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Sample records for advanced laryngeal carcinoma

  1. Planned preoperative radiation therapy for advanced laryngeal carcinoma. [/sup 60/Co

    SciTech Connect

    Kazem, I.; van den Broek, P.; Huygen, P.L.M.

    1982-09-01

    One hundred ten patients with predominantly advanced laryngeal carcinoma were treated in the period 1969-1978 with planned preoperative radiation therapy followed by surgery. Site distribution was: 63 supraglottic, 26 glottic, 15 transglottic and 6 subglottic. There were 4 Stage II patients, 66 Stage III and 40 Stage IV. Preoperative radiation therapy consisted of Telecobalt irradiation to a total dose of 25 Gy given to a target volume encompassing the larynx and regional neck nodes, given in 5 equal daily fractions of 5 Gy in 5 consecutive days. Surgery was performed 2 days later. Total laryngectomy was performed on 48 patients, total laryngectomy with neck dissection on 55 patients, supraglottic laryngectomy on 5 and supraglottic laryngectomy with neck dissection on 2 patients. Crude actuarial 5 and 10 year survival probability for the whole group is 71 and 61%, respectively. The corrected 5 and 10 year survival is 75%. For patients with T/sub 3/-T/sub 4/-N/sub 0/ tumors 5 and 10 year survival probability is: crude 65 and 58%, and corrected 70% respectively. For T/sub 3/-T/sub 4/-N/sub +/ crude: 75 and 60% and corrected: 78%. Of 110 patients, one died postoperative, three died of intercurrent disease, five died as a result of second malignancy, and 23 died of their larynx carcinoma: 12/23 because of locoregional failure, and 11/23 because of distant metastasis. We concluded that short intensive preoperative radiation therapy and surgery offer a high cure rate in the treatment of advanced resectable laryngeal carcinoma. The merits of this technique are outlined in the text.

  2. The predictive value of MRI in detecting thyroid gland invasion in patients with advanced laryngeal or hypopharyngeal carcinoma.

    PubMed

    Lin, Peiliang; Huang, Xiaoming; Zheng, Chushan; Cai, Qian; Guan, Zhong; Liang, Faya; Zheng, Yiqing

    2017-01-01

    The aim of this study was to evaluate the predictive value of magnetic resonance imaging (MRI) in detecting thyroid gland invasion (TGI) in patients with advanced laryngeal or hypopharyngeal carcinoma. In a retrospective chart review, 41 patients with advanced laryngeal or hypopharyngeal carcinoma underwent MRI scan before total laryngectomy and ipsilateral or bilateral thyroidectomy during the past 5 years. The MRI findings were compared with the postoperative pathological results. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Among the 41 patients, 3 had thyroid gland invasion in postoperative pathological results. MRI correctly predicted the absence of TGI in 37 of 38 patients and TGI in all 3 patients. The sensitivity, specificity, PPV, and NPV of MRI were 100.0, 97.4, 75.0, and 100 %, respectively, with the diagnostic accuracy of 97.6 %. In consideration of the high negative predictive value of MRI, it may help surgeons selectively preserve thyroid gland in total laryngectomy and reduce the incidence of hypothyroidism and hypoparathyroidism postoperatively.

  3. Multidisciplinary Management of Laryngeal Carcinoma

    SciTech Connect

    Mendenhall, William M. Mancuso, Anthony A.; Hinerman, Russell W.; Malyapa, Robert S.; Werning, John W.; Amdur, Robert J.; Villaret, Douglas B.

    2007-10-01

    The management of head and neck cancer has evolved into a multidisciplinary approach in which patients are evaluated before treatment and decisions depend on prospective multi-institutional trials, as well as retrospective outcome studies. The choice of one or more modalities to use in a given case varies with the tumor site and extent, as exemplified in the treatment of laryngeal squamous cell carcinomas. The goals of treatment include cure, laryngeal voice preservation, voice quality, optimal swallowing, and minimal xerostomia. Treatment options include transoral laser excision, radiotherapy (both definitive and postoperative), open partial laryngectomy, total laryngectomy, and neck dissection. The likelihood of local control and preservation of laryngeal function is related to tumor volume. Patients who have a relatively high risk of local recurrence undergo follow-up computed tomography scans every 3-4 months for the first 2 years after radiotherapy. Patients with suspicious findings on computed tomography might benefit from fluorodeoxyglucose positron emission tomography to differentiate post-radiotherapy changes from tumor.

  4. Recent Advances in Management of Laryngeal Cancer

    PubMed Central

    2004-01-01

    Laryngeal cancers account for approximately 1.5% (1~2%) of the total cancers in Korea, and 30% of all head and neck cancers, not including thyroid cancer. Early laryngeal cancer is treated by operation, including transoral laser excision or radiotherapy. Advanced laryngeal cancer has been treated with mutilating operations, such as a total laryngectomy. However, a laryngeal preserving approach, which can improve the quality of life, has recently been tried with advanced laryngeal cancer. PMID:20396561

  5. Laryngeal leiomyosarcoma masquerading as laryngeal carcinoma

    PubMed Central

    Singh, Lavleen; Mallick, Saumyaranjan; Singh, Shuchita; Safaya, Rajni

    2013-01-01

    Laryngeal leiomyosarcoma is an exceedingly rare malignant tumour, with fewer than 50 reported cases in scientific literature. Diagnosis is based on immunohistochemistry, supplemented with ultrastructural studies, if required. It is aggressive and associated with variable survival outcomes. A 63-year-old man presented with hoarseness for 7 months and breathlessness for 3 months. Imaging showed a well-defined 3 cm glottic mass. Total laryngectomy was performed. The histopathological examination showed features of leiomyosarcoma. The index case has been presented owing to its rarity, variable clinical manifestations and diagnostic dilemmas and to stress upon the importance of ancillary techniques for confirmation. PMID:23729706

  6. Integrated Analysis of Long Noncoding RNA and mRNA Expression Profile in Advanced Laryngeal Squamous Cell Carcinoma

    PubMed Central

    Lian, Meng; Ma, Hongzhi; He, Ning; Liu, Honggang; Wang, Haizhou; Fang, Jugao

    2016-01-01

    Long non-coding RNA (lncRNA) plays an important role in tumorigenesis. However, the expression pattern and function of lncRNAs in laryngeal squamous cell carcinoma (LSCC) are still unclear. To investigate the aberrantly expressed lncRNAs and mRNAs in advanced LSCC, we screened lncRNA and mRNA expression profiles in 9 pairs of primary Stage IVA LSCC tissues and adjacent non-neoplastic tissues by lncRNA and mRNA integrated microarrays. Gene Ontology and pathway analysis were performed to find out the significant function and pathway of the differentially expressed mRNAs, gene-gene functional interaction network and ceRNA network were constructed to select core mRNAs, and lncRNA-mRNA expression correlation network was built to identify the interactions between lncRNA and mRNA. qRT-PCR was performed to further validate the expressions of selected lncRNAs and mRNAs in advanced LSCC. We found 1459 differentially expressed lncRNAs and 2381 differentially expressed mRNAs, including 846 up-regulated lncRNAs and 613 down-regulated lncRNAs, 1542 up-regulated mRNAs and 839 down-regulated mRNAs. The mRNAs ITGB1, HIF1A, and DDIT4 were selected as core mRNAs, which are mainly involved in biological processes, such as matrix organization, cell cycle, adhesion, and metabolic pathway. LncRNA-mRNA expression correlation network showed LncRNA NR_027340, MIR31HG were positively correlated with ITGB1, HIF1A respectively. LncRNA SOX2-OT was negatively correlated with DDIT4. qRT-PCR further validated the expression of these lncRNAs and mRNAs. The work provides convincing evidence that the identified lncRNAs and mRNAs are potential biomarkers in advanced LSCC for further future studies. PMID:28033431

  7. Relationship between response to induction chemotherapy and disease control in patients with advanced laryngeal carcinoma included in an organ preservation protocol.

    PubMed

    León, Xavier; Valero, Cristina; Rovira, Carlota; Rodriguez, Camilo; López, Montserrat; García-Lorenzo, Jacinto; Quer, Miquel

    2017-03-27

    The aim of the study is to analyze the relationship between the degree of response to induction chemotherapy and the disease control in patients with locally advanced laryngeal carcinomas candidates to total laryngectomy. This retrospective study includes 389 patients with T3-T4 laryngeal tumors candidates to total laryngectomy, diagnosed between 1985 and 2013, treated with induction chemotherapy in an organ preservation protocol. Five-year local recurrence-free survival for patients receiving conservative treatment with radiotherapy after a complete response to induction chemotherapy was 75.4%; for patients with partial response greater than 50%, it was 62.0%; and for patients with the absence of response, it was 32.7%. There were significant differences in local recurrence-free survival and laryngeal dysfunction-free survival according to the response to induction chemotherapy (P = 0.0001) at the expense of patients with absence of response to induction chemotherapy. Patients with partial response greater than 50% treated with radiotherapy had a tendency to have worse local recurrence-free survival and laryngeal dysfunction-free survival than patients with complete response, but the differences did not reach statistical significance. Patients with the absence of response after induction chemotherapy had significant differences in disease-specific survival according to the second treatment: for patients treated with surgery it was 70.2%, whereas for patients treated with radiotherapy, it was 28.2% (P = 0.0001). In patients with the absence of response to induction chemotherapy, conservative treatment with radiotherapy implies a significant decrease in survival.

  8. SU-E-T-809: Volumetric Modulated Arc Radiotherapy Vs. Intensity-Modulated Radiotherapy for Locally Advanced Laryngeal Carcinoma: A Dosimetric Study

    SciTech Connect

    Lu, J-Y; Huang, B-T; Zhang, W-Z; Yan, L-J

    2015-06-15

    Purpose: To compare volumetric modulated arc radiotherapy (VMAT) technique with fixed-gantry intensity-modulated radiotherapy (IMRT) technique for locally advanced laryngeal carcinoma. Methods: CT datasets of eleven patients were included. Dual-arc VMAT and 7-field IMRT plans, which were created based on the Eclipse treatment planning system, were compared in terms of dose-volume parameters, conformity index (CI) and homogeneity index (HI) of planning target volume (PTV), as well as organ-at-risk (OAR) sparing, planning time, monitor units (MUs) and delivery time. Results: Compared with the IMRT plans, the VMAT plans provided lower D2% and better CI/HI for the high-risk PTV (PTV1), and provided better CI and comparable HI for the low-risk PTV (PTV2). Concerning the OAR sparing, the VMAT plans demonstrated significantly lower Dmax of the spinal cord (planning OAR volume, PRV) and brainstem (PRV), as well as lower Dmean and V30Gy of the right parotid. No significant differences were observed between the two plans concerning the doses delivered to the thyroid, carotid, oral cavity and left parotid. Moreover, the VMAT planning (147 ± 18 min) consumed 213% more time than the IMRT planning (48 ± 10 min). The MUs of the VMAT plans (556 ± 52) were 64% less than those of the IMRT plans (1684 ± 409), and the average delivery time (2.1 ± 0.1 min) was 66% less than that of the IMRT plans (6.3 ± 0.7 min). Conclusion: Compared with the IMRT technique, the VMAT technique can achieve superior target dose distribution and better sparing of the spinal cord, brainstem and right parotid, with less MUs and less delivery time. It is recommended for the radiotherapy of locally advanced laryngeal carcinoma.

  9. Usefulness of ultrasonography in assessment of laryngeal carcinoma

    PubMed Central

    Xia, C-X; Zhao, H-X; Yan, F; Li, S-L; Zhang, S-M

    2013-01-01

    Objective: To evaluate the usefulness of ultrasonography in assessing laryngeal cancer. Methods: 72 patients with laryngeal carcinoma proven by surgery and pathology were enrolled. The pre-therapeutic ultrasonography and CT images were retrospectively evaluated, including tumour detection, localisation and invasion of intra- and extralaryngeal structures. A comparative assessment was made between the detection rate, correspondence rate of localisation and sensitivity and specificity of ultrasonography and CT. The mobility of the larynx was observed on real-time ultrasonography and compared with laryngoscopy. Results: The detection rate of ultrasonography [63 (87.5%)/72] was lower than that of CT [72 (100.0%)/72] (p=0.006). The primary foci were accurately located in 59 (93.7%) of 63 lesions using ultrasonography compared with 70 (97.2%) of 72 lesions using CT (p=0.392). In the evaluation of invasion, the sensitivity and specificity of ultrasonography were similar to that of CT in most of the intra- and extralaryngeal structures (p=0.059–1.000). A higher specificity was obtained during the assessment of the paraglottic space involvement when using ultrasonography than CT (94.9% vs 66.7%, p=0.001). For vocal cord fixation, no statistical difference was found between ultrasonography and laryngoscopy (p=0.223). Conclusion: Ultrasonography could be used as a valuable supplementary imaging method to CT and laryngoscopy in the assessment of laryngeal carcinoma, even in male adults with some calcifications of the thyroid cartilage. Advances in knowledge: Our study demonstrates that ultrasonography, which has been used scarcely in the larynx, could supply useful information on the detection, localisation and intra- and extralaryngeal invasion of laryngeal carcinoma. PMID:24004487

  10. Identification of key target genes and pathways in laryngeal carcinoma

    PubMed Central

    Liu, Feng; Du, Jintao; Liu, Jun; Wen, Bei

    2016-01-01

    The purpose of the present study was to screen the key genes associated with laryngeal carcinoma and to investigate the molecular mechanism of laryngeal carcinoma progression. The gene expression profile of GSE10935 [Gene Expression Omnibus (GEO) accession number], including 12 specimens from laryngeal papillomas and 12 specimens from normal laryngeal epithelia controls, was downloaded from the GEO database. Differentially expressed genes (DEGs) were screened in laryngeal papillomas compared with normal controls using Limma package in R language, followed by Gene Ontology (GO) enrichment analysis and pathway enrichment analysis. Furthermore, the protein-protein interaction (PPI) network of DEGs was constructed using Cytoscape software and modules were analyzed using MCODE plugin from the PPI network. Furthermore, significant biological pathway regions (sub-pathway) were identified by using iSubpathwayMiner analysis. A total of 67 DEGs were identified, including 27 up-regulated genes and 40 down-regulated genes and they were involved in different GO terms and pathways. PPI network analysis revealed that Ras association (RalGDS/AF-6) domain family member 1 (RASSF1) was a hub protein. The sub-pathway analysis identified 9 significantly enriched sub-pathways, including glycolysis/gluconeogenesis and nitrogen metabolism. Genes such as phosphoglycerate kinase 1 (PGK1), carbonic anhydrase II (CA2), and carbonic anhydrase XII (CA12) whose node degrees were >10 were identified in the disease risk sub-pathway. Genes in the sub-pathway, such as RASSF1, PGK1, CA2 and CA12 were presumed to serve critical roles in laryngeal carcinoma. The present study identified DEGs and their sub-pathways in the disease, which may serve as potential targets for treatment of laryngeal carcinoma. PMID:27446427

  11. Radiotherapy of advanced laryngeal cancer using three small fractions daily

    SciTech Connect

    Bradley, P.J.; Morgan, D.A. )

    1991-06-01

    Since 1983, the authors have treated advanced (UICC stages 3 and 4) squamous carcinomas of the larynx by primary radiotherapy, using three small fractions a day, 3-4 h interfraction interval, 5 days per week. The early patients received doses per fraction of 1.5 Gy, and a total dose of approximately 70 Gy, given as a split-course over 6 to 7 weeks. While overall tumor control and laryngeal preservation was good, a number of severe late radiation reactions were seen. The schedule was then modified, with a reduction in the fraction size to 1.1 Gy, the total dose to 60 Gy, and the overall time to 4 weeks, with omission of the mid-treatment split. Since 1986, we have treated 26 patients in this way. Acute reactions are brisk, but rapidly healing. Loco-regional control was achieved in 22 patients, only one of whom has relapsed to date, in a solitary node, salvaged by radical neck dissection. Four have died of uncontrolled loco-regional malignancy, and three of intercurrent disease while in clinical remission. No serious late morbidity has been observed in surviving patients, and vocal quality is good in the majority. These results suggest that this hyperfractionated and accelerated radiotherapy schedule may offer an acceptable nonsurgical, voice-preserving treatment for advanced laryngeal carcinoma; it can be used in a normally working radiotherapy department.

  12. Hypoxia-Inducible Factor-1α Expression in Indonesian Laryngeal Squamous Cell Carcinoma Patients

    PubMed Central

    Priyanto, Priyanto; Indrasari, Sagung Rai

    2016-01-01

    Objectives. This research aimed to determine the association between hypoxia-inducible factor-1α (HIF-1α) expression and laryngeal squamous cell carcinoma clinical stage. Methods. We retrospectively analyzed paraffin-embedded tissue from 47 laryngeal squamous cell carcinoma (LSCC) patients from 2011 to 2014. HIF-1α expression was analyzed by immunohistochemistry using an anti-HIF-1α mouse monoclonal antibody. The association between HIF-1α expression and clinical stage was analyzed using the chi square test. Results. The glottis was the predominant site of laryngeal squamous cell carcinoma occurrence, and 43/47 (91.5%) patients presented at an advanced stage. Of the advanced stage patients, 27/43 stained positive for HIF-1α expression and 16/43 stained negative. Of the early stage patients, 2/4 stained positive for HIF-1α expression and 2/4 stained negative. Statistical analysis did not demonstrate significant association of HIF-1α expression. Conclusion. There was no statistically significant association between HIF-1α expression and the clinical stage or histological differentiation of LSCC. PMID:27882053

  13. Microbiota in the Throat and Risk Factors for Laryngeal Carcinoma.

    PubMed

    Gong, Hongli; Shi, Yi; Zhou, Xia; Wu, Chunping; Cao, Pengyu; Xu, Chen; Hou, Dongsheng; Wang, Yuezhu; Zhou, Liang

    2014-12-01

    The compositions and abundances of the microbiota in the ecological niche of the human throat and the possible relationship between the microbiota and laryngeal cancer are poorly understood. To obtain insight into this, we enrolled 27 laryngeal carcinoma patients and 28 subjects with vocal cord polyps as controls. For each subject, we simultaneously collected swab samples from the upper throat near the epiglottis (site I) and tissue samples from the vestibulum laryngis to the subglottic region (site II). The microbiota of the throat were fully characterized by pyrosequencing of barcoded 16S rRNA genes. We found 14 phyla, 20 classes, 38 orders, 85 families, and 218 genera in the throats of enrolled subjects. The main phyla were Firmicutes (54.7%), Fusobacteria (14.8%), Bacteroidetes (12.7%), and Proteobacteria (10.6%). Streptococcus (37.3%), Fusobacterium (11.3%), and Prevotella (10.6%) were identified as the three most predominant genera in the throat. The relative abundances of 23 bacterial genera in site I were significantly different from those in site II (P < 0.05). The relative proportions of 12 genera largely varied between laryngeal cancer patients and control subjects (P < 0.05). Collectively, this study outlined the spatial structure of microbial communities in the human throat. The spatial structure of bacterial communities significantly varied in two anatomical sites of the throat. The bacterial profiles of the throat of laryngeal cancer patients were strongly different from those of control subjects, and several of these microorganisms may be related to laryngeal carcinoma.

  14. Microbiota in the Throat and Risk Factors for Laryngeal Carcinoma

    PubMed Central

    Gong, Hongli; Zhou, Xia; Wu, Chunping; Cao, Pengyu; Xu, Chen; Hou, Dongsheng; Wang, Yuezhu

    2014-01-01

    The compositions and abundances of the microbiota in the ecological niche of the human throat and the possible relationship between the microbiota and laryngeal cancer are poorly understood. To obtain insight into this, we enrolled 27 laryngeal carcinoma patients and 28 subjects with vocal cord polyps as controls. For each subject, we simultaneously collected swab samples from the upper throat near the epiglottis (site I) and tissue samples from the vestibulum laryngis to the subglottic region (site II). The microbiota of the throat were fully characterized by pyrosequencing of barcoded 16S rRNA genes. We found 14 phyla, 20 classes, 38 orders, 85 families, and 218 genera in the throats of enrolled subjects. The main phyla were Firmicutes (54.7%), Fusobacteria (14.8%), Bacteroidetes (12.7%), and Proteobacteria (10.6%). Streptococcus (37.3%), Fusobacterium (11.3%), and Prevotella (10.6%) were identified as the three most predominant genera in the throat. The relative abundances of 23 bacterial genera in site I were significantly different from those in site II (P < 0.05). The relative proportions of 12 genera largely varied between laryngeal cancer patients and control subjects (P < 0.05). Collectively, this study outlined the spatial structure of microbial communities in the human throat. The spatial structure of bacterial communities significantly varied in two anatomical sites of the throat. The bacterial profiles of the throat of laryngeal cancer patients were strongly different from those of control subjects, and several of these microorganisms may be related to laryngeal carcinoma. PMID:25239901

  15. Concurrent Chemotherapy and Intensity-Modulated Radiotherapy for Locoregionally Advanced Laryngeal and Hypopharyngeal Cancers

    SciTech Connect

    Lee, Nancy Y. O'Meara, William; Chan, Kelvin; Della-Bianca, Cesar; Mechalakos, James G.; Zhung, Joanne; Wolden, Suzanne L.; Narayana, Ashwatha; Kraus, Dennis; Shah, Jatin P.; Pfister, David G.

    2007-10-01

    Purpose: To perform a retrospective review of laryngeal/hypopharyngeal carcinomas treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). Methods and Materials: Between January 2002 and June 2005, 20 laryngeal and 11 hypopharyngeal carcinoma patients underwent IMRT with concurrent platinum-based chemotherapy; most patients had Stage IV disease. The prescription of the planning target volume for gross, high-risk, and low-risk subclinical disease was 70, 59.4, and 54 Gy, respectively. Acute/late toxicities were retrospectively scored using the Common Toxicity Criteria scale. The 2-year local progression-free, regional progression-free, laryngectomy-free, distant metastasis-free, and overall survival rates were calculated using the Kaplan-Meier method. Results: The median follow-up of the living patients was 26 months (range, 17-58 months). The 2-year local progression-free, regional progression-free, laryngectomy-free, distant metastasis-free, and overall survival rate was 86%, 94%, 89%, 92%, and 63%, respectively. Grade 2 mucositis or higher occurred in 48% of patients, and all experienced Grade 2 or higher pharyngitis during treatment. Xerostomia continued to decrease over time from the end of RT, with none complaining of Grade 2 toxicity at this analysis. The 2-year post-treatment percutaneous endoscopic gastrostomy-dependency rate for those with hypopharyngeal and laryngeal tumors was 31% and 15%, respectively. The most severe late complications were laryngeal necrosis, necrotizing fascitis, and a carotid rupture resulting in death 3 weeks after salvage laryngectomy. Conclusion: These preliminary results have shown that IMRT achieved encouraging locoregional control of locoregionally advanced laryngeal and hypopharyngeal carcinomas. Xerostomia improved over time. Pharyngoesophageal stricture with percutaneous endoscopic gastrostomy dependency remains a problem, particularly for patients with hypopharyngeal carcinoma and, to a lesser

  16. Expression of the tumor suppressor gene hypermethylated in cancer 1 in laryngeal carcinoma.

    PubMed

    Markowski, Jarosław; Sieroń, Aleksander L; Kasperczyk, Katarzyna; Ciupińska-Kajor, Monika; Auguściak-Duma, Aleksandra; Likus, Wirginia

    2015-05-01

    Hypermethylated in cancer 1 (HIC1) is a putative suppressor gene, cooperating with TP53 in the regulation of apoptosis. The promoter site of this gene contains CpG islands susceptible to methylation. Altered methylation leads to the silencing of HIC1. Persistent loss of HIC1 function reflects the attenuation of proapoptotic characteristics of TP53 and may constitute the background for carcinogenesis. Altered methylation profiles along with diminished expression of HIC1 were documented in a number of solid neoplasms. The aim of this study was to evaluate the expression of the HIC1 gene in laryngeal carcinoma. RNA was extracted from samples of laryngeal cancer and corresponding healthy tissues of 21 patients with advanced laryngeal cancer (T3-T4). The amount of RNA (cDNA) was evaluated using reverse transcription-quantitative polymerase chain reaction with GADPH as the reference gene. Data demonstrated that HIC1 expression was significantly reduced in laryngeal cancer tissues. The relative expression of HIC1 was found to be ~40% lower in tumor samples compared to that in healthy controls. The median tumor/normal tissue ratio for HIC1 was 0.615. These results suggest that low HIC1 expression may be associated with neoplastic transformation in the larynx.

