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Randal S Weber - One of the best experts on this subject based on the ideXlab platform.
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patterns of lateral Neck Metastasis in papillary thyroid carcinoma
Archives of Otolaryngology-head & Neck Surgery, 2004Co-Authors: Michael Elliot Kupferman, Michael Patterson, Susan J Mandel, Virginia A Livolsi, Randal S WeberAbstract:Background Although lymphatic Metastasis does not affect overall survival for patients with differentiated thyroid carcinoma, locoregional control can be improved with cervical lymphadenectomy. The major morbidity of Neck dissection (ND) for the management of regional metastases is spinal accessory (cranial nerve XI) dysfunction. To avoid this complication, some surgeons have advocated a limited ND. Objective To establish the patterns of lateral cervical metastases in differentiated thyroid carcinoma and the role of comprehensive ND, we performed a review of our experience with comprehensive ND. Study Design Retrospective chart review. Patients and Methods Between 1997 and 2002, a total of 39 consecutive patients (31 women and 8 men) underwent 44 NDs for the management of lateral cervical metastases. Preoperative cytologic analysis revealed papillary carcinoma in all 39 patients (100%). All specimens were labeled and mapped by the operating surgeon to identify each level. The incidence of positive disease was determined in relation to the extent of lymphadenectomy for all dissected levels. Results All patients underwent ND at levels II through V; 7 (17%) of the 44 ND specimens included level I nodes. The incidence of metastatic disease in level II nodes was 52% (23/44 specimens). Similarly, 25 specimens (57%) contained histologic metastases at level III. Metastatic disease was noted in 18 level IV nodes (41%) and 9 level V nodes (21%). One (14%) of the 7 specimens with level I nodes contained tumor. Conclusions Cervical metastases from papillary thyroid carcinoma occur in predictable patterns, with disease commonly present at levels II through V. We believe that a comprehensive ND, including removal of transverse cervical and spinal accessory nodes, is necessary for the complete clearance of lateral metastases.
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multivariate predictors of occult Neck Metastasis in early oral tongue cancer
Otolaryngology-Head and Neck Surgery, 2003Co-Authors: Anthony Sparano, Gregory S Weinstein, Ara A Chalian, Michael Yodul, Randal S WeberAbstract:OBJECTIVES: The elective dissection of cervical lymph nodes from patients with early oral tongue cancer and a clinically negative Neck (T1/T2N0), remains an unsettled issue that continues to be investigated. This study examines clinical and histopathologic factors through univariate and multi-variate analysis to correlate the risk of Neck microMetastasis in patients with T1/T2N0 squamous cell carcinoma of the oral tongue.STUDY DESIGN AND METHODS: The clinical files and histologic sections of tumor from 45 clinically determined N0 patients were retrospectively analyzed. The factors examined include degree of tumor cell differentiation, T1/T2 staging, presence of perineural invasion, presence of angiolymphatic invasion, type of invasion front, depth of muscle invasion, and tumor thickness.RESULTS: Independent correlates of positive occult Neck Metastasis included greater tumor thickness (P = 0.01), greater depth of muscle invasion (P = 0.01), T2 stage (P = 0.01), poorly differentiated tumors (P = 0.007), in...
Ryoichi Fujii - One of the best experts on this subject based on the ideXlab platform.
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Selective EP2 and Cox-2 inhibition suppresses cell migration by reversing epithelial-to-mesenchymal transition and Cox-2 overexpression and E-cadherin downregulation are implicated in Neck Metastasis of hypopharyngeal cancer.
