. The acquired steady-state thermal images could help decide which parts of the abdominal flap to use for the reconstruction so that the chance of (partial) necrosis is reduced. In the postoperative stage, DIRT could visualize the arterial and or venous thrombosis before they become clinically obvious as (partial) necrosis. At present DIRT seems to be a valuable investigation for the pre-, per-, and postoperative phases of DIEP-flap reconstructions. Large, high-quality clinical studies are needed to determine its definitive role.

Triple-negative breast cancer-Role of immunology: A systemic review.

Recently, the complex role of immune therapy has been the target of increased attention in breast cancer, particularly in triple-negative breast cancer (TNBC). Although TNBC is sensitive to chemotherapy, the recurrence and mortality rates are worse compared with the other breast cancer types. In addition, TNBC still lacks targeted treatment options. With the improved understanding of the immune system in TNBC, it is expected that new predictive and prognostic markers will be identified, and innovative treatment modalities will be developed. The aim of this review was to provide an overview of the effector cells in the TNBC's microenvironment and to highlight a novel approach to treat this kind of cancer. A computer-based literature research was carried out using PubMed, American Society of Clinical Oncology Annual Meeting (ASCO) and San Antonio Breast Cancer Symposium (SABCS). To date, studies have shown that tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) play a very important role in the TNBC's microenvironment. Tumor-infiltrating lymphocytes can even be considered as biomarkers to predict chemotherapy response in TNBC. Furthermore, TNBC was shown to have immune active subtypes, and therefore, the use of immunotherapy may be an attractive treatment approach. In this respect, several randomized studies have been designed or are currently ongoing to explore the combination of chemotherapy with immunotherapy in TNBC. Combination of chemo- and immunotherapy is likely to be beneficial in a subgroup of patients with TNBC.

The effect of training interventions on physical performance, quality of life, and fatigue in patients receiving breast cancer treatment: a systematic review.

OBJECTIVES: The primary purpose of this systematic review is to structure the available evidence concerning physical exercise programs and their effects on (1) physical performance outcomes, (2) experienced fatigue, and (3) quality of life (QoL) in patients during the initial treatment for breast cancer. DATA SOURCES: A systematic literature search, based upon the PRISMA guideline, up to January 1, 2018, was performed using four databases (Web of Science, Cochrane Library for Clinical Trials, PubMed, and Medline). STUDY SELECTION: Inclusion criteria were as follows: (1) adults > 18 years; (2) patients with breast cancer undergoing initial treatment; (3) interventions with the aim to influence the patient's physical activity, QoL, or fatigue; (4) randomized controlled trials (RCTs) of all ages. The selected studies were scored for methodological quality, and data concerning physical performance, QoL, and fatigue were extracted. Twenty-eight RCTs were included. DATA EXTRACTION: Different treatment modalities during initial treatment were identified (radiation therapy, chemotherapy, and combination therapy), as well as different types of physical training interventions (cardiovascular endurance exercise, strengthening programs, or a combination of both). Therefore, the results were clustered with regard to the above-mentioned grouping; extracting every relevant outcome related to physical performance (6 MWT or VO2peak; grip/muscle strength), QoL (questionnaires), and fatigue (questionnaires). DATA SYNTHESIS: Different training programs (endurance, resistance, or a combination of both) were found. These programs were applied during different phases of initial treatment. Some programs were supervised while others were home based. Overall, most training interventions provided an improvement in physical performance and a decrease in perceived fatigue. QoL was the outcome variable least susceptible to improvement. CONCLUSION: Different types of exercise programs are available for rehabilitation purposes of breast cancer patients during adjuvant therapy. Overall resistance training or resistance training in combination with CV endurance training provides the best results, especially on physical performance and perceived fatigue.

Long-term morbidity after a negative sentinel node in breast cancer patients.