  17. Expression of the tumor suppressor gene hypermethylated in cancer 1 in laryngeal carcinoma

    PubMed Central

    MARKOWSKI, JAROSŁAW; SIEROŃ, ALEKSANDER L.; KASPERCZYK, KATARZYNA; CIUPIŃSKA-KAJOR, MONIKA; AUGUŚCIAK-DUMA, ALEKSANDRA; LIKUS, WIRGINIA

    2015-01-01

    Hypermethylated in cancer 1 (HIC1) is a putative suppressor gene, cooperating with TP53 in the regulation of apoptosis. The promoter site of this gene contains CpG islands susceptible to methylation. Altered methylation leads to the silencing of HIC1. Persistent loss of HIC1 function reflects the attenuation of proapoptotic characteristics of TP53 and may constitute the background for carcinogenesis. Altered methylation profiles along with diminished expression of HIC1 were documented in a number of solid neoplasms. The aim of this study was to evaluate the expression of the HIC1 gene in laryngeal carcinoma. RNA was extracted from samples of laryngeal cancer and corresponding healthy tissues of 21 patients with advanced laryngeal cancer (T3-T4). The amount of RNA (cDNA) was evaluated using reverse transcription-quantitative polymerase chain reaction with GADPH as the reference gene. Data demonstrated that HIC1 expression was significantly reduced in laryngeal cancer tissues. The relative expression of HIC1 was found to be ~40% lower in tumor samples compared to that in healthy controls. The median tumor/normal tissue ratio for HIC1 was 0.615. These results suggest that low HIC1 expression may be associated with neoplastic transformation in the larynx. PMID:26137060

  18. Xanthohumol inhibits proliferation of laryngeal squamous cell carcinoma.

    PubMed

    Li, Yan; Wang, Kai; Yin, Shankai; Zheng, Hongliang; Min, Daliu

    2016-12-01

    Xanthohumol is a flavonoid compound that exhibits antioxidant and anticancer effects, and is used to treat atherosclerosis. The aim of the present study was to investigate the effect of xanthohumol on the cell proliferation of laryngeal squamous cell carcinoma and to understand the mechanism of its action. The effects of xanthohumol on the cell viability and apoptosis rate of laryngeal squamous cell carcinoma SCC4 cells were assessed by Annexin V-fluorescein isothiocyanate/propidium iodide staining. In addition, the expression levels of pro-apoptotic proteins, caspase-3, caspase-8, caspase-9, poly ADP ribose polymerase (PARP) p53 and apoptosis-inducing factor (AIF), as well as anti-apoptotic markers, B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia 1 (Mcl-1), were analyzed by western blotting. The results revealed that treatment with 40 µM xanthohumol significantly inhibited the proliferation of SCC4 cells. Furthermore, xanthohumol treatment (40 µM) induced SCC4 cell apoptosis, as indicated by the significant increase in activity and expression of caspase-3, caspase-8, caspase-9, PARP, p53 and AIF. By contrast, the protein expression of Bcl-2 and Mcl-1 was significantly decreased following treatment with 40 µM xanthohumol. Taken together, the results of the present study indicated that xanthohumol mediates growth suppression and apoptosis induction, which was mediated via the suppression of Bcl-2 and Mcl-1 and activation of PARP, p53 and AIF signaling pathways. Therefore, future studies that investigate xanthohumol as a potential therapeutic agent for laryngeal squamous cell carcinoma are required.

  19. Xanthohumol inhibits proliferation of laryngeal squamous cell carcinoma

    PubMed Central

    Li, Yan; Wang, Kai; Yin, Shankai; Zheng, Hongliang; Min, Daliu

    2016-01-01

    Xanthohumol is a flavonoid compound that exhibits antioxidant and anticancer effects, and is used to treat atherosclerosis. The aim of the present study was to investigate the effect of xanthohumol on the cell proliferation of laryngeal squamous cell carcinoma and to understand the mechanism of its action. The effects of xanthohumol on the cell viability and apoptosis rate of laryngeal squamous cell carcinoma SCC4 cells were assessed by Annexin V-fluorescein isothiocyanate/propidium iodide staining. In addition, the expression levels of pro-apoptotic proteins, caspase-3, caspase-8, caspase-9, poly ADP ribose polymerase (PARP) p53 and apoptosis-inducing factor (AIF), as well as anti-apoptotic markers, B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia 1 (Mcl-1), were analyzed by western blotting. The results revealed that treatment with 40 µM xanthohumol significantly inhibited the proliferation of SCC4 cells. Furthermore, xanthohumol treatment (40 µM) induced SCC4 cell apoptosis, as indicated by the significant increase in activity and expression of caspase-3, caspase-8, caspase-9, PARP, p53 and AIF. By contrast, the protein expression of Bcl-2 and Mcl-1 was significantly decreased following treatment with 40 µM xanthohumol. Taken together, the results of the present study indicated that xanthohumol mediates growth suppression and apoptosis induction, which was mediated via the suppression of Bcl-2 and Mcl-1 and activation of PARP, p53 and AIF signaling pathways. Therefore, future studies that investigate xanthohumol as a potential therapeutic agent for laryngeal squamous cell carcinoma are required. PMID:28105237

  20. Laryngeal acinic cell carcinoma following thyroid irradiation

    SciTech Connect

    Reibel, J.F.; McLean, W.C.; Cantrell, R.W.

    1981-01-01

    Only three examples of acinic cell carcinoma of the larynx or trachea are found in the recent literature. A case of acinic cell carcinoma of the subglottic larynx and trachea was diagnosed and treated at the University of Virginia Medical Center. To our knowledge this is the first such case with a prior history of radiation to the neck. The patient is a 56-year-old woman who was irradiated for hyperthyroidism 46 years ago. When seen she also had parathyroid hyperplasia and multiple thyroid adenomas, conditions that frequently follow irradiation of the thyroid in children. These findings in this case support the concept that radiation may be responsible for inducing this tumor, which otherwise rarely occurs in this location. The use of electron microscopy was extremely useful in the diagnosis of this tumor. She was treated with total laryngectomy and right neck dissection and is now free of disease one year after surgery.

  1. Laryngeal Dysplasia, Squamous Cell Carcinoma, and Variants.

    PubMed

    Thompson, Lester D R

    2017-03-01

    Squamous cell carcinoma (SCC) is a malignant epithelial tumor showing evidence of squamous differentiation. It is the most common malignancy of the larynx, with several variants (verrucous, exophytic or papillary, spindle-cell, basaloid, acantholytic, adenosquamous) recognized, with well-established precursor lesions. Dysplasia is now separated into only low-grade and high-grade categories. Each SCC variant has unique cytomorphologic features and histologic differential diagnoses that are important to consider, as management and outcomes are different.

  2. Survival analysis of laryngeal carcinoma without laryngectomy, radiotherapy, or chemotherapy.

    PubMed

    Yu, Qiong; Zhang, Xueyuan; Ji, Changyou; Yang, Hua; Gao, Minghua; Hong, Suling; Hu, Guohua

    2012-09-01

    This study aimed at investigating the survival rate and prognostic factors of laryngeal carcinoma patients in the absence of the use of laryngectomy, radiotherapy, and chemotherapy. A total of 167 cases of laryngeal carcinoma without the use of laryngectomy, radiotherapy, or chemotherapy were analyzed retrospectively. Surveyed items included age, smoking history, tumor family history, tuberculosis history, primary site, pathological grade, T-stage, N-stage, clinical stage, and whether tracheotomy had been performed. Survival rates were calculated using the Kaplan-Meier method. For univariate analysis, comparison among/between groups was performed using the log-rank test. Multivariate analysis was carried out using the Cox proportional hazard model. Overall median survival time was 16 ± 1.44 months, and overall 1- and 2-year survival rates were 56.4 and 26.5%, respectively. No patient survived over 5 years in cases diagnosed for more than 5 years (except for cases that were lost). The median survival time of clinical stage 0/I/II was 28 ± 3.81 months, and 1- and 2-year survival rates were 79.3 and 59.3%, respectively; the median survival time of III/IV clinical stages was 11 ± 1.32 months, and 1- and 2-year survival rates were 45.5 and 10.6%, respectively. Univariate analysis showed that primary site, pathological grade, T-stage, N-stage, and clinical stage were significant prognostic factors for the survival of the patients (P < 0.05). Whether tracheotomy had been performed was not significant for affecting survival rates. Multivariate analysis showed survival rates were statistically correlated with T-stage and N-stage (P < 0.05). The development of laryngeal carcinoma course was faster, without treatment to the tumor itself, even if palliative surgery such as tracheostomy would not improve the survival rate. In laryngeal carcinoma patients with no surgery, radiotherapy or chemotherapy, the factors affecting the survival rates include primary site, pathological

  3. Opium Addiction and Risk of Laryngeal and Esophageal Carcinoma

    PubMed Central

    Bakhshaee, Mehdi; Raziee, Hamid Reza; Afshari, Reza; Amali, Amin; Roopoosh, Mahmoud; Lotfizadeh, Ali

    2017-01-01

    Introduction: Cigarette smoking and alcohol consumption have a well-known effect on the development of upper aerodigestive tract carcinomas, but such a role for opium is questionable. This study was designed to assess the correlation between opium inhalation and cancer of the larynx and upper esophagus. Materials and Methods: Fifty eight patients with laryngeal cancer, ninety eight patients with upper esophageal cancer and twenty seven healthy individuals with no evidence of head and neck or esophageal malignancies were selected from Otolaryngology and Radiation Oncology Department of Mashhad University of Medical Sciences. Duration and amount of cigarette smoking and opium consumption were recorded through comprehensive interviews. Results: The crude odds ratio for laryngeal cancer was 5.58 (95% CI 2.05-15.15, P=0.000) in cigarette smokers relative to non-smokers and 9.09 (95% CI 3.21-25.64, P=0.000) in opium users relative to non-users. The crude odds ratio for esophageal cancer was 0.44 (95% CI 0.18-1.09, P=0.07) in cigarette smokers relative to non-smokers and 1.44 (95% CI 0.57-3.62, P=0.43) in opium users relative to non-users. After adjusting for smoking, the odds ratio for laryngeal cancer in opium users relative to non-users was 6.06 (95% CI 1.10-33.23, P=0.05). Laryngeal cancer was detected at a significantly lower age in opium users (54.54±10.93 vs 62.92±10.10 years, P=0.02) than in smokers. This effect was not observed in esophageal cancer. Although the duration (year 17.50±14.84 vs 21.91±14.03; P=0.34) and amount (pack/day 0.625 vs 0.978; P=0.06) of smoking were higher among those who were opium dependent, these differences were not statistically significant (P=0.34 and P=0.06, respectively). Conclusion: Opium addiction by snuffing is an independent risk factor for the development laryngeal cancer but not esophageal cancer. Cigarette smoking increases this risk. Opium dependency increases the likelihood of developing laryngeal cancer at a younger

  4. Expression of Th1- Th2- and Th17-associated cytokines in laryngeal carcinoma

    PubMed Central

    Xu, Xiaoqun; Wang, Rui; Su, Qinghong; Huang, Haiyan; Zhou, Peng; Luan, Junwen; Liu, Jingsheng; Wang, Junfu; Chen, Xuemei

    2016-01-01

    T-helper (Th) 0 cell differentiation into Th1 or Th2 cells is dependent on a number of transcription factors that act at specific time points to regulate gene expression. Th17 cells, a subset of interleukin (IL)-17-producing T cells distinct from Th1 or Th2 cells, are considered to exhibit a critical function in inflammation and autoimmune diseases, as well as cancer development. In the present study, the expression of Th1-, Th2- and Th17-associated cytokines in laryngeal cancer and pericarcinoma tissues obtained from 57 laryngeal carcinoma patients was investigated. The association between Th1, Th2 and Th17 infiltration and tumor development was also evaluated. Reverse transcription-polymerase chain reaction and western blotting results revealed that the mRNA and protein expression of Th2 cytokines was lower, while the expression of Th1 and Th17 cytokines was higher in tumor tissues than in pericarcinoma tissues. Furthermore, the early stage cancer patients exhibited a higher level of interferon-γ, IL-2 and IL-17 mRNA expression than those at advanced stages. Cancer tissues exhibited higher Th17 cytokine expression than pericarcinoma tissues. By contrast, Th1 cytokine expression was increased in pericarcinoma tissues compared with cancer tissues. These results indicate that high expression of Th1- and Th17-associated cytokines in laryngeal carcinoma may contribute to suppression of cancer development and a relatively good prognosis. PMID:27588143

  5. Role of Advanced Laryngeal Imaging in Glottic Cancer: Early Detection and Evaluation of Glottic Neoplasms.

    PubMed

    Tibbetts, Kathleen M; Tan, Melin

    2015-08-01

    Laryngeal cancer accounts for approximately 2.4% of new malignancies worldwide each year. Early identification of laryngeal neoplasms results in improved prognosis and functional outcomes. Imaging plays an integral role in the diagnosis, staging, and long-term follow-up of laryngeal cancer. This article highlights advanced laryngeal imaging techniques and their application to early glottic neoplasms.

  6. Salvage total laryngectomy after conservation laryngeal surgery for recurrent laryngeal squamous cell carcinoma.

    PubMed

    De Virgilio, A; Greco, A; Bussu, F; Gallo, A; Rosati, D; Kim, S-H; Wang, C-C; Conte, M; Pagliuca, G; De Vincentiis, M

    2016-10-01

    The aim of the present study was to evaluate the oncological efficacy of salvage total laryngectomy in patients who had previously undergone supracricoid partial laryngectomy or transoral laser microsurgery for treatment of laryngeal squamous cell carcinoma. We retrospectively reviewed the medical, surgical and pathological records of 35 patients who underwent salvage total laryngectomy after recurrence of laryngeal cancer (following supracricoid partial laryngectomy or transoral laser microsurgery). Kaplan-Meier survival curves as well as univariate and multivariate analyses of prognostic factors were performed. No statistically significant differences were seen comparing the supracricoid partial laryngectomy group with the transoral laser microsurgery group for overall survival and disease-specific survival at 3 years (OS = 38% vs. 52%, p = 0.16; DSS = 40% vs. 61%, p = 0.057) or locoregional control at 2 years (LRC = 40% vs. 54%, p = 0.056). A trend indicating worse survival and locoregional control for supracricoid partial laryngectomy patients emerged. Preservation of the osteocartilaginous frame in transoral laser microsurgery could hypothetically result in better salvageability of anterior recurrences with extralaryngeal spread.

  7. Laryngitis

    MedlinePlus

    ... your laryngitis symptoms last more than two weeks. Seek immediate medical attention if you: Have trouble breathing ... go away Have increasing pain Have trouble swallowing Seek immediate medical attention if your child: Makes noisy, ...

  8. Computer Based Correlation of the Texture of P63 Expressed Nuclei with Histological Tumour Grade, in Laryngeal Carcinomas

    PubMed Central

    Ninos, Konstantinos; Kalatzis, Ioannis; Ravazoula, Panagiota; Sakelaropoulos, George; Panayiotakis, George; Economou, George; Cavouras, Dionisis

    2014-01-01

    Background. P63 immunostaining has been considered as potential prognostic factor in laryngeal cancer. Considering that P63 is mainly nuclear stain, a possible correlation between the texture of P63-stained nuclei and the tumor's grade could be of value to diagnosis, since this may be related to biologic information imprinted as texture on P63 expressed nuclei. Objective. To investigate the association between P63 stained nuclei and histologic grade in laryngeal tumor lesions. Methods. Biopsy specimens from laryngeal tumour lesions of 55 patients diagnosed with laryngeal squamous cell carcinomas were immunohistochemically (IHC) stained for P63 expression. Four images were digitized from each patient's IHC specimens. P63 positively expressed nuclei were identified, the percentage of P63 expressed nuclei was computed, and 118 textural, morphological, shape, and architectural features were calculated from each one of the 55 laryngeal lesions. Data were split into the low grade (21 grade I lesions) and high grade (34 grade II and grade III lesions) classes for statistical analysis. Results. With advancing grade, P63 expression decreased, P63 stained nuclei appeared of lower image intensity, more inhomogeneous, of higher local contrast, contained smaller randomly distributed dissimilar structures and had irregular shape. Conclusion. P63 expressed nuclei contain important information related to histologic grade. PMID:25763351

  9. MicroRNA-106b regulates the tumor suppressor RUNX3 in laryngeal carcinoma cells.

    PubMed

    Xu, Ying; Wang, Kai; Gao, Wei; Zhang, Chunming; Huang, Fuhui; Wen, Shuxin; Wang, Binquan

    2013-10-01

    Our study focuses on a set of laryngeal tumors that show reduced RUNX3 expression in the absence of transcriptional silencing of tumor suppressor gene RUNX3 by aberrant methylation of CpG islands. We report that the loss of expression of RUNX3 correlates with up-regulation of miR-106b in human laryngeal carcinoma tissue. The downregulation of RUNX3 is mediated by miR-106b through binding of its 3'UTR. Moreover, miR-106b can promote the proliferation and invasion of laryngeal carcinoma cells by directly targeting RUNX3, and RUXN3 knockdown can abolish this phenotype. These results shed a new insight into the mechanism of miRNA regulation in laryngeal carcinoma.

  10. Expression of prostaglandin E2 prostanoid receptor EP2 and interleukin-1β in laryngeal carcinoma – preliminary study

    PubMed Central

    Mochocki, Marcin; Morawski, Piotr; Kopta, Renata; Brzezińska-Błaszczyk, Ewa; Stasikowska, Olga; Lewy-Trenda, Iwona

    2015-01-01

    Aim of the study Expression of EP2 protein, the prostaglandin E2 (PGE2) receptor, produced by tumour microenvironment inflammatory cells as well as tumour cells, may promote cellular proliferation and growth in an autocrine and paracrine fashion. The phenomenon involving these proteins is regulated by interleukin 1β (IL-1β). Many researchers indicate a connection of EP2 and IL-1β in various types of neoplasms with higher tumour progression and poor prognosis. The aim of this study was to analyse the EP2 expression within laryngeal carcinoma tissue and IL-1β levels in peripheral blood mononuclear cell supernatants and to find relationships between clinicomorphological features. Material and methods A group of 50 patients with verified squamous cell laryngeal carcinoma was analysed in this study. The pathological evaluation included pTNM depth of invasion according to tumour front grading criteria. Immunohistochemical analysis for membranous staining of EP2 in tumour tissues was used. The IL-1β expression was determined by enzyme-linked immunosorbent assay (ELISA). Results Increased EP2 expression in carcinoma cells was confirmed for more advanced tumours (pT3-pT4 vs. pT1-pT2, p < 0.0001 and pN1-3 vs. pN0, p = 0.02). Tumours with the highest aggressiveness identified by deeper invasion of submucosa or cartilage were characterised by the highest expression of EP2 (p < 0.0001). In laryngeal carcinomas characterised by a lower differentiation the highest EP2 expression in tumour cells was noted (p = 0.009). A positive relationship between IL-1β expression and the presence of lymph node metastases was also confirmed (p = 0.04). Conclusions The study indicates the potential effect of EP2 receptor and IL-1β on tumour progression in laryngeal carcinoma. PMID:26034388

  11. Podoplanin expression in the development and progression of laryngeal squamous cell carcinomas

    PubMed Central

    2010-01-01

    Background Podoplanin expression is attracting interest as a marker for cancer diagnosis and prognosis. We therefore investigated the expression pattern and clinical significance of podoplanin during the development and progression of laryngeal carcinomas. Results Podoplanin expression was determined by immunohistochemistry in paraffin-embedded tissue specimens from 84 patients with laryngeal premalignancies and 53 patients with laryngeal squamous cell carcinomas. We found podoplanin expression extending from the basal to the suprabasal layer of the epithelium in 37 (44%) of 84 dysplastic lesions, whereas normal epithelium showed negligible expression. Patients carrying podoplanin-positive lesions had a higher laryngeal cancer incidence than those with negative expression reaching borderline statistical significance (51% versus 30%, P = 0.071). Podoplanin expression in laryngeal carcinomas exhibited two distinct patterns. 20 (38%) cases showed diffuse expression in most tumour cells and 33 (62%) focal expression at the proliferating periphery of tumour nests. High podoplanin expression was inversely correlated with T classification (P = 0.033), disease stage (P = 0.006), and pathological grade (P = 0.04). There was a trend, although not significant, towards reduced disease-specific survival for patients with low podoplanin levels (P = 0.31) and diffuse expression pattern (P = 0.08). Conclusions Podoplanin expression increases in the early stages of laryngeal tumourigenesis and it seems to be associated with a higher laryngeal cancer risk. Podoplanin expression in laryngeal squamous cell carcinomas, however, diminishes during tumour progression. Taken together, these data support a role for podoplanin expression in the initiation but not in the progression of laryngeal cancers. PMID:20196862

  12. Organ Preservation With Concurrent Chemoradiation for Advanced Laryngeal Cancer: Are We Succeeding?

    SciTech Connect

    Lambert, Louise; Fortin, Bernard; Soulieres, Denis; Guertin, Louis; Coulombe, Genevieve; Charpentier, Danielle; Tabet, Jean-Claude; Belair, Manon; Khaouam, Nader; Nguyen-Tan, Phuc Felix

    2010-02-01

    Purpose: To determine the rates of organ preservation and function in patients with advanced laryngeal and hypopharyngeal carcinomas treated with concurrent chemoradiotherapy (CRT). Methods and Materials: Between April 1999 and September 2005, 82 patients with advanced laryngeal (67%) and hypopharyngeal carcinomas (33%) underwent conventional radiotherapy and concurrent platinum-based chemotherapy with curative intent. Sixty-two patients were male (75.6%). The median age was 59 years. Eighteen patients (22%) were in Stage III and 64 (78%) were in Stage IV. The median radiation dose was 70 Gy. The median potential follow-up was 3.9 years. Results: Overall survival and disease-free survival were respectively 63% and 73% at 3 years. Complete response rate from CRT was 75%. Nineteen patients (23%) experienced significant long-term toxicity after CRT: 6 (7.3%) required a percutaneous endoscopic gastrostomy, 5 (6%) had persistent Grade 2 or 3 dysphagia, 2 (2.4%) had pharyngoesophageal stenosis requiring multiple dilations, 2 (2.4%) had chronic lung aspiration, and 7 (8.5%) required a permanent tracheostomy. Four patients (4.9%) underwent laryngectomy without pathologic evidence of disease. At last follow-up, 5 (6%) patients were still dependent on a gastrostomy. Overall, 42 patients (52%) were alive, in complete response, with a functional larynx and no other major complications. Conclusions: In our institution, CRT for advanced hypopharyngeal and laryngeal carcinoma has provided good overall survival and locoregional control in the majority of patients, but a significant proportion did not benefit from this approach because of either locoregional failure or late complications. Better organ preservation approaches are necessary to improve locoregional control and to reduce long-term toxicities.

  13. Computed tomography of the larynx: correlation with anatomic and pathologic studies in cases of laryngeal carcinoma

    SciTech Connect

    Mafee, M.F.; Schild, J.A.; Valvassori, G.E.; Capek, V.

    1983-04-01

    Seven patients with known carcinoma of the larynx underwent computed tomography (CT) of the larynx prior to surgery. Whole-mount sections of the extirpated larynx cut in the horizontal plane were compared with the corresponding level of the preoperaive CT sections to demonstrate the validity of CT scanning in the evaluation of tumors of the larynx. The results indicate that CT scanning accurately demonstrates the anatomic location and gross size of laryngeal tumor, although early invasion of the laryngeal cartilages may be difficult to diagnose with CT. It is concluded that preoperative CT scanning of the larynx is the radiologic procedure of choice for evaluating carcinoma of the larynx.

  14. Intra-Operative Lymphatic Mapping and Sentinel Node Biopsy in Laryngeal Carcinoma: Preliminary Results

    PubMed Central

    Khadivi, Ehsan; Daghighi, Maryam; Khazaeni, Kamran; Dabbagh Kakhki, Vahid Reza; Zarifmahmoudi, Leili; Sadeghi, Ramin

    2015-01-01

    Introduction: Sentinel node mapping has been used for laryngeal carcinoma in several studies, with excellent results thus far. In the current study, we report our preliminary results on sentinel node mapping in laryngeal carcinoma using intra-operative peri-tumoral injection of a radiotracer. Materials and Methods: Patients with biopsy-proven squamous cell carcinoma of the larynx were included in the study. Two mCi/0.4 cc Tc-99m-phytate in four aliquots was injected on the day of surgery, after induction of anesthesia, in the sub-mucosal peri-tumoral location using a suspension laryngoscopy. After waiting for 10 minutes, a portable gamma probe was used to search for sentinel nodes. All patients underwent laryngectomy and modified radical bilateral neck dissection. All sentinel nodes and removed non-sentinel nodes were examined by hematoxylin and eosin (H&E) staining. Results: Ten patients with laryngeal carcinoma were included. At least one sentinel node could be detected in five patients (bilateral nodes in four patients). One patient had pathologically involved sentinel and non-sentinel nodes (no false-negative cases). Conclusion: Sentinel node mapping in laryngeal carcinoma is technically feasible using an intra-operative radiotracer injection. In order to evaluate the relationship of T-stage and the laterality of the tumor with accuracy, larger studies are needed. PMID:26788477

  15. Low expression of PTK6/Brk predicts poor prognosis in patients with laryngeal squamous cell carcinoma

    PubMed Central

    2013-01-01

    Background Protein tyrosine kinase 6 (PTK6), also known as breast tumor kinase (Brk), was a nonreceptor tyrosine kinase containing SH3, SH2, and tyrosine kinase catalytic domains. The deregulated expression of PTK6 was observed in various human cancers. However, little was known about PTK6 expression and its clinicopathological significance in human laryngeal squamous cell carcinoma (LSCC). Materials PTK6 expression was evaluated in 7 pairs of surgically resectable laryngeal tissues by Western blotting and in 13 pairs of surgically resectable laryngeal tissues by reverse transcription-PCR (RT-PCR). Using immunohistochemistry, we performed a retrospective study of the PTK6 expression levels on 134 archival LSCC paraffin-embedded samples. Prognostic outcomes correlated with PTK6 were examined using Kaplan–Meier analysis and Cox proportional hazards model. Results The PTK6 expression level was lower in LSCC tissues than in the adjacent noncancerous epithelial laryngeal tissues by Western blots and RT-PCR. By immunohistochemical analysis, we observed high expression of PTK6 in 25 of 76 (32.9%) adjacent noncancerous epithelial laryngeal tissues and in 39 of 134 (29.1%) of LSCC, respectively. Multivariate analysis demonstrated that pN status and the expression level of PTK6 (P < 0.05) were independent and significant prognostic factors. In the primary LSCC category, median DFS (disease free survival) of high, medium and low PTK6 expression patients were 88.5 months ,74.5 months and 49.0 months (log-rank test, P = 0.002); median OS (overall survival) of high, medium and low PTK6 expression patients were 88.5 months ,76.3 months and 65.7 months (log-rank test, P = 0.002). Reduced cytoplasmic PTK6 expression in LSCC was significantly associated with late pN status (P =0.005, r = 0.27), advanced pTNM stages (III and IV) (P =0.027, r = 0.147), and poor differentiated LSCC (P <0.0001, r = 0.486). In adjacent paracancerous laryngeal

  16. Comparison of CT and MRI in Diagnosis of Laryngeal Carcinoma with Anterior Vocal Commissure Involvement

    PubMed Central

    Wu, Jian-hui; Zhao, Jing; Li, Zeng-hong; Yang, Wei-qiang; Liu, Qi-hong; Yang, Zhi-yun; Liao, Bing; Li, Xiao-ling; Wang, Bin; Qin, Hao; Luo, Jie; Lv, Ke-xing; Wen, Wei-ping; Lei, Wen-bin

    2016-01-01

    This study aimed to compare the accuracy of CT and MRI in determining the invasion of thyroid cartilage by and the T staging of laryngeal carcinoma with anterior vocal commissure (AVC) involvement. A total of 26 cases of laryngeal carcinomas with AVC involvement from May 2012 to January 2014 underwent enhanced CT and MRI scan, out of whom 6 patients also underwent diffusion-weighted magnetic resonance imaging(DWI). T staging and thyroid cartilage involvement were evaluated. All the surgical specimens underwent serial section and were reviewed by two senior pathologists independently. When compared with pathologic staging, the accuracy was 88.46% (23/26) of MRI scan (with a 95% confidence interval 37~77%) and 57.69% (15/26) of CT scan (with a 95% confidence interval 70~98%), respectively (P < 0.01). We also reported three cases who were misdiagnosed on CT or MRI about either the thyroid cartilage was involved or not, and one case of preliminary study of DWI. Compared to CT, MRI exhibited a higher accuracy rate on T staging of laryngeal carcinomas with AVC involvement. Combined utility of CT and MRI could help improve the accuracy of assessment of thyroid cartilage involvement and T staging of laryngeal carcinomas with AVC involvement. PMID:27480073

  17. Parenteral Nutrition for Patients Treated for Locally Advanced Inoperable Tumors of the Head and Neck

    ClinicalTrials.gov

    2017-03-10

    Squamous Cell Carcinoma of the Hypopharynx Stage III; Squamous Cell Carcinoma of the Hypopharynx Stage IV; Laryngeal Squamous Cell Carcinoma Stage III; Laryngeal Squamous Cell Carcinoma Stage IV; Oropharyngeal Squamous Cell Carcinoma Stage III; Oropharyngeal Squamous Cell Carcinoma Stage IV; Squamous Cell Carcinoma of the Oral Cavity Stage III; Squamous Cell Carcinoma of the Oral Cavity Stage IV; Locally Advanced Malignant Neoplasm

  18. The immunohistochemical peptidergic expression of leptin is associated with recurrence of malignancy in laryngeal squamous cell carcinoma.

