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BACKGROUND: In colorectal cancer surgery there is a delicate balance between complete removal of the tumor and sparing as much healthy tissue as possible. Especially in rectal cancer, intraoperative tissue recognition could be of great benefit in preventing positive resection margins and sparing as much healthy tissue as possible. To better guide the surgeon, we evaluated the accuracy of diffuse reflectance spectroscopy (DRS) for tissue characterization during colorectal cancer surgery and determined the added value of DRS when compared to clinical judgement. METHODS: DRS spectra were obtained from fat, healthy colorectal wall and tumor tissue during colorectal cancer surgery and results were compared to histopathology examination of the measurement locations. All spectra were first normalized at 800 nm, thereafter two support vector machines (SVM) were trained using a tenfold cross-validation. With the first SVM fat was separated from healthy colorectal wall and tumor tissue, the second SVM distinguished healthy colorectal wall from tumor tissue. RESULTS: Patients were included based on preoperative imaging, indicating advanced local stage colorectal cancer. Based on the measurement results of 32 patients, the classification resulted in a mean accuracy for fat, healthy colorectal wall and tumor of 0.92, 0.89 and 0.95 respectively. If the classification threshold was adjusted such that no false negatives were allowed, the percentage of false positive measurement locations by DRS was 25% compared to 69% by clinical judgement. CONCLUSION: This study shows the potential of DRS for the use of tissue classification during colorectal cancer surgery. Especially the low false positive rate obtained for a false negative rate of zero shows the added value for the surgeons. Trail registration This trail was performed under approval from the internal review board committee (Dutch Trail Register NTR5315), registered on 04/13/2015, https://www.trialregister.nl/trial/5175 .
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Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/cirugía , Cirugía Colorrectal , Óptica y Fotónica/métodos , Anciano , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Sensibilidad y Especificidad , Análisis Espectral , CirujanosRESUMEN
This pilot study explored the value of localized index node removal after neoadjuvant immunotherapy in patients with stage III melanoma, for use as a response indicator to guide the extent of completion lymph node dissection. Promising technology.
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Antineoplásicos Inmunológicos/uso terapéutico , Ipilimumab/uso terapéutico , Escisión del Ganglio Linfático/métodos , Melanoma/tratamiento farmacológico , Melanoma/cirugía , Terapia Neoadyuvante , Nivolumab/uso terapéutico , Femenino , Humanos , Escisión del Ganglio Linfático/instrumentación , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Metástasis Linfática , Magnetismo , Masculino , Melanoma/diagnóstico por imagen , Melanoma/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Proyectos Piloto , UltrasonografíaRESUMEN
Recognition of the tumor during breast-conserving surgery (BCS) can be very difficult and currently a robust method of margin assessment for the surgical setting is not available. As a result, tumor-positive margins, which require additional treatment, are not found until histopathologic evaluation. With diffuse reflectance spectroscopy (DRS), tissue can be characterized during surgery based on optical parameters that are related to the tissue morphology and composition. Here we investigate which optical parameters are able to detect tumor in an area with a mixture of benign and tumor tissue and hence which parameters are most suitable for intra-operative margin assessment. DRS spectra (400-1600 nm) were obtained from 16 ex vivo lumpectomy specimens from benign, tumor border, and tumor tissue. One mastectomy specimen was used with a custom-made grid for validation purposes. The optical parameter related to the absorption of fat and water (F/W-ratio) in the extended near-infrared wavelength region (~1000-1600 nm) provided the best discrimination between benign and tumor sites resulting in a sensitivity and specificity of 100 % (excluding the border sites). Per patient, the scaled F/W-ratio gradually decreased from grossly benign tissue towards the tumor in 87.5 % of the specimens. In one test case, based on a predefined F/W-ratio for boundary tissue of 0.58, DRS produced a surgical resection plane that nearly overlapped with a 2-mm rim of benign tissue, 2 mm being the most widely accepted definition of a negative margin. The F/W-ratio provided excellent discrimination between sites clearly inside or outside the tumor and was able to detect the border of the tumor in one test case. This work shows the potential for DRS to guide the surgeon during BCS.
