scholarly journals A pre-screening strategy to assess resected tumor margins by imaging cytoplasmic viscosity and hypoxia

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Hui Huang ◽  
Youpei Lin ◽  
Wenrui Ma ◽  
Jiannan Liu ◽  
Jing Han ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Frozen Section ◽  
Clinical Decision ◽  
Screening Strategy ◽  
Molecular Rotor ◽  
Common Procedure ◽  
Tumor Margins ◽  
Multiple Biopsies ◽  
Liver Cancers ◽  
Resected Tumor

To assure complete tumor removal, frozen section analysis is the most common procedure for intraoperative pathological assessment of resected tumor margins. However, during one operation, multiple biopsies may be sent for examination, but only few of them are made into cryosections because of the complex preparation protocols and time-consuming pathological analysis, which potentially increases the risk of overlooking tumor involvement. Here, we propose a fluorescence-based pre-screening strategy that allows high-throughput, convenient, and fast gross assessment of resected tumor margins. A dual-activatable cationic fluorescent molecular rotor was developed to specifically illuminate live tumor cells’ cytoplasm by emitting two different fluorescence signals in response to elevations in hypoxia-induced nitroreductase (a biochemical marker) and cytoplasmic viscosity (a biophysical marker), two characteristics of cancer cells. The ability of the fluorescent molecular rotor in detecting tumor cells was evaluated in mouse and human specimens of multiple tissues by comparing with hematoxylin and eosin staining. Importantly, the fluorescent molecular rotor achieved 100% specificity in discriminating lung and liver cancers from normal tissue, allowing pre-screening of the tumor-free surgical margins and promoting clinical decision. Altogether, this type of fluorescent molecular rotor and the proposed strategy may serve as a new option to facilitate intraoperative assessment of resected tumor margins.

Management of Periocular Neoplasms

2011 ◽  
Author(s):  
Robert C. Kersten
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Treatment Modality ◽  
Frozen Section ◽  
Neck Region ◽  
Complex Nature ◽  
Critical Function ◽  
Medical Practitioners ◽  
Tumor Margins ◽  
Skin Cancers

Epithelial malignancy of the eyelid is a common problem, representing about 14% of skin cancers in the head and neck region. The goals when treating any skin cancer are complete elimination of the tumor and minimal sacrifice of normal adjacent tissues. These concepts are of paramount importance when treating periocular epithelial malignancies because of the complex nature of the periocular tissues and their critical function in protecting the underlying globe, as well as the increased risk that recurrent tumor in this area poses. Many modalities have been advocated, by a variety of medical practitioners, for the treatment of epithelial malignancies in the periocular region. There are two key considerations in selecting a treatment for skin cancers. The first is that the selected modality must be capable of eradicating all tumor cells to which it is applied. The second is that some mechanism must exist to ensure that it is applied to all the existing tumor cells. Because tumors of the lid margins and canthi often exhibit slender strands and shoots of cancer cells that may infiltrate beyond the clinically apparent borders of the neoplasm, appropriate monitoring to ensure that the treatment modality reaches all of the cancer cells is essential. Numerous studies have demonstrated that clinical judgment of tumor margins is inadequate, significantly underestimating the area of microscopic tumor involvement. The introduction of frozen-section control to document adequacy of tumor excision marked a major advancement in the treatment of eyelid malignancies and now represents the standard of care. Any treatment modality that does not use microscopic monitoring of tumor margins must instead encompass a wider area of adjacent normal tissue in hopes that any microscopic extensions of tumor will fall within this area. The purpose of this chapter is to explore alternative methods of periocular cancer treatment. Mohs micrographic technique is a refinement of frozen-section control of tumor borders that, by mapping tumor planes, allows a three-dimensional evaluation of tumor margins rather than the two-dimensional examination provided by routine frozen section. The modality was initiated by Frederick E. Mohs, MD, in 1936.

scholarly journals Comparative Study of PD-L1 Status between Surgically Resected Specimens and Matched Biopsies of Gastric Cancer Reveal Major Discordances: A Potential Issue for Anti-PD-L1 Therapeutic Strategies

