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1.
Artigo em Inglês | MEDLINE | ID: mdl-32554066

RESUMO

PURPOSE: Fluorescently labeled epidermal growth factor receptor (EGFR) antibodies have successfully identified microscopic tumors in multiple in vivo models of human cancers with limited toxicity. The present study sought to demonstrate the ability of fluorescently labeled anti-EGFR, cetuximab-IRDye800, to localize to ameloblastoma (AB) tumor cells in vitro and in vivo. MATERIAL AND METHODS: EGFR expression in AB cells was confirmed by quantitative real-time polymerase chain reaction and immunohistochemistry. Primary AB cells were labeled in vitro with cetuximab-IRDye800 or nonspecific IgG-IRDye800. An in vivo patient-derived xenograft (PDX) model of AB was developed. The tumor tissue from 3 patients was implanted subcutaneously into immunocompromised mice. The mice received an intravenous injection of cetuximab-IRDye800 or IgG-IRDye800 and underwent imaging to detect infrared fluorescence using a Pearl imaging system (LI-COR Biosciences, Lincoln, NE). After resection of the overlying skin, the tumor/background ratios (TBRs) were calculated and statistically analyzed using a paired t test. RESULTS: EGFR expression was seen in all AB samples. Tumor-specific labeling was achieved, as evidenced by a positive fluorescence signal from cetuximab-IRDye800 binding to AB cells, with little staining seen in the negative controls treated with IgG-IRDye800. In the animal PDX model, imaging revealed that the TBRs produced by cetuximab were significantly greater than those produced by IgG on days 7 to 14 for AB-20 tumors. After skin flap removal to simulate a preresection state, the TBRs increased with cetuximab and were significantly greater than the TBRs with the IgG control for PDX tumors derived from the 3 patients with AB. The excised tissues were embedded in paraffin and examined to confirm the presence of tumor. CONCLUSIONS: Fluorescently labeled anti-EGFR demonstrated specificity for AB cells and PDX tumors. The present study is the first report of tumor-specific, antibody-based imaging of odontogenic tumors, of which AB is one of the most clinically aggressive. We expect this technology will ultimately assist surgeons treating AB by helping to accurately assess the tumor margins during surgery, leading to improved long-term local tumor control and less surgical morbidity.

2.
Lancet Gastroenterol Hepatol ; 5(8): 753-764, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32416764

RESUMO

BACKGROUND: Complete surgical resection remains the primary curative option for pancreatic ductal adenocarcinoma, with positive margins in 30-70% of patients. In this study, we aimed to evaluate the use of intraoperative tumour-specific imaging to enhance a surgeon's ability to detect visually occult cancer in real time. METHODS: In this single-centre, open-label, single-arm study, done in the USA, we enrolled patients who had clinically suspicious or biopsy-confirmed pancreatic ductal adenocarcinomas and were scheduled for curative surgery. Eligible patients were 19 years of age or older with a life expectancy of more than 12 weeks and a Karnofsky performance status of at least 70% or an Eastern Cooperative Oncology Group or Zubrod level of one or lower, who were scheduled to undergo curative surgery. Patients were sequentially enrolled into each dosing group and 2-5 days before surgery, patients were intravenously infused with 100 mg of unlabelled panitumumab followed by 25 mg, 50 mg, or 75 mg of the near-infrared fluorescently labelled antibody (panitumumab-IRDye800CW). The primary endpoint was to determine the optimal dose of panitumumab-IRDye800CW in identifying pancreatic ductal adenocarcinomas as measured by tumour-to-background ratio in all patients. The tumour-to-background ratio was defined as the fluorescence signal of the tumour divided by the fluorescence signal of the surrounding healthy tissue. The dose-finding part of this study has been completed. This study is registered with ClinicalTrials.gov, NCT03384238. FINDINGS: Between April, 2018, and July, 2019, 16 patients were screened for enrolment onto the study. Of the 16 screened patients, two (12%) patients withdrew from the study and three (19%) were not eligible; 11 (69%) patients completed the trial, all of whom were clinically diagnosed with pancreatic ductal adenocarcinoma. The mean tumour-to-background ratio of primary tumours was 3·0 (SD 0·5) in the 25 mg group, 4·0 (SD 0·6) in the 50 mg group, and 3·7 (SD 0·4) in the 75 mg group; the optimal dose was identified as 50 mg. Intraoperatively, near-infrared fluorescence imaging provided enhanced visualisation of the primary tumours, metastatic lymph nodes, and small (<2 mm) peritoneal metastasis. Intravenous administration of panitumumab-IRDye800CW at the doses of 25 mg, 50 mg, and 75 mg did not result in any grade 3 or higher adverse events. There were no serious adverse events attributed to panitumumab-IRDye800CW, although four possibly related adverse events (grade 1 and 2) were reported in four patients. INTERPRETATION: To our knowledge, this study presents the first clinical use of panitumumab-IRDye800CW for detecting pancreatic ductal adenocarcinomas and shows that panitumumab-IRDye800CW is safe and feasible to use during pancreatic cancer surgery. Tumour-specific intraoperative imaging might have added value for treatment of patients with pancreatic ductal adenocarcinomas through improved patient selection and enhanced visualisation of surgical margins, metastatic lymph nodes, and distant metastasis. FUNDING: National Institutes of Health and the Netherlands Organization for Scientific Research.

