Pediatric differentiated thyroid carcinoma in stage I: risk factor analysis for disease free survival

<p>Abstract</p> <p>Background</p> <p>To examine the outcomes and risk factors in pediatric differentiated thyroid carcinoma (DTC) patients who were defined as TNM stage I because some patients develop disease recurrence but treatment strategy for such stage I pediatric patients is still controversial.</p> <p>Methods</p> <p>We reviewed 57 consecutive TNM stage I patients (15 years or less) with DTC (46 papillary and 11 follicular) who underwent initial treatment at Ito Hospital between 1962 and 2004 (7 males and 50 females; mean age: 13.1 years; mean follow-up: 17.4 years). Clinicopathological results were evaluated in all patients. Multivariate analysis was performed to reveal the risk factors for disease-free survival (DFS) in these 57 patients.</p> <p>Results</p> <p>Extrathyroid extension and clinical lymphadenopathy at diagnosis were found in 7 and 12 patients, respectively. Subtotal/total thyroidectomy was performed in 23 patients, modified neck dissection in 38, and radioactive iodine therapy in 10. Pathological node metastasis was confirmed in 37 patients (64.9%). Fifteen patients (26.3%) exhibited local recurrence and 3 of them also developed metachronous lung metastasis. Ten of these 15 achieved disease-free after further treatments and no patients died of disease. In multivariate analysis, male gender (p = 0.017), advanced tumor (T3, 4a) stage (p = 0.029), and clinical lymphadenopathy (p = 0.006) were risk factors for DFS in stage I pediatric patients.</p> <p>Conclusion</p> <p>Male gender, tumor stage, and lymphadenopathy are risk factors for DFS in stage I pediatric DTC patients. Aggressive treatment (total thyroidectomy, node dissection, and RI therapy) is considered appropriate for patients with risk factors, whereas conservative or stepwise approach may be acceptable for other patients.</p

Fascin overexpression promotes neoplastic progression in oral squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Fascin is a globular actin cross-linking protein, which plays a major role in forming parallel actin bundles in cell protrusions and is found to be associated with tumor cell invasion and metastasis in various type of cancers including oral squamous cell carcinoma (OSCC). Previously, we have demonstrated that fascin regulates actin polymerization and thereby promotes cell motility in K8-depleted OSCC cells. In the present study we have investigated the role of fascin in tumor progression of OSCC.</p> <p>Methods</p> <p>To understand the role of fascin in OSCC development and/or progression, fascin was overexpressed along with vector control in OSCC derived cells AW13516. The phenotype was studied using wound healing, Boyden chamber, cell adhesion, Hanging drop, soft agar and tumorigenicity assays. Further, fascin expression was examined in human OSCC samples (N = 131) using immunohistochemistry and level of its expression was correlated with clinico-pathological parameters of the patients.</p> <p>Results</p> <p>Fascin overexpression in OSCC derived cells led to significant increase in cell migration, cell invasion and MMP-2 activity. In addition these cells demonstrated increased levels of phosphorylated AKT, ERK1/2 and JNK1/2. Our in vitro results were consistent with correlative studies of fascin expression with the clinico-pathological parameters of the OSCC patients. Fascin expression in OSCC showed statistically significant correlation with increased tumor stage (<it>P </it>= 0.041), increased lymph node metastasis (<it>P </it>= 0.001), less differentiation (<it>P </it>= 0.005), increased recurrence (<it>P </it>= 0.038) and shorter survival (<it>P </it>= 0.004) of the patients.</p> <p>Conclusion</p> <p>In conclusion, our results indicate that fascin promotes tumor progression and activates AKT and MAPK pathways in OSCC-derived cells. Further, our correlative studies of fascin expression in OSCC with clinico-pathological parameters of the patients indicate that fascin may prove to be useful in prognostication and treatment of OSCC.</p

Hypoxia regulates the differentiation and anti-tumor effector functions of γδT cells in oral cancer

Summary Hypoxia within the tumor microenvironment (TME) is a key factor contributing to immunosuppression in tumors, co-relating with poor treatment outcome and decreased overall survival in advanced oral cancer (OC) patients. Vδ2 is a dominant subset of gamma delta T cells (γδT cells) present in the peripheral blood which exhibits potent anti-tumor cytotoxicity and is evolving as a key player of anti-cancer cellular therapy. However, the fate of γδT cells in hypoxic oral tumors remains elusive. In the present study, we compared the effect of hypoxia (1% O2) and normoxia (21% O2) on the expansion, proliferation, activation status, cytokine secretion and cytotoxicity of γδT cells isolated from OC patients and healthy individuals. Hypoxia-exposed γδT cells exhibited reduced cytotoxicity against oral tumor cells. Our data demonstrated that hypoxia reduces the calcium efflux and the expression of degranulation marker CD107a in γδT cells, which explains the decreased anti-tumor cytotoxicity of γδT cells observed under hypoxia. Hypoxia-exposed γδT cells differentiated to γδT17 [γδ T cells that produce interleukin (IL)-17] cells, which corroborated our observations of increased γδT17 cells observed in the oral tumors. Co-culture of γδT cells with CD8 T cells in the presence of hypoxia showed that programmed cell death ligand 1 (PD-L1)high γδT cells brought about apoptosis of programmed cell death 1 (PD-1)high CD8 T cells which could be significantly reversed upon blocking PD-1. Thus, future immunotherapeutic treatment modality for oral cancer may use a combined approach of blocking the PD-1/PD-L1 signaling and targeting hypoxia-inducible factor 1α, which may help in reversing hypoxia-induced immunosuppression.</jats:p

