Mortality After Late Breast Cancer Recurrence in Denmark.

PURPOSE: Late breast cancer (BC) recurrence (ie, ≥ 10 years after primary diagnosis) may have a more favorable prognosis than earlier recurrence. We investigated the risk of BC death after late recurrence, identified prognostic factors, and compared survival after early and late recurrence. METHODS: Using the Danish Breast Cancer Group and other nationwide databases, we identified women with early or late BC recurrence during 2004-2018, who were alive 6 months after recurrence. We followed them until BC death, death from other causes, emigration, 10 years, or December 31, 2018, whichever came first. We calculated mortality rates (MRs) per 1,000 person-years (PY) and cumulative BC mortality, for early versus late recurrence, and by characteristics of the primary tumor and the late recurrence. Using Cox regression, we calculated adjusted hazard ratios (HRs) for BC death, accounting for death from other causes as competing risks. RESULTS: Among 2,004 patients with late recurrence, 721 died of BC with a median survival time of 10 years (MR = 84.8 per 1,000 PY; 10-year cumulative mortality = 50%). Among 1,528 patients with early recurrence, 1,092 BC deaths occurred with a median survival time of 4 years (MR = 173.9 per 1,000 PY; 10-year cumulative mortality = 72%). We observed a lower hazard of BC-specific death among patients who developed late compared with early recurrence (hazard ratio = 0.72; 95% CI, 0.62 to 0.85). Advanced stage at primary diagnosis, distant metastases, adjuvant treatment for locoregional recurrence, and systemic treatment for distant recurrence were associated with increased mortality after late recurrence. Breast-conserving surgery at primary diagnosis, locoregional recurrence, and surgery for recurrence were associated with lower mortality after late recurrence. CONCLUSION: Patients with late recurrence had more favorable prognosis than patients with early recurrence. The localization of recurrent disease was the main prognostic factor for BC death.

The Incidence of Breast Cancer Recurrence 10-32 Years After Primary Diagnosis.

BACKGROUND: Extended, more effective breast cancer treatments have increased the prevalence of long-term survivors. We investigated the risk of late breast cancer recurrence (BCR), 10 years or more after primary diagnosis, and associations between patient and tumor characteristics at primary diagnosis and late BCR up to 32 years after primary breast cancer diagnosis. METHODS: Using the Danish Breast Cancer Group clinical database, we identified all women with an incident early breast cancer diagnosed during 1987-2004. We restricted to women who survived 10 years without a recurrence or second cancer (10-year disease-free survivors) and followed them from 10 years after breast cancer diagnosis date until late recurrence, death, emigration, second cancer, or December 31, 2018. We calculated incidence rates per 1000 person-years and cumulative incidences for late BCR, stratifying by patient and tumor characteristics. Using Cox regression, we calculated adjusted hazard ratios for late BCR accounting for competing risks. RESULTS: Among 36 924 women with breast cancer, 20 315 became 10-year disease-free survivors. Of these, 2595 developed late BCR (incidence rate = 15.53 per 1000 person-years, 95% confidence interval = 14.94 to 16.14; cumulative incidence = 16.6%, 95% confidence interval = 15.8% to 17.5%) from year 10 to 32 after primary diagnosis. Tumor size larger than 20 mm, lymph node-positive disease, and estrogen receptor-positive tumors were associated with increased cumulative incidences and hazards for late BCR. CONCLUSIONS: Recurrences continued to occur up to 32 years after primary diagnosis. Women with high lymph node burden, large tumor size, and estrogen receptor-positive tumors had increased risk of late recurrence. Such patients may warrant extended surveillance, more aggressive treatment, or new therapy approaches.

Validation of an Algorithm to Ascertain Late Breast Cancer Recurrence Using Danish Medical Registries.