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Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Análisis Espectral/métodos , Neoplasias de la Mama/química , Femenino , Humanos , Periodo Intraoperatorio , Mastectomía Segmentaria , Espectroscopía Infrarroja Corta/métodos , AguaRESUMEN
BACKGROUND: Surgery for colorectal cancer aims for complete tumor resection. Optical-based techniques can identify tumor and surrounding tissue through the tissue specific optical properties, absorption and scattering, which are both influenced by the biochemical and morphological composition of the tissue. OBJECTIVE: To evaluate the feasibility of dual-modality Diffuse Reflectance Spectroscopy-Fluorescence Spectroscopy (DRS-FS) for discrimination between healthy and malignant tissue in colorectal surgery. METHODS: Surgical specimens from colorectal cancer patients were measured immediately after resection using a fiber-optic needle capable of dual-modality DRS-FS. Model-based analyses were used to derive scattering and absorption coefficients and intrinsic fluorescence. Volume fractions of chromophores were estimated. Furthermore, optical data were recorded along a trajectory from healthy tissue towards tumor. RESULTS: Spectral characteristics were identified in 1,273 measured spectra from 21 specimens. Combined DRS and FS discriminated tumor from surrounding tissue with a sensitivity of 95% and a specificity of 88%. Significant spectral changes were seen along the trajectory from healthy tissue to tumor. CONCLUSION: This study demonstrates that dual-modality DRS-FS can identify colorectal cancer from surrounding healthy tissue. The quantification of comprehensible parameters allows robust classification and facilitates extrapolation towards the clinical setting. The technique, here demonstrated in a needle like probe, can be incorporated into surgical tools for optically guided surgery in the near future. Lasers Surg. Med. 47:559-565, 2015. © 2015 Wiley Periodicals, Inc.
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BACKGROUND: Cutaneous melanomas are diagnosed worldwide in 231,130 patients per year. The sensitivity and specificity of melanoma diagnosis expresses the need for an additional diagnostic method. Optical coherence tomography (OCT) has shown that it allows morphological (qualitative) description of image features and quantitative analysis of pathology related light scattering by means of the attenuation coefficient (µoct ). OBJECTIVE: We hypothesize that OCT images of nevi will differ qualitatively and quantitatively from melanomas. METHODS: Forty lesions from 33 consecutive patients were imaged with OCT. After data acquisition, excision was performed. Epidermal layer thickness was measured and values of µoct were extracted from 200 OCT images of pigmented lesions. RESULTS: Morphologically, absence of the lower border of the lesion was characteristic for melanoma (P = 0.02). Also, the µoct was different between benign and malignant lesions (P = 0.02). There were no differences in epidermal layer thickness of benign lesions and melanoma. CONCLUSION: Although this preliminary study comprised a small number of patients, quantitative analysis of OCT images in pigmented skin lesions give valuable additional information about lesions characteristics. When using the attenuation coefficient, it might be possible to distinguish between benign lesions and melanomas.
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Melanoma/patología , Nevo Pigmentado/patología , Neoplasias Cutáneas/patología , Tomografía de Coherencia Óptica , Adulto , Epidermis/patología , Femenino , Humanos , Imagenología Tridimensional , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Curva ROCRESUMEN
Optical coherence tomography (OCT) is an optical technique that measures the backscattering of near-infrared light by tissue. OCT yields in 2D and 3D images at micrometer-scale resolution, thus providing optical biopsies, approaching the resolution of histopathological imaging. The technique has shown to allow in vivo differentiation between benign and malignant epithelial tissue, through qualitative assessment of OCT images, as well as by quantitative evaluation, e.g., functional OCT. This study aims to summarize the principles of OCT and to discuss the current literature on the diagnostic value of OCT in the diagnosis of epithelial (pre)malignant lesions. The authors did a systematic search of the electronic databases PubMed and Embase on OCT in the diagnostic process of (pre)malignant epithelial lesions. OCT is able to differentiate between benign and (pre)malignant lesions of epithelial origin in a wide variety of tissues. In this way, OCT can detect skin cancers, oral, laryngeal, and esophageal cancer as well as genital and bladder cancer. OCT is an innovative technique which enables an optical biopsy of epithelial lesions. The incorporation of OCT in specific tools, like handheld and catheter-based probes, will further improve the implementation of this technology in daily clinical practice.