2020 ◽  
pp. 1-7
Author(s):  
Soo Hee Kim ◽  
Hyae Min Jeon ◽  
Hyo Song Kim ◽  
Kum Hee Yun ◽  
Min Ju Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Cells ◽  
Expression Patterns ◽  
Validity And Reliability ◽  
Poor Agreement ◽  
K Value ◽  
Paired Samples ◽  
Biopsy Specimens ◽  
Multiple Biopsies ◽  
Resected Tumor

Background: Inhibitors of programmed death-ligand 1 (PD-L1) have potential therapeutic value in gastric cancer. We investigated PD-L1 expression patterns in paired biopsy and resection specimens. Patients and Methods: Thirty-nine formalin-fixed, paraffin-embedded paired samples were assessed using PD-L1 22C3 pharmDx immunohistochemistry technique. Combined positive score (CPS) was calculated as the ratio of PD-L1 stained cells (tumor cells, lymphocytes, and macrophages) to the total number of viable tumor cells, multiplied by 100. The CPS ≥1 indicated PD-L1 positivity. Results: PD-L1 positivity was evident for 33 (84.6%) of 39 resection cases; all displayed low positivity (1≤CPS<50). Only 10 (30.3%) of 33 positive cases in the resection specimens had simultaneous PD-L1 positivity in the paired biopsy specimens; two cases displayed high positivity (CPS 50 and 70) and eight displayed low positivity (1≤CPS≤50). Among the 29 negative cases with biopsy specimens, 23 (79.3%) displayed PD-L1 low positivity in the paired resection specimens and only six had concordant negativity in both specimens with poor agreement (concordance rate 41.0%, k value = 0.118, correlation coefficient 0.234; p=0.152). All the high microsatellite instability cases had concordant PD-L1 positivity in resection and biopsy specimens. Conclusions: There was relatively poor agreement of PD-L1 expression between biopsy and resected tumor specimens. The biopsy specimens underestimated the PD-L1 status observed for the total resected samples. This indicates the necessity of obtaining multiple biopsies from different areas of the tumor to enhance the validity and reliability of PD-L1 analysis.

Use of in vivo near-infrared laser confocal endomicroscopy with indocyanine green to detect the boundary of infiltrative tumor

2011 ◽  
Vol 115 (6) ◽  
pp. 1131-1138 ◽  
Author(s):  
Nikolay L. Martirosyan ◽  
Daniel D. Cavalcanti ◽  
Jennifer M. Eschbacher ◽  
Peter M. Delaney ◽  
Adrienne C. Scheck ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Tumor Cells ◽  
Near Infrared ◽  
Tumor Resection ◽  
Tumor Detection ◽  
Normal Brain ◽  
Tumor Margins ◽  
Confocal Endomicroscopy ◽  
Infiltrative Tumor

Object Infiltrative tumor resection is based on regional (macroscopic) imaging identification of tumorous tissue and the attempt to delineate invasive tumor margins in macroscopically normal-appearing tissue, while preserving normal brain tissue. The authors tested miniaturized confocal fiberoptic endomicroscopy by using a near-infrared (NIR) imaging system with indocyanine green (ICG) as an in vivo tool to identify infiltrating glioblastoma cells and tumor margins. Methods Thirty mice underwent craniectomy and imaging in vivo 14 days after implantation with GL261-luc cells. A 0.4 mg/kg injection of ICG was administered intravenously. The NIR images of normal brain, obvious tumor, and peritumoral zones were collected using the handheld confocal endomicroscope probe. Histological samples were acquired from matching imaged areas for correlation of tissue images. Results In vivo NIR wavelength confocal endomicroscopy with ICG detects fluorescence of tumor cells. The NIR and ICG macroscopic imaging performed using a surgical microscope correlated generally to tumor and peritumor regions, but NIR confocal endomicroscopy performed using ICG revealed individual tumor cells and satellites within peritumoral tissue; a definitive tumor border; and striking fluorescent microvascular, cellular, and subcellular structures (for example, mitoses, nuclei) in various tumor regions correlating with standard clinical histological features and known tissue architecture. Conclusions Macroscopic fluorescence was effective for gross tumor detection, but NIR confocal endomicroscopy performed using ICG enhanced sensitivity of tumor detection, providing real-time true microscopic histological information precisely related to the site of imaging. This first-time use of such NIR technology to detect cancer suggests that combined macroscopic and microscopic in vivo ICG imaging could allow interactive identification of microscopic tumor cell infiltration into the brain, substantially improving intraoperative decisions.

