Academic literature on the topic 'Extra-capsular spread'

<p class="abstract"><strong>Background:</strong> Squamous cell carcinoma (SCC) of larynx is widely prevalent in India and is one of the leading cancers in males. Tumor Cyclooxygenase-2 (Cox-2) expression can be used as a prognostic and predictive marker in laryngeal SCC.<strong> </strong>The primary objective of the present study was to determine the association between tumor Cox-2 expression and clinico-pathological characteristics and treatment outcome in patients with LSCC. Secondly, to evaluate the clinical utility of Cox-2 expression as a tool, to decide treatment strategy for LSCC.</p><p class="abstract"><strong>Methods:</strong> Seventy two patients with stage III and IV LSCC who underwent upfront surgery were included in this study. Tumor Cox-2 expression was analysed by immunohistochemistry using standard Streptavidin biotin method. </p><p class="abstract"><strong>Results:</strong> Thirty seven patients had pathological node involvement, ipsilateral in 35 and bilateral in two. Cox-2 was intensely expressed in patients with advanced (N2/N3) nodal disease and perineural invasion. There was no significant difference in 5 year disease free survival and overall survival when Cox-2 was correlated with perineural invasion, extra capsular spread and the T and N stage of the disease.</p><p class="abstract"><strong>Conclusions:</strong> Preoperative Cox-2 analysis can be used to individualize need for routine neck dissection in cases of locally advanced laryngeal carcinoma.</p>

<p><strong>Background:</strong> Cervical lymph node status is the most significant prognostic factor in the treatment of patients with OSCC. Adequate clearance of level IIb lymph nodes require traction and elevation of the spinal accessory nerve (SAN) and can lead to consequent shoulder problems.Therefore, avoiding the dissection of level IIb has been increasingly proposed to overcome this complication. The aim of this study was to determine the prevalence of level IIb metastasis in patients with oral squamous cell carcinomas (OSCCs).</p><p><strong>Methods: </strong>A total of 106 newly diagnosed oral cavity cancer patients requiring surgery as the primary modality were included in the study. Preoperative clinical examinations were done and tumor-node-metastasis staging was noted. Intraoperative, level IIb nodal tissue was dissected and sent separately.</p><p><strong>Results: </strong>A total of 106 neck dissections were done out of which male: female ratio of 2.78:1. 49.05% patients were suffering from buccal mucosa carcinoma followed by tongue carcinoma (22.64%). 52.83% of patients had no neck involvement. Among neck positive cases, pN1 was the most common presentation. Out of these, only 8 (7.54%) neck dissections had level IIb positive.</p><p><strong>Conclusions: </strong>Dissection of the level IIb region in patients with OSCC may be required only in cases with advanced N stage, positive level IIa lymph nodes, and extra capsular spread. Further evaluation can be done among various subsites of OSCC, clinical staging of tumour, occult bilateral nodal metastasis to assess the need of resection of level IIb in OSCC.</p>

8514 Background: The benefits of deep pelvic lymph node dissection (DLND) for node-positive melanoma patients continue to be debated. The objective of our analysis was to assess factors associated with metastatic disease to deep pelvic nodes and examine survival outcomes following DLND. Methods: We retrospectively reviewed the records of 804 patients undergoing lymph node dissection (1990-2001). 97 patients underwent a superficial inguinofemoral lymph node dissection along with a DLND for indications which included: suspicious radiologic imaging (n= 31), documented superficial disease and concern for deep involvement (n = 57), and in-transit disease undergoing limb perfusion (n=9). Logistic regression was performed to identify factors associated with the metastatic tumor spread to deep nodes. Associations between clinicopathologic factors and disease-specific survival (DSS) were estimated using the Cox proportional hazards model. Results: Fifty-four patients (56%) had metastatic disease (median 2 positive lymph nodes, range 1–12) within their deep pelvis. With a median follow-up of 7.5 years, the 5-year DSS was 42% for patients with positive deep pelvic nodes and 52% for those with negative deep pelvic nodes (p = 0.07). When the number of metastatic deep nodes was stratified, the 5-year DSS for patients with 1 positive node, 2–3 positive nodes, and >3 positive nodes was 49%, 48%, and 27%, respectively (p = 0.04). Age ≥ 50 years (odds ratio [OR] = 3.5, p = 0.03), increasing number of positive superficial nodes (OR = 2.1, p < 0.001), and suspicious findings on pelvic CT images (OR = 11.9, p < 0.001) were associated with metastatic deep nodes. In the multivariate analysis, the number of positive deep nodes (hazard ratio [HR] = 1.1, p = 0.03), male gender (HR = 1.9, p = 0.03), and extra-capsular nodal extension of tumor (HR = 2.7, p < 0.001) were identified as adverse prognostic factors for DSS. Conclusions: Survival outcomes in patients with melanoma metastatic to ≤ 3 deep pelvic lymph nodes are comparable to those in patients without deep nodal involvement. These favorable outcomes support an aggressive surgical approach (i.e., DLND) in patients ≥ 50 years, with multiple positive superficial nodes, and suspicious CT findings. No significant financial relationships to disclose.