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Epitelio/patología , Tomografía de Coherencia Óptica/métodos , Biopsia , Humanos , Neoplasias/patologíaRESUMEN
Robot-assisted surgery is increasingly used in surgery for cancer. Reduced overview and loss of anatomical orientation are challenges that might be solved with image-guided surgical navigation using electromagnetic tracking (EMT). However, the robot's presence may distort the electromagnetic field, affecting EMT accuracy. The aim of this study was to evaluate the robot's influence on EMT accuracy. For this purpose, two different electromagnetic field generators were used inside a clinical surgical environment: a table top field generator (TTFG) and a planar field generator (PFG). The position and orientation of sensors within the electromagnetic field were measured using an accurate in-house developed 3D board. Baseline accuracy was measured without the robot, followed by stepwise introduction of potential distortion sources (robot and robotic instruments). The absolute accuracy was determined within the entire 3D board and in the clinical working volume. For the baseline setup, median errors in the entire tracking volume within the 3D board were 0.9 mm and 0.3° (TTFG), and 1.1 mm and 0.4° (PFG). Adding the robot and instruments did not affect the TTFG's position accuracy (p = 0.60), while the PFG's accuracies decreased to 1.5 mm and 0.7° (p < 0.001). For both field generators, when adding robot and instruments, accuracies inside the clinical working volume were higher compared to the entire tracking 3D board volume, 0.7 mm and 0.3° (TTFG), and 1.1 mm and 0.7° (PFG). Introduction of a surgical robot and robotic instruments shows limited distortion of the EMT field, allowing sufficient accuracy for surgical navigation in robotic procedures.
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Procedimientos Quirúrgicos Robotizados , Robótica , Cirugía Asistida por Computador , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Fenómenos Electromagnéticos , Cirugía Asistida por Computador/métodosRESUMEN
BACKGROUND: We investigated whether genomic aberrations in primary colorectal cancer (CRC) can identify patients who are at increased risk of developing additional hepatic recurrence after colorectal liver metastases (CLM) resection. METHODS: Primary tumour DNA from 79 CLM resected patients was analysed for recurrent copy number changes (12x135k NimbleGen(™) aCGH). The cohort was divided into three groups: CLM patients with a recurrence-free survival after hepatic resection of at least 5 years (n = 21), patients who developed intra-hepatic recurrence (n = 32), and patients who developed extrahepatic recurrence (n = 26). By contrasting the primary tumour profiles of recurrence free and the extrahepatic recurrence CLM patients, a classifier, the extra-hepatic recurrence classifier (ERC1), predictive for subsequent extrahepatic-recurrence was developed. RESULTS: The ERC1 had an accuracy of 70 % (95 % confidence interval (CI): 55-82 %, misclassification error 30 %, base error rate: 45 %). This analysis identified a region on Chromosome 12p13 as differentially aberrated between these two groups. The classifier was further optimized by contrasting the extrahepatic recurrence group with the combined group of intrahepatic and no recurrence group, resulting in an extrahepatic prognostic classifier (ERC2) able to classify patients with CLMs suitable for hepatic resection with 74 % accuracy (95 % CI: 62-83 %, misclassification error 26 %, base error rate: 32 %). CONCLUSIONS: Patients with CLM who will develop extrahepatic recurrence may be identified with ERCs based on information in the primary tumour. Risk estimates for the occurrence of extrahepatic metastases may allow a reduction of hepatic resections of colorectal liver metastases for those who are unlikely to develop extrahepatic metastases.
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Aberraciones Cromosómicas , Neoplasias Colorrectales/genética , Genómica , Hepatectomía , Neoplasias Hepáticas/genética , Recurrencia Local de Neoplasia/genética , Selección de Paciente , Adulto , Anciano , Cromosomas Humanos Par 12/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Hibridación Genómica Comparativa , ADN de Neoplasias/genética , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Análisis de Secuencia por Matrices de Oligonucleótidos , PronósticoRESUMEN
PURPOSE: Surgical navigation techniques can guide surgeons in localizing pelvic-abdominal malignancies. For abdominal navigation, accurate patient registration is crucial and is generally performed using an intra-operative cone-beam CT (CBCT). However, this method causes 15-min surgical preparation workflow interruption and radiation exposure, and more importantly, it cannot be repeated during surgery to compensate for large patient movement. As an alternative, the accuracy and feasibility of tracked ultrasound (US) registration are assessed in this patient study. METHODS: Patients scheduled for surgical navigation during laparotomy of pelvic-abdominal malignancies were prospectively included. In the operating room, two percutaneous tracked US scans of the pelvic bone were acquired: one in supine and one in Trendelenburg patient position. Postoperatively, the bone surface was semiautomatically segmented from US images and registered to the bone surface on the preoperative CT scan. The US registration accuracy was computed using the CBCT registration as a reference and acquisition times were compared. Additionally, both US measurements were compared to quantify the registration error caused by patient movement into Trendelenburg. RESULTS: In total, 18 patients were included and analyzed. US registration resulted in a mean surface registration error of 1.2 ± 0.2 mm and a mean target registration error of 3.3 ± 1.4 mm. US acquisitions were 4 × faster than the CBCT scans (two-sample t-test P < 0.05) and could even be performed during standard patient preparation before skin incision. Patient repositioning in Trendelenburg caused a mean target registration error of 7.7 ± 3.3 mm, mainly in cranial direction. CONCLUSION: US registration based on the pelvic bone is accurate, fast and feasible for surgical navigation. Further optimization of the bone segmentation algorithm will allow for real-time registration in the clinical workflow. In the end, this would allow intra-operative US registration to correct for large patient movement. TRIAL REGISTRATION: This study is registered in ClinicalTrials.gov (NCT05637359).