scholarly journals The value and practical utility of intraoperative touch imprint cytology of sentinel lymph node(s) in patients with breast cancer: A retrospective cytology-histology correlation study

CytoJournal ◽  
2020 ◽  
Vol 17 ◽  
pp. 11
Author(s):  
Yuji Uno ◽  
Naoko Akiyama ◽  
Sayaka Yuzawa ◽  
Masahiro Kitada ◽  
Hidehiro Takei
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Frozen Section ◽  
Correlation Study ◽  
Imprint Cytology ◽  
Isolated Tumor Cells ◽  
False Negatives ◽  
Metastatic Focus ◽  
Intraoperative Evaluation ◽  
Touch Imprint Cytology

Objective: Intraoperative evaluation of sentinel lymph nodes (SLNs) for patients with breast cancer is widely performed with frozen section (FS), cytology, or a combination of both. Touch imprint cytology (TIC) reportedly has an equivalent sensitivity to FS. We studied its diagnostic utility to detect SLN metastases. Materials and Methods: Cases of 367 patients with breast cancer who underwent intraoperative valuation of SLNs (507 LNs) were evaluated. All FS and corresponding TIC slides of SLNs of each case were reviewed microscopically for the presence of metastases of any size. If present, the metastatic focus was measured on the FS. Results: Of these 507 SLNs, 82 LNs (16.2%) from 69 women were found to have metastases in the FS and consisted of 5 LNs of isolated tumor cells, 15 of micrometastasis, and 62 of macrometastasis. TIC identified metastases in 69 of these 82 SLNs (sensitivity: 84.1%, specificity: 100%, and accuracy: 97.4%). All macrometastases could be detected by TIC, whereas TIC identified approximately 50% of micrometastases and none of isolated tumor cells. The size detection limit of metastatic foci, defined as the smallest dimension of metastasis detected without false negatives, was 2 mm. The smallest metastatic focus identified was 0.8 mm. Conclusions: TIC of SLNs is of great use given its negative predictive value of 100% for identification of macrometastasis in our study. For intraoperative evaluation of SLNs, based on our data, a practical two-step approach is proposed: SLN evaluation should be initially performed by TIC and then proceed to FS histological analysis only when cytologically positive to determine the size of metastatic focus.

scholarly journals Prospective validation of a molecular prognostication panel for clival chordoma

2019 ◽  
Vol 130 (5) ◽  
pp. 1528-1537 ◽  
Author(s):  
Georgios A. Zenonos ◽  
Juan C. Fernandez-Miranda ◽  
Debraj Mukherjee ◽  
Yue-Fang Chang ◽  
Klea Panayidou ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Clinical Decision Making ◽  
Cox Model ◽  
Wide Spectrum ◽  
Progression Free Survival ◽  
Clinical Decision ◽  
Homozygous Deletion ◽  
Ki 67 ◽  
Free Survival ◽  
Clival Chordoma

OBJECTIVEThere are currently no reliable means to predict the wide variability in behavior of clival chordoma so as to guide clinical decision-making and patient education. Furthermore, there is no method of predicting a tumor’s response to radiation therapy.METHODSA molecular prognostication panel, consisting of fluorescence in situ hybridization (FISH) of the chromosomal loci 1p36 and 9p21, as well as immunohistochemistry for Ki-67, was prospectively evaluated in 105 clival chordoma samples from November 2007 to April 2016. The results were correlated with overall progression-free survival after surgery (PFSS), as well as progression-free survival after radiotherapy (PFSR).RESULTSAlthough Ki-67 and the percentages of tumor cells with 1q25 hyperploidy, 1p36 deletions, and homozygous 9p21 deletions were all found to be predictive of PFSS and PFSR in univariate analyses, only 1p36 deletions and homozygous 9p21 deletions were shown to be independently predictive in a multivariate analysis. Using a prognostication calculator formulated by a separate multivariate Cox model, two 1p36 deletion strata (0%–15% and > 15% deleted tumor cells) and three 9p21 homozygous deletion strata (0%–3%, 4%–24%, and ≥ 25% deleted tumor cells) accounted for a range of cumulative hazard ratios of 1 to 56.1 for PFSS and 1 to 75.6 for PFSR.CONCLUSIONSHomozygous 9p21 deletions and 1p36 deletions are independent prognostic factors in clival chordoma and can account for a wide spectrum of overall PFSS and PFSR. This panel can be used to guide management after resection of clival chordomas.

