There is growing appreciation of the potential for high intensity interval training (HIT) to rapidly stimulate metabolic adaptations that resemble traditional endurance training, despite a low total exercise volume. However, much of the work has been conducted on young active individuals and the results may not be applicable to older, less active populations. In addition, many studies have employed "all out", variable-load exercise interventions (e.g., repeated Wingate Tests) that may not be safe, practical or well tolerated by certain individuals. We determined the effect of a short program of low-volume, submaximal, constant-load HIT on skeletal muscle oxidative capacity and insulin sensitivity in sedentary middle-aged individuals who may be at higher risk for inactivity-related chronic diseases. Sedentary but otherwise healthy men (n=3) and women (n=4) with a mean (±SE) age, body mass index and peak oxygen uptake (VO_2peak) of 45±2 yr, 27±2 kg-m^2 and 30±1 ml·kg^-1·min^-1 were recruited. Subjects performed 6 training sessions over 2 wk, each consisting of 10 x 1 min cycling at 60% of peak power elicited during a ramp VO_2peak test (<90% of heart rate reserve) with 1 min recovery between intervals. Needle biopsy samples (v. lateralis) were obtained before training and <72 h after the final training session. Muscle oxidative capacity, as reflected by the maximal activity and protein content of citrate synthase, increased by ~20% after training, which is similar to changes previously reported after 2 wk of Wingate-based HIT in young active subjects. Insulin sensitivity, based on fasting glucose and insulin, improved by ~35% after training. These data support the notion that low-volume HIT may be a practical, time- efficient strategy to induce metabolic adaptations that reduce the risk for inactivity-related disorders in previously sedentary adults. / Thesis / Master of Science (MSc)

Complete resection is correlated to better patient outcome in aggressive cancers such as glioblastoma. Optical biopsy refers to a family of techniques utilizing optical properties of living targets to make diagnoses where a biopsy would conventionally be used. Such a technology can potentially guide neurosurgeons in removing glioblastomas. Diffuse reflectance (DR) and Time-resolved fluorescence (TRF) have previously been investigated for their ability to measure biomarkers indicative of cancer. One of the difficulties faced in using TRF as a diagnostic tool is that multiple endogenous fluorophores will simultaneously contribute to the signal. This makes it difficult to attribute fluorescence lifetimes or spectral changes to one type of molecule in the tissue. This thesis focuses on the challenge of separating the components in a TRF measurement and their fractional contributions. A DR-TRF instrument was designed and built and characterized using fluorescent dyes. An orthonormal basis deconvolution method combined with a Fourier-domain method were tested for their ability to unmix fluorescent components in a hyperspectral TRF measurement. This method was tested on dye mixtures and retrieved fluorescence lifetimes of 4.6±0.4 ns and 2.7±0.2 ns in a mixture of Fluorescein and Coumarin-6 at concentrations of 5 μM each. It was also tested on an ex-vivo brain tissue where the fluorescence was approximated as a sum of 2 components. / Thesis / Master of Applied Science (MASc)

The respiratory epithelial response of the adult horse was evaluated after being housed on pasture and in an enclosed stable for four week periods. six thoroughbred cross horses, ranging from 3 to 6 years old, were housed on a pasture for 2 months, and evaluated at the end of this period. After an additional month on pasture, horses were then moved to a barn and housed in stalls for four weeks. Samples were obtained at the end of this time and horses were returned to pasture for two months. Final samples were then collected. Each evaluation included a physical examination; cytological evaluation of transtracheal aspirate, and histological evaluation of tracheal epithelial biopsies obtained at the level of the main stem bifurcation. Endoscopic evaluation also permitted scoring of pharyngeal lymphoid hyperplasia, and tracheal mucous secretions. No significant changes were noted in any of the parameters evaluated in this study. These results suggest housing normal horses in a stable environment does not an elicit an immediate change in the volume or composition of epithelial secretions. Evaluation of the tracheal epithelium biopsies also did not reveal histologic changes or inflammatory infiltration in response to short-term housing in the stable environment. / Master of Science

Ye / Genetic and epigenetic alterations significantly contribute to development of human cancer. Genotyping tumour tissue in search for these actionable genetic and epigenetic changes has become routine practice in oncology. However, sampling tumour tissue has significant inherent limitations. It provides only a single snapshot in time, prone to selection bias due to intra-tumour heterogeneity, and cannot always be performed owing to its invasive nature. Circulating tumour DNA (ctDNA) based liquid biopsy provides an effective alternative to invasive tissue sampling and have emerged as a minimally invasive, real-time biomarker. Recent advancements in DNA sequencing technologies have revealed enormous potential of ctDNA to improve tumour detection and stratification. In this review, we critically appraise the role of ctDNA as a liquid biopsy for cancer and evaluate the role of circulating tumour DNA as a diagnostic, prognostic and predictive biomarker. We also highlight some technical challenges and constraints associated with circulating DNA analysis.

