Abstract Introduction Multifocal breast cancer is associated with a higher risk of nodal involvement compared to unifocal breast cancer and the drainage pattern from multifocal localisations may be ...different. For this reason, the value of the sentinel node biopsy (SNB) procedure for this indication is debated. The aim of the current analysis was to evaluate the sentinel node identification rate and nodal involvement in patients with a multifocal tumour in the EORTC 10981-22023 AMAROS trial. Patients and Methods From the first 4000 registered patients, 342 were identified with a multifocal tumour on histological examination and compared to a randomly selected control group of 684 patients with a unifocal tumour. The outcome of the SNB was assessed. Results The sentinel node was identified in 96% of the patients with a multifocal tumour and in 98% of those with unifocal disease. In the multifocal group, 51% had a metastasis in the sentinel node compared to 28% in the unifocal group; and further nodal involvement after a positive sentinel node was found in 40% (38/95) and 39% (39/101) respectively. Conclusion In this prospective international multicentre study, the 96% detection rate indicates that the SNB procedure can be highly effective in patients with a multifocal tumour. Though the tumour-positive rate of the sentinel node was twice as high in the multifocal group compared to the unifocal group, further nodal involvement after a positive sentinel node was similar in both groups. This suggests that the SNB procedure is safe in patients with multifocal breast cancer.
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LBA1001
Background: Sentinel node biopsy (SNB) is standard in assessing axillary lymph node status for cN0 breast cancer patients. In case of a positive SNB, if treatment is advised, ...axillary lymph node dissection (ALND) is the current standard. Although ALND provides excellent regional control, it may give harmful side effects. Axillary radiotherapy (ART) instead of ALND was hypothesized to provide comparable regional control and less side effects. Methods: From 2001 to 2010, patients with cT1E2N0 primary breast cancer were enrolled in the EORTC phase III non-inferiority AMAROS trial. Patients were randomized between ALND and ART in case of a positive SNB. Primary endpoint was 5-year axillary recurrence rate. Secondary endpoints were overall survival (OS), disease-free survival (DFS), quality of life (QOL), shoulder movement and lymphedema at 1 and 5 years. Results: Of the 4,806 patients entered in the trial, 744 in the ALND-arm and 681 in the ART-arm had a positive SNB, 60% with a macrometastasis. The two treatment-arms were comparable regarding age, tumor size, grade, tumor type, and adjuvant systemic treatment. With a median follow up of 6.1 years, the 5-year axillary recurrence rate after a positive SNB was 0.54% (4/744) after ALND versus 1.03% (7/681) after ART. The planned non-inferiority test was underpowered because of the unexpectedly low number of events. The axillary recurrence rate after a negative SNB was 0.8% (25/3131). There were no significant differences between treatment arms regarding OS (5 yr estimates: 93.27% ALND, 92.52% ART, p=0.3386) and DFS (5 yr estimates: 86.90% ALND, 82.65% ART, p=0.1788). Lymphedema was found significantly more often after ALND (1yr: 40% ALND, 22% ART, p<0.0001 and 5yr: 28% ALND, 14% ART, p<0.0001). There was a nonsignificant trend toward more early shoulder movement impairment after ART. These findings were compatible with a trend in two QOL items in the arm symptom scale: swelling (ART better) and movement (ALND better). There were no other differences in QOL. Conclusion: ALND and ART after a positive SNB provide excellent and comparable regional control. ART reduces the risk of short-term and long-term lymphedema compared to ALND. Clinical trial information: NCT00014612.
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LBA1001
The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 2013, and in the Annual Meeting Proceedings online supplement ...to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Background
The clinical impact of sentinel lymph node (SN) biopsy in colorectal cancer is still controversial. The aim of our study was to determine the accuracy of this procedure from published data ...and to identify factors that contribute to the conflicting reports.
Methods
A systematic search of the Medline, Embase, and Cochrane databases up to July 2011 revealed 98 potentially eligible studies, of which 57 were analyzed including 3,934 patients (3,944 specimens).