Anastomosing Hemangioma of the Larynx: A Unicorn among Head and Neck Tumors

2020 ◽  
pp. 000348942094364
Author(s):  
Rimlee Dutta ◽  
Aanchal Kakkar ◽  
Pirabu Sakthivel ◽  
Rajeev Kumar
Keyword(s):  
Head And Neck ◽  
Histopathological Examination ◽  
Frozen Section ◽  
Single Case ◽  
Cricoid Cartilage ◽  
Vascular Tumor ◽  
Extent Of Resection ◽  
Multiple Biopsies ◽  
Vascular Origin ◽  
Anastomosing Hemangioma

Objective: Anastomosing hemangioma (AH) is a novel tumor of vascular origin. Though well-documented in the kidney and retroperitoneum, only a single case has been documented in the head and neck, and AH in larynx has not been described. Methods: A 37-year-old male presented with difficulty in breathing, and hoarseness. Imaging revealed a lesion involving left paraglottic and cricothyroid spaces with destruction of cricoid cartilage, suggestive of a malignant cartilageneous neoplasm. Multiple biopsies were non-diagnostic. Results: Intraoperative frozen section during transcervical resection showed a vascular tumor devoid of nuclear atypia. Histopathological examination revealed a vasoformative tumor comprised of anastomosing capillary-sized vessels lined by flat and hobnail endothelial cells, consistent with AH. The patient was disease-free at 12 months. Conclusion: AH are rare neoplasms that may mimic a malignancy on imaging, especially in sites where they have not been documented. Due to their vascular nature, biopsies are often non-diagnostic, making preoperative diagnosis difficult. Frozen section may assist in decision-making on the extent of resection required.

scholarly journals Radiogenomics and Radiomics in Liver Cancers

Diagnostics ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 4 ◽  
Author(s):  
Aman Saini ◽  
Ilana Breen ◽  
Yash Pershad ◽  
Sailendra Naidu ◽  
M. Knuttinen ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Clinical Information ◽  
Clinical Decision ◽  
Molecular Profile ◽  
Imaging Features ◽  
Imaging Data ◽  
Prognostic Information ◽  
Cross Sectional ◽  
Related Field ◽  
Liver Cancers

Radiogenomics is a computational discipline that identifies correlations between cross-sectional imaging features and tissue-based molecular data. These imaging phenotypic correlations can then potentially be used to longitudinally and non-invasively predict a tumor’s molecular profile. A different, but related field termed radiomics examines the extraction of quantitative data from imaging data and the subsequent combination of these data with clinical information in an attempt to provide prognostic information and guide clinical decision making. Together, these fields represent the evolution of biomedical imaging from a descriptive, qualitative specialty to a predictive, quantitative discipline. It is anticipated that radiomics and radiogenomics will not only identify pathologic processes, but also unveil their underlying pathophysiological mechanisms through clinical imaging alone. Here, we review recent studies on radiogenomics and radiomics in liver cancers, including hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and metastases to the liver.

