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BACKGROUND: Cerenkov luminescence imaging (CLI) is a new emerging technology that can be used for optical imaging of approved radiotracers, both in a preclinical, and even more recently, in a clinical context with rapid imaging times, low costs, and detection in real-time (Grootendorst et al. Clin Transl Imaging 4(5):353-66, 2016); Wang et al. Photonics 9(6):390, 2022). This brief review provides an overview of clinical applications of CLI with a focus on intraoperative margin assessment (IMA) to address shortcomings and provide insight for future work in this application. METHODS: A literature review was performed using PubMed using the search words Cerenkov luminescence imaging (CLI), intraoperative margin assessment (IMA), and image-guided surgery. Articles were selected based on title, abstract, content, and application. RESULTS: Original research was summarized to examine advantages and limitations of CLI compared to other modalities for IMA. The characteristics of Cerenkov luminescence (CL) are defined, and results from relevant clinical trials are discussed. Prospects of ongoing clinical trials are reviewed, along with technological advancements related to CLI. CONCLUSION: CLI is a proven method for molecular imaging and shows feasibility for determining intraoperative margins if future work involves establishing quantitative approaches for attenuation and scattering, depth analysis, and radiation safety for CLI at a larger scale.
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Imagem Molecular , Humanos , Imagem Molecular/métodos , Medições Luminescentes/métodos , Cirurgia Assistida por Computador/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/cirurgia , Período Intraoperatório , Luminescência , AnimaisRESUMO
Imprecision in breast conserving surgery results in high rates of take back to theatre for reexcision of margins. This paper reviews the various approaches to improving the precision of oncological margin control in breast conserving surgery. The review describes the rationale for improved tissue characterization over tumor localization and explores technology-free approaches, as well as progress being made to develop and test innovative technological solutions.
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(1) Background: Hyperspectral imaging has emerged as a promising margin assessment technique for breast-conserving surgery. However, to be implicated intraoperatively, it should be both fast and capable of yielding high-quality images to provide accurate guidance and decision-making throughout the surgery. As there exists a trade-off between image quality and data acquisition time, higher resolution images come at the cost of longer acquisition times and vice versa. (2) Methods: Therefore, in this study, we introduce a deep learning spatial-spectral reconstruction framework to obtain a high-resolution hyperspectral image from a low-resolution hyperspectral image combined with a high-resolution RGB image as input. (3) Results: Using the framework, we demonstrate the ability to perform a fast data acquisition during surgery while maintaining a high image quality, even in complex scenarios where challenges arise, such as blur due to motion artifacts, dead pixels on the camera sensor, noise from the sensor's reduced sensitivity at spectral extremities, and specular reflections caused by smooth surface areas of the tissue. (4) Conclusion: This gives the opportunity to facilitate an accurate margin assessment through intraoperative hyperspectral imaging.
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Artefatos , Mastectomia Segmentar , Movimento (Física)RESUMO
BACKGROUND AND OBJECTIVES: This trial aimed to investigate the effects of circumferential shaving on reducing the reoperation rates during breast-conserving surgery (BCS). METHODS: In the study, before 2014, 404 (39.9%) breast cancers (BCs) out of a total of 1012 BCs underwent BCS without intraoperative cavity shaving (ICS) and constituted the no-ICS group. After this date, ICS was added to 608 (60.1%) BCSs (ICS group) and intraoperative margin analysis was not requested from pathologists during these second BCS procedures. RESULTS: The patient and BC characteristics in the no-ICS and ICS groups were similar. Carcinoma detection at the margin and reoperation rates were 13.9% in the no-ICS group and 7.6% in the ICS group (p = 0.001). No significant difference was detected between patients who underwent BCS with intraoperative frozen section analysis (FSA) and patients who underwent BCS with additional ICS (5.6% vs. 7.6%, p = 0.383). CONCLUSIONS: ICS decreased the rates of positive margins and reoperations among patients with BCS to an acceptable level compared with intraoperative FSA. It may be concluded that ICS is feasible to achieve BC margin control.