Results
The pooled SN identification rate was 90.7 % (95 % CI 88.2–93.3), with a significant higher identification rate in studies including more than 100 patients or studies using the ex vivo SN technique. The pooled sensitivity of the SN procedure was 69.6 % (95 % CI 64.7–74.6). Including the immunohistochemical findings increased the pooled sensitivity of SN procedure to 80.2 % (95 % CI 4.7–10.7). Subgroups with significantly higher sensitivity could be identified: ≥4 SNs versus <4 SNs (85.2 vs. 66.3 %,
p
= 0.003), colon versus rectal cancer (77.6 vs. 65.7 %,
p
= 0.04), early T1 or T2 versus advanced T3 or T4 carcinomas (93.4 vs. 58.8 %,
p
= 0.01). Serial sectioning and immunohistochemistry resulted in a mean upstaging of 18.9 % (range 0–50 %). True upstaging defined as micrometastases (pN1mi+) rather than isolated tumor cells (pN0itc+) was 7.7 %.
Conclusions
The SN procedure in colorectal cancer has an overall sensitivity of 70 %, with increased sensitivity and refined staging in early-stage colon cancer. Because the ex vivo SN mapping is an easy technique it should be considered in addition to conventional resection in colon cancer.
Recently concepts from attachment theory are being applied to business situations. In this paper we focus on how relationship specific (RS) versus general (G) attachment styles affect the ...willingness-to-recommend (WtR) by customers. Such WtR refers to the likelihood of customers to recommend the services of their service provider to other customers, based on their experiences with the provider. This WtR is often measured by means of the Net Promoter Score (NPS) which is assumed to be a reliable (credible) market signal as it originates from customers themselves and not from the firm. This study provides insights in this issue using data from 798 members of an online panel from the Netherlands, covering four service industries. Customers are surveyed on their RS and G attachment styles, trust in, satisfaction with, and commitment to their service provider, as well as their WtR this provider. Findings emerge from econometric parallel mediation analyses. This study shows that customers' RS but not the G attachment styles bias their appraisal of trust in, satisfaction with and commitment to the service provider, which in turn affects their WtR. More specifically, across the four service industries, customers scoring higher on RS anxiety and/or avoidance show systematically lower levels of trust in and satisfaction with, and commitment to the firm, ultimately leading to lower WtR. Firms should especially target those customers that score higher on RS avoidance (possibly in combination with higher levels of RS anxiety) as their WtR is strongly biased which might create uncertainty for other customers about the firm's reputation.
Phytophthora species are potent pathogens that can devastate terrestrial plants, causing billions of dollars of damage yearly to agricultural crops and harming fragile ecosystems worldwide. Yet, ...virtually nothing is known about the distribution and pathogenicity of their marine relatives. This is surprising, as marine plants form vital habitats in coastal zones worldwide (i.e. mangrove forests, salt marshes, seagrass beds), and disease may be an important bottleneck for the conservation and restoration of these rapidly declining ecosystems. We are the first to report on widespread infection of Phytophthora and Halophytophthora species on a common seagrass species, Zostera marina (eelgrass), across the northern Atlantic and Mediterranean. In addition, we tested the effects of Halophytophthora sp. Zostera and Phytophthora gemini on Z. marina seed germination in a full-factorial laboratory experiment under various environmental conditions. Results suggest that Phytophthora species are widespread as we found these oomycetes in eelgrass beds in six countries across the North Atlantic and Mediterranean. Infection by Halophytophthora sp. Zostera, P. gemini, or both, strongly affected sexual reproduction by reducing seed germination sixfold. Our findings have important implications for seagrass ecology, because these putative pathogens probably negatively affect ecosystem functioning, as well as current restoration and conservation efforts.