e15541 Background: Head and neck squamous cell carcinoma is leading cancer in the India with Oral squamous cell carcinoma (OSCC) as the most frequent subtype. OSCC is classified as a locoregional disease and its increased frequency is attributed to lack of good biomarkers compared to other epithelial cancers. At the time of diagnosis, above 50% of cases present the manifestation of advanced-stage disease, and are predisposed to disease failure in spite of appropriate treatment. Thus, early diagnosis of OSCC can significantly reduce the disease burden. Here we describe regulatory approved method to establish Circulating tumor cells (CTCs) presence in OSCC Indian patients and its positive correlation with various clinicopathological parameters, suggesting the potential use of CTCs as a significant parameter to stratify oral cancer with respect to the disease advancement. Methods: In a cross-sectional observational study, 230 OSCC patients at the different pathological stage of the disease and treatment mode were enrolled. CTCs were isolated using approved OncoDiscover liquid biopsy technology (Drug controller general of India approved), platform technology based on immunomagnetic CTC enumeration. CTCs were detected for CK18 presence and well-defined, DAPI-stained nuclei. Enumerated CTC subsequently analyzed for various clinic-pathological parameters such as pstage, extra-capsular spread (ECS), lymphovascular emboli (LVE), perineural invasion (PNI) and depth of invasion (DOI). CTC cut off values were obtained to differentiate early vs advanced stages with respect to different clinical stages and parameters. Results: CTCs of OSCC patients correlated positively with the cancer stages (clinical as well as pathological) as well as aggressive pathological features. The presence of aggressive pathological features that often suggest the poor outcome of the disease, we observed a 25-50 % increase in CTC number. Early stage, treatment naïve patients had lower number of CTCs. Mean CTC number in advanced-stage patients was 50 % higher than early-stage OSCC patients. Conclusions: Considering a positive correlation of CTC number with various pathophysiological features, CTC can be contemplated as a reliable parameter to predict the disease outcome in oral cancer. The consistent presence of CTC across all disease stages also suggests a probable nature of OSCC as a biological systematic disease. Clinical trial information: CTRI/2018/03/012905.

8556 Background: The aim of this study was to profile cytochrome CYP1 family (CYP1A1/1A2, and CYP1B1) mono-oxygenase enzymes during the malignant progression of primary melanoma and metastatic disease. Methods: Tissue microarrays of primary (n = 75), and metastatic (n = 104) melanoma were constructed with the patient demographics: (1) primary melanoma; age 22 to 93 (median 59); sex M/F 36/44; Breslow thickness 0.4 to 15 mm (median 2.5 mm); ulceration 25/80, and (2) metastatic melanoma; age 26 to 92 (median 60 mm); sex M/F 54/49; ulceration 30/104; number of nodes 1 to 15 (median 2); extra-capsular spread 20/95. CYP1 protein was detected by IHC using validated selective poly- and monoclonal antibodies. Vector SG (grey) stain for CYP1 was used with nuclear fast red counterstain to aid spectral resolution from background melanin. Staining intensity was scored visually (negative 0, weak 1, moderate 2, strong 3) and using SIM at every pixel of a captured image of each melanoma core. Reference spectra of individual chromophores were used to spectrally ‘un-mix’ CYP1 staining before the mean normalised absorbance intensity was determined. Grading was by the 2002 AJCC classification system: primary stage I n = 27 (1A 8, 1B 19), and stage II n = 48 (2A 22, 2B 16, 2C 10), lymph node metastasis stage III n = 98 (3B 53, 3C 45), visceral metastasis stage IV n = 6. Normal skin (n = 27), benign naevi (n = 14), and dysplastic naevi (n = 21) were also included. Results: CYP1B1 was not in normal skin but was over-expressed in both primary and metastatic melanoma (visual: 71% & 65%, SIM: 91% & 83%). Primary melanoma (stage I & II) was significantly greater (p = 0.004) than metastasis (stage III & IV). CYP1B1 did not correlate with ulceration or Breslow thickness but did correlate with N stage lymph node metastasis (p = 0.005). CYP1B1 expression in dysplastic naevi indicated up-regulation at an early stage of melanoma progression. CYP1A1/1A2 was not expressed in normal skin nor primary/metastatic melanoma. Conclusions: CYP1B1 protein expression is maintained with advancing AJCC stage from primary through to visceral metastasis. Future work will seek to correlate protein expression with functionality with a view to exploiting CYP1B1 in the enzyme/prodrug therapy of malignant melanoma. No significant financial relationships to disclose.