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Neoplasias Abdominales , Neoplasias Pélvicas , Cirugía Asistida por Computador , Humanos , Estudios de Factibilidad , Ultrasonografía , Tomografía Computarizada por Rayos X/métodos , Neoplasias Pélvicas/diagnóstico por imagen , Neoplasias Pélvicas/cirugía , Cirugía Asistida por Computador/métodos , Imagenología TridimensionalRESUMEN
Approximately 20 % of patients with colorectal cancer have synchronous liver metastases at the time of diagnosis. In some instances it is difficult to determine the best treatment strategy in these patients. For example, should the primary tumor be removed in those patients with unresectable liver metastases and who do not have any symptoms of the primary tumor? Or which operation should be performed first in patients with rectal cancer and synchronous resectable liver metastases? Unfortunately, there are no clear answers to these questions from prospective randomized trials. In the present article retrospective studies are analyzed in order to define the best possible treatment strategy for patients with synchronous colorectal liver metastases.
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Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Quimioradioterapia , Neoplasias Colorrectales/mortalidad , Procedimientos Quirúrgicos del Sistema Digestivo , Humanos , Neoplasias Hepáticas/mortalidadRESUMEN
BACKGROUND AND OBJECTIVE: Excision and histological assessment of the first draining node (sentinel lymph node) is a frequently used method to assess metastatic lymph node involvement related to cutaneous melanoma. Due to the time required for accurate histological assessment, nodal status is not immediately available to the surgeon. Hence, in case histological examination shows metastases, the patient has to be recalled to perform additional lymphadenectomy. To overcome these drawbacks we studied the applicability of photoacoustic tomographic imaging as an intra-operative modality for examining the status of resected lymph nodes. MATERIALS AND METHODS: In melanoma patients undergoing lymphadectomy for metastatic disease, six suspect lymph nodes were photoacoustically (PA) imaged using multiple wavelengths. Histopathologal examination showed three nodes without tumor cells (benign nodes) and three nodes with melanoma cells (malignant nodes). PA images were compared with histology and anatomical features were analyzed. In addition, PA spectral analysis was performed on areas of increased signal intensity. RESULTS: After correlation with histopathology, multiple areas containing melanoma cells could be identified in the PA images due to their increased response. Malignant nodes showed a higher PA response and responded differently to an increase in excitation wavelength than benign nodes. In addition, differences in anatomical features between the two groups were detected. CONCLUSIONS: Photoacoustic detection of melanoma metastases based on their melanin content proves to be possible in resected human lymph nodes. The amount of PA signal and several specific anatomical features seem to provide additional characteristics for nodal analysis. However, it is as yet preliminary to designate a highly accurate parameter to distinguish between malignant and benign nodes. We expect to improve the specificity of the technique with a future implementation of an adjusted illumination scheme and depth correction for photon fluence.