Yes / Purpose: Nipple secretions are protein-rich and a potential source of breast cancer biomarkers for breast cancer screening. Previous studies of specific proteins have shown limited correlation with clinicopatholigical features. Our aim, in this pilot study, was to investigate the intra- and inter-patient protein composition of nipple secretions and the implications for their use as liquid biopsies. Experimental design: Matched pairs of NAF (n=15) were characterised for physicochemical properties and SDS PAGE. Four pairs were selected for semi-quantitative proteomic profiling and trypsin-digested peptides analysed using 2D LC Orbitrap Fusion mass spectrometry. The resulting data was subject to bioinformatics analysis and statistical evaluation for functional significance. Results: A total of 1990 unique proteins were identified many of which are established cancer associated markers. Matched pairs shared the greatest similarity (average Pearson correlation coefficient of 0.94), but significant variations between individuals was observed. Conclusions: This was the most complete proteomic study of NAF to date providing a valuable source for biomarker discovery. The high level of milk proteins in healthy volunteer samples compared to the cancer patients was associated with galactorrhoea. Using matched pairs increased confidence in patient-specific protein levels but changes relating to cancer stage require investigation of a larger cohort. / Proteomics research was supported by Yorkshire Cancer Research projects, BPP047 and B381PA.

Yes / There has been tremendous progress in detection of breast cancer in postmenopausal women, resulting in two-thirds of women surviving more than 20 years after treatment. However, breast cancer remains the leading cause of cancerrelated deaths in premenopausal women. Breast cancer is increasing in younger women due to changes in life-style as well as those at high risk as carriers of mutations in high-penetrance genes. Premenopausal women with breast cancer are more likely to be diagnosed with aggressive tumours and therefore have a lower survival rate. Mammography plays an important role in detecting breast cancer in postmenopausal women, but is considerably less sensitive in younger women. Imaging techniques, such as contrast-enhanced MRI improve sensitivity, but as with all imaging approaches, cannot differentiate between benign and malignant growths. Hence, current well-established detection methods are falling short of providing adequate safety, convenience, sensitivity and specificity for premenopausal women on a global level, necessitating the exploration of new methods. In order to detect and prevent the disease in high risk women as early as possible, methods that require more frequent monitoring need to be developed. The emergence of “omics” strategies over the last 20 years, enabling the characterisation and understanding of breast cancer at the molecular level, are providing the potential for long term, longitudinal monitoring of the disease. Tissue and serum biomarkers for breast cancer stratification, diagnosis and predictive outcome have emerged, but have not successfully translated into clinical screening for early detection of the disease. The use of breast-specific liquid biopsies, such as nipple aspirate fluid (NAF), a natural secretion produced by breast epithelial cells, can be collected non-invasively for biomarker profiling. As we move towards an age of active surveillance, home-based liquid biopsy collection kits are increasingly being applied and these could provide a paradigm shift where NAF biomarker profiling is used for routine breast health monitoring. The current status of established and newly emerging imaging techniques for early detection of breast cancer and the potential for alternative biomarker screening of liquid biopsies, particularly those applied to high-risk, premenopausal women, will be reviewed. / Proteomics research was supported by Yorkshire Cancer Research projects, BPP047 and B381PA, and co-funded by the European Regional Development Fund and the Republic of Cyprus through the Research Promotion Foundation projects ΥΓΕΙΑ/ΒΙΟΣ/0311(ΒΙΕ/07) and NEKYP/0311/17.