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Neoplasias da Mama , Carcinoma Ductal de Mama , Humanos , Feminino , Mastectomia Segmentar/métodos , Estudos Retrospectivos , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Reoperação , Secções Congeladas , Margens de Excisão , Carcinoma Ductal de Mama/cirurgia , Carcinoma Ductal de Mama/patologiaRESUMO
OBJECTIVES: Identifying unmet needs for innovative solutions across disease contexts is challenging but important for directing funding and research efforts and informing early-stage decisions during the innovation process. Our aim was to study the merits of care pathway analysis to scope disease contexts and guide the development of innovative devices. We used oncologic surgery as a case study, for which many intraoperative imaging techniques are under development. METHODS: Care pathway analysis is a mapping process, which produces graphical maps of clinical pathways using important outcomes and subsequent consequences. We performed care pathway analyses for glioblastoma, breast, bladder, prostate, renal, pancreatic, and oral cavity cancer. Differences between a "perfect" care pathway and the current care pathway in terms of percentage of inadequate margins, associated recurrences, quality of life, and 5-year overall survival were calculated to determine unmet needs. Data from The Netherlands Cancer Registry and literature were used. RESULTS: Care pathway analysis showed that highest percentages of inadequate margins were found in oral cavity cancer (72.5%), glioblastoma (48.7%), and pancreatic cancer (43.9%). Inadequate margins showed the strongest increase in recurrences in cancer of oral cavity, and bladder (absolute increases of 43.5% and 41.2%, respectively). Impact on survival was largest for bladder and oral cavity cancer with positive margins. CONCLUSIONS: Care pathway analysis provides overviews of current clinical paths in multiple indications. Disease contexts can be compared via effectiveness gaps that show the potential need for innovative solutions. This information can be used as basis for stakeholder involvement processes to prioritize care pathways in need of innovation.
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Procedimentos Clínicos , Glioblastoma , Masculino , Humanos , Qualidade de Vida , Tecnologia , Países BaixosRESUMO
Basal cell carcinoma is the most common cancer worldwide, necessitating the development of techniques to decrease treatment costs through efficiency and efficacy. Mohs micrographic surgery, a specialized surgical technique involving staged resection of the tumor with complete histologic evaluation of the peripheral margins, is highly utilized. Reducing stages by even 5% to 10% would result in significant improvement in care and economic benefits. Noninvasive imaging could aid in both establishing the diagnosis of suspicious skin lesions and streamlining the surgical management of skin cancers by improving presurgical estimates of tumor sizes. Herein, we review the current state of imaging techniques in dermatology and their applications for diagnosis and tumor margin assessment of basal cell carcinoma prior to Mohs micrographic surgery.
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Carcinoma Basocelular , Dermatopatias , Neoplasias Cutâneas , Humanos , Carcinoma Basocelular/diagnóstico por imagem , Carcinoma Basocelular/cirurgia , Cirurgia de Mohs/métodos , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/cirurgia , Dermatopatias/cirurgia , Diagnóstico por Imagem/métodosRESUMO
A clear margin is an important prognostic factor for most solid tumours treated by surgery. Intraoperative fluorescence imaging using exogenous tumour-specific fluorescent agents has shown particular benefit in improving complete resection of tumour tissue. However, signal processing for fluorescence imaging is complex, and fluorescence signal intensity does not always perfectly correlate with tumour location. Raman spectroscopy has the capacity to accurately differentiate between malignant and healthy tissue based on their molecular composition. In Raman spectroscopy, specificity is uniquely high, but signal intensity is weak and Raman measurements are mainly performed in a point-wise manner on microscopic tissue volumes, making whole-field assessment temporally unfeasible. In this review, we describe the state-of-the-art of both optical techniques, paying special attention to the combined intraoperative application of fluorescence imaging and Raman spectroscopy in current clinical research. We demonstrate how these techniques are complementary and address the technical challenges that have traditionally led them to be considered mutually exclusive for clinical implementation. Finally, we present a novel strategy that exploits the optimal characteristics of both modalities to facilitate resection with clear surgical margins.