PURPOSE: About 70% of women with breast cancer survive at least 10 years after diagnosis. We constructed an algorithm to ascertain late breast cancer recurrence-which we define as breast cancer that recurs 10 years or more after primary diagnosis (excluding contralateral breast cancers)-using Danish nationwide medical registries. We used clinical information recorded in medical records as a reference standard. METHODS: Using the Danish Breast Cancer Group clinical database, we ascertained data on 21,134 women who survived recurrence-free 10 years or more after incident stage I-III breast cancer diagnosed in 1987-2004. We used a combination of Danish registries to construct the algorithm-the Danish National Patient Registry for information on diagnostic, therapeutic and procedural codes; and cancer diagnoses from the Danish Pathology Registry, the Danish Cancer Registry and the Contralateral Breast Cancer database. To estimate the positive predictive value (PPV), we selected 105 patients who, according to our algorithm, had late recurrence diagnosed at Aarhus University Hospital. To estimate the sensitivity, specificity and negative predictive value (NPV), we selected 114 patients diagnosed with primary breast cancer at Aalborg University Hospital. We abstracted clinical information on late recurrence for patients with medical record-confirmed late recurrence at Aarhus University Hospital. RESULTS: Our algorithm had a PPV of late recurrence of 85.7% (95% CI: 77.5-91.3%), a sensitivity of 100.0% (95% CI, 39.8-100.0%), a specificity of 97.3 (95% CI, 92.2-99.4) and a NPV of 100% (95% CI, 96.6-100.0%). CONCLUSION: Our algorithm for late recurrence showed a moderate to high PPV and high sensitivity, specificity and negative predictive value. The algorithm could be an important tool for future studies of late breast cancer recurrence.

Surgical repair of long-gap esophageal atresia: A retrospective study comparing the management of long-gap esophageal atresia in the Nordic countries.

BACKGROUND: Several surgical procedures have been described in the reconstruction of long-gap esophageal atresia (LGEA). We reviewed the surgical methods used in children with LGEA in the Nordic countries over a 15-year period and the postoperative complications within the first postoperative year. METHODS: Retrospective multicenter medical record review of all children born with Gross type A or B esophageal atresia between 01/01/2000 and 12/31/2014 reconstructed within their first year of life. RESULTS: We included 71 children; 56 had Gross type A and 15 type B LGEA. Delayed primary anastomosis (DPA) was performed in 52.1% and an esophageal replacement procedure in 47.9%. Gastric pull-up (GPU) was the most frequent procedure (25.4%). The frequency of chromosomal abnormalities, congenital heart defects and other anomalies was significantly higher in patients who had a replacement procedure. The frequency of gastroesophageal reflux (GER) was significantly higher after DPA compared to esophageal replacement (p = 0.013). At 1-year follow-up the mean body weight was higher after DPA than after organ interposition (p = 0.043). CONCLUSION: DPA and esophageal replacement procedures were equally applied. Postoperative complications and follow-up were similar except for the development of GER and the body weight at 1-year follow-up. Long-term results should be investigated. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level III.

A Dietary Assessment App for Hospitalized Patients at Nutritional Risk: Development and Evaluation of the MyFood App.

BACKGROUND: Disease-related malnutrition is a common challenge among hospitalized patients. There seems to be a lack of an effective system to follow-up nutritional monitoring and treatment of patients at nutritional risk after risk assessment. We identify a need for a more standardized system to prevent and treat disease-related malnutrition. OBJECTIVE: We aimed to develop a dietary assessment app for tablets for use in a hospital setting and to evaluate the app's ability to measure individual intake of energy, protein, liquid, and food and beverage items among hospitalized patients for two days. We also aimed to measure patients' experiences using the app. METHODS: We have developed the MyFood app, which consists of three modules: 1) collection of information about the patient, 2) dietary assessment function, and 3) evaluation of recorded intake compared to individual needs. We used observations from digital photography of the meals, combined with partial weighing of the meal components, as a reference method to evaluate the app's dietary assessment system for two days. Differences in the intake estimations of energy, protein, liquid, and food and beverage items between MyFood and the photograph method were analyzed on both group and individual level. RESULTS: Thirty-two patients hospitalized at Oslo University Hospital were included in the study. The data collection period ran from March to May 2017. About half of the patients had ≥90% agreement between MyFood and the photograph method for energy, protein, and liquid intake on both recording days. Dinner was the meal with the lowest percent agreement between methods. MyFood overestimated patients' intake of bread and cereals and underestimated fruit consumption. Agreement between methods increased from day 1 to day 2 for bread and cereals, spreads, egg, yogurt, soup, hot dishes, and desserts. Ninety percent of participants reported that MyFood was easy to use, and 97% found the app easy to navigate. CONCLUSIONS: We developed the MyFood app as a tool to monitor dietary intake among hospitalized patients at nutritional risk. The recorded intake of energy, protein, and liquid using MyFood showed good agreement with the photograph method for the majority of participants. The app's ability to estimate intake within food groups was good, except for bread and cereals which were overestimated and fruits which were underestimated. The app was well accepted among study participants and has the potential to be a dietary assessment tool for use among patients in clinical practice.