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Cuidados Intraoperatorios/métodos , Escisión del Ganglio Linfático , Metástasis Linfática/diagnóstico , Melanoma/patología , Técnicas Fotoacústicas/métodos , Neoplasias Cutáneas/patología , Tomografía , Axila , Biomarcadores de Tumor/metabolismo , Humanos , Conducto Inguinal , Láseres de Estado Sólido , Melaninas/metabolismo , Melanoma/metabolismo , Melanoma/cirugía , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/cirugíaRESUMEN
BACKGROUND: Surgical treatment of colorectal liver metastases has become increasingly aggressive. The influence of this more active surgical approach on patients' health-related quality of life (HRQoL) has hardly been evaluated. This study investigated the impact of surgical and systemic treatment on HRQoL in patients undergoing hepatic resection for colorectal metastases. METHODS: A total of 145 patients with colorectal liver metastases were entered prospectively into the study. Based on HRQoL values derived from the EuroQol-5D, health summary measures were calculated to express the overall impact on four distinct clinical states. The HRQoL instrument was used at baseline, 3 and 6 weeks after surgery, and every 3 months thereafter for up to 3 years. RESULTS: Patients showed a clear deterioration in HRQoL in the first weeks after surgery, followed by a recovery to baseline levels at 3 months after potentially curative surgery. In contrast, a sustained decline was noted when initial surgery for colorectal liver metastases was considered futile and palliative chemotherapy was started immediately. Three years after initial surgery, there were distinct differences in HRQoL between patients with or without recurrence. The latter group still had HRQoL scores at baseline levels, whereas patients with tumour recurrence showed a significant deterioration in HRQoL. Remarkably, there was no decline in HRQoL in patients with recurrent disease who could be treated by secondary surgical intervention. CONCLUSION: Superior overall HRQoL in the first 3 years after initial successful surgical intervention merits an aggressive surgical approach and intensive follow-up to detect recurrence early.
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Neoplasias Colorrectales/mortalidad , Neoplasias Hepáticas/secundario , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Estudios Prospectivos , Años de Vida Ajustados por Calidad de VidaRESUMEN
The main challenge for radical resection in oral cancer surgery is to obtain adequate resection margins. Especially the deep margin, which can only be estimated based on palpation during surgery, is often reported inadequate. To increase the percentage of radical resections, there is a need for a quick, easy, minimal invasive method, which assesses the deep resection margin without interrupting or prolonging surgery. This systematic review provides an overview of technologies that are currently being studied with the aim of fulfilling this demand. A literature search was conducted through the databases Medline, Embase and the Cochrane Library. A total of 62 studies were included. The results were categorized according to the type of technique: 'Frozen Section Analysis', 'Fluorescence', 'Optical Imaging', 'Conventional imaging techniques', and 'Cytological assessment'. This systematic review gives for each technique an overview of the reported performance (accuracy, sensitivity, specificity, positive predictive value, negative predictive value, or a different outcome measure), acquisition time, and sampling depth. At the moment, the most prevailing technique remains frozen section analysis. In the search for other assessment methods to evaluate the deep resection margin, some technologies are very promising for future use when effectiveness has been shown in larger trials, e.g., fluorescence (real-time, sampling depth up to 6 mm) or optical techniques such as hyperspectral imaging (real-time, sampling depth few mm) for microscopic margin assessment and ultrasound (less than 10 min, sampling depth several cm) for assessment on a macroscopic scale.
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Secciones por Congelación , Márgenes de Escisión , Neoplasias de la Boca/diagnóstico por imagen , Neoplasias de la Boca/cirugía , Imagen Óptica/métodos , Técnicas Citológicas , Fluorescencia , Humanos , Imagen por Resonancia Magnética , Neoplasias de la Boca/patología , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
OBJECTIVE: In the Netherlands, the surgical mask is part of the standard surgical attire even for the non-sterile personnel in the operation theatre. Solid evidence on the effect on postoperative infection rates is missing. Due to a national scarcity in surgical masks during the first wave of the COVID-19 crisis the usage of these masks was decreased. In our tertiary referral centre for Surgical Oncology, this led to the decision that, for a period of ten weeks, the surgical masks were only being used by the sterile surgical team and not by non-sterile operation theatre personnel. This retrospective study evaluates the influence of this intervention in terms of postoperative wound infection rates. DESIGN: Retrospective cohort study. METHOD: Consecutive patients undergoing surgery during the first COVID-19 wave (2-3-2020 until 11-05-2020) were compared with patients undergoing surgery in the same period a year earlier. Patients undergoing surgery for soft-tissue malignancies were included. Intra-abdominal surgery was excluded. Primary outcome measurement was wound infection rate within 30 days following surgery. Secondary, a cost reduction analysis was made. RESULTS: In the COVID-19 wave, a total of 219 patients underwent surgery for soft-tissue malignancies, compared to 241 a year earlier. The incidence of postoperative wound infection was 58/460 (12.6%) for the total cohort. There was no difference in infection rate between the COVID-19 period and the same period in 2019; 25/219 (11,4%; 95% CI: 7,8-16,4)) vs. 33/241 (13,7%; 95% CI: 9,8-18,6), p = 0,46) respectively. During the COVID-19 wave, a total of 6.400 of surgical masks were used by the personnel in the operation theatre complex, compared to a total of 11.000 in the same period in 2019. This resulted in a reduction of 42% in usage of surgical masks. CONCLUSION: Based on this mono-centric, explorative retrospective cohort study, it seems that omitting the surgical mask for the non-sterile operation theatre personnel does not influence the postoperative wound infection rate. Despite the fact that our sample size is small, the impressive reduction in usage of 42% demands further research initiatives on a larger scale.