    PubMed

    Gallina, S; Sireci, F; Lorusso, F; DI Benedetto, D V; Speciale, R; Marchese, D; Costantino, C; Napoli, G; Tessitore, V; Cucco, D; Leone, A; Bonaventura, G; Uzzo, M L; Spatola, G F

    2015-02-01

    Leptin is a peptide that plays a key role in the control of satiety, energy expenditure, food intake and various reproductive processes. In the last years, the expression of leptin had been found in malignant cells of various origins. The aim of this study is to evaluate leptin expression in human laryngeal squamous cell carcinoma (SCC) and to investigate its possible role in predicting prognosis. Leptin expression was determined by immunohistochemistry in pathological and healthy tissue specimens from 24 patients with laryngeal SCC. Specimens were stained with an anti-leptin antibody. All measurements were performed using a computer-based image analysis system and scale of staining intensity was determined. All tumoural specimens showed significant immunoreactivity for leptin compared to healthy tissues (p ≤ 0.05), but showed different immunoreactivity that was related to clinicopathological features. High leptin expression was not significantly related with TNM, histological grading (HG) or advanced (III and IV) clinical stage (p > 0.05). Recurrence of malignancy was found to be significantly related with high expression of leptin by Spearman's rank correlation test (r = 0.59; p = 0.002), Fisher's test (p = 0.017) and Kaplan- Meier product-limit estimate (Log-rank test, p ≤ 0.05). In particular, multivariate logistic regression analysis showed that recurrences were significantly related with nodal involvement, HG and leptin expression (p ≤ 0.05). These preliminary results suggest that leptin may be a valuable parameter for predicting prognosis in laryngeal SCC.

  19. The Composition of Microbiome in Larynx and the Throat Biodiversity between Laryngeal Squamous Cell Carcinoma Patients and Control Population

    PubMed Central

    Gong, Hong-Li; Shi, Yi; Zhou, Liang; Wu, Chun-Ping; Cao, Peng-Yu; Tao, Lei; Xu, Chen; Hou, Dong-Sheng; Wang, Yue-Zhu

    2013-01-01

    The throat is an ecological assemblage involved human cells and microbiota, and the colonizing bacteria are important factors in balancing this environment. However, this bacterial community profile has thus been poorly investigated. The purpose of this study was to investigate the microbial biology of the larynx and to analyze the throat biodiversity in laryngeal carcinoma patients compared to a control population in a case-control study. Barcoded pyrosequencing analysis of the 16S rRNA gene was used. We collected tissue samples from 29 patients with laryngeal carcinoma and 31 control patients with vocal cord polyps. The findings of high-quality sequence datasets revealed 218 genera from 13 phyla in the laryngeal mucosa. The predominant communities of phyla in the larynx were Firmicutes (54%), Fusobacteria (17%), Bacteroidetes (15%), Proteobacteria (11%), and Actinobacteria (3%). The leading genera were Streptococcus (36%), Fusobacterium (15%), Prevotella (12%), Neisseria (6%), and Gemella (4%). The throat bacterial compositions were highly different between laryngeal carcinoma subjects and control population (p = 0.006). The abundance of the 26 genera was significantly different between the laryngeal cancer and control groups by metastats analysis (p<0.05). Fifteen genera may be associated with laryngeal carcinoma by partial least squares discriminant analysis (p<0.001). In summary, this study revealed the microbiota profiles in laryngeal mucosa from tissue specimens. The compositions of bacteria community in throat were different between laryngeal cancer patients and controls, and probably were related with this carcinoma. The disruption of this bio-ecological niche might be a risk factor for laryngeal carcinoma. PMID:23824228

  20. [The current role of partial surgery as a strategy for functional preservation in laryngeal carcinoma].

    PubMed

    Rodrigo, Juan Pablo; Coca-Pelaz, Andrés; Suárez, Carlos

    2011-01-01

    With the current advances and recent organ preservation protocols for intermediate or advanced stage laryngeal cancer, based on chemotherapy, the role of surgery seemed replaced except for surgical rescue of tumours not responding to these treatments, total laryngectomy being the surgical option. This type of non-surgical treatment is offered as a strategy for organ preservation, as opposed to total laryngectomy. However, we believe that there are two organ-preservation strategies, surgical and non-surgical. A wide spectrum of surgical techniques is available and such techniques lead to excellent results, both oncological and functional (speech and swallowing). The aim of this paper is to present options for organ-preserving surgery for laryngeal cancer. A review of surgical techniques available for functional preservation in cancer of the larynx at intermediate or advanced stage is presented. In addition to classic approaches such as vertical partial laryngectomy and horizontal or supraglottic laryngectomy, options for conservative laryngeal surgery have improved significantly over the past two decades. Minimally invasive surgery, transoral laser surgery, and supracricoid partial laryngectomy have become important laryngeal preservation approaches for patients with laryngeal cancer. Surgery must define its role in the multidisciplinary treatment of advanced cancers of the larynx, which at present often favours (chemo)radiotherapy protocols.

  1. Paraneoplastic syndromes in patients with laryngeal neuroendocrine carcinomas: clinical manifestations and prognostic significance.

    PubMed

    Ferlito, Alfio; Rinaldo, Alessandra; Bishop, Justin A; Hunt, Jennifer L; Vander Poorten, Vincent; Williams, Michelle D; Triantafyllou, Asterios; Devaney, Kenneth O; Gnepp, Douglas R; Kusafuka, Kimihide; Halmos, Gyorgy B; Westra, William H; Takes, Robert P; Thompson, Lester D R

    2016-03-01

    Paraneoplastic syndromes are associated with a variety of malignant neoplasms and are systemic and non-metastatic manifestations that develop in a minority of cancer patients. This review examines all published cases of paraneoplastic syndromes associated with neuroendocrine carcinomas of the larynx. There are a total of ten patients reported with paraneoplastic syndromes associated with laryngeal neuroendocrine carcinomas in the literature. Of these, nine died and the tenth is alive with liver metastases. There were five cases of small-cell neuroendocrine carcinoma, four cases of moderately differentiated neuroendocrine carcinoma, and one case of well-differentiated neuroendocrine carcinoma associated with paraneoplastic syndromes. As these syndromes have significant clinical relevance, physicians should be aware of the possible presence of paraneoplastic syndromes in the diagnostic process of patients with neuroendocrine carcinoma of the larynx.

  2. Adenovirus with p16 gene exerts antitumor effect on laryngeal carcinoma Hep2 cells.

    PubMed

    Yang, Zhengang; Hu, Jingxia; Li, Dajun; Pan, Xinliang

    2016-08-01

    Laryngeal cancer is an uncommon form of cancer. The tumor suppressor P16, known to be mutated or deleted in various types of human tumor, including laryngeal carcinoma, is involved in the formation and development of laryngeal carcinoma. It has been previously reported that the inactivation or loss of P16 is associated with the acquisition of malignant characteristics. The current study hypothesized that restoring wild‑type P16 activity into P16‑null malignant Hep2 cells may exert an antitumor effect. A recombinant adenovirus carrying the P16 gene (Ad‑P16) was used to infect and express high levels of P16 protein in P16‑null Hep2 cells. Cell proliferation and invasion assays and polymerase chain reaction were performed to evaluate the effects of the P16 gene on cell proliferation and the antitumor effect on Hep2 cells. The results demonstrated that the Hep2 cells infected with Ad‑P16 exhibited significantly reduced cell proliferation, invasion and tumor volume compared with untreated or control adenovirus cells. Furthermore, the expression of laryngeal carcinoma‑associated genes, EGFR, survivin and cyclin D1, were measured in Ad‑P16‑infected cells and were significantly reduced compared with control groups. The results of the current study demonstrate that restoring wild‑type P16 activity into P16-null Hep2 cells exerts an antitumor effect.

  3. Cervical dystonia mimicking dropped-head syndrome after radiotherapy for laryngeal carcinoma.

    PubMed

    Astudillo, Leonardo; Hollington, L; Game, X; Benyoucef, A; Boladeras, A M; Delisle, M B; Simonetta-Moreau, M

    2003-12-01

    We report a case of cervical dystonia mimicking dropped-head syndrome (DHS) in a 57-year-old man treated for laryngeal carcinoma by radiotherapy (74.4 Gy) 3 months before. Cervical computerized tomographic scan and magnetic resonance imaging (MRI) did not find any muscle fat changes but found a high-intensity signal on T2 weighted images in the cervical spinal cord. Clinical and electromyographic findings were consistent with cervical dystonia. A trapezius biopsy was normal. Spontaneous remission of the dystonia was observed for 1 month whereas the laryngeal carcinoma progressed. The link between cervical dystonia and radiotherapy might be acute radiation-induced damage to the cervical spinal cord.

  4. Management of thyroid gland invasion in laryngeal and hypopharyngeal squamous cell carcinoma.

    PubMed

    Arslanoğlu, Seçil; Eren, Erdem; Özkul, Yılmaz; Ciğer, Ejder; Kopar, Aylin; Önal, Kazım; Etit, Demet; Tütüncü, G Yazgı

    2016-02-01

    The objective of this study was to determine the incidence of thyroid gland invasion in laryngeal and hypopharyngeal squamous cell carcinoma; and the association between clinicopathological parameters and thyroid gland invasion. Medical records of 75 patients with laryngeal and hypopharyngeal squamous cell carcinoma who underwent total laryngectomy with thyroidectomy were reviewed, retrospectively. Preoperative computed tomography scans, clinical and operative findings, and histopathological data of the specimens were evaluated. There were 73 male and two female patients with an age range of 41-88 years (mean 60.4 years). Hemithyroidectomy was performed in 62 (82.7 %) and total thyroidectomy was performed in 13 patients (17.3 %). Four patients had histopathologically proven thyroid gland invasion (5.3 %). In three patients, thyroid gland involvement was by means of direct invasion. Thyroid gland invasion was significantly correlated with thyroid cartilage invasion. Therefore, prophylactic thyroidectomy should not be a part of the treatment policy for these tumors.

  5. Cortactin is associated with perineural invasion in the deep invasive front area of laryngeal carcinomas.

    PubMed

    Ambrosio, Eliane Papa; Rosa, Fabíola Encinas; Domingues, Maria Aparecida Custódio; Villacis, Rolando André Rios; Coudry, Renata de Almeida; Tagliarini, José Vicente; Soares, Fernando Augusto; Kowalski, Luiz Paulo; Rogatto, Silvia Regina

    2011-09-01

    The cortactin gene, mapped at 11q13, has been associated with an aggressive clinical course in many cancers because of its function of invasiveness. This study evaluated CTTN protein and its prognostic value in the deep invasive front and superficial areas of laryngeal squamous cell carcinomas. The transcript expression levels were evaluated in a subset of cases. Overexpression of CTTN cytoplasmatic protein (80% of cases in both the deep invasive front and superficial areas) and transcript (30% of samples) was detected in a significant number of cases. In more than 20% of cases, observation verified membrane immunostaining in the deep invasive front and superficial areas. Perineural invasion was significantly associated with N stage and recurrence (P = .0058 and P = .0037, respectively). Higher protein expression levels were correlated with perineural invasion (P = .004) in deep invasive front cells, suggesting that this area should be considered a prognostic tool in laryngeal carcinomas. Although most cases had moderate to strong CTTN expression on the tumor surface, 2 sets of cases revealed a differential expression pattern in the deep invasive front. A group of cases with absent to weak expression of CTTN in the deep invasive front showed good prognosis parameters, and a second group with moderate to strong expression of CTTN were associated with an unfavorable prognosis, suggesting an association with worse outcome. Taken together, these results suggest that the deep invasive front might be considered a grading system in laryngeal carcinomas and that cortactin is a putative marker of worse outcome in the deep invasive front of laryngeal carcinomas.

  6. Possible prognostic value of BORIS transcript variants ratio in laryngeal squamous cell carcinomas - a pilot study.

    PubMed

    Novak Kujundžić, Renata; Grbeša, Ivana; Ivkić, Mirko; Krušlin, Božo; Konjevoda, Paško; Gall Trošelj, Koraljka

    2014-07-01

    BORIS is a paralog of a highly conserved, multi-functional chromatin factor CTCF. Unlike CTCF, which has been shown to possess tumor-suppressive properties, BORIS belongs to the "cancer/testis antigen" family normally expressed only in germ cells and aberrantly activated in a variety of tumors. The consequences of BORIS expression, relative abundance of its isoforms, and its role in carcinogenesis have not been completely elucidated. It activates transcription of hTERT and MYC, genes relevant for laryngeal carcinoma progression. In this study, BORIS expression has been analyzed at the transcriptional level by RT-PCR and protein level by semi-quantitative immunohistochemistry in 32 laryngeal squamous cell carcinomas and adjacent non-tumorous tissue. BORIS was detected in 44 % (14/32) laryngeal squamous cell carcinoma samples, while it was detected only in one normal, tumor-adjacent tissue sample. Tree based survival analysis, using the recursive partitioning algorithm mvpart, extracted the ratio of relative abundance of BORIS transcript variants containing exon 7 (BORIS 7+) and those lacking exon 7 (BORIS 7-) as an independent prognostic factor associated with disease relapse during a 5-year follow-up period. Patients having BORIS 7+/BORIS 7- ratio ≥1 had a higher rate of disease relapse than patients with BORIS 7+/BORIS 7- ratio <1. Hazard ratio for that group, based on Cox Proportional Hazard Regression, was 3.53. This is the first study analyzing expression of BORIS protein and transcript variants in laryngeal squamous cell carcinoma relative to its possible prognostic value for recurrence and overall survival.

  7. Asbestosis, laryngeal carcinoma, and malignant peritoneal mesothelioma in an insulation worker.

    PubMed Central

    Fischbein, A; Luo, J C; Pinkston, G R

    1991-01-01

    Asbestos associated diseases consist of both benign and malignant conditions. A rare constellation of asbestosis, laryngeal carcinoma, and malignant peritoneal mesothelioma occurring in a patient with long term occupational exposure to airborne asbestos fibres is presented. The observation illustrates the powerful disease-causing potential of occupational exposure to asbestos. A brief discussion of multiple primary neoplasms associated with exposure to asbestos is also presented. Images PMID:2039746

  8. HOX genes: potential candidates for the progression of laryngeal squamous cell carcinoma.

    PubMed

    de Barros E Lima Bueno, Rafaela; Ramão, Anelisa; Pinheiro, Daniel Guariz; Alves, Cleidson Padua; Kannen, Vinicius; Jungbluth, Achim A; de Araújo, Luiza Ferreira; Muys, Bruna Rodrigues; Fonseca, Aline Simoneti; Plaça, Jessica Rodrigues; Panepucci, Rodrigo Alexandre; Neder, Luciano; Saggioro, Fabiano P; Mamede, Rui Celso M; Figueiredo, David Livingstone Alves; Silva, Wilson Araújo

    2016-11-01

    Laryngeal squamous cell carcinoma (LSCC) is a very aggressive cancer, considered to be a subtype of the head and neck squamous cell carcinoma (HNSCC). Despite significant advances in the understanding and treatment of cancer, prognosis of patients with LSCC has not improved recently. In the present study, we sought to understand better the genetic mechanisms underlying LSCC development. Thirty-two tumor samples were collected from patients undergoing surgical resection of LSCC. The samples were submitted to whole-genome cDNA microarray analysis aiming to identify genetic targets in LSCC. We also employed bioinformatic approaches to expand our findings using the TCGA database and further performed functional assays, using human HNSCC cell lines, to evaluate viability, cell proliferation, and cell migration after silencing of selected genes. Eight members of the homeobox gene family (HOX) were identified to be overexpressed in LSCC samples when compared to normal larynx tissue. Quantitative RT-PCR analysis validated the overexpression of HOX gene family members in LSCC. Receiver operating characteristic (ROC) statistical method curve showed that the expression level of seven members of HOX gene family can distinguish tumor from nontumor tissue. Correlation analysis of clinical and gene expression data revealed that HOXC8 and HOXD11 genes were associated with the differentiation degree of tumors and regional lymph node metastases, respectively. Additionally, siRNA assays confirmed that HOXC8, HOXD10, and HOXD11 genes might be critical for cell colony proliferation and cell migration. According to our findings, several members of the HOX genes were overexpressed in LSCC samples and seem to be required in biological processes involved in tumor development. This suggests that HOX genes might play a critical role in the physiopathology of LSCC tumors.

  9. Establishment of an animal model of spontaneous cervical lymph node metastasis of laryngeal squamous cell carcinoma and obtaining laryngocarcinoma cells with high metastatic potential.

    PubMed

    Chen, L W; Wang, J L; Zhang, L Y; Yang, S M; Li, C S; Yu, N; Zhao W, J D; Zhao, L D; Li, K; Liu, M B; Zhai, S Q

    2013-01-01

    To establish an animal model of spontaneous cervical lymph node metastasis of laryngeal squamous cell carcinoma and obtain laryngocarcinoma cells with high metastatic potential, laryngeal squamous cell carcinoma cell line HEP-2 in logarithmic phase were inoculated under the lingual margin mucosa of nude mice. HEP-2 cells metastasized to the cervical lymph nodes were isolated, cultured, and re-inoculated under the lingual margin mucosa of nude mice twice. The tumor formation in the tongue and in the cervical lymph nodes was confirmed by pathological examination. Carcinoma cells' ability of invasion and migration was detected by transwell assay. Human specific Alu sequences were detected by PCR, which indicated that the tumor cells originated from human laryngeal squamous cell carcinoma cell line HEP-2. Finally, an animal model of spontaneous lymph node metastasis of laryngeal squamous cell carcinoma was successfully established. Laryngeal squamous cell carcinoma cells with high metastatic potential to lymph nodes were obtained through repeated inoculations. .

  10. Metal-proteinase ADAM12, kinesin 14 and checkpoint suppressor 1 as new molecular markers of laryngeal carcinoma.

    PubMed

    Markowski, Jarosław; Tyszkiewicz, Tomasz; Jarzab, Michał; Oczko-Wojciechowska, Małgorzata; Gierek, Tatiana; Witkowska, Małgorzata; Paluch, Jarosław; Kowalska, Małgorzata; Wygoda, Zbigniew; Lange, Dariusz; Jarzab, Barbara

    2009-10-01

    The assessment of gene expression profile in laryngeal cancer allows implementation of molecular biology methods in diagnostics, as well as in prognosticating the course of disease, thus allowing taking most optimal decisions as regards the method of treatment, scope of surgical procedure, or the necessity of adding complementary radiotherapy. The aim of the project was to analyze the gene expression profile in laryngeal cancer using oligonucleotide microarrays, having in mind searching new molecular markers for that carcinoma. The study comprised a group of 43 patients (38 males and 5 females) suffering from squamous cell laryngeal carcinoma, diagnosed and surgically treated in the years 2005-2007 in the ENT Department of the Silesian Medical University in Katowice, Poland. RNA was isolated from frozen tissue fragments, with the use of columns RNeasy Midi and Mini Kit (Qiagen). For the examination of gene expression profile, oligonucleotide microarrays of high density were used, provided by Affymetrix (U 133 2.0 PLUS) containing over 54,000 probes for over 47,000 transcripts. Four genes previously not examined in that respect in laryngeal carcinoma, occurred to be good markers of the neoplasm. They are: metal-proteinase ADAM12, cyclin-dependent kinase 2-CDK2, kinesin 14-KIF14, suppressor 1 of checkpoint-CHES1. The analysis of gene expression profile allows, in laryngeal carcinoma, to point out to new genes, which in future may become molecular markers of the carcinoma.

  11. Real-time in vivo diagnosis of laryngeal carcinoma with rapid fiber-optic Raman spectroscopy.

    PubMed

    Lin, Kan; Zheng, Wei; Lim, Chwee Ming; Huang, Zhiwei

    2016-09-01

    We assess the clinical utility of a unique simultaneous fingerprint (FP) (i.e., 800-1800 cm(-1)) and high-wavenumber (HW) (i.e., 2800-3600 cm(-1)) fiber-optic Raman spectroscopy for in vivo diagnosis of laryngeal cancer at endoscopy. A total of 2124 high-quality in vivo FP/HW Raman spectra (normal = 1321; cancer = 581) were acquired from 101 tissue sites (normal = 71; cancer = 30) of 60 patients (normal = 44; cancer = 16) undergoing routine endoscopic examination. FP/HW Raman spectra differ significantly between normal and cancerous laryngeal tissue that could be attributed to changes of proteins, lipids, nucleic acids, and the bound water content in the larynx. Partial least squares-discriminant analysis and leave-one tissue site-out, cross-validation were employed on the in vivo FP/HW tissue Raman spectra acquired, yielding a diagnostic accuracy of 91.1% (sensitivity: 93.3% (28/30); specificity: 90.1% (64/71)) for laryngeal cancer identification, which is superior to using either FP (accuracy: 86.1%; sensitivity: 86.7% (26/30); specificity: 85.9% (61/71)) or HW (accuracy: 84.2%; sensitivity: 76.7% (23/30); specificity: 87.3% (62/71)) Raman technique alone. Further receiver operating characteristic analysis reconfirms the best performance of the simultaneous FP/HW Raman technique for laryngeal cancer diagnosis. We demonstrate for the first time that the simultaneous FP/HW Raman spectroscopy technique can be used for improving real-time in vivo diagnosis of laryngeal carcinoma during endoscopic examination.

  12. Expression of p27 and PTEN and clinical characteristics in early laryngeal squamous cell carcinoma and their correlation with recurrence.