Long-term pulmonary function in esophageal atresia-A case-control study.

BACKGROUND: Esophageal atresia (EA) is a congenital anomaly associated with substantial pulmonary morbidity throughout childhood. AIM: The aim of this study was to evaluate pulmonary complications among 59 five to 15-year-old children and adolescents with surgically corrected congenital EA. METHODS: Participants underwent a structured interview, spirometry, body plethysmography, mannitol challenge test, skin prick test, as well as measurements of the diffusion capacity, airway resistance, fraction of exhaled NO, and specific immunoglobulin E in serum. A control group consisted of 25 children being evaluated for gastroesophageal reflux disease. RESULTS: Among the EA patients 33 (55.9%) had respiratory symptoms, 31 (53.4%) had a history of at least three pneumonias, and 32 (54.2%) reported more frequent cough episodes than peers. The Forced Vital Capacity (FVC) was 84.9% ± 13.2% of predicted, forced expiratory volume 1 sec (FEV1) was 78.2% ± 12.4% of predicted, and forced expiratory fraction 25-75% (FEF25-75%) was 71.5 ± 17.8% of predicted in EA patients, lower than disease controls (P < 0.0001 for all). In addition, the total lung capacity (TLC) was lower in patients with EA than in the controls (P < 0.0001). Fifteen patients (28.8%) with EA had obstructive ventilatory impairment, compared to nine patients (17.3%) with restrictive ventilatory impairment, while one had a combination. CONCLUSIONS: The present study demonstrated significantly decreased pulmonary characteristics in EA patients. Restrictive ventilatory impairment occurring in EA is probably due to poor lung growth after thoracotomy. No single factor predicted ventilatory impairment in children and adolescents with EA. Pediatr Pulmonol. 2017;52:98-106. © 2016 Wiley Periodicals, Inc.

Segmented lateral dyke growth in a rifting event at Bárðarbunga volcanic system, Iceland.

Crust at many divergent plate boundaries forms primarily by the injection of vertical sheet-like dykes, some tens of kilometres long. Previous models of rifting events indicate either lateral dyke growth away from a feeding source, with propagation rates decreasing as the dyke lengthens, or magma flowing vertically into dykes from an underlying source, with the role of topography on the evolution of lateral dykes not clear. Here we show how a recent segmented dyke intrusion in the Bárðarbunga volcanic system grew laterally for more than 45 kilometres at a variable rate, with topography influencing the direction of propagation. Barriers at the ends of each segment were overcome by the build-up of pressure in the dyke end; then a new segment formed and dyke lengthening temporarily peaked. The dyke evolution, which occurred primarily over 14 days, was revealed by propagating seismicity, ground deformation mapped by Global Positioning System (GPS), interferometric analysis of satellite radar images (InSAR), and graben formation. The strike of the dyke segments varies from an initially radial direction away from the Bárðarbunga caldera, towards alignment with that expected from regional stress at the distal end. A model minimizing the combined strain and gravitational potential energy explains the propagation path. Dyke opening and seismicity focused at the most distal segment at any given time, and were simultaneous with magma source deflation and slow collapse at the Bárðarbunga caldera, accompanied by a series of magnitude M > 5 earthquakes. Dyke growth was slowed down by an effusive fissure eruption near the end of the dyke. Lateral dyke growth with segment barrier breaking by pressure build-up in the dyke distal end explains how focused upwelling of magma under central volcanoes is effectively redistributed over long distances to create new upper crust at divergent plate boundaries.