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COVID-19 , Máscaras , Humanos , Estudios Retrospectivos , SARS-CoV-2 , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/prevención & controlRESUMEN
The purpose of this study was to evaluate the feasibility of electromagnetic (EM) navigation for guidance on osteotomies in patients undergoing oncologic mandibular surgery. Preoperatively, a 3D rendered model of the mandible was constructed from diagnostic computed tomography (CT) images. Cutting guides and patient specific reconstruction plates were designed and printed for intraoperative use. Intraoperative patient registration was performed using a cone beam CT scan (CBCT). The location of the mandible was tracked with an EM sensor fixated to the mandible. The real-time location of both the mandible and a pointer were displayed on the navigation system. Accuracy measurements were performed by pinpointing four anatomical landmarks and four landmarks on the cutting guide using the pointer on the patient and comparing these locations to the corresponding locations on the CBCT. Differences between actual and virtual locations were expressed as target registration error (TRE). The procedure was performed in eleven patients. TREs were 3.2 ± 1.1 mm and 2.6 ± 1.5 mm using anatomical landmarks and landmarks on the cutting guide, respectively. The navigation procedure added on average half an hour to the duration of the surgery. This is the first study that reports on the accuracy of EM navigation in patients undergoing mandibular surgery.
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Campos Electromagnéticos , Mandíbula/cirugía , Procedimientos Quirúrgicos Ortognáticos/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del ObservadorRESUMEN
In this report we investigated local regulatory mechanisms in graft rejection and their response to local immunosuppressive therapy. For this purpose local immunosuppression was induced in rat kidney allografts by intrarenal infusion of prednisolone. Intrarenal drug delivery resulted in high drug levels within the graft and low systemic drug levels. Systemic drug levels were by themselves not sufficiently immunosuppressive to induce graft survival, and local prednisolone levels within the graft proved to be responsible for prolongation of graft survival. During intrarenal drug delivery, systemic responsiveness to the renal allograft proved normal, since intrarenally treated grafts were infiltrated by MHC class II-positive host cells and, except for a somewhat lower percentage of macrophages, cellular infiltration in intrarenal treated grafts was comparable to untreated grafts. However, T cells and macrophages present in intrarenally treated grafts were not able to destroy the grafted tissue. Local immunosuppressive therapy resulted in inhibition of IL-2-R expression, absence of IFN-gamma, and prevention of MHC class II induction on grafted tissue. These observations strongly indicate the presence of local regulatory mechanisms in graft rejection. The experimental model described can be used for further analysis of these intragraft events. Moreover, the results demonstrate that local immunosuppressive therapy can contribute to effective inhibition of cellular immune response in graft rejection.