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Neoplasias , Análise Espectral Raman , Humanos , Margens de Excisão , Neoplasias/diagnóstico por imagem , Neoplasias/cirurgia , Imagem Óptica/métodosRESUMO
OBJECTIVE: To determine the feasibility and prognostic value of 3D measuring of the ablation margins using a dedicated image registration software. METHODS: This retrospective study included 104 colorectal liver metastases in 68 consecutive patients that underwent microwave ablation between 08/2012 and 08/2019. The minimal ablation margin (MM) was measured in 2D using anatomic landmarks on contrast enhanced CT(CECT) 4-8 weeks post-ablation, and in 3D using an image registration software and immediate post-ablation CECT. Local tumor progression (LTP) was assessed by imaging up to 24 months after ablation. A blinded interventional radiologist provided feedback on the possibility of additional ablation after examining the 3D-margin measurements. RESULTS: The 3D-margin assessment was completed in 79/104 (76%) tumors without the need for target manipulation. In 25/104 (24%) tumors, manipulation was required due to image misregistration. LTP was observed in 40/104 (38.5%) tumors: 92.5% vs 7.5% for those with margin <5mm vs ≥5mm, respectively (p = 0.0001). The 2D and 3D-assessments identified margin <5mm in 17/104 (16%), and in 74/104 (71%) ablated tumors, respectively (p < 0.01). The sensitivity and specificity of the 3D software for predicting LTP was 93% (37/40) and 42% (27/64), respectively. Additional ablation to achieve a MM of 5 mm would have been offered in 26/37 cases if the 3D-margin assessment was available intraoperatively. CONCLUSION: Image registration software can measure ablation margins and detect MM under 5 mm intraoperatively, with significantly higher sensitivity than the 2D technique using landmarks on the post-ablation CECT. The identification of a margin under 5 mm is strongly associated with LTP.
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Ablação por Cateter , Neoplasias Colorretais , Neoplasias Hepáticas , Ablação por Cateter/métodos , Neoplasias Colorretais/patologia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Margens de Excisão , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Re-excision due to positive margins following breast-conserving surgery (BCS) negatively affects patient outcomes and healthcare costs. The inability to visualize margin involvement is a significant challenge in BCS. 5-Aminolevulinic acid hydrochloride (5-ALA HCl), a non-fluorescent oral prodrug, causes intracellular accumulation of fluorescent porphyrins in cancer cells. This single-center Phase II randomized controlled trial evaluated the safety, feasibility, and diagnostic accuracy of a prototype handheld fluorescence imaging device plus 5-ALA for intraoperative visualization of invasive breast carcinomas during BCS. METHODS: Fifty-four patients were enrolled and randomized to receive no 5-ALA or oral 5-ALA HCl (15 or 30 mg/kg). Forty-five patients (n = 15/group) were included in the analysis. Fluorescence imaging of the excised surgical specimen was performed, and biopsies were collected from within and outside the clinically demarcated tumor border of the gross specimen for blinded histopathology. RESULTS: In the absence of 5-ALA, tissue autofluorescence imaging lacked tumor-specific fluorescent contrast. Both 5-ALA doses caused bright red tumor fluorescence, with improved visualization of tumor contrasted against normal tissue autofluorescence. In the 15 mg/kg 5-ALA group, the positive predictive value (PPV) for detecting breast cancer inside and outside the grossly demarcated tumor border was 100.0% and 55.6%, respectively. In the 30 mg/kg 5-ALA group, the PPV was 100.0% and 50.0% inside and outside the demarcated tumor border, respectively. No adverse events were observed, and clinical feasibility of this imaging device-5-ALA combination approach was confirmed. CONCLUSIONS: This is the first known clinical report of visualization of 5-ALA-induced fluorescence in invasive breast carcinoma using a real-time handheld intraoperative fluorescence imaging device. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01837225 . Registered 23 April 2013.