Esophageal atresia: gastroesophageal functional follow-up in 5-15 year old children.

PURPOSE: Esophageal atresia (EA) is one of the most frequent congenital alimentary tract anomalies with a considerable morbidity throughout childhood. This study evaluates the gastroesophageal problems in 5-15 year old children with EA and aims to identify factors predisposing to esophagitis in EA. MATERIAL AND METHODS: Fifty-nine patients primarily operated at Odense University Hospital, Denmark, during 1993-2005 were included in this follow-up study. The patients underwent the following examinations: Interview, upper endoscopy, endoscopic ultrasonography, high-resolution esophageal manometry (HREM), and pH- and multichannel intraluminal impedance (MII) measurements. Twenty-five patients with suspected gastro-esophageal reflux disease (GERD) underwent the same investigations and served as controls. RESULTS: Median age was 10.2 years (7.1-13.3). Thirty-three (55.9%) presented with GERD symptoms, 41 (69.5%) with dysphagia, and 33 (55.9%) with respiratory symptoms. Twenty-nine (49.2%) had endoscopic esophagitis, and 26 (44.1%) histological esophagitis. Median reflux index (RI) was 8.3 (4.8-14.9). In 32 (55.2%) RI was above 7. Ten percent had eosinophilic inflammation. HREM showed dysmotility in the esophagus in all EA patients, 83.3% had no propagating swallows. No predictive factors predisposing the development of endoscopic esophagitis were identified. CONCLUSIONS: Gastroesophageal problems in children born with EA are common. Routine follow-up with endoscopy and pH-metry in EA patients is warranted.

Oesophageal atresia: prevalence, prenatal diagnosis and associated anomalies in 23 European regions.

OBJECTIVE: To describe prevalence, prenatal diagnosis and epidemiological data on oesophageal atresia from 23 well-defined European regions and compare the prevalence between these regions. DESIGN: Population-based study using data from a large European database for surveillance of congenital anomalies (EUROCAT) for two decades (1987-2006). SETTINGS: Twenty-three participating registries based on multiple sources of information including information about live births, fetal deaths with gestational age ≥20 weeks and terminations of pregnancy. PATIENTS: 1222 cases of oesophageal atresia in a population of 5 019 804 births. RESULTS: The overall prevalence was 2.43 cases per 10 000 births (95% CI 2.30 to 2.57). There were regional differences in prevalence ranging from 1.27 to 4.55. Prenatal detection rates varied by registry from >50% of cases to <10% of cases. A total of 546 cases (44.7%) had an isolated oesophageal anomaly, 386 (31.6%) were multiple malformed and 290 (23.7%) had an association or a syndrome. There were 1084 live born cases (88.7%), 43 cases were fetal deaths and 95 cases were terminations of pregnancy. One-week survival for live births was 86.9% and 99.2% if the gestational age was ≥38 weeks and isolated oesophageal atresia was present. Males accounted for 57.3% of all cases and 38.5% of live born cases were born with gestational age <37 weeks. CONCLUSION: There were regional differences in prevalence of oesophageal atresia in Europe. Half of all cases had associated anomalies. Prenatal detection rate increased from 26% to 36.5% over the two decades. Survival in infants with isolated oesophageal atresia born at term is high.

Early dynamic versus late static lymphoscintigraphy for the identification of sentinel lymph nodes in breast cancer.