Glioblastoma (GBM) is the most common adult malignant glioma (MG) variant, and the median survival of persons with GBM is about 2 years, even with aggressive treatments. Dogs and humans are the only species in which brain tumors commonly develop spontaneously, with an estimated post-mortem frequency of primary brain tumors approximating 2% in both species. Gliomas represent about 35% of all canine primary brain tumors, with high-grade oligodendroglioma and astrocytoma phenotypes accounting for about 70% of all canine gliomas. Canine gliomas are also treated using surgical, radiotherapeutic, and chemotherapeutic regimens similar to those used in humans. The efficacy of these therapies in dogs with MG is also poor, with median survival times ranging from 3-8 months, which closely mirrors the dismal prognosis associated with human GBM. Thus, treatment of MG represents a current and critically unmet need in both human and veterinary medicine. In this work, we investigate minimally invasive methods to access the brain for the purposes of ultimately improving the diagnosis and treatment of malignant brain tumors. Chapter 1 reviews the current clinical challenges associated with the treatment of GBM, highlights the value of using the spontaneous canine glioma model in translational brain tumor studies, and introduces High-Frequency Irreversible Electroporation (H-FIRE) and Convection Enhanced Delivery (CED), which are two novel treatment platforms for GBM being developed in our lab. In Chapter 2, we demonstrate that definitive diagnosis of brain tumors, a critical first step in patient management, can be safely and accurately performed in dogs with naturally occurring brain tumors using a stereotactic brain biopsy procedure. Chapter 3 evaluates the in vivo safety and biocompatibility of fiberoptic microneedle devices, a major technical component of our convection-enhanced thermotherapy catheter system (CETCS), chronically implanted in the rodent brain. The CETCS is a novel technology being developed and used in our laboratory to improve the delivery of drugs to brain tumors using CED. This study provides regulatory data fundamental to the commercialization of the CETCS device for brain tumor treatment by illustrating that the device did not cause clinically significant neurological complications and resulted in mild pathologic changes in brain tissue, similar to other types of devices designed and approved for use in the brain. In Chapters 4 and 5 we explore possible bystander effects of H-FIRE on glutamate metabolism in the brain. H-FIRE has been shown to be able to both ablate brain tumors as well as disrupt the blood-brain barrier (BBB). As these therapeutic effects of H-FIRE are dependent on applying electrical fields to the tissue that either reversibly permeabilize the cell membrane, allowing treated cells to survive, or permanently disrupt the structure of the cell membrane, causing cell death, we hypothesized that altering the membrane permeability with HFIRE would increase the extracellular glutamate concentrations and contribute to excitotoxic brain tissue damage. Chapters 4 used in vitro brain cell culture systems and in vivo experiments in normal and glioma-bearing rat brains to determine if glutamate release in the brain occurs as a bystander effect following H-FIRE treatment, identify concentrations of glutamate necessary to induce death of cells or BBB disruption, and characterize glutamatergic gene expression in response to H-FIRE treatment. Chapter 5 describes the use of magnetic resonance spectroscopic and spatial transcriptomic methods to further quantify the in vivo effects of H-FIRE treatment on glutamate release and metabolism in dogs with spontaneous brain tumors. The in vitro results indicated that the magnitude of glutamate release following H-FIRE is insufficient to induce cytotoxicity in normal or neoplastic brain cell lines, and also did not increase the permeability of the BBB. In our in vivo model systems, we documented significant, transient post-H-FIRE increases in glutamate to concentrations previously associated with excitotoxicty, with upregulation of the expression of genes involved with ionotropic and metabotropic glutamatergic receptor signaling. A contemporaneous upregulation of genes associated with glutamate uptake and recycling were also noted, indicating an adaptive, protective response to the glutamate release. Our work summarily demonstrates that the diagnosis and potential treatment of malignant brain tumors can be achieved through the use of minimally invasive techniques that provide local access to brain tissue. While complications will always be possible anytime the brain is manipulated surgically, and further investigations are required to characterize the spectrum and mechanisms of adverse events that can occur following CETCS CED and H-FIRE treatment, our results support the continued development of these novel therapeutic platforms for the treatment of GBM. / Doctor of