3.
Head Neck ; 42(6): 1159-1167, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32298036

RESUMO

The COVID-19 pandemic has placed an extraordinary demand on the United States health care system. Many institutions have canceled elective and non-urgent procedures to conserve resources and limit exposure. While operational definitions of elective and urgent categories exist, there is a degree of surgeon judgment in designation. In the present commentary, we provide a framework for prioritizing head and neck surgery during the pandemic. Unique considerations for the head and neck patient are examined including risk to the oncology patient, outcomes following delay in head and neck cancer therapy, and risk of transmission during otolaryngologic surgery. Our case prioritization criteria consist of four categories: urgent-proceed with surgery, less urgent-consider postpone > 30 days, less urgent-consider postpone 30 to 90 days, and case-by-case basis. Finally, we discuss our preoperative clinical pathway for transmission mitigation including defining low-risk and high-risk surgery for transmission and role of preoperative COVID-19 testing.


Assuntos
Infecções por Coronavirus/epidemiologia , Neoplasias de Cabeça e Pescoço/cirurgia , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Tempo para o Tratamento/estatística & dados numéricos , Agendamento de Consultas , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Prioridades em Saúde , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Seleção de Pacientes , Pneumonia Viral/prevenção & controle , Avaliação de Programas e Projetos de Saúde , Oncologia Cirúrgica/organização & administração , Estados Unidos
4.
Nat Biomed Eng ; 4(3): 247-249, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32165734
5.
Clin Cancer Res ; 26(11): 2582-2594, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31980465

RESUMO

PURPOSE: The efficacy of antibody-based therapeutics depends on successful drug delivery into solid tumors; therefore, there is a clinical need to measure intratumoral antibody distribution. This study aims to develop and validate an imaging and computation platform to directly quantify and predict antibody delivery into human head and neck cancers in a clinical study. EXPERIMENTAL DESIGN: Twenty-four patients received systemic infusion of a near-infrared fluorescence-labeled therapeutic antibody followed by surgical tumor resection. A computational platform was developed to quantify the extent of heterogeneity of intratumoral antibody distribution. Both univariate and multivariate regression analyses were used to select the most predictive tumor biological factors for antibody delivery. Quantitative image features from the pretreatment MRI were extracted and correlated with fluorescence imaging of antibody delivery. RESULTS: This study not only confirmed heterogeneous intratumoral antibody distribution in-line with many preclinical reports, but also quantified the extent of interpatient, intertumor, and intratumor heterogeneity of antibody delivery. This study demonstrated the strong predictive value of tumor size for intratumoral antibody accumulation and its significant impact on antibody distribution in both primary tumor and lymph node metastasis. Furthermore, this study established the feasibility of using contrast-enhanced MRI to predict antibody delivery. CONCLUSIONS: This study provides a clinically translatable platform to measure antibody delivery into solid tumors and yields valuable insight into clinically relevant antibody tumor penetration, with implications in the selection of patients amenable to antibody therapy and the design of more effective dosing strategies.