American Journal of Translational Research, 2020Co-Authors: Yoshihiro Watanabe, Koji Sakamoto, Yorihisa Imanishi, Hiroyuki Ozawa, Seiji Shigetomi, Ryoichi Fujii, Noboru Habu, Kuninori Otsuka, Yoichiro Sato, Mariko SekimizuAbstract:: Cyclooxygenase-2 (Cox-2) has been shown to promote cancer initiation and progression through pleiotropic functions including induction of epithelial-to-mesenchymal transition (EMT) via its predominant product prostaglandin E2 that binds to the cognate receptor EP2. Hence, pharmacological inhibition at the level of EP2 is assumed to be a more selective alternative with less risk to Cox-2 inhibition. However, little is known regarding the anti-cancer effect of an EP2 antagonist on the malignant properties of cancers including hypopharyngeal squamous cell carcinoma (HPSCC). The present study found that both the Cox-2 inhibitor celecoxib and the EP2 antagonist PF-04418948 upregulated CDH-1 expression, restored membranous localization of E-cadherin, and reduced vimentin expression, by downregulating the transcriptional repressors of E-cadherin in BICR6 and FaDu cells. Such Cox-2 or EP2 inhibition-induced EMT reversal led to repressed migration ability in both cells. Immunohistochemical analysis of surgical HPSCC specimens demonstrated an inverse relationship in expression between Cox-2 and E-cadherin both in the context of statistics (P = 0.028) and of reciprocal immunolocalization in situ. Multivariate logistic regression revealed that overexpression of Cox-2 (P < 0.001) and downregulation of E-cadherin (P = 0.016) were both independently predictive of Neck Metastasis. These results suggest that suppression of cell migration ability via reversing EMT by inhibiting the Cox-2/EP2 signaling may contribute to preventing the development and progression of lymphatic Metastasis. Collectively, targeting Cox-2/EP2, especially using EP2 antagonist, can be a promising therapeutic strategy by exerting an anti-metastatic effect via EMT reversal for improving the treatment outcomes of patients with various cancers including HPSCC.
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Abstract 3359: Expression of stem cell markers Oct3/4 and Nanog in the head and Neck squamous carcinoma cells and its clinical implications for delayed Neck Metastasis in stage I/II tongue squamous cell carcinoma
Cancer Research, 2016Co-Authors: Noboru Habu, Koji Sakamoto, Yorihisa Imanishi, Masayuki Shimoda, Kaori Kameyama, Seiji Shigetomi, Ryoichi Fujii, Yutaka Tokumaru, Kuninori Otsuka, Yoichiro SatoAbstract:Background: The side population (SP) of cancer cells is reportedly enriched with cancer stem cells (CSCs), however, the functional role and clinical relevance of CSC marker molecules upregulated in the SP of head and Neck squamous carcinoma (HNSCC) cells are yet to be elucidated. Patients with clinical stage I/II (T1-2N0M0) tongue squamous cell carcinoma (TSCC) typically undergo partial glossectomy alone; however, development of delayed Neck Metastasis (DNM) tends to reduce their survival. In the present study, we aimed to determine the CSC markers in the SP of HNSCC cells along with their functions in cellular behaviors, and to clarify the association of these markers with DNM. Methods: Flow cytometry was applied to isolate SP from main population (MP) in HNSCC cells (SCC4, SAS, and HSC4). The expression of the CSC markers was examined by semi-quantitative RT-PCR and immunocytochemistry. In vitro proliferation, migration, and invasion assays were performed to assess cellular behaviors. Clinicopathological factors and immunohistochemical expressions of Oct3/4 and Nanog were evaluated using surgical specimens from 50 patients with stage I/II TSCC who underwent partial glossectomy alone. Results: SPs were isolated in all three cell lines examined. Expression levels of Oct3/4 