PURPOSE: Sentinel lymph node (SLN) biopsy is an established method for the identification of early breast cancer metastases. SLN lymphoscintigraphy is pivotal in many cases, but the diagnostic value of early dynamic versus late static imaging procedures remains unclear. The objective of this study was to evaluate the diagnostic value of early dynamic versus late static imaging in the identification of SLN in breast cancer patients. MATERIALS AND METHODS: A total of 104 consecutive female patients who were referred for SLN scintigraphy prior to breast cancer surgery were included in this retrospective study. All patients underwent both a 20-minute dynamic lymphoscintigraphy and a 2-hour static acquisition. The images were independently evaluated for the presence, location, and numbers of SLN and echelon nodes in a blinded and random manner by 2 trained observers. Any discrepancy was solved by a third party arbitrator. RESULTS: SLN was identified in 101 of 104 (97%) patients on the static images versus 41 of 104 (39%) of the patients based on the dynamic acquisition. The combined use of dynamic and static images did not increase the diagnostic performance versus late lymphoscintigraphy alone. CONCLUSIONS: Identification of SLN by lymphoscintigraphy in breast cancer can be performed using a 2-hour static image alone.

Intrusion triggering of the 2010 Eyjafjallajökull explosive eruption.

Gradual inflation of magma chambers often precedes eruptions at highly active volcanoes. During such eruptions, rapid deflation occurs as magma flows out and pressure is reduced. Less is known about the deformation style at moderately active volcanoes, such as Eyjafjallajökull, Iceland, where an explosive summit eruption of trachyandesite beginning on 14 April 2010 caused exceptional disruption to air traffic, closing airspace over much of Europe for days. This eruption was preceded by an effusive flank eruption of basalt from 20 March to 12 April 2010. The 2010 eruptions are the culmination of 18 years of intermittent volcanic unrest. Here we show that deformation associated with the eruptions was unusual because it did not relate to pressure changes within a single magma chamber. Deformation was rapid before the first eruption (>5 mm per day after 4 March), but negligible during it. Lack of distinct co-eruptive deflation indicates that the net volume of magma drained from shallow depth during this eruption was small; rather, magma flowed from considerable depth. Before the eruption, a ∼0.05 km(3) magmatic intrusion grew over a period of three months, in a temporally and spatially complex manner, as revealed by GPS (Global Positioning System) geodetic measurements and interferometric analysis of satellite radar images. The second eruption occurred within the ice-capped caldera of the volcano, with explosivity amplified by magma-ice interaction. Gradual contraction of a source, distinct from the pre-eruptive inflation sources, is evident from geodetic data. Eyjafjallajökull's behaviour can be attributed to its off-rift setting with a 'cold' subsurface structure and limited magma at shallow depth, as may be typical for moderately active volcanoes. Clear signs of volcanic unrest signals over years to weeks may indicate reawakening of such volcanoes, whereas immediate short-term eruption precursors may be subtle and difficult to detect.

Infantile hypertrophic pyloric stenosis: a comparative study of incidence and other epidemiological characteristics in seven European regions.

OBJECTIVE: The objective of this study was to present epidemiologic data on infantile hypertrophic pyloric stenosis (IHPS) from seven well-defined European regions, and to compare incidence and changes in incidence over time between these regions. METHODS: This was a population-based study using data from registries of congenital malformations (EUROCAT) for a period of more than two decades (1980-2002). RESULTS: A total of 2534 infants were diagnosed with IHPS during the study period, giving an overall incidence of IHPS of 2.0 per 1000 live births (LB), ranging from 0.86 per 1000 LB to 3.96 per 1000 LB in the seven regions. A significant decrease in incidence was observed in two regions and a significant increase in incidence was observed in two other regions. Young maternal age (<20 years) significantly increased the risk of IHPS by 29% (adjusted by region; p < 0.01), and at maternal age of 30 years and older the risk decreased significantly (p < 0.01). CONCLUSIONS: There were significant differences in the incidence of IHPS in the seven European populations. No uniform pattern of change in incidence was observed as the populations also differed in relation to trend over time with both significant increases and decreases over time. There is evidence that young maternal age is a risk factor for IHPS.

Contribution of multiparameter genetic analysis to the detection of genetic alterations in hematologic neoplasia. An evaluation of combining G-band analysis, spectral karyotyping, and multiplex reverse-transcription polymerase chain reaction (multiplex RT-PCR).