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Ácido Aminolevulínico/uso terapêutico , Neoplasias da Mama/diagnóstico por imagem , Imagem Óptica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Meios de Contraste/uso terapêutico , Feminino , Fluorescência , Humanos , Cuidados Intraoperatórios , Margens de Excisão , Mastectomia Segmentar , Pessoa de Meia-Idade , Imagem Óptica/instrumentação , Valor Preditivo dos Testes , Cirurgia Assistida por ComputadorRESUMO
PURPOSE: Safe breast cancer lumpectomies require microscopically clear margins. Real-time margin assessment options are limited, and 20-40% of lumpectomies have positive margins requiring re-excision. The LUM Imaging System previously showed excellent sensitivity and specificity for tumor detection during lumpectomy surgery. We explored its impact on surgical workflow and performance across patient and tumor types. METHODS: We performed IRB-approved, prospective, non-randomized studies in breast cancer lumpectomy procedures. The LUM Imaging System uses LUM015, a protease-activated fluorescent imaging agent that identifies residual tumor in the surgical cavity walls. Fluorescent cavity images were collected in real-time and analyzed using system software. RESULTS: Cavity and specimen images were obtained in 55 patients injected with LUM015 at 0.5 or 1.0 mg/kg and in 5 patients who did not receive LUM015. All tumor types were distinguished from normal tissue, with mean tumor:normal (T:N) signal ratios of 3.81-5.69. T:N ratios were 4.45 in non-dense and 4.00 in dense breasts (p = 0.59) and 3.52 in premenopausal and 4.59 in postmenopausal women (p = 0.19). Histopathology and tumor receptor testing were not affected by LUM015. Falsely positive readings were more likely when tumor was present < 2 mm from the adjacent specimen margin. LUM015 signal was stable in vivo at least 6.5 h post injection, and ex vivo at least 4 h post excision. CONCLUSIONS: Intraoperative use of the LUM Imaging System detected all breast cancer subtypes with robust performance independent of menopausal status and breast density. There was no significant impact on histopathology or receptor evaluation.
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Neoplasias da Mama , Mastectomia Segmentar , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Feminino , Humanos , Neoplasia Residual , Peptídeo Hidrolases , Estudos Prospectivos , ReoperaçãoRESUMO
AIMS: Lentigo maligna (LM), the most common type of melanoma in situ, is a diagnostically challenging lesion for pathologists due to abundant background melanocytic hyperplasia in sun-damaged skin. Currently, no laboratory methods reliably distinguish benign from malignant melanocytes. However, preferentially expressed antigen in melanoma (PRAME) has shown promise in this regard, and could potentially be applied to diagnosis and margin assessment in difficult cases of LM. METHODS AND RESULTS: Ninety-six cases with a diagnosis of LM (n = 77) or no residual LM (n = 19) following initial biopsy were identified and stained with an antibody directed towards PRAME. Immunohistochemistry (IHC) was scored as positive or negative, and measurement of histological margins by PRAME was performed and compared to the measurement of histological margins using conventional methods [haematoxylin and eosin (H&E) and/or sex-determining region Y-box 10 (SOX10) and/or Melan-A]. Of cases with LM, 93.5% (72 of 77) were PRAME+ and 94.7% (18 of 19) of cases with no residual LM were PRAME- . Of the 35 cases with no margin involvement by PRAME or conventional assessment, 14 cases (40.0%) had no difference in measurement, 17 (48.6%) had a difference of 1 mm or less and four (11.4%) differed by between 1 and 3.5 mm. There was a high correlation between margin assessment methods (r = 0.97, P < 0.0001). CONCLUSIONS: PRAME IHC is a sensitive (93.5%) and specific (94.7%) method for diagnosing LM on biopsy and excision, and measurement of histological margins by PRAME shows a high correlation with conventional methods for margin assessment. Furthermore, the nuclear expression of PRAME makes it a good target for use in dual-colour IHC stains.