Primary angiosarcoma of the larynx: a rare entity

Angiosarcomas are extremely rare malignant tumours of the larynx. We present a case of laryngeal angiosarcoma in a 58-yearold man who presented with hoarseness of voice, dysphagia and neck swelling. The patient underwent a total laryngectomy with a pre-operative and frozen section diagnosis of a poorly differentiated carcinoma of the larynx. Histopathological and immunohistochemical evaluation revealed features of a laryngeal angiosarcoma. The case is presented for its rarity and diagnostic difficulty. </jats:p

Papillary thyroid microcarcinoma: Analysis of outcomes and features predicting risk of recurrence.

e18569 Background: Papillary thyroid microcarcinoma (PTMC) is an enigmatic entity - diverse opinions exist on its clinical course and management. We aimed to analyse disease outcomes and to identify high-risk factors in PTMCs. Methods: This is a retrospective analysis of patients of PTMC treated in our hospital between 2000 and 2014. Clinico-radiological features, treatment details, long term outcomes and recurrence patterns were noted; these were analysed statistically. Results: 160 patients were studied; 61% were females; 86% were aged 55 years or below; 95% cases presented with an enlarged neck node or thyroid nodule or distant metastasis while 5% were incidentalomas. Total thyroidectomy with radioiodine ablation was done in 77% while hemithyroidectomy was done in 23% patients. Follow up ranged between 2 and 238 months. There were 11 (7%) disease related events (nodal or distant metastases or death due to persistent disease). 4 (2.5%) patients died of disease. On univariate analysis, a larger thyroid primary (p 0.001), pre-operatively radiologically identifiable disease in the thyroid (p 0.02) and the lesion not being an incidentaloma (p 0.01) were associated with development of adverse events. Multivariate analysis confirmed the latter two factors as high risk (p 0.05 and 0.00). Nodal metastasis increased with a larger primary (p 0.001), which was multifocal (p 0.00), bilateral (p 0.01) and showed extrathyroid extension (p 0.00). Distant metastases were related with advanced age (p 0.02), presence of involved nodes (p 0.04), larger primary tumour (p 0.15), multifocal tumour (p 0.17), bilateral foci (p 0.02) and extrathyroidal extension (p 0.06). Correspondingly, Kaplan Meier curves showed a better overall survival (OS) and disease free survival (DFS) with incidentalomas as compared to cases presenting with symptoms (Median OS 84 months vs 78 months; Median DFS 79 months vs 77 months) and cases where the lesion was not seen on radiology (Median OS 80 months vs 76 months; Median DFS 80 months vs 75 months). However neither was significant statistically. Addition of Radioiodine ablation did not confer survival advantage (p 0.6). Conclusions: PTMCs are associated with adverse events despite the size of the primary lesion. Stratification as per the above risk factors can improve event free survival. Conversely, aggressive treatment may be deferred in cases of lesions discovered incidentally or on routine screening. </jats:p

Is routine neck dissection warranted at salvage laryngectomy?

AbstractBackgroundThere is controversy regarding management of the neck at salvage laryngectomy. The aim of this study was to perform an analysis to determine the incidence of occult node positivity in this group and analyse factors affecting it.MethodA retrospective analysis of 171 patients who underwent salvage total laryngectomy between 2000 and 2015 for recurrent or residual disease following definitive non-surgical treatment and were clinico-radiologically node negative at the time salvage laryngectomy was carried out.ResultsA total of 171 patients with laryngeal or hypopharyngeal cancers underwent concurrent neck dissection at laryngectomy. There were 162 patients (94.7 per cent) who underwent bilateral neck dissection, and 9 patients (5.3 per cent) who underwent ipsilateral neck dissection. The occult lateral nodal metastasis rate was 10.5 per cent. Of various factors, initial node positive disease was the only factor predicting occult metastasis on univariable and multivariable analysis (p = 0.001).ConclusionRisk of occult metastasis is high in patients who have node positive disease before starting radiotherapy. This group should be offered elective neck dissection.</jats:sec