6.
JCO Oncol Pract ; 16(1): e84-e91, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31693450

RESUMO

PURPOSE: Patients with cancer face daunting coordination problems at a vulnerable time. Lay navigation programs offer 1 approach to address these problems, but how to best implement these programs presents challenges. We sought to describe those implementation challenges at 1 academic cancer center to inform future efforts. METHODS: We performed a mixed methods study using standard implementation outcomes 1 year after program initiation. Quantitative data from the electronic medical record and qualitative data from in-depth interviews, focus groups, and ethnographic observations were included in analyses. The study took place at a National Cancer Institute-designated comprehensive cancer center across 12 tumor-specific clinics. RESULTS: Supportive care concerns, scheduling, and clinical-related issues were the most frequent issues navigators encountered. Effective navigation required continuous, time-consuming, invisible work, including building and maintaining a broad knowledge base of resources and health system processes, as well as cultivating relationships with diverse and changing clinical teams. The acceptability and appropriateness of lay navigator activities were mixed among clinic and social work staff, related to negotiating lines between clinical and nonclinical care. CONCLUSION: After 1 year of implementation, lay navigators still found it difficult to interpret and prioritize complex patient needs in a way that all clinical staff found appropriate. Negotiating these issues has made it difficult to develop the strong relationships with clinical teams that are needed for an integrated approach to patient care. To successfully coordinate patient care, it seems that lay navigation programs should be integrated with clinical teams to provide more seamless patient care.

7.
Laryngoscope ; 130(1): 128-138, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31025711

RESUMO

OBJECTIVE: To discuss the current available techniques for intraoperative margin assessment in the surgical treatment of oral squamous cell carcinoma (OSCC) through a review of the available literature. METHODS: A systematic review was undertaken of the available English literature between 2008 through 2018 regarding surgical margins in OCSS. A total of 893 relevant articles were returned; 144 met criteria for review; and 64 articles were included. RESULTS: In this review, we discuss the data surrounding the use of frozen section in OCSS. Additionally, alternative techniques for margin assessment are discussed, including Mohs, molecular analysis, nonfluorescent dyes, fluorescent dyes, autofluorescent imaging, narrow-band imaging, optical coherence tomography, confocal microscopy, high-resolution microendoscopy, and spectroscopy. For each technique, particular emphasis is placed on the local recurrence, disease-free survival, and overall survival rates when available. CONCLUSION: This review provides support for the practice of specimen-driven margin assessment when using frozen section analysis to improve the utility of the results. Finally, several alternatives for intraoperative margin assessment currently under investigation, including pathologic, wide-field imaging and narrow-field imaging techniques, are presented. We aim to fuel further investigation into methods for margin assessment that will improve survival for patients with OSCC through a critical analysis of the available techniques. LEVEL OF EVIDENCE: NA Laryngoscope, 130:128-138, 2020.

8.
Mol Imaging Biol ; 22(1): 156-164, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31054001

RESUMO

PURPOSE: To identify the optimal dosing strategy for fluorescence-guided surgery in patients with head and neck squamous cell carcinoma, we conducted a dose-ranging study evaluating the anti-epidermal growth factor receptor (EGFR) therapeutic antibody, panitumumab, that was fluorescently labeled with the near-infrared dye IRDye800CW. PROCEDURES: Patients (n = 24) received either 0.5 or 1.0 mg/kg panitumumab-IRDye800CW in the weight-based dosing group or 25 or 50 mg panitumumab-IRDye800CW in the fixed dosing group. Following surgery, whole primary specimens were imaged in a closed-field device and the mean fluorescence intensity (MFI) and tumor-to-background ratio (TBR) were assessed. Clinical variables, including dose, time of infusion-to-surgery, age, unlabeled dose, gender, primary tumor site, and tumor size, were analyzed to evaluate the factors affecting the fluorescence intensity in order to identify the optimal dose for intraoperative fluorescence imaging. RESULTS: A total of 24 primary tumor specimens were imaged and analyzed in this study. Although no correlations between TBR and dose of panitumumab-IRDye800CW were found, there were moderate-strong correlations between the primary tumor MFI and panitumumab-IRDye800CW dose for fixed dose (mg) (R2 = 0.42) and for dose/weight (mg/kg) (R2 = 0.54). Results indicated that the optimal MFI was at approximately 50 mg for fixed dose and 0.75 mg/kg for dose/weight. No significant differences were found for the primary tumor MFI and TBRs between the weight-based dosing and the fixed dosing groups. MFIs significantly increased when the infusion-to-surgery window was reduced to within 2 days (vs. 3 days or more, p < 0.05). CONCLUSIONS: Antibody-based imaging for surgical resection is under investigation in multiple clinical trials. Our data suggests that a fixed dose of 50 mg is an appropriate diagnostic dose for successful surgical fluorescence imaging.