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Sarda Melanótica de Hutchinson , Coloração e Rotulagem/métodos , Idoso , Biomarcadores Tumorais/análise , Humanos , Sarda Melanótica de Hutchinson/diagnóstico , Sarda Melanótica de Hutchinson/patologia , Imuno-Histoquímica/métodos , Antígeno MART-1/análise , Masculino , Melanócitos/patologia , Melanoma/diagnóstico , Melanoma/patologia , Pessoa de Meia-Idade , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Melanoma Maligno CutâneoRESUMO
PURPOSE: Radioguided occult lesion localization (ROLL) of pulmonary nodules is an alternative to hook-wire. Both required of a histological margin assessment. The activity emerging from the radiotracer allows to obtain an intraoperative scintigraphic image of the surgical specimen by a portable gamma-camera (PGC) fitted with an optical view, which provides information about the localization of the nodule in relation to the margins. The aim of this study was to evaluate the intraoperative use of a PGC for margin assessment of pulmonary nodules. METHODS: ROLL technique was used in 38 nodules (36 pulmonary, 1 chest wall, and 1 pleural nodules). A PGC intraoperative image of the surgical specimen was obtained in 32. Scintigraphic results were compared to the histological assessment. Other factors, such as nodule size, distance from the pleural surface, or distance covered by the needle, were considered as possible factors for non-centered lesions. RESULTS: PGC images showed that the lesion was in contact with the margins in 8/32 cases and centered in 24. In all cases in which the lesion was considered as centered by the PGC, the margins were free of involvement (NPV 100%), although the PPV is low. CONCLUSIONS: The use of a PGC for margin assessment after pulmonary nodule resection is feasible and provides a high NPV in our series. In addition, the short intraoperative time required for its use makes the PGC a useful tool for providing supplementary information to histopathologic results. Further studies from different surgical teams are required for an external validation.
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Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Cirurgia Assistida por Computador , Câmaras gama , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , CintilografiaRESUMO
BACKGROUND: Re-excision rates following breast conserving surgery (BCS) remain as high as ~ 35%, with positive margins detected during follow-up histopathology. Additional breast cancer resection surgery is not only taxing on the patient and health care system, but also delays adjuvant therapies, increasing morbidity and reducing the likelihood of a positive outcome. The ability to precisely resect and visualize tumor margins in real time within the surgical theater would greatly benefit patients, surgeons and the health care system. Current tumor margin assessment technologies utilized during BCS involve relatively lengthy and labor-intensive protocols, which impede the surgical work flow. METHODS: In previous work, we have developed and validated a fluorescence imaging method termed dual probe difference specimen imaging (DDSI) to accurately detect benign and malignant tissue with direct correlation to the targeted biomarker expression levels intraoperatively. The DDSI method is currently on par with touch prep cytology in execution time (~ 15-min). In this study, the main goal was to shorten the DDSI protocol by decreasing tissue blocking and washing times to optimize the DDSI protocol to < 10-min whilst maintaining robust benign and malignant tissue differentiation. RESULTS: We evaluated the utility of the shortened DDSI staining methodology using xenografts grown from cell lines with varied epidermal growth factor receptor (EGFR) expression levels, comparing accuracy through receiver operator characteristic (ROC) curve analyses across varied tissue blocking and washing times. An optimized 8-min DDSI methodology was developed for future clinical translation. CONCLUSIONS: Successful completion of this work resulted in substantial shortening of the DDSI methodology for use in the operating room, that provided robust, highly receptor specific, sensitive diagnostic capabilities between benign and malignant tissues.
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Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Diagnóstico por Imagem/métodos , Sondas Moleculares , Animais , Neoplasias da Mama/cirurgia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Estadiamento de Neoplasias , Coloração e Rotulagem/métodosRESUMO
OBJECTIVE: We investigated the accuracy of digital breast tomosynthesis compared to full-field digital mammography for evaluating tumor-free resection margins in the intraoperative specimen during breast-conserving surgery, reducing re-excision rates. MATERIALS AND METHODS: In total, 170 patients, with proven breast cancer and eligible for breast-conserving surgery, were enrolled. Intraoperative specimens underwent digital mammography and digital breast tomosynthesis. Two breast radiologists, with ten years of experience in breast imaging, in batch mode, evaluated tumor-free resection margins and the distance between the margins and lesion. Histopathological findings were considered the standard of reference. RESULTS: We used the correlation analysis to evaluate the agreement between measures of tumor-free resection margins obtained with digital mammography and the true value (histopathological findings), and between digital breast tomosynthesis and histopathological findings. The size evaluation determined by digital breast tomosynthesis was more accurately correlated with that found by pathology; the calculated Pearson's correlation coefficient of digital breast tomosynthesis and digital mammography to the pathologically determined tumor-free resection margins were 0.92 and 0.79 in CC view and 0.92 and 0.72 in LL view, respectively. Compared with the pathologically determined tumor-free resection margins, the size determined by both imaging modalities was, on average, overestimated. Bland-Altman analysis showed an excellent inter readers agreement. CONCLUSIONS: Digital breast tomosynthesis is more accurate in assessment of margin status than digital mammography; it could be a more accurate technique than full-field digital mammography for the intraoperative delineating of tumor resection margins.