and Nanog were higher in SP cells than MP cells. Additionally, cell migration and invasion abilities were higher in SP cells than MP cells, whereas there was no difference in proliferation. Univariate analysis showed that expression of Oct3/4 and Nanog, vascular invasion, muscular invasion, and mode of invasion were significantly correlated with DNM. Multivariate logistic regression revealed that Oct3/4 expression (risk ratio = 14.78, p = 0.002) and vascular invasion (risk ratio = 12.93, p = 0.017) were independently predictive of DNM. Regarding the diagnostic performance, Oct3/4 showed the highest accuracy, sensitivity, and negative predictive value of 82.0%, 61.5%, and 86.8%, respectively, while vascular invasion showed the highest specificity and positive predictive value of 94.6% and 71.4%, respectively. Conclusion: These results suggest that Oct3/4 and Nanog represent probable CSC markers in HNSCC, which contribute to the development of DNM in part by enhancing cell motility and invasiveness. Moreover, along with vascular invasion, expression of Oct3/4 in the primary cancer cells can be considered a potential predictor for selecting patients at high risk of developing DNM. Citation Format: Noboru Habu, Yorihisa Imanishi, Kaori Kameyama, Masayuki Shimoda, Yutaka Tokumaru, Koji Sakamoto, Ryoichi Fujii, Seiji Shigetomi, Kuninori Otsuka, Yoichiro Sato, Yoshihiro Watanabe, Hiroyuki Ozawa, Toshiki Tomita, Masato Fujii, Kaoru Ogawa. Expression of stem cell markers Oct3/4 and Nanog in the head and Neck squamous carcinoma cells and its clinical implications for delayed Neck Metastasis in stage I/II tongue squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3359.
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Expression of Oct3/4 and Nanog in the head and Neck squamous carcinoma cells and its clinical implications for delayed Neck Metastasis in stage I/II oral tongue squamous cell carcinoma
BMC Cancer, 2015Co-Authors: Noboru Habu, Koji Sakamoto, Yorihisa Imanishi, Masayuki Shimoda, Kaori Kameyama, Seiji Shigetomi, Ryoichi Fujii, Yutaka Tokumaru, Kuninori Otsuka, Yoichiro SatoAbstract:Background The side population (SP) of cancer cells is reportedly enriched with cancer stem cells (CSCs), however, the functional role and clinical relevance of CSC marker molecules upregulated in the SP of head and Neck squamous carcinoma (HNSCC) cells are yet to be elucidated. Patients with clinical stage I/II (T1-2N0M0) tongue squamous cell carcinoma (TSCC) typically undergo partial glossectomy; however, development of delayed Neck Metastasis (DNM) tends to reduce their survival. In the present study, we aimed to determine the CSC markers in the SP of HNSCC cells along with their functions in cellular behaviors, and to clarify the association of these markers with DNM.
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overexpression of sip1 and downregulation of e cadherin predict delayed Neck Metastasis in stage i ii oral tongue squamous cell carcinoma after partial glossectomy
Annals of Surgical Oncology, 2012Co-Authors: Koji Sakamoto, Yorihisa Imanishi, Toshiki Tomita, Masayuki Shimoda, Kaori Kameyama, Katsushi Shibata, Nobuya Sakai, Hiroyuki Ozawa, Seiji Shigetomi, Ryoichi FujiiAbstract:Background Patients with clinical stage I/II (T1–2N0M0) oral tongue squamous cell carcinoma (TSCC) usually undergo partial glossectomy alone. However, 14–48% of them develop delayed Neck Metastasis (DNM), which may lead to an unfavorable course. Recently epithelial-to-mesenchymal transition (EMT) has been thought to play a crucial role in cancer Metastasis. The present study aimed to examine the associations of EMT-involved molecular factors and clinicopathological factors with DNM in stage I/II TSCC.
Jonas T Johnson - One of the best experts on this subject based on the ideXlab platform.