Pathologic Evaluation of Axillary Dissection Specimens Following Unexpected Identification of Tumor Within Sentinel Lymph Nodes

2011 ◽  
Vol 135 (1) ◽  
pp. 131-134
Author(s):  
Jessica Gutierrez ◽  
Daniel Dunn ◽  
Margit Bretzke ◽  
Eric Johnson ◽  
John O'Leary ◽  
...  
Keyword(s):  
Lymph Node ◽  
Sentinel Node ◽  
Tumor Cells ◽  
Axillary Dissection ◽  
Frozen Section ◽  
Axillary Node ◽  
Axillary Node Dissection ◽  
Node Dissection ◽  
Isolated Tumor Cells ◽  
Sentinel Nodes

Abstract Context—Axillary lymph node dissection has been the standard of care after identification of a positive sentinel lymph node for breast cancer patients. Objective—To determine the likelihood of non–sentinel lymph node involvement for patients with negative sentinel node by frozen section, who are subsequently found to have tumor cells in the sentinel node by permanent section levels and/or cytokeratin immunohistochemistry. Design—One hundred three patients with invasive breast cancer exhibiting negative frozen section evaluation of their sentinel node, but later found to have isolated tumor cells (n  =  46), micrometastasis (n  =  46), or metastases (n  =  11) in their sentinel node by permanent sections or immunohistochemistry, were enrolled in this prospective cohort study and underwent completion axillary dissection. Results—Six of 46 patients (13%) with isolated tumor cells in their sentinel node, 15 of 46 patients (33%) with micrometastasis in their sentinel node, and 2 of 11 patients (18%) with metastasis in their sentinel node had additional findings in the nonsentinel nodes. These findings resulted in a pathologic stage change in 2 patients. Predictors of positive nonsentinel nodes were 2 or more positive sentinel nodes (P  =  .002), sentinel nodes with micrometastasis versus isolated tumor cells (P  =  .03), and those with angiolymphatic invasion (P  =  .04). Conclusions—Our findings lend support to axillary node dissection for patients with micrometastasis or metastasis in their sentinel nodes. However, studies with clinical follow-up are needed to determine whether axillary node dissection is necessary for patients with isolated tumor cells in sentinel nodes.

scholarly journals Ex Vivo Fluorescein-Assisted Confocal Laser Endomicroscopy (CONVIVO® System) in Patients With Glioblastoma: Results From a Prospective Study

2020 ◽  
Vol 10 ◽  
Author(s):  
Francesco Acerbi ◽  
Bianca Pollo ◽  
Camilla De Laurentis ◽  
Francesco Restelli ◽  
Jacopo Falco ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Frozen Section ◽  
Correct Diagnosis ◽  
Central Core ◽  
High Rate ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Tumor Margins ◽  
Tissue Specimens ◽  
A Prospective Study

BackgroundConfocal laser endomicroscopy (CLE) allowing intraoperative near real-time high-resolution cellular visualization is a promising method in neurosurgery. We prospectively tested the accuracy of a new-designed miniatured CLE (CONVIVO® system) in giving an intraoperative first-diagnosis during glioblastoma removal.MethodsBetween January and May 2018, 15 patients with newly diagnosed glioblastoma underwent fluorescein-guided surgery. Two biopsies from both tumor central core and margins were harvested, dividing each sample into two specimens. Biopsies were firstly intraoperatively ex vivo analyzed by CLE, subsequently processed for frozen and permanent fixation, respectively. Then, a blind comparison was conducted between CLE and standard permanent section analyses, checking for CLE ability to provide diagnosis and categorize morphological patterns intraoperatively.ResultsBlindly comparing CONVIVO® and frozen sections images we obtained a high rate of concordance in both providing a correct diagnosis and categorizing patterns at tumor central core (80 and 93.3%, respectively) and at tumor margins (80% for both objectives). Comparing CONVIVO® and permanent sections, concordance resulted similar at central core (total/partial concordance in 80 and 86.7% for diagnosis and morphological categorization, respectively) and lower at tumor margins (66.6% for both categories). Time from fluorescein injection and time from biopsy sampling to CONVIVO® scanning was 134 ± 31 min (122–214 min) and 9.23 min (1–17min), respectively. Mean time needed for CONVIVO® images interpretation was 5.74 min (1–7 min).ConclusionsThe high rate of diagnostic/morphological consistency found between CONVIVO® and frozen section analyses suggests the possibility to use CLE as a complementary tool for intraoperative diagnosis of ex vivo tissue specimens during glioblastoma surgery.

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