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Neoplasias da Mama/diagnóstico , Mamografia/métodos , Margens de Excisão , Mastectomia Segmentar/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
PURPOSE: To explore the ability of intraoperative specimen radiography (SR) to correctly identify positive margins in patients receiving breast conserving surgery (BCS). To assess whether the reoperation rate can be reduced by using this method. METHODS: This retrospective study included 470 consecutive cases receiving BCS due to a primarily diagnosed breast cancer. SR was carried out in two planes, assessing the specimen regarding the presence of the lesion and its relation to all margins. If indicated, re-excision of selective orientations was advised. Under consideration of gross inspection and the SR-findings, it was up to the surgeon whether to perform re-resections. The recommendations for re-excision were, separately for each orientation, compared to the histopathological results, serving as gold standard. RESULTS: Intraoperative SR was performed in 470 cases, thus 2820 margins were assessed. Of those, 2510 (89.0%) were negative and 310 (11.0%) positive. SR identified 2179 (77.3%) margins correctly as negative, whereas 331 (11.7%) clear margins were misjudged as positive. Of 310 infiltrated margins, SR identified 114 (4.0%) correctly, whereas 196 (7.0%) infiltrated margins were missed. This resulted in a sensitivity/specificity of 36.8%/86.8% and PPV/NPV of 25.6%/91.8%. Through targeted re-resections positive margins could be reduced by 31.0% [310 to 214 (7.6%)]. On case level, the rate of secondary procedures could be reduced by 37.0% [from 162 to 102 (21.7%)]. CONCLUSIONS: SR is a helpful tool to identify infiltrated margins and to reduce the rate of secondary surgeries by recommending targeted re-excisions of according orientations in order to obtain a final negative margin status.
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Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Cuidados Intraoperatórios , Mastectomia Segmentar , Radiografia , Idoso , Biópsia , Feminino , Humanos , Cuidados Intraoperatórios/métodos , Margens de Excisão , Mastectomia Segmentar/métodos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radiografia/métodos , Cirurgia Assistida por Computador , Terapêutica , Resultado do TratamentoRESUMO
Better knowledge of the breast tumor microenvironment is required for surgical resection and understanding the processes of tumor development. Raman spectroscopy is a promising tool that can assist in uncovering the molecular basis of disease and provide quantifiable molecular information for diagnosis and treatment evaluation. In this work, eighty-eight frozen breast tissue sections, including forty-four normal and forty-four tumor sections, were mapped in their entirety using a 250-µm-square measurement grid. Two or more smaller regions of interest within each tissue were additionally mapped using a 25 µm-square step size. A deep learning algorithm, convolutional neural network (CNN), was developed to distinguish histopathologic features with-in individual and across multiple tissue sections. Cancerous breast tissue were discriminated from normal breast tissue with 90 % accuracy, 88.8 % sensitivity and 90.8 % specificity with an excellent Area Under the Receiver Operator Curve (AUROC) of 0.96. Features that contributed significantly to the model were identified and used to generate RGB images of the tissue sections. For each grid point (pixel) on a Raman map, color was assigned to intensities at frequencies of 1002â¯cm-1 (Phenylalanine), 869â¯cm-1 (Proline, CC stretching of hydroxyproline-collagen assignment, single bond stretching vibrations for the amino acids proline, valine and polysaccharides) and 1309â¯cm-1 (CH3/CH2 twisting or bending mode of lipids). The Raman images clearly associate with hematoxylin and eosin stained tissue sections and allow clear visualization of boundaries between normal adipose, connective tissue and tumor. We demonstrated that this simple imaging technique allows high-resolution, straightforward molecular interpretation of Raman images. Raman spectroscopy provides rapid, label-free imaging of microscopic features with high accuracy. This method has application as laboratory tool and can assist with intraoperative tissue assessment during Breast Conserving surgery.