    PubMed

    Yang, Jun-Quan; Liang, Zhen; Wu, Meng; Sun, Yu-Man; Liu, Hong-Xia

    2015-01-01

    Laryngeal squamous cell carcinoma is a common malignant tumor of otolaryngeal region. At present, effective treatment of laryngeal squamous cell carcinoma still depends on surgery and radiotherapy. In recent years, application of CO2 laser resection in the treatment of stage T1 glottic carcinoma can remove the tumor completely and reduce the injury of laryngeal tissues. But recurrence still happened in some postoperative patients. Here, we selected 131 patients to compare the therapeutic effects of CO2 laser resection and traditional split laryngeal surgery on the early laryngeal cancer, examined the expression of p27 and PTEN by immunohistochemistry in early laryngeal squamous cell carcinoma tissues in correlation to clinical outcome. After two years follow-up 14/85 (16.5%) of CO2 laser treatment group presented with local recurrence (recurrent group), while that of split laryngeal surgery group was 6/46 (13.0%). There was no statistical significance in recurrence rate between the two groups (P>0.05). 10 of all the 111 (9.0%) non-recurrent patients did not follow the doctor's advice to quit smoking after the operation, while 12 in the 20 (60.0%) recurrent patients did not; the difference between the two groups was statistically significant (P<0.01). The positive rates of p27 were 80.2% (105/131) and 43.5% (57/131), and that of PTEN were 83.2% (109/131) and 48.9% (64/131) in the cancer adjacent tissues (negative surgical margin tissues) and in laryngeal carcinoma tissues, respectively (P<0.001). The expression rates of p27 and PTEN in laryngeal carcinoma tissues of the recurrent group were 20.0% (4/20), 10.0% (2/20) and that in non recurrent group were 47.7% (53/111) and 55.9% (62/111), respectively, with a significant difference (P<0.001). In addition, the expression of p27 and PTEN in tumor resected marginal tissues of the recurrence group was 50.0% (10/20), 40.0% (8/20) and that in non recurrence group was 85.6% (95/111) and 91.0% (101/111), respectively; the

  13. Changing the paradigm: the potential for targeted therapy in laryngeal squamous cell carcinoma

    PubMed Central

    Ludwig, Megan L.; Birkeland, Andrew C.; Hoesli, Rebecca; Swiecicki, Paul; Spector, Matthew E.; Brenner, J. Chad

    2016-01-01

    Laryngeal squamous cell carcinoma (LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21st century. PMID:27144065

  14. Identification and characterization of CD133+CD44+ cancer stem cells from human laryngeal squamous cell carcinoma cell lines

    PubMed Central

    Wang, Jue; Wu, Yongyan; Gao, Wei; Li, Fei; Bo, Yunfeng; Zhu, Meixia; Fu, Rong; Liu, Qingqing; Wen, Shuxin; Wang, Binquan

    2017-01-01

    Background: Laryngeal squamous cell carcinoma ranks second among head and neck squamous-cell carcinomas. Cancer stem cells can support cancer growth and malignant behavior. Therefore, cancer stem cells isolated from laryngeal squamous cell carcinoma tissue could be used to investigate the initiation, progression, and treatment strategies of this cancer. Methods: We isolated CD133-CD44-, CD133-CD44+, CD133+CD44- and CD133+CD44+ cell populations from laryngeal squamous-cell carcinoma cell lines Hep2 and TU-177 by magnetic-activated cell sorting. Sphere formation, cell proliferation, migration, invasion, colony formation, resistance to radio- and chemotherapy, and in vivo tumorigenicity of these populations were evaluated. Moreover, we investigated the expression of the stem-cell markers (sex determining region Y)-box 2 (SOX2) and octamer-binding transcription factor 4 (OCT4) in CD133-CD44-, CD133-CD44+, CD133+CD44-, CD133+CD44+ cell populations and parental Hep2 and TU-177 cells. Results: As compared with CD133-CD44-, CD133-CD44+, CD133+CD44- populations and parental cells, CD133+CD44+ cells showed higher cell viability, migration and invasive capability and colony formation ability as well as stronger resistance to cisplatin and irradiation. Moreover, levels of SOX2 and OCT4 and tumorigenicity in nude mice were greater in CD133+CD44+ Hep2 and TU-177 cells than other cell populations and parental cells. Conclusion: The CD133+CD44+ population of laryngeal squamous-cell carcinoma Hep2 and TU-177 cells have stem cell properties and showed more malignant features than CD133+CD44- and CD133-CD44+ cell populations. CD133+CD44+ cancer stem cells may be a promising target for developing anticancer drugs and treatment strategies for laryngeal squamous cell carcinoma. PMID:28261352

  15. Papillary thyroid carcinoma and laryngeal squamous cell carcinoma manifesting as a collision tumor of the neck: A case report

    PubMed Central

    WANG, XIN; CUI, XIANG-YAN; FANG, NING; CHEN, WEI-LUN; YU, HONG; ZHU, WEI

    2013-01-01

    A 55-year-old male presented with a rapidly expanding mass on the right side of the neck and progressive hoarseness. An electronic laryngoscopy and a computed tomography scan were performed, and the patient was subsequently diagnosed with tumors of the larynx and the thyroid gland. An en bloc near-total thyroidectomy combined with a total laryngectomy was performed. The final pathological analysis revealed a collision tumor that was derived from a laryngeal squamous cell carcinoma and a papillary thyroid carcinoma. Collision tumors of the head and neck are rare. The therapy for a collision tumor should consist of a combination of the treatments that are normally used for each focus. PMID:24260054

  16. Expression and distribution of aggrecanases in human larynx: ADAMTS-5/aggrecanase-2 is the main aggrecanase in laryngeal carcinoma.

    PubMed

    Filou, S; Stylianou, M; Triantaphyllidou, I E; Papadas, T; Mastronikolis, N S; Goumas, P D; Papachristou, D J; Ravazoula, P; Skandalis, S S; Vynios, D H

    2013-04-01

    Members of the ADAMTS family of proteases degrade proteoglycans and thereby have the potential to alter tissue architecture and regulate cellular functions. Aggrecanases are the main enzymes responsible for aggrecan degradation, due to their specific cleavage pattern. In this study, the expression status, the macromolecular organization and localization of ADAMTS-1, ADAMTS-4/aggrecanase-1 and ADAMTS-5/aggrecanase-2 in human normal larynx and laryngeal squamous cell carcinoma (LSCC) were investigated. On mRNA level, the results showed that ADAMTS-4 was the highest expressed enzyme in normal larynx, whereas ADAMTS-5 was the main aggrecanase in LSCC presenting a stage-related increase up to stage III (8-fold higher expression compared to normal), and thereafter decreased in stage IV. Accordingly, immunohistochemical analysis showed that ADAMTS-5, but not ADAMTS-4, was highly expressed by carcinoma cells. Sequential extraction revealed an altered distribution and organization of multiple molecular forms (latent, activated and fragmented forms) of the enzymes within the cancerous and their corresponding macroscopically normal laryngeal tissues, compared to the normal ones. Importantly, these analyses indicated that critical macromolecular changes occurred from the earliest LSCC stages not only in malignant parts of the tissue but also in areas that were not in proximity to carcinoma cells and appeared otherwise normal. Overall, the results of the present study show that ADAMTS-5/aggrecanase-2 is the main aggrecanase present in laryngeal carcinoma suggesting a critical role for the enzyme in aggrecan degradation and laryngeal tissue destruction during tumor progression.

  17. Hsp90 Inhibitor AT13387 in Treating Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Radiation Therapy and Cisplatin

    ClinicalTrials.gov

    2017-01-31

    Human Papillomavirus Infection; Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma

  18. Obtaining Normal Tissue Constraints Using Intensity Modulated Radiotherapy (IMRT) in Patients with Oral Cavity, Oropharnygeal, and Laryngeal Carcinoma

    SciTech Connect

    Skinner, William K.J.

    2009-01-01

    The purpose of this study was to evaluate normal tissue dose constraints while maintaining planning target volume (PTV) prescription without reducing PTV margins. Sixteen patients with oral cavity carcinoma (group I), 27 patients with oropharyngeal carcinoma (group II), and 28 patients with laryngeal carcinoma (group III) were reviewed. Parotid constraints were a mean dose to either parotid < 26 Gy (PP1), 50% of either parotid < 30 Gy (PP2), or 20 cc of total parotid < 20 Gy (PP3). Treatment was intensity modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB). All patients met constraints for cord and brain stem. The mandibular constraints were met in 66%, 29%, and 57% of patients with oral, oropharyngeal, and laryngeal cancers, respectively. Mean dose of 26 Gy (PP1) was achieved in 44%, 41%, and 38% of oral, oropharyngeal, and laryngeal patients. PP2 (parotid constraint of 30 Gy to less than 50% of one parotid) was the easiest to achieve (group I, II, and III: 82%, 76%, and 78%, respectively). PP3 (20 cc of total parotid < 20 Gy) was difficult, and was achieved in 25%, 17%, and 35% of oral, oropharyngeal, and laryngeal patients, respectively. Mean parotid dose of 26 Gy was met 40% of the time. However, a combination of constraints allowed for sparing of the parotid based on different criteria and was met in high numbers. This was accomplished without reducing PTV-parotid overlap. What dose constraint best correlates with subjective and objective functional outcomes remains a focus for future study.

  19. Restoration of voice function by using biological feedback in laryngeal and hypopharyngeal carcinoma patients

    NASA Astrophysics Data System (ADS)

    Choinzonov, E. L.; Balatskaya, L. N.; Chizhevskaya, S. Yu.; Meshcheryakov, R. V.; Kostyuchenko, E. Yu.; Ivanova, T. A.

    2016-08-01

    The aim of the research is to develop and introduce a new technique of post-laryngectomy voice rehabilitation of laryngeal and hypopharyngeal carcinoma patients. The study involves comparing and analyzing 82 cases of voice function restoration by using biological feedback based on mathematical modeling of voice production. The advantage of the modern technology-based method in comparison with the conventional one is proved. Restoration of voice function using biofeedback allows taking into account patient's abilities, adjusting parameters of voice trainings, and controlling their efficiency in real-time mode. The data obtained indicate that the new method contributes to the rapid inclusion of self-regulation mechanisms of the body and results in the overall success rate of voice rehabilitation in totally laryngectomized patients reaching 92%, which reduces the rehabilitation period to 18 days, compared to 86% and 38 days in the control group, respectively. Restoration of disturbed functions after successful treatment is an important task of rehabilitation and is crucial in terms of the quality of cancer patients' lives. To assess life quality of laryngeal cancer patients, the EORTC Quality of Life Core Questionnaire (QLQ-C30), and head and neck module (QLQ-H&N35) were used. The analyzed results proved that the technique of biofeedback voice restoration significantly improves the quality of life of laryngectomized patients. It allows reducing the number of disabled people, restoring patients' ability to work-related activities, and significantly improving social adaptation of these patients.

  20. Laryngeal carcinoma: high-resolution computed tomography and thick anatomic sections

    SciTech Connect

    Reid, M.H.

    1984-06-01

    High-resolution 2-mm thick sequential CT scans of 23 patients with primary laryngeal carcinoma were reviewed to judge the value of CT in early tumor detection and the ability of CT to establish tumor extent reliably, particularly early cartilage invasion. In tumors large enough to be imaged, there were no false negatives. False-positive results for clearly identified tumors were related to the interpretation of tumor on CT where only edema was present at surgery. Both early and gross cartilage invasion were well correlated with surgically resected specimen sections. Early cartilage involvement by tumor can be detected by the development of a fenestrated chrondral margin. Other benign expansive cartilage processes, such as occur with chondromas, have calcified cartilage fragment distributions that are out of proportion to any soft-tissue mass present.

  1. Gene polymorphisms are associated with clinical outcome in Chinese resected laryngeal carcinoma patients

    PubMed Central

    Chen, Peng; Chen, Zhengshuai; Li, Jinglie; Yang, Hua; Zhu, Yuanyuan; Zhang, Ning; Yan, Mengdan; Shao, Yuan; Chen, Chao; Jin, Tianbo

    2016-01-01

    We examined the multigenetic index on the progression of laryngeal carcinoma in Chinese population. This study aims to assess the effects of single nucleotide polymorphisms (SNPs) on survival of Laryngeal Carcinoma (LC) patients. Eighteen SNPs were selected and genotyped using the Sequenom iPLEX genotyping system in a cohort of 170 resected Chinese LC patients. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis. Overall, the median survival time (MST) was 38.00 months. The one, three and five year Kaplan-Meier survival rate was 0.847 ± 0.028, 0.572 ± 0.038 and 0.471 ± 0.041 respectively. The risks of death with the Hazard Ratio (HR) [95% confidence intervals] (CI) of 2.40 (1.15–4.50), 2.17 (1.45–3.25), 2.39 (1.58–3.62), 3.29 (2.10–5.18), respectively. There was significant associations between the SNPs and OS when the entire study population was examined. The rs1321311 TG genotype (vs.GG), rs2494938 AA genotype (vs. GG) and rs9363918 TG genotype (vs. GG) were associated with a worse prognosis for OS (adjusted HR = 1.64; 95%confidence interval = 1.07–2.51; P = 0.022, adjusted HR = 2.85; P =0.12; adjusted HR = 1.78; P = 0.009; respectively). The results suggest for the first time that these gene polymorphisms may serve as an independent prognostic marker for LC patients. PMID:27765935

  2. The prognostic value of systemic and local inflammation in patients with laryngeal squamous cell carcinoma

    PubMed Central

    Wang, Jie; Wang, Shengzi; Song, Xinmao; Zeng, Wenjiao; Wang, Shuyi; Chen, Fu; Ding, Hao

    2016-01-01

    Background Cancer-related systemic inflammation has been demonstrated to be associated with poor outcome in multiple types of cancers. Meanwhile, the local inflammation, which is characterized by dense intratumoral immune infiltrate, is a favorable predictor of survival outcome. Purpose To evaluate the role of systemic and local inflammation in predicting outcome in patients with laryngeal squamous cell carcinoma. Patients and methods In this retrospective study, 120 patients who had undergone postoperative radiotherapy were enrolled. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as calculated from pretreatment whole blood counts, were used to indicate systemic inflammation. The optimal cutoff values of NLR and PLR were determined using receiver operating characteristic curve analysis. Tumor infiltrating lymphocytes (TILs) density, as assessed by pathologist review of hematoxylin and eosin-stained slides, was used to represent local inflammation. Overall survival (OS) and recurrence-free survival (RFS) were assessed using the Kaplan–Meier method and multivariate Cox regression analysis. Results The best cutoff was 2.79 for NLR and 112 for PLR. Kaplan–Meier analysis revealed that high NLR, high PLR, and low TILs density were significantly correlated with inferior OS and RFS, respectively (all P<0.05). The Cox proportional multivariate hazard model showed that a high pretreatment PLR and a low TILs density were both independently correlated with poor OS and RFS, respectively (all P<0.05). Conclusion Markers of systemic and local inflammation, especially PLR and TILs density, are reliable prognostic factors in patients with laryngeal squamous cell carcinoma. PMID:27920556

  3. Salvage surgery in post-chemoradiation laryngeal and hypopharyngeal carcinoma: outcome and review.

    PubMed

    Putten, L; Bree, R; Doornaert, P A; Buter, J; Eerenstein, S E J; Rietveld, D H F; Kuik, D J; Leemans, C R

    2015-06-01

    Our objective was to evaluate recurrence patterns of hypopharyngeal and laryngeal carcinoma after chemoradiation and options for salvage surgery, with special emphasis on elderly patients. In a retrospective study all patients who underwent chemoradiation for hypopharyngeal and laryngeal carcinoma in a tertiary care academic center from 1990 through 2010 were evaluated. Primary outcome measures were the survival and complication rates of patients undergoing salvage surgery, especially in elderly patients. Secondary outcome measures were the predictors for salvage surgery for patients with locoregional recurrence after failed chemoradiotherapy. A review of the literature was performed. Of the 136 included patients, 60 patients had recurrent locoregional disease, of whom 22 underwent salvage surgery. Fifteen patients underwent a total laryngectomy with neck dissection(s) and 7 neck dissection without primary tumour surgery. Independent predictors for salvage surgery within the group of 60 patients with recurrent disease, were age under the median of 59 years (p = 0.036) and larynx vs. hypopharynx (p = 0.002) in multivariate analyses. The complication rate was 68% (14% major and 54% minor), with fistulas in 23% of the patients. Significantly more wound related complications occurred in patients with current excessive alcohol use (p = 0.04). Five-year disease free control rate of 35%, overall survival rate of 27% and disease specific survival rate of 35% were found. For the 38 patients who were not suitable for salvage surgery, median survival was 12 months. Patients in whom the tumour was controlled had a 5-year overall survival of 70%. In patients selected for salvage surgery age was not predictive for complications and survival. In conclusion, at two years follow-up after chemoradiation 40% of the patients were diagnosed with recurrent locoregional disease. One third underwent salvage surgery with 35% 5-year disease specific survival and 14% major complications

  4. Association between UGT1A1 Polymorphism and Risk of Laryngeal Squamous Cell Carcinoma

    PubMed Central

    Huangfu, Hui; Pan, Hong; Wang, Binquan; Wen, Shuxin; Han, Rui; Li, Li

    2016-01-01

    Laryngeal cancer is one of the largest subgroups of head and neck cancers. In addition to smoking and alcohol consumption, genetic polymorphisms are also risk factors for the development of laryngeal cancer. However, the exact relation between genetic variants and pathogenesis of laryngeal cancer has remained elusive. The aim of this study was to examine UGT1A1*6 (rs4148323 A/G) polymorphisms in 103 patients with laryngeal cancer and 220 controls using the high resolution melting curve (HRM) technique and to explore the association between UGT1A1*6 (rs4148323 A/G) polymorphisms and laryngeal cancer. The results showed an association between the rs4148323 G allele and increased risk of laryngeal cancer. While there was no statistically significant difference between rs4148323 genotype frequencies and different histological grades or different clinical stages of laryngeal cancer, stratification analysis indicated smoking or alcohol consumption and rs4148323 G allele combined to increase the risk of laryngeal cancer. In conclusion, the rs4148323 G allele is associated with the high UGT1A1 enzyme activity, and might increase the risk of laryngeal cancer. Furthermore, smoking or alcohol consumption and the rs4148323 G allele act synergistically to increase the risk of laryngeal cancer. PMID:26751466

  5. Analysis of Postsurgical Health-Related Quality of Life and Quality of Voice of Patients With Laryngeal Carcinoma

    PubMed Central

    Luo, Jie; Wu, Jieli; Lv, Kexing; Li, Kaichun; Wu, Jianhui; Wen, Yihui; Li, Xiaoling; Tang, Haocheng; Jiang, Aiyun; Wang, Zhangfeng; Wen, Weiping; Lei, Wenbin

    2016-01-01

    Abstract This study aims to analyze the postsurgical health-related quality of life (HRQOL) and quality of voice (QOV) of patients with laryngeal carcinoma with an expectation of improving the treatment and HRQOL of these patients. Based on the collection of information of patients with laryngeal carcinoma regarding clinical characteristics (age, TNM stage, with or without laryngeal preservation and/or neck dissection, with or without postoperative irradiation and/or chemotherapy, etc.), QOV using Voice Handicap Index (VIH) scale and HRQOL using EORTC QLQ-C30 and EORTCQLQ-H&N35 scales, the differences of postsurgical HRQOL related to their clinical characteristics were analyzed using univariate nonparametric tests, the main factors impacting the postsurgical HRQOL were analyzed using regression analyses (generalized linear models) and the correlation between QOV and HRQOL analyzed using spearman correlation analysis. A total of 92 patients were enrolled in this study, on whom the use of EORTC QLQ-C30, EORTC QLQ-H&N35 and VHI scales revealed that: the differences of HRQOL were significant among patients with different ages, TNM stages, and treatment modalities; the main factors impacting the postsurgical HRQOL were pain, speech disorder, and dry mouth; and QOV was significantly correlated with HRQOL. For the patients with laryngeal carcinoma included in our study, the quality of life after open surgeries were impacted by many factors predominated by pain, speech disorder, and dry mouth. It is suggested that doctors in China do more efforts on the patients’ postoperative pain and xerostomia management and speech rehabilitation with the hope of improving the patients’ quality of life. PMID:26735538

  6. Genetic polymorphisms and plasma levels of BCL11A contribute to the development of laryngeal squamous cell carcinoma

    PubMed Central

    Zhou, Jian; Yang, Yue; Zhang, Duo; Zhou, Liang; Tao, Lei; Lu, Li-Ming

    2017-01-01

    Objective We investigated the association between B-cell lymphoma/leukaemia 11A (BCL11A) rs11886868 and rs4671393 polymorphism, plasma BCL11A concentration, and the hazard of developing laryngeal squamous cell carcinoma (LSCC). Participants and method In this research, 330 LSCC patients, 310 healthy controls, and 155 vocal leukoplakia patients were genotyped for the BCL11A (rs11886868 C/T and rs4671393 A/G) genotypes by pyrosequencing; the BCL11A concentration was measured using ELISA. Results LSCC Patients had a notably higher occurrence of CT at rs11886868 (OR = 2.64, P = 0.025) than the control group; they also had higher GG at rs4671393 (OR = 2.53, P = 0.018). Advanced (III and IV) stage LSCC patients had a notably greater frequency of CT at rs11886868 than those with initial (I and II) stage LSCC (OR = 2.71, P = 0.044 vs. OR = 2.58, P = 0.051). Additionally, there was a 1.59 fold increase in susceptibility for initial stage LSCC related to the G allele (AG/GG) at rs4671393 (P = 0.005); while for patients of advanced stage LSCC the OR was 1.73 (P = 0.002). Moreover, the OR of lymph node metastasis patients at rs4671393 G alleles was 2.41 (P < 0.01); it was 1.38 (P = 0.035) in patients without lymph metastasis. Patients with high incidences of the rs4671393 variation genotype had high plasma BCL11A levels. Conclusions BCL11A rs11886868 and rs4671393 genotype variations and correspondingly high BCL11A plasma levels are related to LSCC, besides, differences in plasma levels and genotype distribution may be related to lymph node metastasis status and the stage of LSCC. PMID:28225775

  7. MiR-300 suppresses laryngeal squamous cell carcinoma proliferation and metastasis by targeting ROS1.

    PubMed

    Ge, Wensheng; Han, Chaodong; Wang, Jing; Zhang, Yunping

    2016-01-01

    Laryngeal squamous cell carcinoma (LSCC) is a common aggressive head and neck cancer with high mortality and incidence. MicroRNAs (miRNAs) are short, non-coding and endogenous RNAs that posttranscriptionally inhibit gene expression. In this study, we showed that miR-300 expression was downregulated in LSCC tissues compared with adjacent no-tumor tissues. MiR-300 overexpression inhibited Hep-2 cell proliferation, as well as the expression of ki-67 and PCNA. Moreover, overexpression of miR-300 repressed the cell invasion in Hep-2 cells. We identified c-ros oncogene 1 receptor tyrosine kinase (ROS1) as a direct target gene of miR-300 in Hep-2 cell. Furthermore, ROS1 expression was upregulated in LSCC tissues compared with adjacent no-tumor tissues. Interesting, there were an inverse correlation between ROS1 and miR-300 expression in the LSCC tissues. Overexpression of ROS1 increased the Hep-2 cells proliferation and invasion. Overexpression of ROS1 abrogated miR-300 induced cell growth and invasion inhibition. Therefore, our data suggested that miR-300 acted as a tumor suppressive gene in LSCC.

  8. SHISA3 Promoter Methylation Is a Potential Diagnostic and Prognostic Biomarker for Laryngeal Squamous Cell Carcinoma

    PubMed Central

    Zhou, Chongchang; Li, Jinyun; Ye, Dong; Deng, Hongxia; Cao, Bin; Hao, Wenjuan; Lin, Lexi

    2017-01-01

    The purpose of this study was to evaluate the contribution of SHISA3 promoter methylation to laryngeal squamous cell carcinoma (LSCC). SHISA3 promoter methylation status and expression were determined using methylation-specific polymerase chain reaction (MSP) and quantitative real-time PCR (qRT-PCR) in 93 paired LSCC and adjacent normal tissues, respectively. Furthermore, the regulatory function of the SHISA3 promoter fragment was analyzed using a luciferase reporter assay. The results reveal that there is a significant increase in SHISA3 methylation in LSCC tissues compared with corresponding nontumor tissues (P = 4.58E − 12). The qRT-PCR results show a significant association between SHISA3 methylation and expression in LSCC (P = 1.67E − 03). In addition, the area under the receiver operating characteristic curve was 0.91. Consequently, a log-rank test and multivariate Cox analysis suggest that SHISA3 promoter hypermethylation is a predictor of poor overall survival for LSCC (log-rank P = 0.024; HR = 2.71; 95% CI = 1.024–7.177; P = 0.047). The results indicate that SHISA3 promoter hypermethylation might increase the risk of LSCC through regulation of gene expression and is a potential diagnostic and prognostic biomarker for LSCC. PMID:28299336

  9. DIRC3 and near NABP1 genetic polymorphisms are associated laryngeal squamous cell carcinoma patient survival

    PubMed Central

    Bai, Yanxia; Chen, Zhengshuai; Li, Jingjie; Li, Bin; Jin, Tianbo; Cao, Peilong; Shao, Yuan

    2016-01-01

    Laryngeal squamous cell carcinoma (LSCC) is one of the most common and aggressive malignancies of the upper digestive tract. The present study is a retrospective analysis of data from a prospective longitudinal study. A total of 170 male LSCC patients (average age, 60.75±10.082) at the First Affiliated Hospital of Xi'an Jiaotong University School of Medicine were recruited between January 2002 and April 2013 for this study. We assessed correlations between patient characteristics and survival, and sequenced genomic DNA from patient peripheral blood samples. We found that the single nucleotide polymorphisms (SNPs), rs11903757, with closest proximity to NABP1 and SDPR, and rs966423 in DIRC3, were associated with survival in LSCC patients. Median follow-up was 38 months (range 3–122) and median survival time was 48 months. LSCC patients with total laryngectomy, poor differentiation, T3-T4 stage, N1-N2 stage or III-IV TNM stage had reduced survival. This is the first study to demonstrate that the rs11903757 GT (HR=2.036; 95% CI, 1.071–3.872; p=0.030) and rs966423 TT (HR=11.677; 95% CI, 3.901–34.950; p=0.000) genotypes predict poor patient outcome. These polymorphisms may serve as useful clinical markers to predict patient survival, and to guide individual patient therapeutic decisions. PMID:27793000

  10. Genotoxic effects of green tea extract on human laryngeal carcinoma cells in vitro.

    PubMed

    Durgo, Ksenija; Kostić, Sandra; Gradiški, Katarina; Komes, Draženka; Osmak, Maja; Franekić, Jasna

    2011-06-01

    Green tea (Camellia sinensis) contains several bioactive compounds which protect the cell and prevent tumour development. Phytochemicals in green tea extract (mostly flavonoids) scavenge free radicals, but also induce pro-oxidative reactions in the cell. In this study, we evaluated the potential cytotoxic and prooxidative effects of green tea extract and its two main flavonoid constituents epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) on human laryngeal carcinoma cell line (HEp2) and its cross-resistant cell line CK2. The aim was to see if the extract and its two flavonoids could increase the sensitivity of the cisplatin-resistant cell line CK2 in comparison to the parental cell line. The results show that EGCG and green tea extract increased the DNA damage in the CK2 cell line during short exposure. The cytotoxicity of EGCG and ECG increased with the time of incubation. Green tea extract induced lipid peroxidation in the CK2 cell line. The pro-oxidant effect of green tea was determined at concentrations higher than those found in traditionally prepared green tea infusions.

  11. LAMP3 and TP53 overexpression predicts poor outcome in laryngeal squamous cell carcinoma.

    PubMed

    Qiu, Xiaoxia; You, Yiwen; Huang, Jianfei; Wang, Xudong; Zhu, Huijun; Wang, Zhiwei

    2015-01-01

    Lysosomal associated membrane protein 3 (LAMP3) is a newly identified tumor-specific and hypoxia-induced protein. It is a downstream target gene of tumor suppressor TP53 and its expression has been associated with hypoxia-induced metastasis and poor overall survival in cervical, breast and gastrointestinal cancers. However, little is known of LAMP3 protein expression in laryngeal squamous cell carcinoma (LSCC) and its prognostic value. We determined protein expression of LAMP3 and TP53 in LSCC tissues (n=117) by immunohistochemistry analysis on tissue microarray (TMA), their expression was correlated with patients' clinical parameters and overall survival. LAMP3 and TP53 protein expression was significantly higher in cancerous tissues compared to adjacent normal surgical margin tissues. Both high LAMP3 and high TP53 protein expression was significantly associated with tumor stage and size. Significant correlation between LAMP3 and TP53 expression was observed. Patients with high LAMP3 or high TP53 expression had a poor overall survival. Our data suggest that both epithelial LAMP3 expression and TP53 expression are independent prognostic markers for LSCC.