9.
IEEE Trans Med Imaging ; 39(4): 1127-1137, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31567074

RESUMO

We present software-based methods for automatic phase control and for mosaicing high-speed, Lissajous-scanned images. To achieve imaging speeds fast enough for mosaicing, we first increase the image update rate tenfold from 3 to 30 Hz, then vertically interpolate each sparse image in real-time to eliminate fixed pattern noise. We validate our methods by imaging fluorescent beads and automatically maintaining phase control over the course of one hour. We then image fixed mouse brain tissues at varying update rates and compare the resulting mosaics. Using reconstructed image data as feedback for phase control eliminates the need for phase sensors and feedback controllers, enabling long-term imaging experiments without additional hardware. Mosaicing subsampled images results in video-rate imaging speeds, nearly fully recovered spatial resolution, and millimeter-scale fields of view.

10.
JCO Oncol Pract ; 16(1): e75-e83, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31647691

RESUMO

PURPOSE: A navigation program with lay navigators that targets patients with cancer who are receiving multiple treatment modalities was launched with the goal of improving care coordination. PATIENTS AND METHODS: Pseudo-randomization and mixed methods were used to evaluate the program: patients with even-numbered medical records were assigned to navigation help, and patients with odd-numbered medical records made up the control group. Eligible patients were those scheduled to receive at least two treatment modalities. Intent-to-treat, as-treated, and high-user cohorts with propensity matched controls were used to assess the outcomes: patient experience, emergency room (ER) use, and unplanned hospitalizations. In-depth patient interviews explored how and why patients interacted with the navigator program and overall patient experience. RESULTS: Marginally lower incidence rate ratios (IRRs) for both ER visits (IRR, 1.17; 95% CI, 1.00 to 1.36) and unplanned hospitalizations (IRR, 1.18; 95% CI, 0.97 to 1.43) occurred in as-treated patients who used navigation help and who lived within 50 miles of Stanford Hospital compared with their matched controls; other cohort analyses had similar results. Survey scores for patients who received help with navigation did not differ significantly from those for corresponding controls in any of the analytic cohorts. Patient interviews suggested that the navigation program had low visibility among patients and that lay navigators drove use of the program. Patient-reported positive experiences included getting help with complex scheduling, alleviating anxiousness through access to information and educational resources, and getting help with activities outside traditional health care; negative experiences stemmed from having expectations that were not met. CONCLUSION: Marginally lower rates of ER visits and unplanned hospitalizations for a small subset of patients, low penetration of the navigation program, and mixed comments from patient interviews suggest that a navigation program with a broad scope that targets a large population is not effective. Modifying the program to have a narrower scope of practice may help better target anxious or high-risk patients.