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Neoplasias da Mama/patologia , Análise Espectral Raman , Microambiente Tumoral , Aprendizado Profundo , Feminino , HumanosRESUMO
BACKGROUND AND OBJECTIVES: There is a clinical need to assess the resection margins of tongue cancer specimens, intraoperatively. In the current ex vivo study, we evaluated the feasibility of hyperspectral diffuse reflectance imaging (HSI) for distinguishing tumor from the healthy tongue tissue. STUDY DESIGN/MATERIALS AND METHODS: Fresh surgical specimens (n = 14) of squamous cell carcinoma of the tongue were scanned with two hyperspectral cameras that cover the visible and near-infrared spectrum (400-1,700 nm). Each pixel of the hyperspectral image represents a measure of the diffuse optical reflectance. A neural network was used for tissue-type prediction of the hyperspectral images of the visual and near-infrared data sets separately as well as both data sets combined. RESULTS: HSI was able to distinguish tumor from muscle with a good accuracy. The diagnostic performance of both wavelength ranges (sensitivity/specificity of visual and near-infrared were 84%/80% and 77%/77%, respectively) appears to be comparable and there is no additional benefit of combining the two wavelength ranges (sensitivity and specificity were 83%/76%). CONCLUSIONS: HSI has a strong potential for intra-operative assessment of tumor resection margins of squamous cell carcinoma of the tongue. This may optimize surgery, as the entire resection surface can be scanned in a single run and the results can be readily available. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
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Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/cirurgia , Imageamento Hiperespectral , Margens de Excisão , Neoplasias da Língua/diagnóstico por imagem , Neoplasias da Língua/cirurgia , Carcinoma de Células Escamosas/patologia , Estudos de Viabilidade , Humanos , Cuidados Intraoperatórios , Sensibilidade e Especificidade , Técnicas de Cultura de Tecidos , Neoplasias da Língua/patologiaRESUMO
Breast conservation surgery (BCS) aims to excise all cancerous tissue while minimizing the amount of healthy breast tissue removed. Up to 30% of patients undergoing BCS require a second operation for re-excision to obtain negative margins. Previous studies reported a lower re-excision rate with intraoperative use of the MarginProbe device (Dune Medical Devices). This device utilizes radiofrequency spectroscopy to detect differences between cancerous and normal tissue. From July 2009 to January 2010, our institution enrolled 46 patients electing for BCS in a prospective double-arm randomized controlled trial and had a significantly lower re-excision rate than that reported in the multicenter trial. Intraoperatively, after performing conventional lumpectomy with excision of any additional shavings deemed necessary based on palpation and visual inspection alone, patients were then randomized. In the device arm, the surgeon used the MarginProbe to interrogate the lumpectomy specimen, taking additional shavings from the cavity surfaces corresponding to the parts of the specimen read as positive by the device. In the control arm, only standard intraoperative assessments were performed. All specimens were evaluated by pathologists who were blinded to the study arm. In this population, 72% had invasive ductal carcinoma (IDC), 20% had ductal carcinoma in situ (DCIS), and 8% had invasive lobular carcinoma (ILC). Average age was 64 years old. The average size of the specimen was 5.6 cm, the average volume was 37.8 cm3 , and the average weight was 32.7 g. The mean size of DCIS was 1.4 cm. For invasive specimens, 32 were T1 and 7 were T2. Prior to randomization, 43 patients were thought to have positive or close margins and therefore underwent additional shavings. Twenty-three patients were randomized to the device arm and 23 to the control arm. In the device arm, 14 (60%) patients had IDC, 7 (30%) had DCIS, and 2 (8%) had ILC, vs the control arm where 19 (82%) patients had IDC, 2 (8%) had DCIS, and 2 (8%) had ILC. Eight (35%) patients in the control group vs 1 (4%) in the device group underwent re-excision for margin involvement (P < .05). The use of the MarginProbe device at our institution significantly improved the ability of our surgeons to obtain clear margins during initial BCS. Our results show a lower re-excision rate (4%) than those published in the multicenter trial (19.8%). We postulate that in the face of more patients having DCIS in our device group (30%), our surgeons responded by taking thicker shavings when the MarginProbe device reported margin involvement during the initial lumpectomy, resulting in greater success achieving clear final margins on the shaved tissue and a significantly lower re-excision rate than previously reported with the MarginProbe device.
