Background
Combining radioactive colloids and a near‐infrared (NIR) fluorophore permits preoperative planning and intraoperative localization of deeply located sentinel lymph nodes (SLNs) with direct ...optical guidance by a single lymphatic tracer. The aim of this clinical trial was to evaluate and optimize a hybrid NIR fluorescence and radioactive tracer for SLN detection in patients with breast cancer.
Methods
Patients with breast cancer undergoing SLN biopsy were enrolled. The day before surgery, a periareolar injection of indocyanine green (ICG)–99mTc‐radiolabelled nanocolloid was administered and a lymphoscintigram acquired. Blue dye was injected immediately before surgery. Intraoperative SLN localization was performed using a γ probe and the Mini‐FLARETM NIR fluorescence imaging system. Patients were divided into two dose groups, with one group receiving twice the particle density of ICG and nanocolloid, but the same dose of radioactive 99mTc.
Results
Thirty‐two patients were enrolled in the trial. At least one SLN was identified before and during operation. All 48 axillary SLNs could be detected by γ tracing and NIR fluorescence imaging, but only 42 of them stained blue. NIR fluorescence imaging permitted detection of lymphatic vessels draining to the SLN up to 29 h after injection. Doubling the particle density did not yield a difference in fluorescence intensity (median 255 (range 98–542) versus 284 (90–921) arbitrary units; P = 0.590) or signal‐to‐background ratio (median 5·4 (range 3·0–15·4) versus 4·9 (3·5–16·3); P = 1·000) of the SLN.
Conclusion
The hybrid NIR fluorescence and radioactive tracer permitted accurate preoperative and intraoperative detection of the SLNs in patients with breast cancer. Registration number: NTR3685 (Netherlands Trial Register; http://www.trialregister.nl).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Breast cancer is the most common type of cancer in several parts of the world and the number of elderly patients is increasing. The aim of this study was to describe stage at diagnosis, treatment, ...and relative survival of elderly patients compared to younger patients in the Netherlands. Adult female patients with their first primary breast cancer diagnosed between 1995 and 2005 were selected. Stage, treatment, and relative survival were described for young and elderly (≥65 years) patients and within the cohort of elderly patients according to 5-year age groups. Overall, 127,805 patients were included. Elderly breast cancer patients were diagnosed with a higher stage of disease. Moreover, within the elderly differences in stage were observed. Elderly underwent less surgery (99.2-41.2%); elderly received hormonal treatment as monotherapy more frequently (0.8-47.3%); and less adjuvant systemic treatment (79-53%). Elderly breast cancer patients with breast cancer had a decreased relative survival. Although relative survival was lower in the elderly, the percentage of patients who die of their breast cancer less than 50% above age 75. In conclusion, the relative survival for the elderly is lower as compared to their younger counterparts while the percentage of deaths due to other causes increases with age. This could indicate that the patient selection is poor and fit patients could suffer from “under treatment”. In the future, specific geriatric screening tools are necessary to identify fit elderly patients who could receive more “aggressive” treatment while best supportive care should be given to frail elderly patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Background Despite recent developments in preoperative breast cancer imaging, intraoperative localization of tumor tissue can be challenging, resulting in tumor-positive resection margins ...during breast conserving surgery. Based on certain physicochemical similarities between Technetium(99m Tc)-sestamibi (MIBI), an SPECT radiodiagnostic with a sensitivity of 83–90% to detect breast cancer preoperatively, and the near-infrared (NIR) fluorophore Methylene Blue (MB), we hypothesized that MB might detect breast cancer intraoperatively using NIR fluorescence imaging. Methods Twenty-four patients with breast cancer, planned for surgical resection, were included. Patients were divided in 2 administration groups, which differed with respect to the timing of MB administration. N = 12 patients per group were administered 1.0 mg/kg MB intravenously either immediately or 3 h before surgery. The mini-FLARE imaging system was used to identify the NIR fluorescent signal during surgery and on post-resected specimens transferred to the pathology department. Results were confirmed by NIR fluorescence microscopy. Results 20/24 (83%) of breast tumors (carcinoma in N = 21 and ductal carcinoma in situ in N = 3) were identified in the resected specimen using NIR fluorescence imaging. Patients with non-detectable tumors were significantly older. No significant relation to receptor status or tumor grade was seen. Overall tumor-to-background ratio (TBR) was 2.4 ± 0.8. There was no significant difference between TBR and background signal between administration groups. In 2/4 patients with positive resection margins, breast cancer tissue identified in the wound bed during surgery would have changed surgical management. Histology confirmed the concordance of fluorescence signal and tumor tissue. Conclusions This feasibility study demonstrated an overall breast cancer identification rate using MB of 83%, with real-time intraoperative guidance having the potential to alter patient management.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Aims/hypotheses
Our aim was to examine the independent and combined (cross-sectional) associations of sedentary time (ST), higher intensity physical activity (HPA) and cardiorespiratory fitness (CRF) ...with metabolic syndrome and diabetes status.