Salt marshes fronting coastal structures, such as seawalls and dikes, may offer important ecosystem‐based coastal defence by reducing the wave loading and run‐up levels during storms. We question (i) ...how the long‐term salt marsh development in the Dutch Wadden Sea relates to the tidal‐flat foreshore bathymetry and (ii) how the wave run‐up onto dikes, which enhances the risk of dike failure, depends on foreshore bathymetry, the presence/absence of marshes, marsh vegetation properties, tidal range and wind exposure.
We analysed 15 years of vegetation and bathymetry maps along the entire Dutch Wadden Sea coast, in combination with detailed process‐based measurements at five locations during 3 years, to understand where salt marshes naturally form and what features determine their contribution to coastal protection.
The horizontal extent of marshes along the dikes remained relatively stable over the past decade. The presence of marshes was associated with higher elevations of adjacent tidal flats (above ~0.5 m NAP), while landward‐directed marsh retreat was associated with surface erosion of the fronting tidal flats.
Wave run‐up during storms was lower at sites with wider marshes and higher foreshore elevations. This was attributed to the marsh attenuation effect, which led to a reduction in wave heights at the dike toe. As the tidal range varies across the Dutch Wadden Sea, areas to the East with generally higher water levels experienced higher wave run‐up.
Synthesis and applications. We found that (i) marshes, where present, effectively protected the dikes from wave loading and (ii) the sites where marshes typically do not develop spontaneously were the most vulnerable to high wave run‐up. This catch‐22 problem implies that increasing reliance on nature‐based coastal defences along soft‐bottom coasts may require human interventions to stimulate marsh formation at the locations where it is most needed. Alternatively, ‘hard engineering’ solutions may remain necessary where implementing nature‐based solutions are either too costly, unachievable, or at the expense of other ecological values, such as causing the loss of mudflats that are important for migratory birds.
Samenvatting
Kwelders (ook wel schorren genaamd) die voor dijken liggen, kunnen de kosten van hoogwaterbescherming mogelijk verlagen doordat ze de hoogte van golfaanvallen en de golfoploop (te meten als de vloedlijn‐hoogte) tijdens stormen verminderen. Wij onderzoeken (1) hoe de lange‐termijn ontwikkeling van kwelders in de Nederlandse Waddenzee samenhangt met de hoogte van wadplaten en (2) hoe de golfoploop tegen de dijk wordt bepaald door de hoogte ligging van het voorland, de aan/afwezigheid van kwelders, vegetatie kenmerken, getij‐amplitude en blootstelling aan de wind.
Om te begrijpen waar kwelders kunnen voorkomen en welke eigenschappen belangrijk zijn voor hoogwaterbescherming, analyseerden we gedurende 15 jaar de verandering in vegetatie en wadplaat‐morfologie van de Nederlandse Waddenzee kust, en combineerden we dit met 3‐jaar meten op 5 locaties.
Het kwelder oppervlak van bleef relatief stabiel over het laatste decennium. Kwelders liggen vooral op plekken waar de naastgelegen wadplaten relatief hoog zijn (meer dan 0.5 m NAP), terwijl afkalving van kwelders vooral optrad waar de voorgelegen wadplaten door erosie verlagen.
Dijken ondervonden minder golfoploop tijdens stormen op plaatsen met bredere kwelders en hogere voorlanden. Doordat de getijdenamplitude (verschil tussen hoog en laag water) in de Waddenzee van west naar oost toeneemt, wordt ook de golfoploop op de dijk naar het oosten groter.
Synthese en toepassing. Uit het onderzoek blijkt dat (i) kwelders dijken effectief beschermen tegen golfaanvallen, maar (ii) dat juist op die plekken waar de golfoploop tegen de dijk het hoogst is, de kwelders niet spontaan ontwikkelen. Om kwelders dus daar te krijgen waar we ze het hardste nodig hebben om de golfoploop te verlagen, zal dat alleen lukken met menselijke ingrepen (zoals bijvb. kwelderwerken). Op plekken waar maatregelen om kweldervorming te stimuleren technisch onmogelijk zijn, te duur zijn of onwenselijk zijn omdat het ten kosten zou gaan van wadplaten die belangrijk zijn voor migrerende vogels, kan het beter zijn om voor ‘harde technische’ oplossingen te kiezen.