Philosophy / Glioblastoma (GBM) is the most common adult malignant glioma (MG) variant, and the median survival of persons with GBM is about 2 years, even with aggressive treatments. Dogs and humans are the only species in which brain tumors commonly develop spontaneously, with an estimated post-mortem frequency of primary brain tumors approximating 2% in both species. Gliomas represent about 35% of all canine primary brain tumors, with high-grade oligodendroglioma and astrocytoma phenotypes accounting for about 70% of all canine gliomas. Canine gliomas are also treated using surgical, radiotherapeutic, and chemotherapeutic regimens similar to those used in humans. The efficacy of these therapies in dogs with MG is also poor, with median survival times ranging from 3-8 months, which closely mirrors the dismal prognosis associated with human GBM. Thus, treatment of MG represents a current and critically unmet need in both human and veterinary medicine. In this work, we investigate minimally invasive methods to access the brain for the purposes of ultimately improving the diagnosis and treatment of malignant brain tumors. Chapter 1 reviews the current clinical challenges associated with the treatment of GBM, highlights the value of using the spontaneous canine glioma model in translational brain tumor studies, and introduces High-Frequency Irreversible Electroporation (H-FIRE) and Convection Enhanced Delivery (CED), which are two novel treatment platforms for GBM being developed in our lab. In Chapter 2, we demonstrate that definitive diagnosis of brain tumors, a critical first step in patient management, can be safely and accurately performed in dogs with naturally occurring brain tumors using a stereotactic brain biopsy procedure. Chapter 3 evaluates the in vivo safety and biocompatibility of fiberoptic microneedle devices, a major technical component of our convection-enhanced thermotherapy catheter system (CETCS), chronically implanted in the rodent brain. The CETCS is a novel technology being developed and used in our laboratory to improve the delivery of drugs to brain tumors using CED. This study provides regulatory data fundamental to the commercialization of the CETCS device for brain tumor treatment by illustrating that the device did not cause clinically significant neurological complications and resulted in mild pathologic changes in brain tissue, similar to other types of devices designed and approved for use in the brain. In Chapters 4 and 5 we explore possible bystander effects of H-FIRE on glutamate metabolism in the brain. H-FIRE has been shown to be able to both ablate brain tumors as well as disrupt the blood-brain barrier (BBB). As these therapeutic effects of H-FIRE are dependent on applying electrical fields to the tissue that either reversibly permeabilize the cell membrane, allowing treated cells to survive, or permanently disrupt the structure of the cell membrane, causing cell death, we hypothesized that altering the membrane permeability with HFIRE would increase the extracellular glutamate concentrations and contribute to excitotoxic brain tissue damage. Chapters 4 used in vitro brain cell culture systems and in vivo experiments in normal and glioma-bearing rat brains to determine if glutamate release in the brain occurs as a bystander effect following H-FIRE treatment, identify concentrations of glutamate necessary to induce death of cells or BBB disruption, and characterize glutamatergic gene expression in response to H-FIRE treatment. Chapter 5 describes the use of magnetic resonance spectroscopic and spatial transcriptomic methods to further quantify the in vivo effects of H-FIRE treatment on glutamate release and metabolism in dogs with spontaneous brain tumors. The in vitro results indicated that the magnitude of glutamate release following H-FIRE is insufficient to induce cytotoxicity in normal or neoplastic brain cell lines, and also did not increase the permeability of the BBB. In our in vivo model systems, we documented significant, transient post-H-FIRE increases in glutamate to concentrations previously associated with excitotoxicty, with upregulation of the expression of genes involved with ionotropic and metabotropic glutamatergic receptor signaling. A contemporaneous upregulation of genes associated with glutamate uptake and recycling were also noted, indicating an adaptive, protective response to the glutamate release. Our work summarily demonstrates that the diagnosis and potential treatment of malignant brain tumors can be achieved through the use of minimally invasive techniques that provide local access to brain tissue. While complications will always be possible anytime the brain is manipulated surgically, and further investigations are required to characterize the spectrum and mechanisms of adverse events that can occur following CETCS CED and H-FIRE treatment, our results support the continued development of these novel therapeutic platforms for the treatment of GBM.