We investigated 150 acute myeloid leukemia (AML) patients and 48 acute lymphoblastic leukemia (ALL) patients by multiplex RT-PCR to 7evaluate the adjuvant diagnostic effect, vis-à-vis G-banding and spectral karyotyping (SKY), and the potentials of this method for providing means for monitoring residual disease by real-time quantitative RT-PCR. An abnormal G-banded karyotype was found in 57% of AML and 68% of ALL cases. Ninety-six patients were investigated by SKY in parallel which extended or confirmed the G-banding finding in 94/96 cases. In patients with an abnormal G-banded karyotype, classification of chromosomes involved in structural aberrations by SKY was possible in 98% of the cases and SKY extended the G-banded karyotype in 34% of cases. In 32 cases, an mRNA hybrid was detected by PCR. These cases constitute 16% of the cases investigated at diagnosis (AML: 11% and ALL: 31%). In 13 of these cases, we detected an mRNA hybrid the equivalent of which was not found by G-banding or SKY (AML: 4% and ALL: 13%). By including multiplex RT-PCR, we were able to detect abnormalities in 62% of the investigated patients as opposed to 59% by G-banding. Genetic techniques complement each other and selection of relevant and targeted primer kits for the multiplex RT-PCR assay is recommended.

Recurrent genomic imbalances in B-cell splenic marginal-zone lymphoma revealed by comparative genomic hybridization.

The cytogenetics of splenic marginal zone lymphoma (SMZL) is less well characterized than the cytogenetics of other non-Hodgkin B-cell lymphomas. The aim of this study was to address this issue by identifying characteristic copy number imbalances in SMZL, for which purpose we analyzed 20 SMZL cases by comparative genomic hybridization (CGH), adding chromosome banding and fluorescence in situ hybridization (FISH) in some cases. CGH identified copy number imbalances in 70% of the cases. Imbalances were recurrently observed for chromosomes 3 (20%), 6 (20%), 7 (25%), 12 (20%), and 14 (10%). The minimally involved regions of these chromosomes were gains of 3q25 approximately qter and 12q13 approximately q15, and loss of 6q23, 7q31, and 14q22 approximately q24. A compilation of our data with data from 3 previous SMZL CGH studies revealed a significant heterogeneity between the studies. Eleven imbalances were recurrently observed in the compiled data set, as opposed to only 5 in our data set. The most frequently observed imbalances in the 73 SMZL cases of the compiled data set were gains of 3q (27%) and 12q (15%), and loss of 7q (18%). Our data suggest that SMZL constitute a genetically heterogeneous disease where gain of 3q25 and loss of 7q31 are the most likely imbalances to be involved in the pathogenesis of the disease.

Post-earthquake ground movements correlated to pore-pressure transients.

Large earthquakes alter the stress in the surrounding crust, leading to triggered earthquakes and aftershocks. A number of time-dependent processes, including afterslip, pore-fluid flow and viscous relaxation of the lower crust and upper mantle, further modify the stress and pore pressure near the fault, and hence the tendency for triggered earthquakes. It has proved difficult, however, to distinguish between these processes on the basis of direct field observations, despite considerable effort. Here we present a unique combination of measurements consisting of satellite radar interferograms and water-level changes in geothermal wells following two magnitude-6.5 earthquakes in the south Iceland seismic zone. The deformation recorded in the interferograms cannot be explained by either afterslip or visco-elastic relaxation, but is consistent with rebound of a porous elastic material in the first 1-2 months following the earthquakes. This interpretation is confirmed by direct measurements which show rapid (1-2-month) recovery of the earthquake-induced water-level changes. In contrast, the duration of the aftershock sequence is projected to be approximately 3.5 years, suggesting that pore-fluid flow does not control aftershock duration. But because the surface strains are dominated by pore-pressure changes in the shallow crust, we cannot rule out a longer pore-pressure transient at the depth of the aftershocks. The aftershock duration is consistent with models of seismicity rate variations based on rate- and state-dependent friction laws.