  12. Expression of ezrin and moesin related to invasion, metastasis and prognosis of laryngeal squamous cell carcinoma.

    PubMed

    Wang, X; Liu, M; Zhao, C Y

    2014-09-29

    We examined the expression of ezrin and moesin in laryngeal squamous cell carcinoma (LSCC) and their correlation with patient clinicopathological characteristics and overall survival. Immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR) for ezrin and moesin were applied to 60 carcinoma tissues, adjacent normal tissues, and 33 metastatic lymph nodes. Survival functions were estimated using the Kaplan-Meier method and compared by the log-rank test. RT-PCR demonstrated that the intensity ratios of ezrin and moesin to β-actin were higher in LSCC than in adjacent normal mucous membrane (P < 0.05). Furthermore, intensity ratios were higher in cervical metastatic lymph nodes than in LSCC (P < 0.05). Immunohistochemical staining showed that ezrin and moesin were well distributed in the cell membrane and cytoplasm. Expression was significantly different between LSCC and adjacent normal tissues (P < 0.05); moreover, expression in the cervical metastatic lymph nodes was higher than in LSCC (P < 0.05). Expression of ezrin and moesin was significantly related to clinical stage, T stage, and cervical lymph node metastasis (P < 0.05), except that moesin showed no significant relationship with clinical stage (P > 0.05). Patients with negative ezrin and moesin expression had a significantly longer overall survival time compared to patients with moderate and intense ezrin and moesin expression (P < 0.001, P < 0.05). Ezrin and moesin expression is related to LSCC invasion and metastasis, and may be important molecular markers for predicting prognosis and therapeutic targets in LSCC patients.

  13. Potential role of Notch1 signaling pathway in laryngeal squamous cell carcinoma cell line Hep-2 involving proliferation inhibition, cell cycle arrest, cell apoptosis, and cell migration.

    PubMed

    Jiao, Jing; Qin, Zhaobing; Li, Sha; Liu, Hongtao; Lu, Zhaoming

    2009-10-01

    Head and neck cancer is the sixth most common cancer worldwide and laryngeal cancer represents the largest subgroup. However, the molecular mechanism underlying its malignant behavior and progression is not clarified. Accumulating evidence has shown that Notch1 signaling pathway plays a central role in carcinogenesis, but its potential role in regulating the development of laryngeal carcinoma, has not been characterized. Here, we identified that Notch1 signaling pathway was activated in laryngeal carcinoma accompanied with up-regulation of Notch1 and Hes1 expression. Overexpression of Notch1 in laryngeal carcinoma cell line Hep-2 led to suppression of tumor cellular proliferation and arrested cell cycle in the G0/G1 phase and induced cell apoptosis, which were coupled with the down-regulation of cyclin D1, cyclin E, cdk2 and bcl-2 and up-regulation of caspase-3, caspase-9 and p53. Most importantly, up-regulation of Notch1 expression also reduced the migration of Hep-2 cells, which was closely associated with down-regulation of MMP-2 and MMP-9. The finding may lay a foundation for further investigations into the Notch1 signaling pathway as a potential target for laryngeal carcinoma.

  14. Challenges of advanced hepatocellular carcinoma

    PubMed Central

    Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

    2016-01-01

    Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials. PMID:27678348

  15. The immunohistochemical expression of p21WAF1/Cip1 and Proliferating cell nuclear antigen in laryngeal squamous cell carcinomas.

    PubMed

    Li, X; Izumaru, S; Sakamoto, K; Miyajima, Y; Nakashima, T

    2006-12-01

    The purpose of this study was to assess the significance of the expression of p21WAF1/Cip1 and proliferating cell nuclear antigen (PCNA) in human laryngeal squamous cell carcinomas. Forty-eight patients (25 supraglottic, 23 glottic) who had undergone operations between 1998 and 2003 were included in this study. The Envision immunohistochemistry method was utilized to stain these tissue specimens. The results showed that the immunostaining of p21WAF1/Cip1 do not show any correlation with differentiation, N stage, metastasis, survival, recurrence or the laryngeal site of involvement. A significant inverse correlation was detected between p21WAF1/Cip1 and the T stage. In contrast, the percentage of PCNA labelled cells showed a significant correlation with the T stage, but not with other clinicopathological parameters. There were differences in the expression of p21WAF1/Cip1 and PCNA between the supraglottic and the glottic carcinomas. In conclusion, our findings suggest that p21WAF1/Cip1 and PCNA may play an important role in the progression of carcinoma of the supraglottic larynx.

  16. [Prognostic factors in the radio-surgical treatment of laryngeal carcinoma].

    PubMed

    Valente, G; Garetto, M L; Ragona, R; Rosmino, C; Palestro, G; Bussi, M; Giordano, C; Gabriele, P

    1995-03-01

    We examined a homogeneous group of 116 patients with laryngeal and hypopharyngeal carcinomas, treated with surgery followed by radiotherapy according to the conventional procedure. The tumors occurred in the larynx in 88 cases (75.86%) and in the hypopharynx in 28 (24.14%); correlations between overall survival and disease-free survival on the one hand, and clinical and histological parameters on the other hand were established with a multivariate analysis using the Cox method. After 5 years 75.86% of the patients were alive. This variable was negatively influenced by pN (pN0 89.8%, pN1 76.2%, pN2 69%); pT (pT3 82.5%, pT4 62.5%), by vascular embolization (90% of patients alive with no vascular embolization versus 69.7% with vascular embolization), by the grade of peritumoral inflammation (64.3% of patients alive with slight peritumoral inflammation, 69.2% with medium-grade inflammation and 87.3% with strong inflammation), and finally by a great number of plasma cells and few granulocytes; 78.44% of these patients remained disease-free. This variable was negatively affected by pN (pN0 91.8%, pN1 76.2%, pN2 60%), patients' age and extracapsular spread (85.5% of disease-free patients with no extracapsular spread, vs. 51.55% with extracapsular spread); and positively influenced by basal cell differentiation (95% of disease-free patients versus 71.8%). Overall and disease-free survival rates which differed at the beginning, coincided after two years because of local recurrences. On the basis of these results we conclude that the correct assessment of morphologic variables should be considered as a useful tool for treatment planning.

  17. Deprivation of asparagine triggers cytoprotective autophagy in laryngeal squamous cell carcinoma.

    PubMed

    Ji, Yunxiang; Li, Li; Tao, Qilei; Zhang, Xuyao; Luan, Jingyun; Zhao, Shuwei; Liu, Huanhai; Ju, Dianwen

    2017-03-28

    Laryngeal squamous cell carcinoma (LSCC), one of the most common malignancies in the head and neck, has poor prognosis and high mortality. The need of novel and effective treatment for LSCC is urgent. Asparaginase, an enzyme-depriving asparagine, has been employed for the treatment of various cancers. In this study, we reported for the first time that asparaginase could induce remarkable cytotoxicity and caspase-dependent apoptosis in human LSCC Tu212 and Tu686 cells. Meanwhile, autophagy was triggered by asparaginase in LSCC cells, which was confirmed by accumulation of autophagosomes and the conversion of light chain 3-I (LC3-I) to LC3-II. Importantly, inhibition of autophagy by chloroquine (CQ) significantly enhanced asparaginase-induced cytotoxicity, indicating that autophagy has a cytoprotective role in asparaginase-treated LSCC cells. Meanwhile, we found that mitochondrial-originated reactive oxygen species (ROS) participated in asparaginase-induced autophagy and cytotoxicity. N-acetyl-L-cysteine (NAC), a common antioxidant, was employed to scavenge ROS, and our results demonstrated that NAC could significantly block asparaginase-induced autophagy and attenuate asparaginase-induced cytotoxicity, indicating that intracellular ROS played a crucial role in asparagine deprivation therapy. Furthermore, western blot analysis showed that asparaginase-induced autophagy was mediated by inactivation of Akt/mTOR and activation of the Erk signaling pathway in Tu212 and Tu686 cells. Therefore, these results indicated the protective role of autophagy in asparaginase-treated LSCC cells and provided a new attractive therapeutic strategy for LSCC by asparaginase alone or in combination with autophagic inhibitors.

  18. Clinical value of serum HMGB1 in diagnosis and prognosis of laryngeal squamous cell carcinoma.

    PubMed

    Qiu, Guangbin; Li, Yunhui; Liu, Zheng; Wang, Mengran; Ge, Jingjing; Bai, Xiaozhong

    2014-12-01

    Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignancies in the head and neck region. Recently, aberrantly expressed high-mobility group box 1 (HMGB1) has received a great deal of attention as a potential biomarker for cancer diagnosis and prognosis. Therefore, the aim of this study was to estimate HMGB1 levels in serum in LSCC patients and healthy controls and evaluated the potential of serum HMGB1 as a noninvasive biomarker for diagnosis and prognosis in LSCC. Serum HMGB1 levels were analyzed in 71 LSCC patients and 50 healthy controls. The serum HMGB1 level was significantly higher in LSCC patients compared with the healthy controls (4.81 ± 2.33 vs. 3.21 ± 1.08 ng/mL, P < 0.001). High serum HMGB1 was significantly associated with T classification (P = 0.005), N classification (P = 0.002), and clinical stage (P = 0.001). The area under ROC curve was 0.716, and the sensitivity and specificity were 42.3 and 92.0%, respectively. The Kaplan-Meier plots showed that patients with high serum HMGB1 had a poorer overall survival than those with low serum HMGB1 (P = 0.036). Serum HMGB1 levels are significantly associated with the progression of LSCC. In this population, HMGB1 has a poor sensitivity, but a high specificity for the diagnosis of LSCC. Serum HMGB1 level has potential as a biomarker for the prognosis in LSCC patients.

  19. Erlotinib for advanced hepatocellular carcinoma

    PubMed Central

    Zhang, Jing; Zong, Yuan; Xu, Gang-Zhu; Xing, Ke

    2016-01-01

    Objectives: To evaluate the efficacy and safety of erlotinib for the treatment of advanced hepatocellular carcinoma (HCC). Methods: A systematic literature search was undertaken in June 2015. Phase II/III trials of erlotinib for the treatment of advanced HCC were included. A descriptive analysis was applied. The study was conducted in College of Medicine, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China, between June 2015 and January 2016. Results: Ten trials, comprising 9 phase II and one phase III trial, were included in the systematic review. The tumor response rate was 0% in 4 of the phase II trials, <10% in 3 of the phase II trials and the phase III trial, and >20% in 2 of the phase II trials. The disease control rate was 42.5-79.6% in most studies. Three studies reported a median progression-free survival (PFS) of 6.5-9.0 months, although PFS was <3.5 months in most studies. Most trials reported a median overall survival of 6.25-15.65 months. The most frequent grade 3/4 toxicities were fatigue (11.9%), diarrhea (10%), increased alanine and aspartate transaminases (7.3%), and rash/desquamation (6.9%). Conclusion: Erlotinib provides efficacious and well-tolerated treatment for advanced HCC. However, more detailed investigations of HCC pathogenesis and evaluation of sensitive patient subsets are needed to improve outcomes of patients with advanced HCC. Additional well-designed, randomized, controlled trials are needed to evaluate the efficacy and safety of erlotinib as monotherapy or combination with other drugs for advanced HCC. PMID:27761555

  20. 2-Deoxy-2[F-18]FDG-PET for Detection of Recurrent Laryngeal Carcinoma after Radiotherapy: Interobserver Variability in Reporting

    PubMed Central

    van der Putten, L.; Hoekstra, O. S.; Kuik, D. J.; Comans, E. F. I.; Langendijk, J. A.; Leemans, C. R.

    2008-01-01

    Purpose To evaluate accuracy and interobserver variability in the assessment of 2-deoxy-2[F-18]fluoro-d-glucose-positron emission tomography (FDG-PET) for detection of recurrent laryngeal carcinoma after radiotherapy. Procedures Eleven experienced nuclear physicians from eight centres assessed 30 FDG-PET scans on the appearance of local recurrence (negative/equivocal/positive). Conservative (equivocal analysed as negative) and sensitive (equivocal analysed as positive) assessment strategies were compared to the reference standard (recurrence within 6months after PET). Results Seven patients had proven recurrences. For the conservative and sensitive strategy, the mean sensitivity was 87% and 97%, specificity 81% and 63%, positive predictive values 61% and 46% and negative predictive values 96% and 99%, respectively. Interobserver variability showed a reasonable relation in comparison to the reference standard (kappa = 0.55). Conclusions FDG-PET has acceptable interobserver agreement and yields good negative predictive value for detection of recurrent laryngeal carcinoma. It could therefore be used as first diagnostic step and may reduce futile invasive diagnostics. PMID:18622649

  1. Inhibiting GLUT-1 expression and PI3K/Akt signaling using apigenin improves the radiosensitivity of laryngeal carcinoma in vivo.

    PubMed

    Bao, Yang-Yang; Zhou, Shui-Hong; Lu, Zhong-Jie; Fan, Jun; Huang, Ya-Ping

    2015-10-01

    Hypoxia is an important factor in radioresistance of laryngeal carcinoma. Glucose transporter-1 (GLUT-1) is an important hypoxic marker in malignant tumors, including laryngeal carcinoma. Apigenin is a natural phytoestrogen flavonoid that has potential anticancer effects. Various studies have reported that the effects of apigenin on lowering GLUT-1 expression were involved in downregulation of the PI3K/Akt pathway. Thus, apigenin may improve the radiosensitivity of laryngeal carcinoma by suppressing the expression of GLUT-1 via the PI3K/Akt pathway. The effect of GLUT-1 and PI3K/Akt pathway-related factor expressions by apigenin or antisense oligonucleotides (AS-ODNs) on the radiosensitivity of laryngeal carcinoma in vivo was assessed. The xenograft volume, xenograft weight and apoptosis detection were performed to determine radiosensitivity. The results showed that apigenin or apigenin plus GLUT-1 AS-ODNs improved the radiosensitivity of xenografts. Apigenin or apigenin plus GLUT-1 reduced the expression of GLUT-1, Akt, and PI3K mRNA after X-ray radiation. We found similar results at the protein level. The results suggest that the effects of apigenin on inhibiting xenograft growth and enhancing xenograft radiosensitivity may be associated with suppressing the expression of GLUT-1 via the PI3K/Akt pathway. In addition, apigenin may enhance the effects of GLUT-1 AS-ODNs via the same mechanism.

  2. Downregulation of miR-34a contributes to the proliferation and migration of laryngeal carcinoma cells by targeting cyclin D1.

    PubMed

    Ye, Jin; Li, Laisheng; Feng, Pinning; Wan, Jianxin; Li, Jingjia

    2016-07-01

    Laryngeal carcinoma is one of the most common head and neck cancers. MicroRNAs are a class of small non-coding RNAs 18-25 nucleotides in length that post-transcriptionally regulate gene expression and have a pivotal role in many biological processes including cancer development. In this study, we investigated the role of miR-34a in laryngeal carcinoma and confirmed the regulation of cyclin D1 (CCND1) by miR-34a. We examined miR-34a expression levels in 71 laryngeal carcinoma patient specimens by quantitative reverse transcription-PCR, and analyzed the clinicopathological significance of the obtained data. Then, functional assays were performed to investigate the potential effects of miR-34a on cancer cell proliferation and migration. In addition, western blotting, luciferase reporter assay and several algorithms were conducted to confirm that CCND1 is directly regulated by miR-34a. We demonstrated that the miR-34a expression level was significantly downregulated in laryngeal carcinoma clinical specimens compared with that observed in their paired adjacent normal tissues. Additionally, miR-34a expression was also inversely correlated with lymph node metastasis and clinical stage. Functional assays showed that ectopic expression of miR-34a inhibited cell proliferation and migration in laryngeal carcinoma cells. Bioinformatic analysis identified CCND1 as a potential target of miR-34a. Moreover, we confirmed that miR-34a inhibited the expression of CCND1 by directly binding to its 3'-untranslated region. Silencing of CCND1 induced effects similar to those of miR-34a ectopic expression, and in laryngeal carcinoma tissues, miR-34a and CCND1 were inversely correlated. Our data suggest that tumor suppressor miR-34a could serve as a new potential diagnostic marker and that ectopic expression of miR-34a may be used as a therapeutic target for laryngeal carcinoma.

  3. Chromosomal imbalances exclusively detected in invasive front area are associated with poor outcome in laryngeal carcinomas from different anatomical sites.

    PubMed

    Ambrosio, Eliane Papa; Silveira, Cássia Gisele Terrassani; Drigo, Sandra Aparecida; Sacomano, Vivian de Souza; Molck, Miriam Coelho; Rocha, Rafael Malagoli; Domingues, Maria Aparecida Custódio; Soares, Fernando Augusto; Kowalski, Luiz Paulo; Rogatto, Silvia Regina

    2013-10-01

    Laryngeal squamous cell carcinoma (LSCC) is a malignant neoplasm exhibiting aggressive phenotype, high recurrence rate, and risk of developing second primary tumors. Current evidence suggests that cells in the invasive front of carcinomas have different molecular profiles compared to those in superficial areas. This study aimed to identify candidate genes in the invasive front and superficial cells from laryngeal carcinomas that would be useful as molecular markers. Invasive front and tumor surface cells of 32 LSCC were evaluated by high-resolution comparative genomic hybridization. Both CCND1 copy number gains and cyclin D1 protein expression were evaluated to confirm gains of 11q13.3. Losses of 3q26.2-q29 and 18q23 were confirmed by loss of heterozygosity analysis. The most frequent chromosomal alterations observed only in invasive front cells involved gains of 1p, 4q, and 9p and losses of 3p, 11p, 12p, 13q, 17q, 18p, 19q, 20q, 21q, and Xp. Gains of 11q13 were detected in both components from glottis and supraglottis but only in invasive front cells from transglottic tumors. Fluorescence in situ hybridization confirmed gains of CCND1/CPE11 in a subset of cases. In supraglottic tumors, cyclin D1 positivity was associated with distant metastasis (P = 0.0018) and with decreased disease-free survival (P = 0.042). Loss of heterozygosity at 3q26.2 and 18q23 were associated with lymph node involvement (P = 0.055) and worsened prognosis, respectively. In conclusion, this study revealed regions that could be targeted in the search for molecular markers in LSCC. Cyclin D1 may be useful as a prognostic marker in supraglottic tumors.

  4. HLA class I gene expression on human primary tumours and autologous metastases: demonstration of selective losses of HLA antigens on colorectal, gastric and laryngeal carcinomas.

    PubMed Central

    López-Nevot, M. A.; Esteban, F.; Ferrón, A.; Gutiérrez, J.; Oliva, M. R.; Romero, C.; Huelin, C.; Ruiz-Cabello, F.; Garrido, F.

    1989-01-01

    The expression of HLA class I antigens was studied in 99 primary tumour (colorectal, gastric and laryngeal carcinomas) and 57 autologous metastases using immunohistological techniques and monoclonal antibodies against class I monomorphic determinants, HLA-B isotypic determinants and HLA polymorphic determinants. Fourteen per cent of colorectal, 9.6% of gastric and 20% of laryngeal carcinomas completely lacked class I molecules. Selective losses of HLA-B antigens were also detected in 8.8, 3.4 and 5.8% of these tumours respectively. Taking into account complete and selective loss of HLA-B the average alteration in the class I molecules expression totalled 21%. The comparison of class I expression between primary tumours and autologous metastases showed differences in 24% of the patients. These differences consisted mainly in a decrease of class I expression by metastases. Nevertheless, four types of divergence were detected in laryngeal carcinomas, namely: +/-, +/+, -/+, -/-. In addition, a clear correlation between degree of differentiation and class I expression was observed in laryngeal tumours. Finally, when class I gene RFLPs were compared with DNA from 15 tumours and autologous normal mucosa or peripheral lymphocytes, no differences were detected between these samples. Images Figure 1 Figure 2 PMID:2649129

  5. New advances in hepatocellular carcinoma

    PubMed Central

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-01-01

    Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

  6. Combinatorial effects of geopropolis produced by Melipona fasciculata Smith with anticancer drugs against human laryngeal epidermoid carcinoma (HEp-2) cells.

    PubMed

    Bartolomeu, Ariane Rocha; Frión-Herrera, Yahima; da Silva, Livia Matsumoto; Romagnoli, Graziela Gorete; de Oliveira, Deilson Elgui; Sforcin, José Maurício

    2016-07-01

    The identification of natural products exerting a combined effect with therapeutic agents could be an alternative for cancer treatment, reducing the concentration of the drugs and side effects. Geopropolis (Geo) is produced by some stingless bees from a mixture of vegetable resins, gland secretions of the bees and soil. It has been used popularly as an antiseptic agent and to treat respiratory diseases and dermatosis. To determine whether Geo enhances the anticancer effect of carboplatin, methotrexate and doxorubicin (DOX), human laryngeal epidermoid carcinoma (HEp-2) cells were treated with Geo alone or in combination with each drug. Cell growth, cytotoxicity and apoptosis were evaluated using 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release, and flow cytometry. Scratch assay was used to analyze cell migration and transmission electron microscopy to observe morphologic alterations. The influence of Geo on drug resistance was also investigated assessing P-glycoprotein (P-gp) action. Geo inhibited cell proliferation and migration. The combination Geo+DOX led to the highest cytotoxic activity and induced apoptosis, leading to loss of membrane integrity. Geo had no effect on P-gp-mediated efflux of DOX. Data indicate that Geo combined with DOX could be a potential clinical chemotherapeutic approach for laryngeal cancer treatment.

  7. Why to start the concomitant boost in accelerated radiotherapy for advanced laryngeal cancer in week 3

    SciTech Connect

    Terhaard, Chris H.J. . E-mail: C.H.J.Terhaard@AZU.nl; Kal, Henk B.; Hordijk, Gerrit-Jan

    2005-05-01

    Purpose: We analyzed toxicity and the local control rates for advanced laryngeal cancer, treated with two accelerated fractionation schedules. The main difference between the schedules was the onset of the concomitant boost, in Week 3 or Week 4. Overall treatment time and total dose were equivalent. Methods and Materials: In a prospective, nonrandomized study of T{sub 3}, T{sub 4}, and advanced T{sub 2} laryngeal cancer, concomitant boost schedules were used in 100 patients. Thirty patients received a schedule of twice daily 1.2 Gy in Weeks 1-3, followed by twice daily 1.7 Gy in Weeks 4 and 5; total dose was 70 Gy (the hyperfractionated accelerated schedule [HAS] regimen). Seventy patients were treated with 5 times 2 Gy in Weeks 1 and 2, followed by daily 1.8 Gy and 1.5 Gy (boost) in Weeks 3-5; total dose 69.5 Gy (the accelerated schedule only [ASO] regimen). Distribution of T stage was 47%, 40%, and 12% for T{sub 2}, T{sub 3}, and T{sub 4}, respectively. In 24% of the patients, lymph nodes were positive. Pretreatment tracheotomy or stridor or both occurred in 8 patients. The distribution of prognostic factors was not significantly different between the two fractionation schedules. Acute and late toxicity was assessed. Results were estimated by the use of actuarial methods. For late toxicity and local control univariate and multivariate analyses were performed. Tumor control probability analysis was used to model cure rate differences. Results: Overall acute mucositis score was equal for both schedules. Acute mucositis started and decreased significantly earlier in the HAS regimen. In all patients acute mucositis healed completely. The treatment was completed within 38 days in all patients. The regional control rate was 100% for clinical N{sub 0}, and 75% for the clinical N{sub +} patients. The 3-year local control rate was 59% and 78% for the HAS and ASO regimens, respectively (p = 0.05); the ultimate local control was 80% and 94%, respectively. In multivariate

  8. Laryngeal Cancer: 12-Year Experience of a Single Center.

    PubMed

    Calkovsky, V; Wallenfels, P; Calkovska, A; Hajtman, A

    2016-01-01

    Laryngeal cancer is about the twentieth most common cancer in the world and more than 150,000 new cases are diagnosed annually. The aim of the study was to evaluate the history, diagnostics, treatment outcomes, and prognosis in patients with laryngeal cancer in Northern Slovakia. We analyzed retrospectively 227 patients (207 males, 20 females) with laryngeal carcinoma treated in the period 2003-2014 at the Clinic of Otorhinolaryngology and Head and Neck Surgery of the Jessenius Faculty of Medicine and Martin University Hospital in Martin, Slovakia. The majority of patients were in the sixth (38.0 %) and seventh decade of life (30.8 %). Two hundred and seventeen patients (95.6 %) were smokers or ex-smokers. Sixty-six percent of patients were diagnosed with glottic or transglottic carcinoma, related probably to the anatomical structure of the larynx and exposure to inhalation pollutants. It is alarming that the majority of patients with malignant laryngeal disease were admitted to the hospital in advanced stages. In 151 (66.5 %) of patients, the extent of infiltration was T3 or T4, and 156 (68 %) patients were in disease stage III and IV. The incidence and mortality of laryngeal cancer suggest the need to intensify the prevention and to search for an early clinical stage of laryngeal cancer using a targeted screening.

  9. Apigenin suppresses GLUT-1 and p-AKT expression to enhance the chemosensitivity to cisplatin of laryngeal carcinoma Hep-2 cells: an in vitro study.