No / This case study describes a qualitative investigation of the experiences of 14 experienced mammography radiographers who successfully undertook a formal programme of education and training in stereotactic needle core biopsy (SNCB) of the breast. They now routinely perform SNCB within symptomatic and screening breast services in a variety of NHS hospitals across the country. All 14 radiographers completed a semi-structured postal questionnaire approximately six months after the end of the course. A tentative theory derived from the data suggests that the professional challenge associated with radiographer-performed SNCB builds personal confidence and effects positive change. Three main categories emerging from the data e challenge, confidence and change are underpinned by two main themes e educational, professional and service drivers that promote the realisation of goals and vision; and personal, peer and external motivation sustained by respect, recognition and reward. SNCB role extension as explored in this study is having a positive and transformational impact on patient users of breast diagnostic clinical services and on the professional health carers providing them. The key drivers for this as identified in the study are a formal educational experience, professional role extension opportunities and the NHS modernisation process. The participants experienced positive change as individuals and as professional breast cancer multidisciplinary team members. Academic and financial rewards, respect and recognition from colleagues across professional disciplines and from patients, were key motivators that sustained the process. This study indicates that radiographer-performed SNCB can help deliver the NHS Plan and the NHS Cancer Plan and in doing so has the potential to improve the working lives of health care professionals and ultimately to improve the quality of care for patients.

Hintergrund und Zielsetzung: Jährlich erkranken in Westeuropa 4% der Gesamtbevölkerung an Akutem Nierenversagen (ANV). Zudem leiden 8,5% der Bevölkerung an einer Chronischen Niereninsuffizienz (CNI). Valide epidemiologische Daten über Erkrankungen der Niere existierten für Deutschland jedoch nicht, da zu diesem Zeitpunkt Erkrankungsfälle noch nicht flächendeckend systematisch erfasst wurden und das Deutsche Nierenregister noch im Aufbau war. Die vorliegende retrospektive Analyse untersucht und dokumentiert räumliche und zeitliche Veränderungen des histomorphologischen Befundspektrums aus Eigennierenbiopsien im Großraum Leipzig über den Zeitraum 1993-2012. Methoden: Als Grundlage der Arbeit dient ein zeitlich und geographisch strukturiertes Nierenbiopsieregister, welches für die vorliegende Arbeit aus den gesammelten histologischen Eigennierenbiopsiebefunden erstellt wurde. Zu jedem Fall wurde zur räumlichen Zuordnung, wenn ermittelbar, die Postleitzahl (PLZ) des Wohnortes des jeweiligen Patienten eingetragen. Bei einer annähernd vollständigen Erfassung der PLZ wurde für den jeweiligen Zeitraum für das Stadtgebiet Leipzig eine Inzidenzberechnung durchgeführt. Für das Leipziger Umland war dies nicht vorgesehen, da von einer unvollständigen Erfassung auszugehen war. Die statistische Auswertung erfolgte über Kontingenztafeln per Chi-Quadrat-Test oder per Varianzanalyse. Ergebnisse: In die Analyse des erstellten Biopsieregisters wurden n=943 Erstbiopsien eingeschlossen, unter vorherigem Ausschluss pädiatrischer Fälle und Folgebiopsien. Die IgA-Nephropathie (IgANP) war mit 19,5% die häufigste gestellte Diagnose, gefolgt von der Hypertensiven Nephropathie (HZNP) bzw. der Fokal-Segmentalen Glomerulosklerose (FSGS) und der Granulomatose mit Polyangiitis (GPA). Die räumliche Verteilung innerhalb der Untersuchungsregion unterlag teilweise großen Schwankungen. Die IgANP wurde im Leipziger Umland 36% häufiger beobachtet als im Leipziger Stadtgebiet. Auch im Zeitverlauf waren Schwankungen zu beobachten. Im Zeitraum 2009-2012 war die HTNP/FSGS mit 18.9% die häufigste Diagnose, gefolgt von der GPA mit 17,8% und der IgANP mit 15,6%. Zudem nahm die Häufigkeit der Glomerulopathie der dünnen Basalmembran (TBMD) bzw. des Alport-Syndroms stark ab. Auch die regionale Verteilung schwankte im Zeitverlauf stark. Auf Basis der ermittelten Postleitzahlen wurden für den Leipziger Stadtraum für den Zeitraum 2001-2009 jährliche Inzidenzen berechnet. Am Häufigsten trat dabei die GPA mit 0,9 (0,0-2,2) Fällen pro 100.000 Einwohner auf, gefolgt von der HTNP/FSGS mit 0,8 (0,2-2,2) und der IgANP mit 0,8 (0,2-1,4). Schlussfolgerung: Das Nephropathiespektrum im Großraum Leipzigs deckt sich, soweit konsolidierte Vergleichszahlen existieren, mit der bestehenden Literatur. In den Vergleichsstudien zeigte sich eine große Heterogenität. Einige Schwankungen, wie bei der HTNP/Alport-Syndrom oder bei der diabetischen Nephropathie (DNP) beobachtet, sind klar auf Variabilitäten in der Indikationsstellung zurückzuführen. Andere mögliche Einflussfaktoren wurden diskutiert. / Background and Objectives: Annually, 4% of Western Europe\'s population fall ill with acute kidney injury (AKI). Furthermore, 8.5% of the same population are affected by chronic kidney disease (CKD). In Germany, valid nationwide epidemiological data on renal pathology didn\'t exist at the time of this study, although progress has been made with creating the German kidney biopsy register. This study analyzes temporal and spatial variances in the histomorphological spectrum of renal diseases of native kidney biopsies in the metropolitan area of Leipzig, Germany, from 1993 through 2012. Methods: For this study, a temporally and spatially structured kidney biopsy register was created from nephro-pathologic biopsy results. Spatial analysis was implemented by giving every entry its corresponding postal code. Unidentifiable entries were omitted. If the postal code was determined for every case within a timeframe, incidences for the city of Leipzig were calculated for the timeframe. Incidence for the surrounding areas were not calculated, because coverage was expected to be incomplete. Statistical analysis was done via Chi-Squared-Test or analysis of variances. Results: For this study n=943 cases were analyzed, omitting pediatric and follow-up biopsies. The leading diagnosis was IgA nephropathy (IgANP) with 19.5% (male: 22.1%, female: 15.4%), followed by hypertensive nephropathy (HTNP) resp. focal-segmental glomerulosclerosis (FSGS) and granulomatosis with polyangiitis (GPA). Spatial variance between the analyzed regions was high. Compared to the city of Leipzig, IgANP was observed one third more frequently in the surrounding regions. High temporal variance was also observed. From 2009 through 2012, HTNP/FSGS became leading diagnosis with 18.9%, followed by GPA with 17.8% and IgANP with 15.6%. Furthermore, frequency of thin base membrane disease (TBMD) resp. Alport\'s syndrome decreased sharply. Variance in spatial distribution was also observed over time. On the basis of determined postal codes, incidences for the city of Leipzig were calculated for the years 2001 through 2009. Highest annual incidence was observed in GPA with 0.9 (0.0-2.2) cases per 100 000 people, followed by HTNP/FSGS with 0.8 (0.2-2.2), IgANP with 0.8 (0.2-1.4). Conclusions: The spectrum of kidney pathology for the metropolitan area of Leipzig is in accordance with the data in literature, as far as consolidated figures were available. Results in compared studies were highly heterogenous. Some differences, e.g. decrease in TBMD resp. Alport\'s Syndrome or fluctuation of DNP, can be attributed to variance in indication for biopsy. External factors were discussed.

Objective: The purpose of this study was to determinate the rate of underestimation of core biopsy (CB) of nonpalpable breast lesions, under image guidance, with validation at surgical excision histologic examination at Instituto Nacional de Câncer (INCA). Materials e methods: We retrospectively reviewed 352 CB that were submmited to surgery, from February 2000 to December 2005, and which histopathologic findings were at INCA database system. CB results were compared to surgical findings and underestimation rate was determined by dividing the number of lesions that proved to be carcinoma at surgical excision by the total number of high risk lesions and intracuctal carcinoma evaluated with excisional biopsy. Clinical, imaging, core biopsy and pathologic features were analyzed to identify factors that affect the rate of underestimation. Results: All patients were female, which mean age was 56,1 years old (26-86). Mass lesion was the most frequent finding (71,3%), being 69,9% less than 20mm, as well as BI-RADS® 4 (71,0%). The main guidance was stereotactic (57,1%), all using 14-gauge needles. The mean number of core samples was eight (4-22), being 99,7% at least five samples. The patients tolerated CB in 99,1% of cases, but bleeding occurred in 6,6%. The inconclusive CB findings occurred in 15,6%, (55/352). It