OBJECTIVE: Morbidity after sentinel lymph node biopsy is often underestimated. The aim of this study was to inventory arm and shoulder complaints in sentinel node-negative breast cancer patients post-surgery after long-term follow-up. METHODS: Sentinel node-negative breast cancer patients with at least 2 years of follow-up after surgery were included in this study. Self-reported arm and shoulder morbidities were assessed using a survey. Patients (n = 126) were asked if they ever developed complaints, if these complaints were still present and whether they were ever treated for these complaints. RESULTS: After a mean follow-up of 55.5 months (range 25-86 months), the prevalence of the self-reported arm and shoulder complaints was 25.8% for pain, 12.0% for numbness, 6.4% for paraesthesias, 7.1% for lymphedema, 8.0% for axillary web syndrome, 26.2% for loss of strength and 19.5% for limitations in range of motion. About 38.1% of the patients were treated by a physical therapist concerning the experienced complaints after SLNB. CONCLUSION: Up to 7 years post-surgery a considerable amount of sentinel node-negative patients still suffer from arm and shoulder complaints. These complaints affect the activities of daily living. Therefore, more research is needed regarding the value of early detection and treatment of these complaints.

What is the best method to determine excessive arm volume in patients with breast cancer-related lymphoedema in clinical practice? Reliability, time efficiency and clinical feasibility of five different methods.

OBJECTIVE: To investigate the reliability, time efficiency and clinical feasibility of five commonly used methods for assessing excessive arm volume in patients with breast cancer-related lymphoedema (BCRL). DESIGN: Cross-sectional study. SETTING: University Hospitals Leuven, Belgium. SUBJECTS: 30 participants with unilateral BCRL. METHODS: Excessive arm volume was determined by five different methods: traditional volumetry with overflow, volumetry without overflow, inverse volumetry, optoelectronic volumetry and calculated volume based on circumference measurements. To investigate intra- and inter-rater reliability, measurements were performed twice by the same assessor and once by a different assessor. Intraclass correlation coefficients (ICCs), standard errors of the measurement (SEMs) and systematic changes between the means were calculated. To determine time efficiency, the mean setup time, execution time and total time were examined for each method. Furthermore, 12 limitations regarding clinical feasibility were listed and scored for each method. Finally, an overall ranking score was determined between the methods. RESULTS: Mean age was 65 (±8) years and mean body mass index was 28 (±4) kg/m2. Intra- and inter-rater reliability ranged between strong and very strong. Calculated arm volume based on circumferences (mean excessive arm volume: assessor A: 477 (±367) mL; assessor B: 470 (±367) mL; assessor A (second time): 493 (±362) mL) showed the highest intra- and inter-rater ICCs of .987 and .984, respectively. Optoelectronic volumetry was the fastest method, representing a mean total time of 1 minute and 43 (±26) seconds for performing a bilateral measurement. The least limitations were reported on the calculated volume based on the circumference method (3 out of 12 limitations). CONCLUSION: Calculated volume based on arm circumferences is the best measurement method for evaluating excessive arm volume over time in terms of reliability, low error rate, low cost, few limitations and the time spent.

RANK-RANKL Signaling in Cancer of the Uterine Cervix: A Review.

RANK ligand (RANKL) is a member of the tumor necrosis factor alpha superfamily of cytokines. It is the only known ligand binding to a membrane receptor named receptor activator of nuclear factor-kappa B (RANK), thereby triggering recruitment of tumor necrosis factor (TNF) receptor associated factor (TRAF) adaptor proteins and activation of downstream pathways. RANK/RANKL signaling is controlled by a decoy receptor called osteoprotegerin (OPG), but also has additional more complex levels of regulation. The existing literature on RANK/RANKL signaling in cervical cancer was reviewed, particularly focusing on the effects on the microenvironment. RANKL and RANK are frequently co-expressed in cervical cancer cells lines and in carcinoma of the uterine cervix. RANKL and OPG expression strongly increases during cervical cancer progression. RANKL is directly secreted by cervical cancer cells, which may be a mechanism they use to create an immune suppressive environment. RANKL induces expression of multiple activating cytokines by dendritic cells. High RANK mRNA levels and high immunohistochemical OPG expression are significantly correlated with high clinical stage, tumor grade, presence of lymph node metastases, and poor overall survival. Inhibition of RANKL signaling has a direct effect on tumor cell proliferation and behavior, but also alters the microenvironment. Abundant circumstantial evidence suggests that RANKL inhibition may (partially) reverse an immunosuppressive status. The use of denosumab, a monoclonal antibody directed to RANKL, as an immunomodulatory strategy is an attractive concept which should be further explored in combination with immune therapy in patients with cervical cancer.