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Terapia de Inmunosupresión , Trasplante de Riñón , Prednisolona/farmacología , Animales , Rechazo de Injerto , Antígenos de Histocompatibilidad/análisis , Inmunohistoquímica , Interferón gamma/biosíntesis , Interleucina-2/biosíntesis , Riñón/efectos de los fármacos , Riñón/inmunología , Macrófagos/inmunología , Masculino , Prednisolona/administración & dosificación , Ratas , Ratas Endogámicas BN , Ratas Endogámicas Lew , Linfocitos T/inmunologíaRESUMEN
Angiogenesis, the formation of new blood vessels, is a multi-step process regulated by pro- and anti-angiogenic factors. In order to grow and metastasize, tumors need a constant supply of oxygen and nutrients. For their growth beyond the size of 1-2 mm tumors are dependent on angiogenesis. Recently, various new anti-cancer agents (e.g. bevacizumab, sorafenib and sunitinib) have become available that specifically inhibit angiogenesis in tumors. To evaluate the effects of these new anti-angiogenic agents it would be of interest to scintigraphically image the process of angiogenesis in tumors. Several markers have been described that are preferentially expressed on newly formed blood vessels in tumors (alpha(v)beta(3) integrin, vascular endothelial growth factor and its receptor, prostate-specific membrane antigen) and in the extracellular matrix surrounding newly formed blood vessels (extra-domain B of fibronectin, Tenascin-C, matrix metalloproteinases, Robo-4). Several ligands targeting these markers have been tested as a radiotracer for imaging angiogenesis in tumors. The potential of some of these tracers such as radiolabeled cyclic RGD peptides and radiolabeled anti-PSMA antibodies has already been tested cancer patients, while for markers such as Robo-4 the ligand has not yet been identified. Here the preclinical and clinical studies with these new tracers to image angiogenesis in tumors are reviewed.
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Inhibidores de la Angiogénesis/uso terapéutico , Neoplasias/diagnóstico , Neovascularización Patológica/diagnóstico , Animales , Antígenos de Superficie , Biomarcadores de Tumor/metabolismo , Proteínas de la Matriz Extracelular , Glutamato Carboxipeptidasa II , Humanos , Integrina alfaVbeta3/metabolismo , Metaloproteinasas de la Matriz , Neoplasias/tratamiento farmacológico , Neoplasias/fisiopatología , Neovascularización Patológica/tratamiento farmacológico , Oligopéptidos/metabolismo , Radiofármacos , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial VascularRESUMEN
We wanted to find out whether ultrasound (US) can be used to assess the deep resection margins after excision of squamous cell carcinoma (SCC) of the tongue, as intraoperative feedback on their condition might help to prevent them being too close. Resected specimens of cancers of the tongue from 31 patients with SCC of the tongue were suspended in US gel and scanned with a small 5-10MHz US probe. The tumour was readily visible and US could differentiate it from muscle tissue. The margin of normal tongue musculature surrounding the tumour was measured on the US images, and the minimal resection margin was noted and compared with that reported by the histopathologist. The mean (SD) deep resection margins measured on the US images differed by 1.1 (0.9) mm from those reported by the histopathologist (Pearson's correlation coefficient: 0.79, p<0.01). The US measurements took a maximum of five minutes. It is feasible to use US to assess resection specimens of SCC of the tongue as an adjunct to existing strategies (such as frozen section analysis) to help achieve the desired deep surgical margins. The method is easy to incorporate into surgical routine as it does not take long.
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Carcinoma de Células Escamosas , Neoplasias de la Lengua , Secciones por Congelación , Humanos , Márgenes de Escisión , LenguaRESUMEN
INTRODUCTION: In the 8th edition of the AJCC/UICC cancer staging system (AJCC8), the depth of invasion (DOI) of the oral cavity tumor is the discriminative factor in tumor staging over the previously used greatest dimension (GD). In order to obtain a complete representation of how accurate we stage oral cavity cancer clinically, we evaluated the accuracy of measurements of the tumor dimensions on ultrasound (US) and magnetic resonance (MR) imaging by comparing this with the histopathology as the "golden standard". Secondly, we compared the pathological tumor staging of these tumors according to the AJCC7 and AJCC8, to evaluate the effect of the incorporation of the DOI in the AJCC8. MATERIALS AND METHODS: In a retrospective analysis, including 85 oral cavity tumors, the GD and tumor thickness (TT) measured on US and MR, were compared to histopathology with a Pearson correlation coefficient (R) and a Bland-Altman plot. The tumors were staged according to both the AJCC7 and AJCC8. RESULTS: TT was more reliably measured with US (Râ¯=â¯0.67, limits of agreementâ¯=â¯10.7â¯mm), whereas GD was more reliably measured with MR (Râ¯=â¯0.69, limits of agreementâ¯=â¯25.7â¯mm). The AJCC8 staging resulted into a higher tumor stage in 21% of the cases, compared to the AJCC7. CONCLUSION: For preoperative tumor staging, the TT is best estimated by the use of US. The incorporation of DOI in the AJCC8 can result in a higher tumor stage in more than twenty percent of the patients, with an associated worse prognosis for the patient.