Methods
In 1933 adults (aged 40–75 years) ST and HPA (surrogate measure for moderate to vigorous physical activity) were measured with the activPAL3. CRF was assessed by submaximal cycle–ergometer testing. Metabolic syndrome was defined according to the Adult Treatment Panel (ATP) III guidelines. Diabetes status (normal, prediabetes i.e. impaired glucose tolerance and/or impaired fasting glucose or type 2 diabetes) was determined from OGTT. (Multinomial) logistic regression analyses were used to calculate likelihood for the metabolic syndrome, prediabetes and type 2 diabetes according to ST, HPA and CRF separately and combinations of ST–CRF and HPA–CRF.
Results
Higher ST, lower HPA and lower CRF were associated with greater odds for the metabolic syndrome and type 2 diabetes independently of each other. Compared with individuals with high CRF and high HPA (CRF
high
–HPA
high
), odds for the metabolic syndrome and type 2 diabetes were higher in groups with a lower CRF regardless of HPA. Individuals with low CRF and low HPA (CRF
low
–HPA
low
) had a particularly high odds for the metabolic syndrome (OR 5.73 95% CI 3.84, 8.56) and type 2 diabetes (OR 6.42 95% CI 3.95, 10.45). Similarly, compared with those with high CRF and low ST (CRF
high
–ST
low
), those with medium or low CRF had higher odds for the metabolic syndrome, prediabetes and type 2 diabetes, irrespective of ST. In those with high CRF, high ST was associated with significantly high odds for the metabolic syndrome (OR 2.93 95% CI 1.72, 4.99) and type 2 diabetes (OR 2.21 95% CI 1.17, 4.17). The highest odds for the metabolic syndrome and type 2 diabetes were observed in individuals with low CRF and high ST (CRF
low
–ST
high
) (OR 95% CI: the metabolic syndrome, 9.22 5.74, 14.80; type 2 diabetes, 8.38 4.83, 14.55).
Conclusions/interpretation
These data suggest that ST, HPA and CRF should all be targeted in order to optimally reduce the risk for the metabolic syndrome and type 2 diabetes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Lymph node status in colon cancer is critical for prognosis estimation and treatment allocation. The purpose of this study was to compare the performance of one-step nucleic acid ...amplification (OSNA) through detection of cytokeratin 19 mRNA levels with routine pathological examination (RP) and multilevel fine pathological examination (FP) in sentinel lymph nodes (SLN), detected using the ex vivo SLN mapping (SLNM) procedure, in presurgically defined nonmetastatic colon cancer patients.
Methods
In this prospective study, 325 SLNs of 128 patients from the Jeroen Bosch Hospital in ‘s-Hertogenbosch and the Leiden University Medical Center were investigated by RP (H&E), FP (H&E and Keratin Pan immunohistochemical staining), and OSNA. The SLNs were harvested by the SLNM procedure, using Patent blue or Indocyanine green. SLNs were divided and separate parts were used for RP, FP, and the OSNA assay.
Results
The diagnostic value of OSNA was 82.1 and 100 % for both FP and combined method (OSNA and FP) compared with RP. An upstaging rate of 20.2 % was obtained with the use of OSNA only and 36.4 % with the use of FP only. An upstaging rate of 46.5 % was obtained by combining the two methods together.
Conclusions
OSNA and FP appeared to be promising tools for the detection of lymph node micro- and macrometastases in SLNs after SLNM. The performances of OSNA and FP in this study were superior to RP. Because OSNA allows analysis of the whole lymph node, sampling bias can be avoided. OSNA therefore may improve tumor staging.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The European Organisation for Research and Treatment of Cancer 10981-22023 AMAROS trial evaluated axillary lymph node dissection (ALND) versus axillary radiotherapy (ART) in patients with cT1-2, ...node-negative breast cancer and a positive sentinel node (SN) biopsy. At 5 years, both modalities showed excellent and comparable axillary control, with significantly less morbidity after ART. We now report the preplanned 10-year analysis of the axillary recurrence rate (ARR), overall survival (OS), and disease-free survival (DFS), and an updated 5-year analysis of morbidity and quality of life.
In this open-label multicenter phase III noninferiority trial, 4,806 patients underwent SN biopsy; 1,425 were node-positive and randomly assigned to either ALND (n = 744) or ART (n = 681).