11.
Laryngoscope ; 130(2): 347-353, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31287566

RESUMO

OBJECTIVE: Analyze the cause and significance of a shift in the timing of free flap failures in head and neck reconstruction. STUDY DESIGN: Retrospective multi-institutional review of prospectively collected databases at tertiary care centers. METHODS: Included consecutive patients undergoing free flap reconstructions of head and neck defects between 2007 and 2017. Selected variables: demographics, defect location, donor site, free flap failure cause, social and radiation therapy history. RESULTS: Overall free flap failure rate was 4.6% (n = 133). Distribution of donor tissue by flap failure: radial forearm (32%, n = 43), osteocutaneous radial forearm (6%, n = 8), anterior lateral thigh (23%, n = 31), fibula (23%, n = 30), rectus abdominis (4%, n = 5), latissimus (11%, n = 14), scapula (1.5%, n = 2). Forty percent of flap failures occurred in the initial 72 hours following reconstruction (n = 53). The mean postoperative day for flap failure attributed to venous congestion was 4.7 days (95% confidence interval [CI], 2.6-6.7) versus 6.8 days (CI 5.3-8.3) for arterial insufficiency and 16.6 days (CI 11.7-21.5) for infection (P < .001). The majority of flap failures were attributed to compromise of the arterial or venous system (84%, n = 112). Factors found to affect the timing of free flap failure included surgical indication (P = .032), defect location (P = .006), cause of the flap failure (P < .001), and use of an osteocutaneous flap (P = .002). CONCLUSION: This study is the largest to date on late free flap failures with findings suggesting a paradigm shift in the timing of flap failures. Surgical indication, defect site, cause of flap failure, and use of osteocutaneous free flap were found to impact timing of free flap failures. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:347-353, 2020.

12.
Eur J Nucl Med Mol Imaging ; 47(6): 1412-1426, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31773232

RESUMO

PURPOSE: There is a clinical need for agents that target glioma cells for non-invasive and intraoperative imaging to guide therapeutic intervention and improve the prognosis of glioma. Matrix metalloproteinase (MMP)-14 is overexpressed in glioma with negligible expression in normal brain, presenting MMP-14 as an attractive biomarker for imaging glioma. In this study, we designed a peptide probe containing a near-infrared fluorescence (NIRF) dye/quencher pair, a positron emission tomography (PET) radionuclide, and a moiety with high affinity to MMP-14. This novel substrate-binding peptide allows dual modality imaging of glioma only after cleavage by MMP-14 to activate the quenched NIRF signal, enhancing probe specificity and imaging contrast. METHODS: MMP-14 expression and activity in human glioma tissues and cells were measured in vitro by immunofluorescence and gel zymography. Cleavage of the novel substrate and substrate-binding peptides by glioma cells in vitro and glioma xenograft tumors in vivo was determined by NIRF imaging. Biodistribution of the radiolabeled MMP-14-binding peptide or substrate-binding peptide was determined in mice bearing orthotopic patient-derived xenograft (PDX) glioma tumors by PET imaging. RESULTS: Glioma cells with MMP-14 activity showed activation and retention of NIRF signal from the cleaved peptides. Resected mouse brains with PDX glioma tumors showed tumor-to-background NIRF ratios of 7.6-11.1 at 4 h after i.v. injection of the peptides. PET/CT images showed localization of activity in orthotopic PDX tumors after i.v. injection of 68Ga-binding peptide or 64Cu-substrate-binding peptide; uptake of the radiolabeled peptides in tumors was significantly reduced (p < 0.05) by blocking with the non-labeled-binding peptide. PET and NIRF signals correlated linearly in the orthotopic PDX tumors. Immunohistochemistry showed co-localization of MMP-14 expression and NIRF signal in the resected tumors. CONCLUSIONS: The novel MMP-14 substrate-binding peptide enabled PET/NIRF imaging of glioma models in mice, warranting future image-guided resection studies with the probe in preclinical glioma models.