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papillary thyroid cancer controversies in the management of Neck Metastasis
Laryngoscope, 2008Co-Authors: Carter H Davidson, Brian J Park, Jonas T JohnsonAbstract:Objective/Hypothesis: To describe our institution's experience with the management of cervical Metastasis in papillary thyroid carcinoma (PTC) and suggest a treatment strategy based on the incidence of pathologic nodes and cervical recurrence in patients undergoing varied surgical approaches to address lymphadenopathy over the study dates. Materials and Methods: Between December 1, 1972 and September 1, 2007, 183 total patients diagnosed with PTC at the University of Pittsburgh Medical Center were treated with lymphadenectomy. Pathologic parameters, including number of pathologic nodes and extent of lymphadenectomy were correlated to disease recurrence. Study Design: Retrospective chart review. Results: The incidence of pathologic nodes in lymphadenectomy specimens (57.9%) and the recurrence rate (33.7%) were high, in our study population. In comparing techniques with address lymphadenopathy, the highest recurrence rate was observed in patients with pathologic nodes treated with “lymph node plucking” procedures at the time of thyroidectomy and those patients with multiple nodes involved. Few patients with no pathologic nodes, regardless of lymphadenectomy extent recurred. Conclusions: Our data show that limited Neck dissection and disease burden are associated with the highest rates of cervical recurrence in regional metastatic PTC. Comprehensive functional Neck dissection would seem to offer the patient the best opportunity for control of cervical Metastasis. The American Thyroid Association recommends thyroglobulin monitoring and ultrasound evaluation of the Neck in all postoperative patients. Therefore patients with the diagnosis of papillary thyroid cancer need preoperative ultrasound of the lateral Neck and fine needle aspiration of suspicious nodes to avoid undertreating patients scheduled for total thyroidectomy. Neck dissection of the compartments in which pathologic nodes were detected (central, lateral, or both) should then be undertaken at the time of initial thyroidectomy. Eliminating all disease remains elusive and the prognosticsignificance of cervical disease persistence and recurrence is still unknown. Patients with cervical Metastasis are at substantial risk of regional recurrence, necessitating repeat surgery. Parathyroid implantation should be considered at the time of the initial surgery to reduce the risk of hypoparathyroidism should subsequent procedures be required. More information will be necessary to better understand the prognostic significance of these regional metastases. In the interim, many patients may be overtreated, whereas some remain at risk of death because of disease.
Ping Wang - One of the best experts on this subject based on the ideXlab platform.
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papillary thyroid microcarcinomas located at the middle part of the middle third of the thyroid gland correlates with the presence of Neck Metastasis
Surgery, 2015Co-Authors: Dapeng Xiang, Yuanliang Xu, Zhiyu Li, Yurong Hong, Ping WangAbstract:Background Papillary thyroid microcarcinomas (PTMCs), located at upper poles of the thyroid, are associated with lateral Neck Metastasis (LNM) according to previous reports. Controversy remains regarding the correlation between the location of PTMCs and central Neck Metastasis (CNM). Methods Medical records of 949 patients with PTMCs diagnosed between 2010 and 2013 were reviewed retrospectively. With a subdivision of the middle third of the thyroid gland, correlations between tumor location and CNM/LNM along with other clinicopathologic factors were analyzed by binary logistic regression. Results PTMCs located in the middle part of the middle third of the thyroid gland (MPMT) showed the greatest rate of CNM (57.5%) among all locations. PTMCs located at isthmus showed the second greatest rate of CNM (44.3%). In the multivariate analysis, MPMT, tumor size >0.5 cm, young and middle age, male sex, multifocality within the affected lobe, and capsular invasion were correlated with CNM. PTMCs located at upper poles and MPMT showed comparatively high rates of LNM (8.6% and 8.3%). Consistent with previous reports, an upper pole location, MPMT, and a tumor size >0.5 cm greatly correlated with LNM in the multivariate analysis. Eleven patients had skip metastases, which only occurred with upper/lower pole locations and MPMT. Conclusion PTMCs located in the MPMT correlated with both CNM and LNM. Tumor location along with other clinicopathologic factors such as young and middle age, male sex, and tumor size >0.5 cm could facilitate preoperative stratification and guide operative management for patients with PTMC.
Koji Sakamoto - One of the best experts on this subject based on the ideXlab platform.