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Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos , Cuidados Intraoperatórios , Mastectomia Segmentar , Pessoa de Meia-Idade , Estudos Prospectivos , Reoperação , Estudos RetrospectivosRESUMO
BACKGROUND: To analyze the feasibility and accuracy of micro-computed tomography (micro-CT) for surgical margin assessment in breast excision specimen. MATERIALS AND METHODS: Two data sets of 30 micro-CT scans were retrospectively evaluated for positive resection margins by four observers in two phases, using pathology as a gold standard. Results of phase 1 were evaluated to define micro-CT evaluation guidelines for phase 2. Interobserver agreement was also assessed (kappa). In addition, a prospective study was conducted in which 40 micro-CT scans were directly acquired, reconstructed, and evaluated for positive resection margins by one observer. A suspect positive resection margin on micro-CT was annotated onto the specimen with ink, enabling local validation by pathology. Main outcome measures were accuracy, sensitivity, specificity, and positive predictive value (PPV). RESULTS: Average accuracy, sensitivity, specificity, and PPV for the four observers were 63%, 38%, 70%, and 22%, respectively, in phase 1 and 72%, 40%, 78%, and 26%, respectively, in phase 2. The interobserver agreement was fair [kappa (range), 0.31 (0.12-0.80) in phase 1 and 0.23 (0-0.43) in phase 2]. In the prospective study 70% of the surgical resection margins were correctly evaluated. Ten specimens were annotated for positive resection margins, which correlated with three positive and three close (<1 mm) margins on pathology. Sensitivity, specificity, and PPV were 38%, 78%, and 30%, respectively. CONCLUSIONS: Micro-CT imaging of breast excision specimen has moderate accuracy and considerable interobserver variation for analysis of surgical resection margins. Especially sensitivity and PPV need to be improved before micro-CT-based margin assessment can be introduced in clinical practice.
Assuntos
Neoplasias da Mama/cirurgia , Mama/diagnóstico por imagem , Margens de Excisão , Mastectomia Segmentar , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Países Baixos , Variações Dependentes do Observador , Período Pós-Operatório , Estudos Prospectivos , Estudos Retrospectivos , Sensibilidade e Especificidade , Microtomografia por Raio-XRESUMO
BACKGROUND: Roughly 23% of breast conserving surgery (BCS) patients undergo a second re-excision procedure due to pathologically positive surgical margins. We investigated the feasibility and potential value of micro-Computed Tomography (micro-CT) as a surgical margin guidance tool during BCS. METHODS: A cohort of 32 BCS specimens was prospectively imaged with a pre-clinical micro-CT system upon arrival in the surgical pathology laboratory. Reconstructed micro-CT scans were evaluated retrospectively by an experienced breast radiologist, who provided binary determinations whether lesions extended to the specimen margin. These readings were then compared to the final pathological diagnosis and to 2D specimen radiography readings. RESULTS: Of the 32 specimens imaged, 28 had malignant and four had benign pathological diagnoses. Overall five (four malignant, one benign) of the 32 specimens had lesion tissue extending to the margin. For all 32 specimens, micro-CT reconstructions were calculated (< 4 min. acquisition + reconstruction time) and each specimen was volumetrically analyzed by a radiologist. Of the 28 malignant specimen readings, 18 matched the final pathological diagnosis [64%, 95 CI (47%-81%)], with a negative predictive value of 89% [95 CI (74%-96%)]. Micro-CT readings revealed changes in the tumor location and margin status as compared to single-projection radiography readings. CONCLUSIONS: Micro-CT scanning of BCS specimens enabled margin status assessment over the entirety of the surgical surface in a clinically relevant time frame, provided additional spatial information over single-projection radiography, and may be a potentially useful BCS guidance tool.