    PubMed

    Xu, Ying-Ying; Wu, Ting-Ting; Zhou, Shui-Hong; Bao, Yang-Yang; Wang, Qin-Ying; Fan, Jun; Huang, Ya-Ping

    2014-01-01

    Glucose transporter-1 (GLUT-1) and PI3K/Akt are known to be closely involved in resistance to chemotherapy. Co-targeted therapy reducing GLUT-1 expression and PI3K/Akt pathway activity may overcome the chemoresistance of human cancers. Apigenin may inhibit the expression of GLUT-1 and the PI3K/Akt pathway. We hypothesized that over-expression of GLUT-1 and p-Akt was associated with the resistance to cisplatin of laryngeal carcinoma Hep-2 cells. We explored whether apigenin inhibited GLUT-1 and p-Akt, resulting in sensitization of laryngeal carcinoma Hep-2 cells to cisplatin. Real-time RT-PCR and Western blotting confirmed the presence of GLUT-1 mRNA, and GLUT-1 and p-Akt proteins in Hep-2 cells. We found that resistance or insensitivity of Hep-2 cells to cisplatin might be associated with such expression. Apigenin markedly enhanced the cisplatin-induced suppression of Hep-2 cell growth. This effect was concentration- and time-dependent. Thus apigenin may significantly reduce the levels of GLUT-1 mRNA, and GLUT-1 and p-Akt proteins, in cisplatin-treated Hep-2 cells, in a concentration- and time-dependent manner. To conclude, overexpression of GLUT-1 mRNA may be associated with the resistance to cisplatin of laryngeal carcinoma Hep-2 cells. Apigenin may enhance the sensitivity to cisplatin of laryngeal carcinoma cells via inhibition of GLUT-1 and p-Akt expression.

  10. The role of miR-145 in stem cell characteristics of human laryngeal squamous cell carcinoma Hep-2 cells.

    PubMed

    Karatas, Omer Faruk; Suer, Ilknur; Yuceturk, Betul; Yilmaz, Mehmet; Hajiyev, Yusif; Creighton, Chad J; Ittmann, Michael; Ozen, Mustafa

    2016-03-01

    The cancer stem-like cells (CSLCs) are tumorigenic cells promoting initiation, progression, and spread of the tumor. Accumulating evidences suggested the presence of CSLCs in distinct tumors including laryngeal squamous cell carcinoma (LSCC). MicroRNAs have been proposed as significant regulators of carcinogenesis, and several of them have been demonstrated to have direct roles in survival of CSLCs. In this study, we aimed to explore the role of miR-145, which is downregulated in LSCC, on cancer stem cell potency of laryngeal cancer cells. We initially showed the downregulation of miR-145 expression in tumor tissue samples and in CD133-enriched CSLCs. Quantitative reverse-transcription PCR (qRT-PCR) analysis of miR-145-transfected Hep-2 cells demonstrated the inhibitory role of miR-145 on stem cell markers like SOX2, OCT4, KLF4, and ABCG2. We, then, investigated the stem cell features of miR-145-overexpressing Hep-2 cells by sphere formation assay, single-cell cloning assay, and aldehyde dehydrogenase (ALDH) assay, which all demonstrated the inhibition of stem cell potency upon miR-145 overexpression. Further qRT-PCR analysis demonstrated altered expression of epithelial to mesenchymal transition markers in miR-145-overexpressing Hep-2 cells. In conclusion, we demonstrated the regulatory role of miR-145 in stem cell characteristics of Hep-2 cells. Based on these results, we propose that miR-145 might carry crucial roles in LSCC tumorigenesis, prognosis, metastasis, chemoresistance, and recurrence through regulating stem cell properties of tumor cells.

  11. Combined chemoradiotherapy with local microwave hyperthermia for treatment of T3N0 laryngeal carcinoma: a retrospective study with long-term follow-up.

    PubMed

    Kouloulias, V; Triantopoulou, S; Vrouvas, J; Gennatas, K; Ouzounoglou, N; Kouvaris, J; Karaiskos, P; Aggelakis, P; Antypas, C; Zygogianni, A; Papavasiliou, K; Platoni, K; Kelekis, N

    2014-06-01

    The purpose of our study was to test the efficacy and toxicity of hyperthermia in conjunction with chemoradiotherapy for T3N0 laryngeal cancer. From 1997-2006, 25 patients diagnosed with T3N0 laryngeal carcinoma who denied laryngectomy were selected for this retrospective study. Patients received a total dose of 70 Gy (2 Gy per fraction, 5 days per week) in combination with 6 weekly sessions of hyperthermia, in addition to weekly cisplatin chemotherapy. The hyperthermia device was operated as a 433 MHz microwave heating with water loaded and water-cooled waveguides. The temperature was monitored subcutaneously in the skin under the aperture of the waveguide. The median follow-up was 60 months, while 23 of 25 patients (92%) presented complete response to treatment. The two patients that did not respond to thermoradiotherapy underwent total laryngectomy, and during follow-up were alive and free of disease. According to EORTC/RTOG criteria, toxicity was mild: three patients (12%) presented grade III, eight (32%) presented grade II and 14 (56%) presented grade I acute skin toxicity. Grade III laryngeal late toxicity (vocal cord malfunction due to severe oedema) was noted in two patients (8%) at 6-8 months post-thermo-chemoradiotherapy. Tmin was correlated (Spearman rho, p < 0.05) with response to treatment as well as with acute skin toxicity and laryngeal function. When a patient with T3N0 laryngeal carcinoma denies laryngectomy, an alternative treatment is combined thermo-chemoradiotherapy which seems to be effective and generally tolerable with radiation-induced skin toxicity and/or late side effects. A larger patient cohort is needed to confirm these results.

  12. Histoplasmosis laryngeal

    PubMed Central

    Moriones Robayo, Carlos Alberto

    2014-01-01

    Laryngeal histoplasmosis is a fungal infection that is frequent in Colombia. Laryngeal histoplasmosis usually occurs in immunocompromised patients through the dissemination of the fungus from the lungs to other organs. Histoplasmosis isolated laryngeal (primary) is rare. If a patient presents with a history of immunosuppression by renal transplant, primary laryngeal histoplasmosis with supraglottic granulomatous inflammation that was treated with amphotericin B and Itraconazole, with complete resolution of laryngeal lesions. PMID:25767308

  13. Voice and swallowing outcomes of an organ-preservation trial for advanced laryngeal cancer

    SciTech Connect

    Fung, Kevin . E-mail: kevin.fung@lhsc.on.ca; Lyden, Teresa H.; Lee, Julia; Urba, Susan G.; Worden, Frank; Eisbruch, Avraham; Tsien, Christina; Bradford, Carol R.; Chepeha, Douglas B.; Hogikyan, Norman D.; Prince, Mark E.P.; Teknos, Theodoros N.; Wolf, Gregory T.

    2005-12-01

    Introduction: Organ-preservation treatment approaches for advanced laryngeal cancer patients that use combination chemoradiotherapy result in cure rates similar to primary laryngectomy with postoperative radiotherapy. In the national VA Larynx Cancer Trial, successful organ preservation was associated with an overall improvement in quality of life but not in subjective speech compared with long-term laryngectomy survivors. As part of a Phase II clinical trial, a prospective study of speech and swallowing results was conducted to determine if larynx preservation is associated with improved voice and swallowing compared with results in patients who require salvage laryngectomy. Subjects: A total of 97 patients with advanced laryngeal cancer (46 Stage III, 51 Stage IV) were given a single course of induction chemotherapy (cisplatin 100 mg/m{sup 2} on Day 1 and 5-FU 1,000 mg/m{sup 2}/day x 5 days), followed by assessment of response. Patients with less than 50% response underwent early salvage laryngectomy, and patients with 50% or better response underwent concurrent chemoradiation (72 Gy and cisplatin 100 mg/m{sup 2} on Days 1, 22, and 43), followed by two cycles of adjuvant chemotherapy (DDP/5-FU). Direct laryngoscopy and biopsy were performed 8 weeks after radiation therapy to determine final tumor response. Late salvage surgery was performed on patients with persistent or recurrent disease. Methods: Completed survey data on voice and swallowing utilizing the Voice-Related Quality of Life Measure (V-RQOL) and the List Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) were obtained from 56 patients who were alive and free of disease at the time of survey, with a minimum follow-up of 8 months. Comparisons were made between patients with an intact larynx (n = 37) vs. laryngectomy (n = 19), as well as early (n = 12) vs. late salvage laryngectomy (n = 7). Multivariate analysis was performed to determine factors predictive of voice and swallowing

  14. Hepatocellular carcinoma: Advances in diagnostic imaging.

    PubMed

    Sun, Haoran; Song, Tianqiang

    2015-10-01

    Thanks to the growing knowledge on biological behaviors of hepatocellular carcinomas (HCC), as well as continuous improvement in imaging techniques and experienced interpretation of imaging features of the nodules in cirrhotic liver, the detection and characterization of HCC has improved in the past decade. A number of practice guidelines for imaging diagnosis have been developed to reduce interpretation variability and standardize management of HCC, and they are constantly updated with advances in imaging techniques and evidence based data from clinical series. In this article, we strive to review the imaging techniques and the characteristic features of hepatocellular carcinoma associated with cirrhotic liver, with emphasis on the diagnostic value of advanced magnetic resonance imaging (MRI) techniques and utilization of hepatocyte-specific MRI contrast agents. We also briefly describe the concept of liver imaging reporting and data systems and discuss the consensus and controversy of major practice guidelines.

  15. High expression levels of COX-2 and P300 are associated with unfavorable survival in laryngeal squamous cell carcinoma.

    PubMed

    Chen, Yan-Feng; Luo, Rong-Zhen; Li, Yong; Cui, Bo-Kang; Song, Ming; Yang, An-Kui; Chen, Wen-Kuan

    2013-03-01

    In order to provide a basis for clinical treatment decisions, we explored whether there was a correlation between the expression of COX-2 and P300 and clinical factors in a group of patients with laryngeal squamous cell carcinoma (LSCC). A retrospective analysis of clinicopathological data was conducted in 80 patients with LSCC who presented between January 1997 and December 1998. An immunohistochemistry tissue microarray was conducted of 80 surgically resected LSCC and 20 adjacent normal tissue specimens. Survival analysis and Kaplan-Meier curves were used to compare the effects of clinicopathological factors on survival. The Cox model was applied for multivariate analysis. The expression level of COX-2/P300 in LSCC tissues and adjacent normal tissues were 47.5/50.0 versus 0.0/15.0 %. The expression of COX-2 and P300 was correlated with higher T category, N category, clinical staging, histological grade and recurrence (P < 0.05). P300 expression was correlated with COX-2 expression (P < 0.05). Univariate survival analysis showed that P300, COX-2, N category, clinical staging and recurrence factors were closely correlated with unfavorable survival (P < 0.05). Multivariate analysis showed that COX-2 expression, histological grade and recurrence were independent prognostic factors for LSCC. High expression levels of COX-2 and P300 indicated poor survival outcomes for patients with LSCC.

  16. The effect of substitution therapy on symptoms in patients with hypothyroidism following treatment for laryngeal and hypopharyngeal carcinomas.

    PubMed

    Lo Galbo, A M; Verdonck-De Leeuw, I M; Lips, P; Kuik, D J; Leemans, C R; De Bree, R

    2013-08-01

    Hypothyroidism is a well-known complication following treatment of laryngeal or hypopharyngeal carcinomas, and may cause various psychological and physical problems that negatively affect quality of life. The aim of this study was to evaluate the effect of substitution therapy on symptoms in patients with hypothyroidism. A study-specific questionnaire on physical and psychological problems (before and after substitution therapy) was sent to 70 patients who had been treated between 1977 and 2008 with clinical or subclinical hypothyroidism. Ninety-four percent returned the questionnaire. Symptoms on energy levels were reported most often (67% always tired and 70% lack of energy). Moodiness and emotional and physical symptoms were reported more often in substituted (sub)clinical hypothyroidism. Substitution therapy resulted in an improvement of energy (P = 0.013), sense of general interest and enjoyment (P = 0.022) and a reduction of puffy face (P = 0.041). Most symptoms in patients with thyroid dysfunction do not improve after substitution therapy. Nevertheless, due to its impact on health-related quality of life and the low burden of substitution therapy, screening for hypothyroidism and subsequent substitution therapy remains important.

  17. Folate deficiency and aberrant expression of cell adhesion molecule 1 are potential indicators of prognosis in laryngeal squamous cell carcinoma

    PubMed Central

    Chang, Hao; Ma, Min; Ma, Rui; Zhang, Chao; Zeng, Wei; Xing, Lu Qi

    2016-01-01

    The etiology of laryngeal squamous cell carcinoma (LSCC) has not yet been adequately examined. Therefore, the present study aimed to investigate the association between serum folate deficiency and abnormal expression of the cell adhesion molecule 1 (CADM1) protein in the progression of LSCC. Samples were collected from 60 patients with LSCC and 30 healthy people. Radioimmunoassays and immunohistochemical staining were performed to measure serum folate levels and CADM1 protein expression, respectively. The results demonstrated that CADM1 expression in LSCC specimens was significantly lower than in adjacent normal tissues (χ2=28.229, P<0.001), which was associated with histological differentiation and clinical stage (P=0.010 and 0.020, respectively). Levels of serum folate in patients with LSCC were significantly lower than those observed in healthy individuals (P=0.002). Furthermore, TSLCl expression and serum folate levels were positively correlated in LSCC (r=0.642, P=0.001). Thus, the present study determined that decreased CADM1 protein expression and low levels of serum folate were correlated with an increased severity of LSCC. PMID:28105160

  18. Prognostic value of the C-reactive protein/albumin ratio in patients with laryngeal squamous cell carcinoma

    PubMed Central

    Yu, Shi-tong; Zhou, Zhiwei; Cai, Qian; Liang, Faya; Han, Ping; Chen, Renhui; Huang, Xiao-ming

    2017-01-01

    Purpose The present study was designed to retrospectively evaluate the prognostic value of the C-reactive protein/albumin (CRP/ALB) ratio in laryngeal squamous cell carcinoma (LSCC). Methods One hundred and twenty-nine newly diagnosed LSCC patients admitted between May 2006 and October 2011 were retrospectively reviewed. Their serum CRP and ALB were quantified preoperatively. The relationship between the CRP/ALB ratio and the clinicopathologic features was analyzed. Receiver operating characteristic curve was used to calculate the prognostic value of the CRP/ALB ratio. Then, the Cox proportional hazards model was used in univariate and multivariate analyses to identify significant prognostic factors associated with disease-free survival and overall survival. Results The cutoff value for CRP/ALB ratio was 0.047. An elevated CRP/ALB ratio was significantly associated with nodal metastasis, late disease stage, and recurrence. Also, high values of CRP/ALB ratio were significant predictors for poor overall survival and disease-free survival on multivariate analysis. Conclusion Pretreatment CRP/ALB ratio may be a significant prognostic marker in LSCC. PMID:28243123

  19. Antiangiogenic Therapies for Advanced Hepatocellular Carcinoma

    PubMed Central

    Sampat, Keeran R.

    2013-01-01

    Hepatocellular carcinoma (HCC) is a significant cause of death worldwide. HCC is a highly vascular tumor, and proangiogenic cytokines such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor may play crucial roles in this disease. Sorafenib, a multikinase inhibitor that blocks VEGF and PDGF signaling, was the first systemic therapy to demonstrate improved survival in patients with advanced HCC. Several other drugs targeting VEGF are in development. Because of the anticipation of eventual resistance to anti-VEGF therapies, drugs that also target alternative proangiogenic pathways are being investigated. Recent clinical and preclinical data along with ongoing studies are reviewed. PMID:23576483

  20. Advanced treatment for basal cell carcinomas.

    PubMed

    Atwood, Scott X; Whitson, Ramon J; Oro, Anthony E

    2014-07-01

    Basal cell carcinomas (BCCs) are very common epithelial cancers that depend on the Hedgehog pathway for tumor growth. Traditional therapies such as surgical excision are effective for most patients with sporadic BCC; however, better treatment options are needed for cosmetically sensitive or advanced and metastatic BCC. The first approved Hedgehog antagonist targeting the membrane receptor Smoothened, vismodegib, shows remarkable effectiveness on both syndromic and nonsyndromic BCCs. However, drug-resistant tumors frequently develop, illustrating the need for the development of next-generation Hedgehog antagonists targeting pathway components downstream from Smoothened. In this article, we will summarize available BCC treatment options and discuss the development of next-generation antagonists.

  1. Advanced Treatment for Basal Cell Carcinomas

    PubMed Central

    Atwood, Scott X.; Whitson, Ramon J.; Oro, Anthony E.

    2014-01-01

    Basal cell carcinomas (BCCs) are very common epithelial cancers that depend on the Hedgehog pathway for tumor growth. Traditional therapies such as surgical excision are effective for most patients with sporadic BCC; however, better treatment options are needed for cosmetically sensitive or advanced and metastatic BCC. The first approved Hedgehog antagonist targeting the membrane receptor Smoothened, vismodegib, shows remarkable effectiveness on both syndromic and nonsyndromic BCCs. However, drug-resistant tumors frequently develop, illustrating the need for the development of next-generation Hedgehog antagonists targeting pathway components downstream from Smoothened. In this article, we will summarize available BCC treatment options and discuss the development of next-generation antagonists. PMID:24985127

  2. Value of Narrow Band Imaging (NBI) Endoscopy in the Early Diagnosis of Laryngeal Cancer and Precancerous Lesions

    ClinicalTrials.gov

    2016-09-07

    Chronic Inflammation of Hypopharynx; Hoarseness; Macroscopic Laryngeal Lesions; Histological Confirmation of Dysplasia; Carcinoma in Situ; Invasive Carcinoma of Larynx; Invasive Carcinoma of Hypo Pharynx; Recurrent Respiratory Papillomatosis

  3. Immunohistochemical markers of distant metastasis in laryngeal and hypopharyngeal squamous cell carcinomas.

    PubMed

    Rodrigo, Juan P; Martínez, Patricia; Allonca, Eva; Alonso-Durán, Laura; Suárez, Carlos; Astudillo, Aurora; García-Pedrero, Juana María

    2014-03-01

    Metastasis remains a major cause of mortality in head and neck squamous cell carcinoma (HNSCC). Current clinicopathological features have shown limited predictability for the risk of distant metastasis in individual patients, and therefore more accurate and reliable markers are needed. The aim of this study was to investigate the ability of various molecular markers present in primary tumors to predict the risk of developing distant metastasis. Restrictive clinical criteria were applied for patient selection in order to carry out a case-control study with comparable clinical features on a group-wide basis and a similar risk of metastasis. All patients were surgically treated (with postoperative radiotherapy when appropriate) and classified as stage IV disease. Immunohistochemical analysis was performed for a panel of proteins known to participate in cellular processes relevant to metastatic dissemination (E-cadherin, annexin A2, cortactin, FAK, EGFR, p53, and p-AKT). Results showed that the loss of E-cadherin expression was significantly correlated with the risk of distant metastasis (P = 0.002; log-rank test), while the loss of annexin A2 expression was nearly statistically significant (P = 0.06). None of the other protein markers assessed were associated with the development of distant metastasis. Therefore, according to our data the loss of epithelial adhesion seems to play a central role in the development of metastasis in HNSCC, and more importantly, immunohistochemical assessment of key proteins involved in cell adhesion regulation, such as E-cadherin could represent a useful tool to evaluate easily and routinely the metastatic potential of these carcinomas.

  4. Development of TRAIL Resistance by Radiation-Induced Hypermethylation of DR4 CpG Island in Recurrent Laryngeal Squamous Cell Carcinoma

    SciTech Connect

    Lee, Jong Cheol; Lee, Won Hyeok; Min, Young Joo; Cha, Hee Jeong; Han, Myung Woul; Chang, Hyo Won; Kim, Sun-A; Choi, Seung-Ho; Kim, Seong Who; Kim, Sang Yoon

    2014-04-01

    Purpose: There are limited therapeutic options for patients with recurrent head and neck cancer after radiation therapy failure. To assess the use of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) as a salvage chemotherapeutic agent for recurrent cancer after radiation failure, we investigated the effect of clinically relevant cumulative irradiation on TRAIL-induced apoptosis. Methods and Materials: Using a previously established HN3 cell line from a laryngeal carcinoma patient, we generated a chronically irradiated HN3R isogenic cell line. Viability and apoptosis in HN3 and HN3R cells treated with TRAIL were analyzed with MTS and PI/annexin V-FITC assays. Western blotting and flow cytometry were used to determine the underlying mechanism of TRAIL resistance. DR4 expression was semiquantitatively scored in a tissue microarray with 107 laryngeal cancer specimens. Methylation-specific polymerase chain reaction and bisulfite sequencing for DR4 were performed for genomic DNA isolated from each cell line. Results: HN3R cells were more resistant than HN3 cells to TRAIL-induced apoptosis because of significantly reduced levels of the DR4 receptor. The DR4 staining score in 37 salvage surgical specimens after radiation failure was lower in 70 surgical specimens without radiation treatment (3.03 ± 2.75 vs 5.46 ± 3.30, respectively; P<.001). HN3R cells had a methylated DR4 CpG island that was partially demethylated by the DNA demethylating agent 5-aza-2′-deoxycytidine. Conclusion: Epigenetic silencing of the TRAIL receptor by hypermethylation of a DR4 CpG island might be an underlying mechanism for TRAIL resistance in recurrent laryngeal carcinoma treated with radiation.

  5. Co-Inhibition of GLUT-1 Expression and the PI3K/Akt Signaling Pathway to Enhance the Radiosensitivity of Laryngeal Carcinoma Xenografts In Vivo.

    PubMed

    Luo, Xing-Mei; Xu, Bin; Zhou, Min-Li; Bao, Yang-Yang; Zhou, Shui-Hong; Fan, Jun; Lu, Zhong-Jie

    2015-01-01

    In the present study, we investigated the role of GLUT-1 and PI3K/Akt signaling in radioresistance of laryngeal carcinoma xenografts. Volume, weight, radiosensitization, and the rate of inhibition of tumor growth in the xenografts were evaluated in different groups. Apoptosis was evaluated by TUNEL assay. In addition, mRNA and protein levels of GLUT-1, p-Akt, and PI3K in the xenografts were measured. Treatment with LY294002, wortmannin, wortmannin plus GLUT-1 AS-ODN, and LY294002 plus GLUT-1 AS-ODN after X-ray irradiation significantly reduced the size and weight of the tumors, rate of tumor growth, and apoptosis in tumors compared to that observed in the 10-Gy group (p<0.05). In addition, mRNA and protein expression of GLUT-1, p-Akt, and PI3K was downregulated. The E/O values of LY294002, LY294002 plus GLUT-1 AS-ODN, wortmannin, and wortmannin plus GLUT-1 AS-ODN were 2.7, 1.1, 1.8, and 1.8, respectively. Taken together, these data indicate that GLUT-1 AS-ODN as well as the inhibitors of PI3K/Akt signaling may act as radiosensitizers of laryngeal carcinoma in vivo.

  6. Inflammation and Cancer: Role of Annexin A1 and FPR2/ALX in Proliferation and Metastasis in Human Laryngeal Squamous Cell Carcinoma

    PubMed Central

    Gastardelo, Thaís Santana; Cunha, Bianca Rodrigues; Raposo, Luís Sérgio; Maniglia, José Victor; Cury, Patrícia Maluf; Lisoni, Flávia Cristina Rodrigues; Tajara, Eloiza Helena; Oliani, Sonia Maria

    2014-01-01

    The anti-inflammatory protein annexin A1 (ANXA1) has been associated with cancer progression and metastasis, suggesting its role in regulating tumor cell proliferation. We investigated the mechanism of ANXA1 interaction with formylated peptide receptor 2 (FPR2/ALX) in control, peritumoral and tumor larynx tissue samples from 20 patients, to quantitate the neutrophils and mast cells, and to evaluate the protein expression and co-localization of ANXA1/FPR2 in these inflammatory cells and laryngeal squamous cells by immunocytochemistry. In addition, we performed in vitro experiments to further investigate the functional role of ANXA1/FPR2 in the proliferation and metastasis of Hep-2 cells, a cell line from larynx epidermoid carcinoma, after treatment with ANXA12–26 (annexin A1 N-terminal-derived peptide), Boc2 (antagonist of FPR) and/or dexamethasone. Under these treatments, the level of Hep-2 cell proliferation, pro-inflammatory cytokines, ANXA1/FPR2 co-localization, and the prostaglandin signalling were analyzed using ELISA, immunocytochemistry and real-time PCR. An influx of neutrophils and degranulated mast cells was detected in tumor samples. In these inflammatory cells of peritumoral and tumor samples, ANXA1/FPR2 expression was markedly exacerbated, however, in laryngeal carcinoma cells, this expression was down-regulated. ANXA12–26 treatment reduced the proliferation of the Hep-2 cells, an effect that was blocked by Boc2, and up-regulated ANXA1/FPR2 expression. ANXA12–26 treatment also reduced the levels of pro-inflammatory cytokines and affected the expression of metalloproteinases and EP receptors, which are involved in the prostaglandin signalling. Overall, this study identified potential roles for the molecular mechanism of the ANXA1/FPR2 interaction in laryngeal cancer, including its relationship with the prostaglandin pathway, providing promising starting points for future research. ANXA1 may contribute to the regulation of tumor growth and

  7. Multi-modality management for loco-regionally advanced laryngeal and hypopharyngeal cancer: balancing the benefit of efficacy and functional preservation.

    PubMed

    Qian, Wei; Zhu, Guopei; Wang, Yulong; Wang, Xiaoshen; Ji, Qinghai; Wang, Yu; Dou, Shengjin

    2014-09-01

    The 5-year overall survival (OS) of loco-regionally advanced laryngeal and hypopharyngeal carcinoma (LA-LHC) has declined over the past two decades following the wide application of non-surgical approaches. We aimed to define the new role of open surgery combined with adjuvant chemoradiotherapy in the treatment of LA-LHC for improving survival while maintaining a functional larynx. In the current study, 90 LA-LHC patients treated with open surgery followed by postoperative RT/CRT in our institute from May 2005 to December 2012 were retrospectively analyzed. OS, disease-free survival (DFS), loco-regional failure-free survival (LRFFS) and distant metastasis-free survival (DMFS) were calculated, and prognostic factors were analyzed. Functional larynx preservation results were evaluated according to the head and neck quality of life (QoL) Scale. With a median follow-up period of 37 months, the 3- and 5-year OS, DFS, LRFFS and DMFS were 71.3, 63.7, 85.9, 73.7 and 55.9, 53.0, 81.6, 71.9 %, respectively. Vascular embolism and extracapsular extension (ECE) of the lymph nodes were prognostic factors for poorer OS (p = 0.045 and 0.046, respectively). Vascular embolism was the only prognostic factor for poorer DMFS (p = 0.005). Patients who underwent a conservative partial laryngectomy (CPL) experienced a higher QoL in the domains of speech, swallowing and emotion. Functional larynx preservation was achieved in 36/45 patients (80 %) who received CPL. The results of our study demonstrated that CPL followed by adequate adjuvant therapy could achieve superior oncological results compared with non-surgical approaches in LA-LHC patients while also maintaining satisfactory functional larynx in a majority of patients.