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Selective EP2 and Cox-2 inhibition suppresses cell migration by reversing epithelial-to-mesenchymal transition and Cox-2 overexpression and E-cadherin downregulation are implicated in Neck Metastasis of hypopharyngeal cancer.
American Journal of Translational Research, 2020Co-Authors: Yoshihiro Watanabe, Koji Sakamoto, Yorihisa Imanishi, Hiroyuki Ozawa, Seiji Shigetomi, Ryoichi Fujii, Noboru Habu, Kuninori Otsuka, Yoichiro Sato, Mariko SekimizuAbstract:: Cyclooxygenase-2 (Cox-2) has been shown to promote cancer initiation and progression through pleiotropic functions including induction of epithelial-to-mesenchymal transition (EMT) via its predominant product prostaglandin E2 that binds to the cognate receptor EP2. Hence, pharmacological inhibition at the level of EP2 is assumed to be a more selective alternative with less risk to Cox-2 inhibition. However, little is known regarding the anti-cancer effect of an EP2 antagonist on the malignant properties of cancers including hypopharyngeal squamous cell carcinoma (HPSCC). The present study found that both the Cox-2 inhibitor celecoxib and the EP2 antagonist PF-04418948 upregulated CDH-1 expression, restored membranous localization of E-cadherin, and reduced vimentin expression, by downregulating the transcriptional repressors of E-cadherin in BICR6 and FaDu cells. Such Cox-2 or EP2 inhibition-induced EMT reversal led to repressed migration ability in both cells. Immunohistochemical analysis of surgical HPSCC specimens demonstrated an inverse relationship in expression between Cox-2 and E-cadherin both in the context of statistics (P = 0.028) and of reciprocal immunolocalization in situ. Multivariate logistic regression revealed that overexpression of Cox-2 (P < 0.001) and downregulation of E-cadherin (P = 0.016) were both independently predictive of Neck Metastasis. These results suggest that suppression of cell migration ability via reversing EMT by inhibiting the Cox-2/EP2 signaling may contribute to preventing the development and progression of lymphatic Metastasis. Collectively, targeting Cox-2/EP2, especially using EP2 antagonist, can be a promising therapeutic strategy by exerting an anti-metastatic effect via EMT reversal for improving the treatment outcomes of patients with various cancers including HPSCC.
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Abstract 3359: Expression of stem cell markers Oct3/4 and Nanog in the head and Neck squamous carcinoma cells and its clinical implications for delayed Neck Metastasis in stage I/II tongue squamous cell carcinoma
Cancer Research, 2016Co-Authors: Noboru Habu, Koji Sakamoto, Yorihisa Imanishi, Masayuki Shimoda, Kaori Kameyama, Seiji Shigetomi, Ryoichi Fujii, Yutaka Tokumaru, Kuninori Otsuka, Yoichiro SatoAbstract:Background: The side population (SP) of cancer cells is reportedly enriched with cancer stem cells (CSCs), however, the functional role and clinical relevance of CSC marker molecules upregulated in the SP of head and Neck squamous carcinoma (HNSCC) cells are yet to be elucidated. Patients with clinical stage I/II (T1-2N0M0) tongue squamous cell carcinoma (TSCC) typically undergo partial glossectomy alone; however, development of delayed Neck Metastasis (DNM) tends to reduce their survival. In the present study, we aimed to determine the CSC markers in the SP of HNSCC cells along with their functions in cellular behaviors, and to clarify the association of these markers with DNM. Methods: Flow cytometry was applied to isolate SP from main population (MP) in HNSCC cells (SCC4, SAS, and HSC4). The expression of the CSC markers was examined by semi-quantitative RT-PCR and immunocytochemistry. In vitro proliferation, migration, and invasion assays were performed to assess cellular behaviors. Clinicopathological factors and immunohistochemical expressions of Oct3/4 and Nanog were evaluated using