Per intention-to-treat analysis, 10-year ARR cumulative incidence was 0.93% (95% CI, 0.18 to 1.68; seven events) after ALND and 1.82% (95% CI, 0.74 to 2.94; 11 events) after ART (hazard ratio HR, 1.71; 95% CI, 0.67 to 4.39). There were no differences in OS (HR, 1.17; 95% CI, 0.89 to 1.52) or DFS (HR, 1.19; 95% CI, 0.97 to 1.46). ALND was associated with a higher lymphedema rate in updated 5-year analyses (24.5%
11.9%;
< .001). Quality-of-life scales did not differ by treatment through 5 years. Exploratory analysis showed a 10-year cumulative incidence of second primary cancers of 12.1% (95% CI, 9.6 to 14.9) after ART and 8.3% (95% CI, 6.3 to 10.7) after ALND.
This 10-year analysis confirms a low ARR after both ART and ALND with no difference in OS, DFS, and locoregional control. Considering less arm morbidity, ART is preferred over ALND for patients with SN-positive cT1-2 breast cancer.
The retention of phosphorus in surface waters through co-precipitation of phosphate with Fe-oxyhydroxides during exfiltration of anaerobic Fe(II) rich groundwater is not well understood. We developed ...an experimental field set-up to study Fe(II) oxidation and P immobilization along the flow-path from groundwater into surface water in an agricultural experimental catchment of a small lowland river. We physically separated tube drain effluent from groundwater discharge before it entered a ditch in an agricultural field. Through continuous discharge measurements and weekly water quality sampling of groundwater, tube drain water, exfiltrated groundwater, and surface water, we investigated Fe(II) oxidation kinetics and P immobilization processes. The oxidation rate inferred from our field measurements closely agreed with the general rate law for abiotic oxidation of Fe(II) by O2. Seasonal changes in climatic conditions affected the Fe(II) oxidation process. Lower pH and lower temperatures in winter (compared to summer) resulted in low Fe oxidation rates. After exfiltration to the surface water, it took a couple of days to more than a week before complete oxidation of Fe(II) is reached. In summer time, Fe oxidation rates were much higher. The Fe concentrations in the exfiltrated groundwater were low, indicating that dissolved Fe(II) is completely oxidized prior to inflow into a ditch. While the Fe oxidation rates reduce drastically from summer to winter, P concentrations remained high in the groundwater and an order of magnitude lower in the surface water throughout the year. This study shows very fast immobilization of dissolved P during the initial stage of the Fe(II) oxidation process which results in P-depleted water before Fe(II) is completely depleted. This cannot be explained by surface complexation of phosphate to freshly formed Fe-oxyhydroxides but indicates the formation of Fe(III)-phosphate precipitates. The formation of Fe(III)-phosphates at redox gradients seems an important geochemical mechanism in the transformation of dissolved phosphate to structural phosphate and, therefore, a major control on the P retention in natural waters that drain anaerobic aquifers.
Summary
Background Regional lymph node involvement is the most important prognostic factor in cutaneous melanoma. As only 20% of patients with melanoma have occult nodal disease and would benefit ...from a regional lymphadenectomy, the sentinel lymph node (SLN) biopsy was introduced. Near‐infrared (NIR) fluorescence has been hypothesized to improve SLN mapping.
Objectives To assess the potential of intraoperative NIR fluorescence imaging to improve SLN mapping in patients with melanoma and to examine the optimal dose of indocyanine green adsorbed to human serum albumin (ICG:HSA).
Methods Fifteen consecutive patients with cutaneous melanoma underwent the standard SLN procedure using 99mtechnetium‐nancolloid and patent blue. In addition, intraoperative NIR fluorescence imaging was performed after injection of 1·6 mL of 600, 800, 1000 or 1200 μmol L−1 of ICG:HSA in four quadrants around the primary excision scar.
Results NIR fluorescence SLN mapping was successful in 93% of patients. In one patient, no SLN could be identified using either conventional methods or NIR fluorescence. A total of 30 SLNs (average 2·0, range 1–7) were detected, 30 radioactive (100%), 27 blue (73%) and 30 NIR fluorescent (100%). With regard to the effect of concentration on signal‐to‐background ratios a trend (P = 0·066) was found favouring the 600, 800 and 1000 μmol L−1 groups over the 1200 μmol L−1 group.
Conclusion This study demonstrates feasibility and accuracy of SLN mapping using ICG:HSA. Considering safety, cost and pharmacological characteristics, an ICG:HSA concentration of 600 μmol L−1 appears optimal for SLN mapping in cutaneous melanoma, although lower doses need to be assessed.
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