We found that (i) marshes, where present, effectively protected the dikes from wave loading and (ii) the sites where marshes typically do not develop spontaneously were the most vulnerable to high wave run‐up. This catch‐22 problem implies that increasing reliance on nature‐based coastal defences along soft‐bottom coasts may require human interventions to stimulate marsh formation at the locations where it is most needed. Alternatively, ‘hard engineering’ solutions may remain necessary where implementing nature‐based solutions are either too costly, unachievable, or at the expense of other ecological values, such as causing the loss of mudflats that are important for migratory birds.
Hibernation is an energy-conserving behavior consisting of periods of inhibited metabolism ('torpor') with lowered body temperature. Torpor bouts are interspersed by arousal periods, in which ...metabolism increases and body temperature returns to euthermia. In deep torpor, the body temperature typically decreases to 2-10 °C, and major physiological and immunological changes occur. One of these alterations constitutes an almost complete depletion of circulating lymphocytes that is reversed rapidly upon arousal. Here we show that torpor induces the storage of lymphocytes in secondary lymphoid organs in response to a temperature-dependent drop in plasma levels of sphingosine-1-phosphate (S1P). Regulation of lymphocyte numbers was mediated through the type 1 S1P receptor (S1P₁), because administration of a specific antagonist (W146) during torpor (in a Syrian hamster at ~8 °C) precluded restoration of lymphocyte numbers upon subsequent arousal. Furthermore, S1P release from erythrocytes via ATP-binding cassette (ABC)-transporters was significantly inhibited at low body temperature (4 °C) but was restored upon rewarming. Reversible lymphopenia also was observed during daily torpor (in a Djungarian hamster at ± 25 °C), during forced hypothermia in anesthetized (summer-active) hamsters (at ± 9 °C), and in a nonhibernator (rat at ~19 °C). Our results demonstrate that lymphopenia during hibernation in small mammals is driven by body temperature, via altered plasma S1P levels. S1P is recognized as an important bioactive lipid involved in regulating several other physiological processes as well and may be an important factor regulating additional physiological processes in hibernation as well as in mediating the effects of therapeutic hypothermia in patients.
ObjectivesDespite the many proven advantages of a physically active lifestyle in patient populations, prescription of exercise is currently not widely implemented in routine clinical practice. The ...aims of this study were twofold: (1) to assess perceptions of clinicians on the current practice of exercise is medicine (E=M) prescription in two Dutch university medical centres and (2) to determine their perceived barriers and facilitators for the implementation of E=M in routine clinical care in Dutch university medical centres.DesignA mixed methodologies study, using both online questionnaires and semi-structured interviews.SettingDutch university medical centres.ParticipantsClinicians working within the departments of medical oncology, orthopaedics and rehabilitation medicine of two university medical centres.ResultsForty-five clinicians (response rate of 51%) completed the questionnaire, and 19 clinicians were interviewed. The results showed that even though clinicians had a positive attitude towards prescribing E=M, only a few reported to regularly prescribe E=M to their patients. The 52 identified facilitators and barriers for implementation of E=M were categorised into four main themes: (1) beliefs toward the implementation of E=M (eg, clinicians knowledge and skills, and social support), (2) factors related to the patient perspective (eg, patient priorities or motivation), (3) factors related to the referral options (eg, knowledge of and trust in local referral options) and (4) practical considerations when implementing E=M (eg, time constraints).ConclusionsOur study showed that even though many clinicians have a positive attitude toward an active lifestyle, many are not prescribing E=M on a regular basis. In order for clinicians to effectively implement E=M, strategies should focus on increasing clinicians E=M referral skills, improving clinicians knowledge of E=M referral options and develop a support system to ensure that E=M is high on the priority list of clinicians.
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