surgical specimens from 50 patients with stage I/II TSCC who underwent partial glossectomy alone. Results: SPs were isolated in all three cell lines examined. Expression levels of Oct3/4 and Nanog were higher in SP cells than MP cells. Additionally, cell migration and invasion abilities were higher in SP cells than MP cells, whereas there was no difference in proliferation. Univariate analysis showed that expression of Oct3/4 and Nanog, vascular invasion, muscular invasion, and mode of invasion were significantly correlated with DNM. Multivariate logistic regression revealed that Oct3/4 expression (risk ratio = 14.78, p = 0.002) and vascular invasion (risk ratio = 12.93, p = 0.017) were independently predictive of DNM. Regarding the diagnostic performance, Oct3/4 showed the highest accuracy, sensitivity, and negative predictive value of 82.0%, 61.5%, and 86.8%, respectively, while vascular invasion showed the highest specificity and positive predictive value of 94.6% and 71.4%, respectively. Conclusion: These results suggest that Oct3/4 and Nanog represent probable CSC markers in HNSCC, which contribute to the development of DNM in part by enhancing cell motility and invasiveness. Moreover, along with vascular invasion, expression of Oct3/4 in the primary cancer cells can be considered a potential predictor for selecting patients at high risk of developing DNM. Citation Format: Noboru Habu, Yorihisa Imanishi, Kaori Kameyama, Masayuki Shimoda, Yutaka Tokumaru, Koji Sakamoto, Ryoichi Fujii, Seiji Shigetomi, Kuninori Otsuka, Yoichiro Sato, Yoshihiro Watanabe, Hiroyuki Ozawa, Toshiki Tomita, Masato Fujii, Kaoru Ogawa. Expression of stem cell markers Oct3/4 and Nanog in the head and Neck squamous carcinoma cells and its clinical implications for delayed Neck Metastasis in stage I/II tongue squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3359.
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Expression of Oct3/4 and Nanog in the head and Neck squamous carcinoma cells and its clinical implications for delayed Neck Metastasis in stage I/II oral tongue squamous cell carcinoma
BMC Cancer, 2015Co-Authors: Noboru Habu, Koji Sakamoto, Yorihisa Imanishi, Masayuki Shimoda, Kaori Kameyama, Seiji Shigetomi, Ryoichi Fujii, Yutaka Tokumaru, Kuninori Otsuka, Yoichiro SatoAbstract:Background The side population (SP) of cancer cells is reportedly enriched with cancer stem cells (CSCs), however, the functional role and clinical relevance of CSC marker molecules upregulated in the SP of head and Neck squamous carcinoma (HNSCC) cells are yet to be elucidated. Patients with clinical stage I/II (T1-2N0M0) tongue squamous cell carcinoma (TSCC) typically undergo partial glossectomy; however, development of delayed Neck Metastasis (DNM) tends to reduce their survival. In the present study, we aimed to determine the CSC markers in the SP of HNSCC cells along with their functions in cellular behaviors, and to clarify the association of these markers with DNM.
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overexpression of sip1 and downregulation of e cadherin predict delayed Neck Metastasis in stage i ii oral tongue squamous cell carcinoma after partial glossectomy
Annals of Surgical Oncology, 2012Co-Authors: Koji Sakamoto, Yorihisa Imanishi, Toshiki Tomita, Masayuki Shimoda, Kaori Kameyama, Katsushi Shibata, Nobuya Sakai, Hiroyuki Ozawa, Seiji Shigetomi, Ryoichi FujiiAbstract:Background Patients with clinical stage I/II (T1–2N0M0) oral tongue squamous cell carcinoma (TSCC) usually undergo partial glossectomy alone. However, 14–48% of them develop delayed Neck Metastasis (DNM), which may lead to an unfavorable course. Recently epithelial-to-mesenchymal transition (EMT) has been thought to play a crucial role in cancer Metastasis. The present study aimed to examine the associations of EMT-involved molecular factors and clinicopathological factors with DNM in stage I/II TSCC.