The authors report a case of a woman who underwent heart surgery in median sternotomy after breast reconstruction using prosthesis in 1984. After this open heart surgery in 2008, she developed an injury at right breast implant with intra and extra capsular silicone gel spread out the prosthesis.

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide with an incidence of ~600,000 cases per year and younger age groups, particularly between 40-69 years, are increasingly becoming affected. OSCC has an overall five-year survival of only ~30% when metastatic disease is present. The most adverse prognostic clinical predictor for OSCC is extracapsular spread (ECS) from lymph node metastasis. The molecular determinants of ECS are undetermined and their characterization could significantly assist patient management, identifying those having increased risk and suggesting new possibilities for therapy. The aim of this study was to identify genetic variants associated with ECS. Previous work using aCGH had found an unexpectedly low frequency of TP53 alteration in OSCCs from a local cohort enriched for cases with ECS. SNP genotyping was therefore used to further investigate allelic imbalance of TP53 and for comparison CCND1 in primary tumour samples from the series (n=46; 19 node negative [N-], 7 [N+ECS-], 20 [N+ECS-]). CCND1 gain and TP53 loss were found to be associated with nodal status but not ECS. Five OSCC primary tumour cell lines (2 N- & 3 N+ECS+) were then screened by whole genome sequencing for genetic variants that may be associated with ECS. Variants were found in a broad range of genes but poor coverage (< 5 fold mean coverage) from some regions of the genome, in particular NOTCH1, suggested that there may have been technical limitations. However, pathway analysis implicated the NOTCH pathway may have had significance, consistent with literature reports. Additional next generation sequencing assays targeting NOTCH1 were therefore developed and used to analyze the gene in these cell lines. High coverage (150-200 fold mean coverage) of NOTCH1 sequences were achieved and in one of the ECS+ve cell lines (Liv7K), a rare, potentially deleterious nonsynonymous polymorphism (rs61751543) was found. Further screening for NOTCH1 and TP53 genetic variants associated with ECS was therefore performed for primary tumour samples (n=50; 21[N-], 11 [N+ECS-], 18 [N+ECS-]). Sanger resequencing was used for independent confirmation of candidate variants identified. Poorly covered samples (n=10) were excluded. 7/40 (17.5%) samples showed NOTCH1 variants, with 6/14 (43%) ECS+ samples confirmed to have NOTCH1 variants, compared to 1/26 (3.8%) ECS-, Fisher’s exact test p =0.0044. None of these samples displayed variants in TP53. Using this approach, comparing the frequency of the variants to node status, we produced evidence for a unique subset of ECS positive OSCC cases characterized by having disruption of NOTCH1 and absence of TP53 alteration. The NOTCH1 variants were clustered within the region for the extracellular domain (ECD), suggesting that intercellular communication and response could be disrupted. Further functional studies using an ECS +ve primary OSCC cell line as well as invasive and noninvasive controls, showed invasive cell lines demonstrated decreased cell growth and migration in response to Notch inhibition by DAPT (25 μM) treatment, with western blotting revealing absence of Notch1 and 3 after week three and Notch4 by week four only in Liv7K. These findings suggested the importance of further functional studies to assess the effect of Notch inhibition on markers of aggressive phenotype. Taken together our observations overall pave the way to future studies exploring the downstream effects of NOTCH1 ECD mutations and their potential role in OSCC.