  8. Changes of leukocyte adherence ability under the influence of magnetic field in the course of a treatment of patients with laryngeal and pharyngeal carcinoma.

    PubMed

    Cocek, A; Hahn, A; Ambrus, M; Dohnalová, A; Jandová, A; Pokorný, J

    2008-01-01

    The authors were monitoring adherence ability of T lymphocytes in vitro in patients with laryngeal and pharyngeal carcinoma at the presence of tumor-specific and viral LDH antigen. The results were assessed and expressed in percent of non adherent T lymphocytes (NAL). First, NAL in patients before initiating the treatment was compared with NAL control group (voluntary blood donors). The ability of the adherence in T lymphocytes in the control group is statistically significantly higher. Further on, NAL in the course of a successful oncological treatment was monitored at the interval of 6 months following the treatment, and further on at yearly intervals. NAL level drops statistically significantly within 6 months and then hold on at levels with no statistical difference unlike the control group, however, the ability of T lymphocyte in patients to adhere remains statistically significantly lower. Statistically significantly higher levels of NAL are at the presence of LDH viral antigen. Further on, the authors were following the influence of magnetic sinusoidal field of power frequency (50 Hz) of a low induction (0.5, 0.1, and 0.05 mT) on NAL. NAL values under the influence of an experimental magnetic field before initiating the treatment as well as in the course of a successful oncological treatment are statistically significantly lower. It means that magnetic filed increases the adherence ability of T lymphocytes in patients with laryngeal and pharyngeal cancer in vitro.

  9. Helical tomotherapy and larynx sparing in advanced oropharyngeal carcinoma: a dosimetric study.

    PubMed

    Gielda, Benjamin T; Millunchick, Cheryl H; Smart, Joseph P; Marsh, James C; Turian, Julius V; Coleman, Joy L

    2010-01-01

    Intensity-modulated radiation therapy (IMRT) is gaining acceptance as a standard treatment technique for advanced squamous cell carcinoma (SCC) of the oropharynx. Dose to the uninvolved larynx and surrounding structures can pose a problem in patients with significant neck disease, potentially compromising laryngeal function and quality of life. Tomotherapy may allow greater laryngeal sparing. Seven patients with stage IV SCC of the oropharynx were replanned using Tomotherapy version 3.1. All contours/planning target volumes (PTVs) from the original plans were preserved, with the exception of the larynx, which was drawn to include all soft tissue encompassed by the thyroid/cricoid cartilage. A simultaneous integrated boost technique was used with PTV 1, 2, and 3 receiving 69.96, 59.40, and 54.00 Gy, respectively in 33 fractions. Dosimetry was evaluated via the Pinnacle treatment planning system (TPS). Equivalent uniform dose (EUD) was calculated from the dose volume histogram (DVH) using the general method with "a" = 5.0. Mean larynx dose for all patients was 24.4 Gy. Mean EUD to the larynx was 34.2 Gy. Homogeneity was adequate; average maximum dose was 109.7% of the highest prescription. All other organs at risk (OAR) were adequately spared. Tomotherapy can spare the uninvolved larynx in the setting of advanced SCC of the oropharynx to levels that are similar to or better than those reported with other techniques. Sparing is achieved without compromising target coverage or other OAR sparing. The clinical benefit of this sparing remains to be determined in a prospective study.

  10. Helical Tomotherapy and Larynx Sparing in Advanced Oropharyngeal Carcinoma: A Dosimetric Study

    SciTech Connect

    Gielda, Benjamin T.; Millunchick, Cheryl H.; Smart, Joseph P.; Marsh, James C.; Turian, Julius V.; Coleman, Joy L.

    2010-10-01

    Intensity-modulated radiation therapy (IMRT) is gaining acceptance as a standard treatment technique for advanced squamous cell carcinoma (SCC) of the oropharynx. Dose to the uninvolved larynx and surrounding structures can pose a problem in patients with significant neck disease, potentially compromising laryngeal function and quality of life. Tomotherapy may allow greater laryngeal sparing. Seven patients with stage IV SCC of the oropharynx were replanned using Tomotherapy version 3.1. All contours/planning target volumes (PTVs) from the original plans were preserved, with the exception of the larynx, which was drawn to include all soft tissue encompassed by the thyroid/cricoid cartilage. A simultaneous integrated boost technique was used with PTV 1, 2, and 3 receiving 69.96, 59.40, and 54.00 Gy, respectively in 33 fractions. Dosimetry was evaluated via the Pinnacle treatment planning system (TPS). Equivalent uniform dose (EUD) was calculated from the dose volume histogram (DVH) using the general method with 'a' = 5.0. Mean larynx dose for all patients was 24.4 Gy. Mean EUD to the larynx was 34.2 Gy. Homogeneity was adequate; average maximum dose was 109.7% of the highest prescription. All other organs at risk (OAR) were adequately spared. Tomotherapy can spare the uninvolved larynx in the setting of advanced SCC of the oropharynx to levels that are similar to or better than those reported with other techniques. Sparing is achieved without compromising target coverage or other OAR sparing. The clinical benefit of this sparing remains to be determined in a prospective study.

  11. Cytotoxicity and genotoxicity of coronaridine from Tabernaemontana catharinensis A.DC in a human laryngeal epithelial carcinoma cell line (Hep-2)

    PubMed Central

    Rizo, Walace Fraga; Ferreira, Luis Eduardo; Colnaghi, Vanessa; Martins, Juliana Simões; Franchi, Leonardo Pereira; Takahashi, Catarina Satie; Beleboni, Rene Oliveira; Marins, Mozart; Pereira, Paulo Sérgio; Fachin, Ana Lúcia

    2013-01-01

    Cancer has become a major public health problem worldwide and the number of deaths due to this disease is increasing almost exponentially. In the constant search for new treatments, natural products of plant origin have provided a variety of new compounds to be explored as antitumor agents. Tabernaemontana catharinensis is a medicinal plant that produces alkaloids with expressive antitumor activity, such as heyneanine, coronaridine and voacangine. The aim of present study was firstly to screen the cytotoxic activity of the indole alkaloids heyneanine, coronaridine and voacangine against HeLa (human cervix tumor), 3T3 (normal mouse embryo fibroblasts), Hep-2 (human laryngeal epithelial carcinoma) and B-16 (murine skin) cell lines by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide); and secondly to analyze the apoptotic activity, cell membrane damage and genotoxicity of the compound that showed the best cytotoxic activity against the tumor cell lines tested. Coronaridine was the one that exhibited greater cytotoxic activity in the laryngeal carcinoma cell line Hep-2 (IC50 = 54.47 μg/mL) than the other alkaloids tested (voacangine IC50 = 159.33 g/mL, and heyneanine IC50 = 689.45 μg/mL). Coronaridine induced apoptosis in cell lines 3T3 and Hep-2, even at high concentrations. The evaluation of genotoxicity by comet assay showed further that coronaridine caused minimal DNA damage in the Hep-2 tumor cell line, and the LDH test showed that it did not affect the plasma membrane. These results suggest that further investigation of coronaridine as an antitumor agent has merit. PMID:23569415

  12. miR-375 and miR-205 Regulate the Invasion and Migration of Laryngeal Squamous Cell Carcinoma Synergistically via AKT-Mediated EMT

    PubMed Central

    Wang, Bin; Lv, Kexing; Chen, Weixiong; Zhao, Jing; Luo, Jie; Wu, Jianhui; Li, Zenghong; Qin, Hao; Wong, Thian-Sze; Yang, Weiqiang; Fu, Qing-Ling

    2016-01-01

    Previous studies have found that miR-375 and miR-205 were significantly dysregulated in laryngeal squamous cell carcinoma, which contributed to the invasion and migration of LSCC. However, the mechanisms of miR-375 and miR-205 regulating the invasion and migration of LSCC remain unknown. qRT-PCR was performed in 40 pairs of tissue samples to investigate the expression of miR-375 and miR-205 in LSCC and paracarcinoma tissues. To investigate whether or not miR-375 and miR-205 regulated the invasion and migration of LSCC synergistically via AKT-mediated epithelial-mesenchymal transition, miR-375 mimic and miR-205 inhibitor were transfected into SNU899 cells and miR-375 inhibitor and miR-205 mimic were transfected into SNU899 cells, respectively, with or without AKT inhibitor. Then the expressions of miR-375 and miR-205 were validated by qRT-PCR, cell migration and invasion were determined by wound healing assay and transwell invasive assay, and western blot analysis was performed to detect the expression of related proteins. Our results showed that miR-375 and miR-205 regulated the invasion and migration of LSCC via AKT-mediated EMT synergistically. In conclusion, our findings provided not only new information about the molecular mechanism of miRNAs regulating invasion and migration of LSCC, but also a theoretical principle for potential targeting therapy of laryngeal squamous carcinoma. PMID:28078305

  13. Laryngeal actinomycosis.

    PubMed

    Lensing, Forrester; Abele, Travis; Wiggins, Richard; Quigley, Edward

    2014-01-01

    Actinomyces odontolyticus, a component of normal human flora, has been implicated in cervicofacial actinomycosis, which most commonly involves the perimandibular soft tissues and is characterized by slowly progressive abscess and sinus tract formation. Actinomycosis has rarely been reported to involve the larynx, and the imaging findings of laryngeal involvement have not been reported. We present a case of laryngeal actinomycosis with findings on computed tomography, magnetic resonance imaging, and positron emission tomography.

  14. Clinical implication of computed tomography findings in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx.

    PubMed

    Ryu, In Sun; Lee, Jeong Hyun; Roh, Jong-Lyel; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon; Cho, Kyung-Ja

    2015-10-01

    Accurate tumor staging including involvement of laryngeal cartilage is important to treatment planning. Clinicians rely on imaging findings and determine initial laryngectomy for T4-stage cancer with functionless larynx or extralaryngeal spread (ELS). We examined the accuracy and prognostic value of preoperative CT findings for tumor staging in patients with locally advanced laryngeal and hypopharyngeal cancer. Ninety-four consecutive patients with clinically T3-T4-stage squamous cell carcinoma of the larynx or hypopharynx who underwent curative resection of primary tumor were reviewed. Preoperative CT findings were interpreted by a radiologist without pathologic information. Pathologic findings were used as the gold standard for correlating radiographic findings. CT imaging identified 23 (72%) of 32 cases of pathologically documented thyroid cartilage penetration and 24 (73%) of 33 cases of pathologically documented ELS. The positive predictive values for thyroid cartilage penetration and ELS were 70 and 80%, respectively. Pretreatment CT imaging up-staged 6 of 46 pT3 cases and all of 8 pT2 cases, while it down-staged 7 of 40 pT4 cases. The accuracy for clinical staging by CT imaging was 78%. Subglottic extension of the CT image was an independent variable for predicting thyroid cartilage penetration and ELS (P = 0.014). Thyroid cartilage penetration with or without ELS on CT scans is significantly associated with unfavorable DFS outcome of patients (P = 0.020). CT imaging is suboptimal in diagnosing TCP or ELS of advanced laryngeal cancer, but may be useful to predict patient survival by identifying clinically TCP.

  15. Modern management of locally advanced cervical carcinoma.

    PubMed

    Dueñas-Gonzalez, Alfonso; Cetina, Lucely; Mariscal, Ignacio; de la Garza, Jaime

    2003-10-01

    Radiation was until recently the key and only modality for the routine treatment of locally advanced cervical carcinoma. However after years of studying multi-modality treatments as an alternative to radiation alone in randomized phase III trials, the standard treatment has changed to chemo-radiation based on cisplatin. Three recent meta-analyses have confirmed that cisplatin-based chemo-radiation adds an absolute 12% benefit in five-year survival over radiation therapy alone. Neoadjuvant chemotherapy followed by radiation has not been of proven benefit, but when neoadjuvant chemotherapy is followed by surgery, an absolute increase of 15% in five-year survival over radiation alone is seen. This benefit in survival is comparable to that obtained with the current chemo-radiation schedules based on cisplatin. Despite these encouraging results there remains room for improvement as the five-year survival of patients treated with chemo-radiation ranges from nearly 80% in bulky IB tumours to only 25% in stage IVA disease. Other therapeutic approaches need to be fully evaluated including the use of chemo-radiation after neoadjuvant chemotherapy; the use of new drug combinations and the multi-modality combination of neoadjuvant chemotherapy followed by radical surgery plus adjuvant chemo-radiation. Likewise, the addition of radiosensitizers to cisplatin, preoperative chemo-radiation and/or adjuvant chemotherapy may eventually improve the currents results of cisplatin-based chemo-radiation. Nevertheless, it is hard to foresee a dramatic increase in cure rate, even with the most optimal combination of cytotoxic drugs, surgery and radiation, and thus the testing of molecular targeted therapies against cervical cancer is a logical step to follow.

  16. Definitive Chemoradiotherapy for Advanced Pulmonary Sarcomatoid Carcinoma

    PubMed Central

    Takeda, Kazuya; Matsushita, Haruo; Kubozono, Masaki; Tanabe, Takaya; Ishikawa, Yojiro; Yamamoto, Takaya; Kozumi, Maiko; Takahashi, Noriyoshi; Katagiri, Yu; Tasaka, Shun; Fukui, Katsuya; Takeda, Ken; Fujishima, Fumiyoshi; Ichinose, Masakazu; Jingu, Keiichi

    2016-01-01

    Pulmonary sarcomatoid carcinoma is a rare subtype of non-small cell lung cancer with a poor prognosis. We herein report on a case of pulmonary sarcomatoid carcinoma that was treated successfully by concurrent chemoradiotherapy. A 65-year-old man was diagnosed to have pulmonary pleomorphic carcinoma (clinical T4N2M0 stage IIIB). He received concurrent chemoradiotherapy (60 Gy of radiotherapy in 30 fractionations and two courses of chemotherapy with carboplatin and paclitaxel). After chemoradiotherapy, a significant reduction of the tumor size was observed. Two courses of adjuvant chemotherapy were performed. He is currently alive at 15 months after the first treatment without any recurrence or metastasis. PMID:27853077

  17. Conditional Survival Analysis of Patients With Locally Advanced Laryngeal Cancer: Construction of a Dynamic Risk Model and Clinical Nomogram

    PubMed Central

    Sheu, Tommy; Vock, David M.; Mohamed, Abdallah S. R.; Gross, Neil; Mulcahy, Collin; Zafereo, Mark; Gunn, G. Brandon; Garden, Adam S.; Sevak, Parag; Phan, Jack; Lewin, Jan S.; Frank, Steven J.; Beadle, Beth M.; Morrison, William H.; Lai, Stephen Y.; Hutcheson, Katherine; Marai, G. Elisabeta; Canahuate, Guadalupe M.; Kies, Merrill; El-Naggar, Adel; Weber, Randal S.; Rosenthal, David I.; Fuller, Clifton D.

    2017-01-01

    Conditional survival (CS), the survival beyond a pre-defined time interval, can identify periods of higher mortality risk for patients with locally advanced laryngeal cancer who face treatment-related toxicity and comorbidities related to alcohol and smoking in the survivorship setting. Using Weibull regression modeling, we analyzed retrospectively abstracted data from 638 records of patients who received radiation to identify prognostic factors for overall survival (OS) and recurrence free survival (RFS) for the first 3 years of survival and for OS conditional upon 3 years of survival. The CS was iteratively calculated, stratifying on variables that were statistically significant on multivariate regression. Predictive nomograms were generated. The median total follow up time was 175 months. The 3- and 6- year actuarial overall survival (OS) was 68% (95% confidence interval [CI] 65–72%) and 49% (CI 45–53%). The 3-year conditional overall survival (COS) at 3 years was 72% (CI 65–74%). Black patients had worse COS over time. Nodal disease was significantly associated with recurrence, but after 3 years, the 3-year conditional RFS converged for all nodal groups. In conclusion, the CS analysis in this patient cohort identified subgroups and time intervals that may represent opportunities for intervention. PMID:28276466

  18. Advances in the management of cutaneous squamous cell carcinoma

    PubMed Central

    Parikh, Sonal A.

    2014-01-01

    Cutaneous squamous cell carcinoma is one of the most common non-melanoma skin cancers worldwide. While most cutaneous squamous cell carcinomas are easily managed, there is a high-risk subset of tumors that can cause severe morbidity and mortality. Tumor characteristics as well as patient characteristics contribute to the classification of cutaneous squamous cell carcinomas as low-risk vs. high-risk. Advances in the treatment of cutaneous squamous cell carcinomas largely relate to the management of this high-risk subset. Surgical and non-surgical management options, including newer targeted molecular therapies, will be discussed here. Larger, multicenter studies are needed to determine the exact significance of individual risk factors with respect to aggressive clinical behavior and the risks of metastasis and death, as well as the role of surgical and adjuvant therapies in patients with high-risk cutaneous squamous cell carcinomas. PMID:25165569

  19. Risk of Recurrence in Laryngeal Cancer

    PubMed Central

    Sørum Falk, Ragnhild; Folkvard Evensen, Jan; Boysen, Morten; Brøndbo, Kjell

    2016-01-01

    A cohort study was undertaken to analyze the risk of recurrence among 1616 patients with primary squamous cell carcinoma of the larynx from 1983 to 2010 at a single, tertiary academic center in Oslo, Norway. The cohort was followed from the date of diagnosis to September 2011. Competing risk regression analysis assessed the association between various risk factors and the risk of recurrence, where death was considered a competing event. Recurrence was observed in 368 patients (23%) during the study period. The majority (71%) of recurrences involved the location of the primary tumor. The overall risk of recurrence during the first three years after initiating treatment was 20.5%. Increased risk of recurrence was observed in patients with supraglottic cancer, younger patients, those with T2–T3 tumors and in patients treated in the earlier part of the study period. Significant factors for recurrence in glottic carcinomas were age, treatment in the earlier part of the study and T-status, whereas age was a significant factor in supraglottic cancer. N-status appeared less significant. In conclusion, follow-up of laryngeal squamous cell carcinoma should place particular emphasis on the site of the primary tumor, younger patients, cases of supraglottic cancer and T2-T4 primary tumors, especially during the first three years after treatment. More studies are needed to assess the impact of surgical versus non-surgical treatment, and eventually the significance of recurrence, for disease-specific and overall survival in cases of advanced laryngeal squamous cell carcinoma. PMID:27716797

  20. Advances in the pathology of penile carcinomas.

    PubMed

    Chaux, Alcides; Cubilla, Antonio L

    2012-06-01

    The incidence of penile cancer varies from country to country, with the highest figures reported for countries in Africa, South America, and Asia and lowest in the United States and Europe. Causes of this variation are not clear, but they are thought to be related to human papillomavirus infection, smoking, lack of circumcision, chronic inflammation, and poor genital hygiene. Most penile tumors are squamous cell carcinomas, and a variegated spectrum of distinct morphologies is currently recognized. Each one of these subtypes has distinctive pathologic and clinical features. About half of penile carcinomas are usual squamous cell carcinomas, and the rest corresponds to verrucous, warty, basaloid, warty-basaloid, papillary, pseudohyperplastic, pseudoglandular, adenosquamous, sarcomatoid, and cuniculatum carcinomas. Previous studies have found a consistent association of tumor cell morphology and human papillomavirus presence in penile carcinomas. Those tumors composed of small- to intermediate-sized, basaloid ("blue") cells are often human papillomavirus positive, whereas human papillomavirus prevalence is lower in tumors showing large, keratinizing, maturing eosinophilic ("pink") cells. Human papillomavirus-related tumors affect younger patients, whereas human papillomavirus-unrelated tumors are seen in older patients with phimosis, lichen sclerosus, or squamous hyperplasia. This morphologic distinctiveness is also observed in penile intraepithelial neoplasia. The specific aim of this review is to provide a detailed discussion on the macroscopic and microscopic features of all major subtypes of penile cancer. We also discuss the role of pathologic features in the prognosis of penile cancer, the characteristics of penile precursor lesions, and the use of immunohistochemistry for the diagnosis of invasive and precursor lesions.

  1. Vismodegib induces significant clinical response in locally advanced trichoblastic carcinoma.

    PubMed

    Lepesant, P; Crinquette, M; Alkeraye, S; Mirabel, X; Dziwniel, V; Cribier, B; Mortier, L

    2015-10-01

    Patients with advanced basal cell carcinoma due to local extension or metastatic disease were previously at a therapeutic impasse. Targeted inhibition of the sonic hedgehog pathway by vismodegib represents a new therapeutic strategy. Adnexal carcinomas are rare malignant skin tumours derived from epithelial annexes. Conventional treatment of adnexal tumours is based on surgical excision. Although the radiosensitivity of adnexal carcinomas has not been established, radiotherapy could be offered alone or in combination in locally advanced or inoperable disease. Chemotherapy represents a therapeutic option in the treatment of metastatic adnexal tumours. Currently there is no effective treatment for these tumours when they become metastatic or unresectable, and treatment is palliative. Sunitinib represents a new therapeutic strategy, with efficiency described in the literature for a small number of patients. However, its efficacy is partial, and its tolerance is not always good. We report a patient with trichoblastic carcinoma, initially diagnosed as basal cell carcinoma, treated effectively with vismodegib. The remarkable response we have observed in this patient suggests an encouraging therapeutic role of vismodegib in trichoblastic carcinoma that should be evaluated in a carefully designed trial.

  2. Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III-IV Squamous Cell Carcinoma of the Head and Neck Who Have Undergone Surgery

    ClinicalTrials.gov

    2016-10-04

    Head and Neck Squamous Cell Carcinoma; Laryngeal Squamous Cell Carcinoma, Spindle Cell Variant; Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Laryngeal Verrucous Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oral Cavity Verrucous Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma

  3. Nursing Management of Advanced Merkel Cell Carcinoma.

    PubMed

    Lowry, Pamela A; Freeman, Morganna L; Russell, Jeffery S

    2016-11-01

    Merkel cell carcinoma (MCC) is a rare and lethal skin cancer with few known treatment options. Management of this disease is challenging, and oncology nurses must understand the medical, physical, and psychosocial burden that MCC places on the patient and family caregivers. Patients must navigate a complex medical and insurance network that often fails to support patients with rare cancers. Nurses must advocate for these patients to ensure quality comprehensive cancer care.

  4. The bioactive potential of red raspberry (Rubus idaeus L.) leaves in exhibiting cytotoxic and cytoprotective activity on human laryngeal carcinoma and colon adenocarcinoma.

    PubMed

    Durgo, Ksenija; Belščak-Cvitanović, Ana; Stančić, Angela; Franekić, Jasna; Komes, Draženka

    2012-03-01

    In this article, the bioactive potential of red raspberry leaves, a by-product of this widely spread plant, mostly valued for its antioxidant-rich fruits, was determined. The polyphenolic profile and antioxidative properties of red raspberry leaf extract were determined and examined for potential biological activity. Cytotoxic effect, antioxidative/prooxidative effect, and effect on total glutathione concentration were determined in human laryngeal carcinoma (HEp2) and colon adenocarcinoma (SW 480) cell lines. SW 480 cells are more susceptible to raspberry leaf extract in comparison with HEp2 cells. The antioxidative nature of raspberry leaf extract was detected in HEp2 cells treated with hydrogen peroxide, as opposed to SW 480 cells, where raspberry leaf extract induced reactive oxygen species formation. Raspberry leaf extract increased total glutathione level in HEp2 cells. This effect was reinforced after 24 hours of recovery, indicating that induction was caused by products formed during cellular metabolism of compounds present in the extract. Comparison of the results obtained on these two cell lines indicates that cellular response to raspberry extract will depend on the type of the cells that are exposed to it. The results obtained confirmed the biological activity of red raspberry leaf polyphenols and showed that this traditional plant can supplement the daily intake of valuable natural antioxidants, which exhibit beneficial health effects.

  5. Rapid hyperfractionated radiotherapy. Clinical results in 178 advanced squamous cell carcinomas of the head and neck

    SciTech Connect

    Nguyen, T.D.; Demange, L.; Froissart, D.; Panis, X.; Loirette, M.

    1985-07-01

    The authors present a series of 178 patients with Stage III or IV squamous cell carcinoma of the head and neck treated by rapid irradiation using multiple and small fractions per day. An initial group of 91 patients (G1) received a total dose of 72 Gy in 80 sessions and 10 days, according to the following split course schedule: J1 to J5, 36 Gy in 40 sessions, eight daily fractions of .9 Gy separated by 2 hours; J6 to J20, rest period; J21 to J25, same as in J1 except that the spinal cord was shielded. This protocol was altered for the following 87 patients (G2) by lessening the total dose to 60 to 66 Gy and the number of fractions to 60. The rest period was lengthened to 4 weeks. All patients but five completed the whole program and the minimal follow-up period was 24 months. At the end of irradiation, 121 patients achieved a total remission, but local recurrences occurred in 56%. Moreover, acute intolerance was considered as severe in 34% of G1 patients, and included extensive mucosal necrosis and bleeding. Although this rate was significantly reduced in G2 patients, late complications were observed in 20 of the 25 survivors, and included trismus, cervical sclerosis, and recurrent laryngeal edema. The crude survival rate is 13% at 2 years. Although this study was not randomized, this particular type of accelerated and hyperfractionated combination of irradiation did not really improve the clinical results in advanced carcinoma of the head and neck. Other schedules and probably other tumors, less extended, should be tested.