13.
JCO Oncol Pract ; 16(2): e139-e147, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31804877

RESUMO

PURPOSE: The use of medical scribes has emerged as a strategy to increase clinic workflow efficiency and reduce physician burnout. While oncology clinics may be ideally suited to scribe integration because of the high burden of documentation, oncology-specific scribe research has been limited. The objective of this study was to determine the effect of scribe integration on clinic workflow efficiency and physician satisfaction and quality of life in outpatient oncology clinics. METHODS: We conducted a retrospective, concurrent qualitative and quantitative analysis of patient visit durations and survey data for 129 attending physicians affiliated with an academic hospital's cancer center between January 2017 and January 2019. Thirty-three physicians were paired with scribes in each physician's individual clinic or clinics. RESULTS: In terms of clinic efficiency, physicians with scribes had a 12.1% decrease in their overall average patient visit duration compared with their own time before receiving a scribe (P < .0001) and spent significantly less time completing charts at the end of the day (P = .04). Compared with their peers, oncologists with scribes showed a 10%-20% decrease in the duration of all patient visits. Scribes also contributed to patient care, as shown by 90% of physicians surveyed who strongly agreed that they spent less time at the computer and more time with patients; 100% of physicians surveyed strongly agreed that scribes improved their quality of life. CONCLUSION: The integration of medical scribes into oncology clinics across several oncologic disciplines has the potential to reduce burnout through increasing physician satisfaction and quality of life, improving patient care, and streamlining clinic workflow.

14.
Head Neck ; 42(1): 59-66, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31571335

RESUMO

BACKGROUND: Despite the rapid growth of fluorescence imaging, accurate sampling of tissue sections remains challenging. Development of novel technologies to improve intraoperative assessment of tissue is needed. METHODS: A novel contact probe-based fluorescence dosimeter device, optimized for IRDye800CW quantification, was developed. After evaluation of the device in a phantom setup, its clinical value was defined ex vivo in patients with head and neck squamous cell carcinoma who received panitumumab-IRDye800CW. RESULTS: Ten patients were enrolled with a total of 216 data points obtained. Final histopathology showed tumor in 119 spots and normal tissue in 97 spots. Fluorescence-to-excitation ratios in tumor tissue were more than three times higher than those in normal tissue. The area under the curve was 0.86 (95% CI: 0.81-0.91) for tumor detection. CONCLUSIONS: Fluorescence-guided tissue preselection using a fluorescence dosimeter could have substantial impact on tissue sampling for frozen section analysis and potentially reduce sampling errors.

15.
Laryngoscope ; 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31854462

RESUMO

OBJECTIVE: Endoscopic resection of sinonasal squamous cell carcinoma has become the standard of care, but challenges remain in obtaining clear resection margins. The current study evaluated the feasibility of endoscopic fluorescence-guided surgery (FGS) to improve surgical resection in a human sinus surgical model. METHODS: A fluorescence endoscope optimized for near-infrared (NIR) fluorescence detection was evaluated in a phantom study. Various endoscope diameters (4 and 10 mm) and viewing angles (0, 30, and 45 degrees) were evaluated to determine the sensitivity of the system for IRDye800CW detection at various working distances (1-5 cm). Endoscopic FGS was then validated in a three-dimensional human sinus surgical model to which squamous cell tumors derived from mice were inserted. Mice had received intravenous panitumumab-IRDye800CW and upon fluorescence-guided tumor resection, mean fluorescence intensity (MFI) and tumor-to-background ratio (TBR) were calculated in in situ and ex vivo settings. RESULTS: A significantly higher fluorescence intensity was found when using the 10-mm diameter endoscope compared to the 4mm diameter endoscope (P < .001). No significant difference in MFI was found among the viewing angles of the 4-mm diameter endoscope. Using the human sinus model, the highest MFI and TBR were obtained at a 1-cm working distance compared to longer working distances. CONCLUSION: We demonstrate that clinically acceptable TBRs were obtained with several working distances to discriminate tumor tissue from adjacent normal tissue in a human sinus model, and that endoscopic FGS may have great potential in identifying residual tumor tissue regions during surgery. Laryngoscope, 2019.

17.
Nat Commun ; 10(1): 5044, 2019 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-31695030

RESUMO

Identification of lymph node (LN) metastasis is essential for staging of solid tumors, and as a result, surgeons focus on harvesting significant numbers of LNs during ablative procedures for pathological evaluation. Isolating those LNs most likely to harbor metastatic disease can allow for a more rigorous evaluation of fewer LNs. Here we evaluate the impact of a systemically injected, near-infrared fluorescently-labeled, tumor-targeting contrast agent, panitumumab-IRDye800CW, to facilitate the identification of metastatic LNs in the ex vivo setting for head and neck cancer patients. Molecular imaging demonstrates a significantly higher mean fluorescence signal in metastatic LNs compared to benign LNs in head and neck cancer patients undergoing an elective neck dissection. Molecular imaging to preselect at-risk LNs may thus allow a more rigorous examination of LNs and subsequently lead to improved prognostication than regular neck dissection.