was benign in 26,4%, high risk lesion in 12,8% and malignant in 45,2%. The segmentectomia was the more frequent surgery (70,2%), being benign in 26,7%, high risk in 18,2% and malign in 55,1%. There was agreement between CB and surgery in 82,1% (Kappa = 0,75). False-negative rate was 5,4% and the lesion was completely removed in 3,4%. Underestimation rate was 9,1%, and was associated with BI-RADS® 5 (p = 0,049), microcalcifications (p < 0,001) and stereotactic guidance (p = 0,002). All underestimated cases were less than 20 mm of diameter and there were at least five fragments. Underestimation rate of high risk lesions was 31,1% and there was no significant associations. Atypical ductal hyperplasia underestimation rate was 41,2% and there was not associations. Papillary lesions underestimation was 31,2% and was associated with stereotactic guidance (p = 0,036). Phyllodes tumor underestimation was 16,7% but it was not possible to make associations. There was one lobular neoplasia case that was concordant to surgery. Ductal carcinoma in situ underestimation was 41,9% and there was not significant associations. Conclusions: The core breast biopsy under image guidance is a reliable procedure but it remains the recommendation of surgical excision for high risk lesions detected at CB as well as it was not possible to assess clinical, imaging, core biopsy and pathologic features that could predict underestimation and avoid excision. Representative samples are much more important than number of fragments. / Objetivo: Determinar o grau de subestimação de core biopsy (CB), guiada por imagem, de lesões impalpáveis da mama e que foram subsequentemente submetidas à exérese cirúrgica no Hospital do Câncer III/ Instituto Nacional de Câncer (INCA). Materiais e métodos: Foram revisadas retrospectivamente 352 CB que foram submetidas à cirurgia entre fevereiro de 2000 e dezembro de 2005, e cujo laudo histopatológico estava registrado no sistema interno de informação do INCA. Os resultados da CB foram comparados com os da cirurgia e a taxa de subestimação foi calculada dividindo o número de carcinoma in situ e/ou invasivo à cirurgia pelo número de lesões de alto risco ou carcinoma in situ que foram submetidas à cirurgia. Foram analisadas características clínicas, imaginológicas, da CB e patológicas que poderiam influir na subestimação. Resultados: Todas as pacientes eram do sexo feminino, com média de idade de 56,1 anos (26-86). O nódulo foi o tipo de lesão mais frequente (71,3%) com 69,9% menor do que 20 mm, bem como BI-RADS® categoria 4 (71,0%). O tipo de guia mais utilizado foi a estereotaxia (57,1%), todos utilizando agulhas 14-gauge. O número médio de fragmentos foi de oito (4-22), com 99,7% apresentando pelo menos cinco fragmentos. O procedimento foi bem tolerado em 99,1% dos casos, mas ocorreu hematoma em 6,6%. A CB foi inconclusiva em 15,6%. O laudo histopatológico da CB foi benigno em 26,4%, lesão de alto risco em 12,8% e maligno em 45,2%. A segmentectomia foi a cirurgia mais frequente (70,2%), com laudo benigno em 26,7%, lesão de alto risco em 18,2% e maligno em 55,1%. A concordância entre a CB e a cirurgia foi de 82,1% (Kappa = 0,75). Falso-negativo foi de 5,4% e a lesão foi completamente removida em 3,4%. A taxa de subestimação foi de 9,1% e esteve associada com BI-RADS® categorias 5 (p = 0,049), microcalcificações (p < 0,001) e estereotaxia (p = 0,002). Todos os casos subestimados possuíam menos de 20 mm e em todos foram retirados pelo menos cinco fragmentos. A taxa de subestimação para lesões de alto risco foi de 31,1% e não apresentou variáveis associadas à subestimação. Já a taxa de subestimação de hiperplasia ductal atípica foi de 41,2% e também não houve associações. A subestimação de lesões papilíferas foi 31,2% e apresentou associação com estereotaxia (p = 0,036). Tumor filóides foi subestimado em 16,7%, mas não foi possível estabelecer associações. Houve apenas um caso de neoplasia lobular à CB que foi concordante com a cirurgia. A subestimação de carcinoma ductal in situ foi 41,9% e também não apresentou associações relevantes. Conclusões: CB guiada por imagem é um procedimento confiável, contudo permanece a recomendação de ressecção cirúrgica de lesões de alto risco detectadas à CB. Além disso, não foi possível estabelecer características clínicas, imaginológicas, da CB e patológicas que pudessem predizer subestimação e evitar a cirurgia. Amostras representativas da lesão são mais importantes que o número de fragmentos.