Background: Extracapsular spread (ECS) of lymph node metastases is associated with poor prognosis and its detection in head and neck cancer (H&NC) is crucial for treatment planning. Commonly used imaging modalities to detect ECS in H&NC include computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and ultrasonography (US). Currently there is no gold standard imaging modality to detect ECS in H&NC, leaving clinicians to rely heavily on clinical examination and surgical histopathology for ECS based treatment decisions. The purpose of this study was to undertake a systematic review using Joanna Briggs Institute (JBI) methodology that aimed at identifying and synthesising the best available evidence regarding the accuracy of conventional imaging modalities and their abilities to detect ECS in the specific population group of patients with human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). Inclusion criteria: Type of participants: Participants were those with a confirmed diagnosis of HPV+ OPSCC and suspected diagnosis of cervical lymph node metastases and ECS. Participants were not excluded due to age, sex, race or education status. Type of index tests: This review examined studies that utilised a conventional imaging modality to detect radiologic ECS in HPV+ OPSCC. Type of reference test: This review examined studies that utilised surgical histopathology as the reference standard for the diagnosis of ECS (gold standard for ECS detection). Type of outcomes: This review examined two primary and four secondary outcomes of interest. The primary outcomes of interest included: sensitivity and specificity measures with 95% confidence intervals for each imaging modality used to detect ECS in HPV+ OPSCC. The secondary outcomes included: positive predictive value (PPV), negative predictive value (NPV), area under the ROC curve (AUC) and interobserver agreements (K) (where applicable) for the different imaging modalities. Diagnosis of interest: The phenomena of interest in this review was ECS of cervical lymph node metastases (also known as extra-nodal extension (ENE)). Type of studies: This review examined published studies that examined the diagnostic accuracy (including sensitivity and specificity) of an imaging modality used to detect ECS in HPV+ OPSCC. Diagnostic cohort studies were the preferred study design for inclusion. All six of the included studies were retrospective cohort studies. Methods: Methodological approach: The methodological approach to the review was based on JBI guidance for systematic reviews involving diagnostic test accuracy (DTA) studies. Search strategy: A comprehensive search using a three-phased approach was conducted across four databases, one clinical trials register, as well as a manual search for primary studies (published) in the reference lists of all included studies. There was no restriction on publication date, however. only studies in English were included in the review. Methodological quality: Two reviewers assessed the methodological quality of the included studies using the QUADAS-2 tool. The QUADAS-2 tool is structured around assessing for risk of bias in four domains; Patient Selection, Index Test, Reference Standard, and Flow and Timing. Data extraction: Quantitative data was extracted using the JBI data extraction tool for DTA studies. Data analysis Meta-analysis and assessment of heterogeneity was conducted on four CT studies using a random-effects model. The remaining two studies underwent a narrative synthesis. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to assess the certainty in the evidence. Results: Out of 1772 hits, six retrospective cohort studies were included in the review and four underwent meta-analysis. Four investigated the diagnostic ability of CT, one investigated PET/CT, and one investigated 'CT and MRI' (with no separation of index test to outcomes). Meta-analysis of the four CT studies showed CT had an overall sensitivity of 77% (60-94%) and specificity of 60% (47-73%). PET/CT had a sensitivity of 86% (73-94%) and specificity of 76% (61-87%). 'CT and MRI' had a sensitivity of 62% (53-70%) and specificity of 78% (70-84%). No meta-analysis or comparison meta-regression could be performed on the PET/CT or 'CT and MRI' studies. Conclusions: The findings of this review imply pooled CT specificity values (60%) are too low to suggest clinical value for CT as a diagnostic tool to detect ECS in HPV+ OPSCC. Pending further research, the use of CT and PET/CT however might have clinically acceptable sensitivity and negative predictive values to help confirm the absence of radiologic ECS in HPV+ OPSCC. No studies on MRI or US were identified for assessment of ECS in HPV+ OPSCC. Implications for practice: There is insufficient evidence to suggest CT or PET/CT are reliable diagnostic tools for radiological detection of ECS in HPV+ OPSCC. Further studies of high-quality involving CT, PET/CT, MRI and US are required to help establish clinical guidance and a gold standard for radiologic ECS detection in HPV+ OPSCC.
Thesis (MClinSc) -- University of Adelaide, Joanna Briggs Institute, 2022