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática/diagnóstico por imagem , Imagem Molecular/métodos , Imagem Óptica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Corantes Fluorescentes , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Linfonodos/cirurgia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Coloração e Rotulagem
18.
J Am Coll Surg ; 229(6): 560-567.e1, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31568855

RESUMO

BACKGROUND: In head and neck cancer, surgical resection using primarily visual and tactile feedback is considered the gold standard for solid tumors. Due to high numbers of tumor-involved surgical margins, which are directly correlated to poor clinical outcomes, intraoperative optical imaging trials have rapidly proliferated over the past 5 years. However, few studies report on intraoperative in situ imaging data that could support surgical resection. To demonstrate the clinical application of in situ surgical imaging, we report on the imaging data that are directly (ie in real-time) available to the surgeon. STUDY DESIGN: Fluorescence intensities and tumor-to-background ratios (TBRs) were determined from the intraoperative imaging data-the view as seen by the surgeon during tumor resection-of 20 patients, and correlated to patient and tumor characteristics including age, sex, tumor site, tumor size, histologic differentiation, and epidermal growth factor receptor (EGFR) expression. Furthermore, different lighting conditions in regard to surgical workflow were evaluated. RESULTS: Under these circumstances, intraoperative TBRs of the primary tumors averaged 2.2 ± 0.4 (range 1.5 to 2.9). Age, sex, tumor site, and tumor size did not have a significant effect on open-field intraoperative molecular imaging of the primary tumors (p > 0.05). In addition, variation in EGFR expression levels or the presence of ambient light did not seem to alter TBRs. CONCLUSIONS: We present the results of successful in situ intraoperative imaging of primary tumors alongside the optimal conditions with respect to both molecular image acquisition and surgical workflow. This study illuminates the potentials of open-field molecular imaging to assist the surgeon in achieving successful cancer removal.

19.
Oral Oncol ; 97: 50-55, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31421471

RESUMO

OBJECTIVE: High-grade dysplasia is associated with a risk of malignant transformation, and it is necessary to distinguish from normal epithelium or low-grade dysplasia, especially in the intraoperative setting. We hypothesize that an anti-epidermal growth factor receptor (EGFR) contrast agent can be used to differentiate high-grade dysplasia from low-grade dysplasia and normal epithelium. MATERIALS AND METHODS: Patients with biopsy proven head and neck squamous cell carcinoma (HNSCC) were enrolled in a clinical trial using systemically injected fluorescently labeled anti-EGFR antibody (panitumumab-IRDye800CW) (NCT02415881). Paraffin embedded tumor specimens from 11 patients were evaluated by fluorescence histopathology. Hematoxylin and eosin (H&E) slides were reviewed by a board-certified pathologist, and regions of invasive squamous cell carcinoma, high-grade dysplasia and low-grade dysplasia were delineated. EGFR expression was assessed for each patient by way of immunohistochemistry. RESULTS: 11 patients were included in the study with a total of 219 areas on tissue sections analyzed; 68 normal epithelium, 53 low-grade dysplasia, 48 high-grade dysplasia, and 50 malignant regions. The signal-to-background ratio (SBR) increased proportionally with increasing grade of dysplasia; normal epithelium (1.5 ±â€¯0.1), low-grade dysplasia (1.8 ±â€¯0.1), high-grade dysplasia: (2.3 ±â€¯0.2). High-grade dysplasia had a significantly higher SBR when compared to normal or low-grade dysplasia (p < 0.05). Fluorescence histopathology positively correlated with EGFR expression by immunohistochemistry, which also increased proportionally with increasing degree of dysplasia. CONCLUSION: Molecular imaging with an anti-EGFR agent can successfully discriminate high-grade dysplastic lesions from low-grade dysplasia and normal epithelium.

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