  6. Cisplatin, Intensity-Modulated Radiation Therapy, and Pembrolizumab in Treating Patients With Stage III-IV Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2017-03-30

    Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IV Hypopharyngeal Squamous Cell Carcinoma; Stage IV Laryngeal Squamous Cell Carcinoma; Stage IV Oral Cavity Squamous Cell Carcinoma; Stage IV Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma

  7. Adenoid cystic carcinoma of breast: Recent advances

    PubMed Central

    Miyai, Kosuke; Schwartz, Mary R; Divatia, Mukul K; Anton, Rose C; Park, Yong Wook; Ayala, Alberto G; Ro, Jae Y

    2014-01-01

    Adenoid cystic carcinoma (ACC) of the breast is a rare special subtype of breast cancer characterized by the presence of a dual cell population of luminal and basaloid cells arranged in specific growth patterns. Most breast cancers with triple-negative, basal-like breast features (i.e., tumors that are devoid of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, and express basal cell markers) are generally high-grade tumors with an aggressive clinical course. Conversely, while ACCs also display a triple-negative, basal-like phenotype, they are usually low-grade and exhibit an indolent clinical behavior. Many discoveries regarding the molecular and genetic features of the ACC, including a specific chromosomal translocation t(6;9) that results in a MYB-NFIB fusion gene, have been made in recent years. This comprehensive review provides our experience with the ACC of the breast, as well as an overview of clinical, histopathological, and molecular genetic features. PMID:25516849

  8. Vocal Cord Actinomycosis Mimicking a Laryngeal Tumor

    PubMed Central

    Yoshihama, Keisuke; Kato, Yasumasa; Baba, Yuh

    2013-01-01

    Laryngeal carcinoma and laryngeal papilloma are the most commonly encountered tumorous lesions in the larynx. Herein, we report a case of the mass arising from the left vocal cord in a 49-year-old Japanese man. Endoscopic examination suggested that the mass is a tumor such as carcinoma and papilloma. Pathological examination showed that the specimen demonstrated actinomycosis in the left vocal cord. Although vocal cord actinomycosis is extremely rare, the otolaryngologist should recognize this condition during the inspection of the larynx. PMID:23573444

  9. SU-E-J-265: Feasibility Study of Texture Analysis for Prognosis of Local Tumor Recurrence Within 5-Years for Pharyngeal-Laryngeal Carcinoma Patients Received Radiotherapy Treatment

    SciTech Connect

    Huang, W; Tu, S

    2015-06-15

    Purpose: Pharyngeal and laryngeal carcinomas (PLC) are among the top leading cancers in Asian populations. Typically the tumor may recur and progress in a short period of time if radiotherapy fails to deliver a successful treatment. Here we used image texture features extracted from images of computed tomography (CT) planning and conducted a retrospective study to evaluate whether texture analysis is a feasible approach to predict local tumor recurrence for PLC patients received radiotherapy treatment. Methods: CT planning images of 100 patients with PLC treated by radiotherapy at our facility between 2001 and 2010 are collected. These patients were received two separate CT scans, before and mid-course of the treatment delivery. Before the radiotherapy, a CT scanning was used for the first treatment planning. A total of 30 fractions were used in the treatment and patients were scanned with a second CT around the end of the fifteenth delivery for an adaptive treatment planning. Only patients who were treated with intensity modulated radiation therapy and RapidArc were selected. Treatment planning software of Eclipse was used. The changes of texture parameters between two CT acquisitions were computed to determine whether they were correlated to the local tumor recurrence. The following texture parameters were used in the preliminary assessment: mean, variance, standard deviation, skewness, kurtosis, energy, entropy, inverse difference moment, cluster shade, inertia, cluster prominence, gray-level co-occurrence matrix, and gray-level run-length matrix. The study was reviewed and approved by the committee of our institutional review board. Results: Our calculations suggested the following texture parameters were correlated with the local tumor recurrence: skewness, kurtosis, entropy, and inertia (p<0.0.05). Conclusion: The preliminary results were positive. However some works remain crucial to be completed, including addition of texture parameters for different image

  10. miR-144-3p, a tumor suppressive microRNA targeting ETS-1 in laryngeal squamous cell carcinoma.

    PubMed

    Zhang, Si-Yi; Lu, Zhong-Ming; Lin, Ye-Feng; Chen, Liang-Si; Luo, Xiao-Ning; Song, Xin-Han; Chen, Shao-Hua; Wu, Yi-Long

    2016-03-08

    Regional lymph node metastasis and distant metastasis are critical in the prognosis of laryngeal squamous cell carcinoma (LSCC). This study investigated the roles of miR-144-3p and E26 transformation specific-1 (ETS-1) in the invasion and migration of LSCC cells. The effects of miR-144-3p and ETS-1 on FaDu and Hep2 cell growth, migration and invasion were determined. Suppression of ETS-1 by miR-144-3p was confirmed using luciferase assays; the effects of ETS-1 silencing were determined using a xenograft tumor model. The expression of ETS-1 was analyzed in 71 paraffin-embedded tissue biopsies and eight fresh frozen biopsies obtained from LSCC patients. miR-144-3p inhibited the growth, invasion and migration of FaDu and Hep2 cells in part through suppression of epithelial-mesenchymal transition as determined by increased E-cadherin and α-catenin and reduced fibronectin and vimentin expression. Additionally, ETS-1 is a molecular target of miR-144-3p, and silencing ETS-1 expression inhibited FaDu and Hep2 cell invasion and migration as well as reduced Hep2 xenograft tumor volume. In LSCC, the expression of ETS-1 is upregulated with disease progression, and higher ETS-1 expression, which was negatively associated with miR-144-3p levels, adversely corresponded with prognoses. Thus, upregulated ETS-1 levels may promote LSCC metastasis, resulting in poor patient prognosis.

  11. The Expression and Relationship of CD68-Tumor-Associated Macrophages and Microvascular Density With the Prognosis of Patients With Laryngeal Squamous Cell Carcinoma

    PubMed Central

    Sun, Shujun; Pan, Xinliang; Zhao, Limin; Zhou, Jianming; Wang, Hongzeng; Sun, Yonghong

    2016-01-01

    Objectives. We sought to identify the expression of CD68-tumor-associated macrophages (TAMs) and CD34-microvascular density (MVD) in laryngeal squamous cell carcinoma (LSCC), to study the relationship with clinical pathological parameters and to determine whether their expression is predictive of disease. Methods. Pathologically confirmed 45 LSCC tissue and 20 peritumoral non-tumor tissue were examined. Immunohistochemical studies were used to detect the expression of CD68-TAMs and CD34-MVD. Results. The positive expression rate of CD68 in LSCC tissue was 82% (37/45), which was higher than the 10% (2/20) expression rate of the peritumoral tissue (P<0.05). The CD34-MVD positive expression rate in the LSCC tissue was 26.5±6.4, which obviously higher than 12.2±4.0 expression rate of the peritumoral tissue (P<0.05). The positive expression rates of both CD68 and CD34-MVD were higher in the lymph node metastasis (LNM) positive group than in the LNM negative group. The expression of CD68 had positive correlation with CD34-MVD. The 5-year disease-free survival rate in the group with the low CD68 expression was significantly higher than that in the group with high CD68 expression (76% vs. 42%, respectively). Conclusion. The high expression of CD68-TAMs in LSCC and its positive correlation with CD34-MVD illustrates that both play an important role in promoting the metastasis and angiogenesis of this cancer. Their expression was also positively correlated with the prognoses of these patients, suggesting that they could be used as important prognostic markers for LSCC. PMID:27337949

  12. MicroRNA 744-3p promotes MMP-9-mediated metastasis by simultaneously suppressing PDCD4 and PTEN in laryngeal squamous cell carcinoma

    PubMed Central

    Li, John Zeng-Hong; Gao, Wei; Lei, Wen-Bin; Zhao, Jing; Chan, Jimmy Yu-Wai; Wei, William Ignace; Ho, Wei-Kuen; Wong, Thian-Sze

    2016-01-01

    MicroRNA controls cancer invasion by governing the expression of gene regulating migration and invasion. Here, we reported a novel regulatory pathway controlled by miR-744-3p, which enhanced expression of matrix metallopeptidase 9 (MMP-9) in laryngeal squamous cell carcinoma (LSCC). We profiled the differential micoRNA expression pattern in LSCC cell lines and normal epithelial cultures derived from the head and neck mucosa using microRNA microarray. MiR-7-1-3p, miR-196a/b and miR-744-3p were expressed differentially in the LSCC cell lines. Subsequent validation using real-time PCR revealed that high miR-744-3p level was positively correlated with regional lymph node metastasis of LSCC. Real-time cellular kinetic analysis showed that suppressing miR-744-3p could inhibit migration and invasion of LSCC cell lines and reduce the number of lung metastatic nodules in nude mice modules. In silico analysis revealed that miR-744-3p targeted 2 distinct signaling cascades which eventually upregulated MMP-9 expression in LSCC. First, miR-744-3p could suppress programmed cell death 4 (PDCD4), a direct suppressor of NF-κB (p65). PDCD4 could also prevent AKT activation and suppress MMP-9 expression. Further, suppressing miR-744-3p expression could restore phosphatase and tensin homolog (PTEN) expression. PTEN could inhibit AKT activation and inhibit MMP-9 expression in LSCC cells. The results revealed that suppressing miR-744-3p was effective to inhibit LSCC metastasis by inactivating AKT/mTOR and NF-κB (p65) signaling cascade. Targeting miR-744-3p could be a valuable therapeutic intervention to suppress the aggressiveness of LSCC. PMID:27533461

  13. Laryngeal histoplasmosis.

    PubMed

    Ansari, Hina A; Saeed, Noora; Khan, Nazoora; Hasan, Naba

    2016-08-17

    Histoplasmosis is a fungal infection, having interesting synonyms such as Cave disease, Darling's disease, Ohio Valley disease, reticuloendotheliosis, Spelunker's lung and Caver's disease. The aetiological agent is a dimorphic fungus, Histoplasma capsulatum, causing chronic granulomatous disease. The route of transmission is by inhalation of dust particles from soil contaminated by excrement of birds or bats, harbouring the small spores or microconidia, which is considered the infectious form of fungus. The spectrum of illness ranges from subclinical infection of the lung to progressive disseminated disease. The major bulk of histoplasmosis infections are asymptomatic or present with mild influenza like illness and involve immunocompetent individuals. However, the immunocompromised or immunodeficient cases have disseminated/haematogenous infections with multiple organs involved and are usually fatal unless treated immediately. Laryngeal involvement is associated with the disseminated form of the disease. Histoplasmosis of larynx is a rare entity and poses diagnostic difficulty to otolaryngologists because clinically it may be mistaken for malignancy. We report an unusual case of laryngeal histoplasmosis in a man aged 60 years who presented with provisional diagnosis of tuberculosis/malignancy.

  14. Combination treatment including targeted therapy for advanced hepatocellular carcinoma

    PubMed Central

    Xie, Yuan; Wang, Anqiang; Zhang, Haohai; Yang, Xiaobo; Wan, Xueshuai; Lu, Xin; Sang, Xinting; Zhao, Haitao

    2016-01-01

    Management of advanced hepatocellular carcinoma (HCC), one of the most lethal cancers worldwide, has presented a therapeutic challenge over past decades. Most patients with advanced HCC and a low possibility of surgical resection have limited treatment options and no alternative but to accept local or palliative treatment. In the new era of cancer therapy, increasing numbers of molecular targeted agents (MTAs) have been applied in the treatment of advanced HCC. However, mono-targeted therapy has shown disappointing outcomes in disease control, primarily because of tumor heterogeneity and complex cell signal transduction. Because incapacitation of a single target is insufficient for cancer suppression, combination treatment for targeted therapy has been proposed and experimentally tested in several clinical trials. In this article, we review research studies aimed to enhance the efficacy of targeted therapy for HCC through combination strategies. Combination treatments involving targeted therapy for advanced HCC are compared and discussed. PMID:27626176

  15. Progress in systemic therapy of advanced hepatocellular carcinoma

    PubMed Central

    Gong, Xin-Lei; Qin, Shu-Kui

    2016-01-01

    Primary liver cancer, mainly consisting of hepatocellular carcinoma (HCC), is one of common malignancies worldwide, and prevalent among the Chinese population. A diagnosis of early stage HCC has proven to be very difficult because of its insidious feature in onset and development. At the time of diagnosis, most HCC cases are locally advanced and/or distant metastatic, which results in difficulty to be treated and poor prognosis. For advanced HCC, systemic therapy is frequently adopted as an important palliative method. In recent years, clinical studies and observations have often reported about systemic anti-cancer therapy of advanced HCC, including molecular target therapy, systemic chemotherapy and immunotherapy. In this article, we review these treatment modalities to provide a reference for clinicians. PMID:27547002

  16. Dosimetric Predictors of Laryngeal Edema

    SciTech Connect

    Sanguineti, Giuseppe . E-mail: gisangui@utmb.edu; Adapala, Prashanth; Endres, Eugene J. C; Brack, Collin; Fiorino, Claudio; Sormani, Maria Pia; Parker, Brent

    2007-07-01

    Purpose: To investigate dosimetric predictors of laryngeal edema after radiotherapy (RT). Methods and Materials: A total of 66 patients were selected who had squamous cell carcinoma of the head and neck with grossly uninvolved larynx at the time of RT, no prior major surgical operation except for neck dissection and tonsillectomy, treatment planning data available for analysis, and at least one fiberoptic examination of the larynx within 2 years from RT performed by a single observer. Both the biologically equivalent mean dose at 2 Gy per fraction and the cumulative biologic dose-volume histogram of the larynx were extracted for each patient. Laryngeal edema was prospectively scored after treatment. Time to endpoint, moderate or worse laryngeal edema (Radiation Therapy Oncology Group Grade 2+), was calculated with log rank test from the date of treatment end. Results: At a median follow-up of 17.1 months (range, 0.4- 50.0 months), the risk of Grade 2+ edema was 58.9% {+-} 7%. Mean dose to the larynx, V30, V40, V50, V60, and V70 were significantly correlated with Grade 2+ edema at univariate analysis. At multivariate analysis, mean laryngeal dose (continuum, hazard ratio, 1.11; 95% confidence interval, 1.06-1.15; p < 0.001), and positive neck stage at RT (N0-x vs. N +, hazard ratio, 3.66; 95% confidence interval, 1.40-9.58; p = 0.008) were the only independent predictors. Further stratification showed that, to minimize the risk of Grade 2+ edema, the mean dose to the larynx has to be kept {<=}43.5 Gy at 2 Gy per fraction. Conclusion: Laryngeal edema is strictly correlated with various dosimetric parameters; mean dose to the larynx should be kept {<=}43.5 Gy.

  17. RUNX3 inhibits laryngeal squamous cell carcinoma malignancy under the regulation of miR-148a-3p/DNMT1 axis.

    PubMed

    Jili, Su; Eryong, Lu; Lijuan, Lu; Chao, Zhang

    2016-12-01

    Laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignant cancer and accounts for 1% to 2% of all malignancies diagnosed worldwide. Runt-related transcription factor 3 (RUNX3), an important tumor suppressor, is known to related to lymph node metastasis and the development of LSCC. However, the biological roles and potential mechanisms RUNX3 expression was not well understood. In this study, we reported that the RUNX3 was significantly downregulated and highly methylated in LSCC compared with their matched normal. The enforced expression of RUNX3 inhibited LSCC cell migration, invasion, and proliferation, whereas the inhibition of RUNX3 did the opposite. We identified that RUNX3 was regulated by miR-148a-3p and found that the expression level of miR-148-3p was significantly decreased and positively related with the expression of RUNX3 in LSCC. We also identified that DNA methyltransferase enzyme DNA (cytosine-5-)-methyltransferase 1 (DNMT1) was targeted by miR-148a-3p in LSCC. The knockdown of DNMT1 promoted the expression of RUNX3 and inhibited migration, invasion, and proliferation in LSCC cells. In summary, our study demonstrated that miR-148a-3p may regulate RUNX3 expression through the modulation of DNMT1-dependent DNA methylation in LSCC, providing a novel target and a potential therapeutic pathway against LSCC. LSCC is a highly aggressive malignant cancer and accounts for 1% to 2% of all malignancies diagnosed worldwide. In this study, we reported that RUNX3, an important tumor suppressor, was significantly downregulated and highly methylated in LSCC compared with their matched normal. The overexpression of RUNX3 inhibited LSCC cell migration, invasion, and proliferation, whereas the inhibition of RUNX3 did the opposite. Moreover, RUNX3 was regulated by miR-148a-3p, which targeted DNA methyltransferase enzyme DNMT1 in LSCC cells. Therefore, miR-148a-3p may regulate RUNX3 expression through the modulation of DNMT1-dependent DNA methylation in

  18. Recent advances and key challenges in investigations of the flow inside human oro-pharyngeal-laryngeal airway

    NASA Astrophysics Data System (ADS)

    Pollard, A.; Uddin, M.; Shinneeb, A.-M.; Ball, C. G.

    2012-07-01

    The oro-pharyngeal-laryngeal human airway is a complex geometry; the flow physics within are subjected to and influenced by a variety of different factors that produce jet-like flow, re-circulating flows that are enhanced by curvature, detached and secondary flows. Simulation and experiment are the tools available to the fluid dynamics researcher. Simulation results obtained from direct and large-eddy simulation, and Reynolds-averaged Navier-Stokes and associated models of turbulence are reviewed. Experimental data obtained through the use of flow visualisation, hot-wire anemometry and particle image velocimetry are also reviewed. A comparison of data obtained from the application of these tools reveals many inconsistencies that are explored in this article. While much progress has been made to understand some of the physics of the flow in the human airway, we continue to uncover new and significant fluid dynamic behaviour. Finally, future research directions are suggested.

  19. Laryngeal melanosis.

    PubMed

    Dutta, V; Reddy, P S

    2003-10-01

    We describ a case iaryngcul melanosis in a 62 year old male. the pigmentation was visible on gross examination during laryngoscopy ana histologicatly a single foci showing changes of carcinoma in situ was identified. The biopsy tissue, however did not reveal any frank changes of malignancy.

  20. Liver abscess in advanced hepatocellular carcinoma after sorafenib treatment.

    PubMed

    Shin, Seung Kak; Jung, Young Kul; Yoon, Hyun Hwa; Kwon, Oh Sang; Kim, Yun Soo; Choi, Duck Joo; Kim, Ju Hyun

    2014-01-25

    Hepatocellular carcinoma (HCC) is a critical global health issue and the third most common cause of cancer-related deaths worldwide. The majority of patients who present HCC are already at an advanced stage and their tumors are unresectable. Sorafenib is a multi-kinase inhibitor of the vascular endothelial growth factor pathway and was recently introduced as a therapy for advanced HCC. Furthermore, studies have shown that oral sorafenib has beneficial effects on survival. However, many patients experience diverse side effects, and some of these are severe. Liver abscess development has not been previously documented to be associated with sorafenib administration in HCC. Here, we report the case of a HCC patient that developed a liver abscess while being treated with sorafenib.

  1. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma.

    PubMed

    Kang, Tae Wook; Rhim, Hyunchul

    2015-09-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC.

  2. Vismodegib: in locally advanced or metastatic basal cell carcinoma.

    PubMed

    Keating, Gillian M

    2012-07-30

    Vismodegib is the first Hedgehog pathway inhibitor to be approved in the US, where it is indicated for the treatment of adults with metastatic basal cell carcinoma (BCC), or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation. Vismodegib selectively and potently inhibits the Hedgehog signalling pathway by binding to Smoothened, thereby inhibiting the activation of Hedgehog target genes. Oral vismodegib was effective in the treatment of patients with locally advanced (n = 63) or metastatic (n = 33) BCC, according to the results of an ongoing, noncomparative, multinational, pivotal, phase II trial (ERIVANCE BCC). In this trial (using a clinical cutoff date of 26 November 2010), the independent review facility overall response rate was 42.9% in patients with locally advanced BCC and 30.3% in patients with metastatic BCC. In both patients with locally advanced BCC and those with metastatic BCC, the median duration of response was 7.6 months and median progression-free survival was 9.5 months. Oral vismodegib had an acceptable tolerability profile in patients with advanced BCC.

  3. Targeting EGFR and sonic hedgehog pathways for locally advanced eyelid and periocular carcinomas

    PubMed Central

    Yin, Vivian T; Merritt, Helen; Esmaeli, Bita

    2014-01-01

    For patients with metastatic or locally advanced eyelid and periocular carcinoma not amenable to surgical excision, targeted therapies have shown efficacy with better tolerability compared to cytotoxic chemotherapy. Overexpression of epithelial growth factor receptor was found in squamous cell carcinomas. Vismodegib targets the mutation in the hedgehog pathway identified in basal cell carcinoma and basal cell nevus syndrome. Targeted therapies provide a novel and potentially effective treatment alternative for patients with eyelid carcinoma not amendable for surgery, including those with metastatic, locally advanced disease, advanced age, and significant comorbidities. High cost, need for long-term treatment, and toxicity are relative limitations. PMID:25232546

  4. Technical advances in external radiotherapy for hepatocellular carcinoma

    PubMed Central

    Park, Shin-Hyung; Kim, Jae-Chul; Kang, Min Kyu

    2016-01-01

    Radiotherapy techniques have substantially improved in the last two decades. After the introduction of 3-dimensional conformal radiotherapy, radiotherapy has been increasingly used for the treatment of hepatocellular carcinoma (HCC). Currently, more advanced techniques, including intensity-modulated radiotherapy (IMRT), stereotactic ablative body radiotherapy (SABR), and charged particle therapy, are used for the treatment of HCC. IMRT can escalate the tumor dose while sparing the normal tissue even though the tumor is large or located near critical organs. SABR can deliver a very high radiation dose to small HCCs in a few fractions, leading to high local control rates of 84%-100%. Various advanced imaging modalities are used for radiotherapy planning and delivery to improve the precision of radiotherapy. These advanced techniques enable the delivery of high dose radiotherapy for early to advanced HCCs without increasing the radiation-induced toxicities. However, as there have been no effective tools for the prediction of the response to radiotherapy or recurrences within or outside the radiation field, future studies should focus on selecting the patients who will benefit from radiotherapy. PMID:27621577

  5. Advanced primary peritoneal carcinoma: clinicopathological and prognostic factor analyses

    PubMed Central

    Zhang, Chao; Li, Xiao-ping; Cui, Heng; Shen, Dan-hua; Wei, Li-hui

    2008-01-01

    Objective: To investigate the factors favoring a positive prognosis for advanced primary peritoneal carcinoma (PPC). Methods: Twenty-four cases meeting the criteria for PPC were analyzed retrospectively for the clinicopathologic profiles. Immunohistochemistry was used to determine the expressions of p53, Top2α, Ki-67 and Her-2/neu. Then all these clinicopathological factors and molecular markers were correlated with the prognosis. Results: There were 15 cases of primary peritoneal serous papillary carcinoma (PPSPC), 6 cases of mixed epithelial carcinoma (MEC) and 3 cases of malignant mixed Mullerian tumor (MMMT). All patients underwent cytoreductive surgery with optimal debulking achieved in 3 cases. Among those receiving first-line chemotherapy, 13 patients received the TP regimen (paclitaxel-cisplatin or carboplatin) and 7 patients received the PAC regimen (cisplatin-doxorubicin-cyclophosphamide). The median overall survival of all patients was 42 months, while the breakdown for survival time for patients with PPSPC, MMT and MEC was 44, 13 and 19 months, respectively. The expressions of p53, Top2α and Ki-67 were all demonstrated in 11 cases respectively. None showed the expression of Her-2/neu. There were significant differences in the median survival between patients with PPSPC and those with MMMT (44 months vs 13 months, P<0.05), also between patients receiving TP combination and those receiving the PAC regimen (75 months vs 28 months, P<0.05). Another significant difference in the median progression-free survival (PFS) was identified between patients with positive p53 immunostaining and those with negative p53 immunostaining (15 months vs 47 months, P<0.05), whereas age, menopausal status, residual tumor size and the other molecular factors did not significantly impact survival. Conclusion: Patients with PPC should be treated with a comprehensive management plan including appropriate cytoreductive surgery and responsive chemotherapy. Overestimating an

  6. Transcatheter embolization of advanced renal cell carcinoma with radioactive seeds

    SciTech Connect

    Lang, E.K.; deKernion, J.B.

    1981-11-01

    Advanced renal cell carcinoma was treated by transcatheter embolization with radioactive seeds. There were 14 patients with nonresectable or metastatic disease (stage IV) and 8 with stage II tumors treated. In 8 patients the tumor was implanted with radon seeds, complemented by 2,500 rad of external beam therapy, and 10 were treated by embolization with 125iodine seeds. The total dose delivered ranged form 1,600 to 14,000 rad. Several patients also had intra-arterial chemotherapy. Survival was improved over previously reported studies: 13 of 22 (59 per cent) at risk for 2 years and 5 of 15 (33 per cent) for 5 years. Distant metastases did not resolve but significant local palliation was achieved. Tumor size decreased in all patients, 8 of whom subsequently underwent nephrectomy. Other local effects included pain control (10 per cent), weight gain (75 per cent) and control of hemorrhage (88 per cent). Toxicity was minimal and consisted of mild nausea or pain. This approach, using a low energy emitter, allows selective high dose radiation of the tumor, while sparing the adjacent normal tissues. In contrast to renal artery occlusion with inert embolic material, subsequent nephrectomy in patients with disseminated disease is not necessary. Transcatheter embolization with radioactive seeds should be considered a reasonable palliative procedure in patients with nonresectable primary renal cell carcinoma.

  7. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma

    PubMed Central

    Kang, Tae Wook; Rhim, Hyunchul

    2015-01-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC. PMID:26674766

  8. Advances in the management of basal cell carcinoma

    PubMed Central

    Carucci, John A.

    2015-01-01

    Basal cell carcinoma (BCC), a malignant neoplasm derived from non-keratinizing cells that originate in the basal layer of the epidermis, is the most common cancer in humans. Several factors such as anatomic location, histologic features, primary or recurrent tumors, and patient characteristics influence the choice of treatment modality for BCC. Mohs micrographic surgery (MMS) facilitates optimal margin control and conservation of normal tissue for the management of BCC; however, other treatment modalities may also be implemented in the correct clinical scenario. Other treatment modalities that will be reviewed include simple excision, electrodesiccation and curettage, cryotherapy, topical immunotherapy and chemotherapy, photodynamic therapy, and radiation therapy. In addition, targeted molecular therapeutic options for the treatment of advanced or metastatic BCC will be discussed in this informal review based on recent literature obtained by using PubMed with relevant search terms. PMID:26097726

  9. Current Management of Advanced Resectable Oral Cavity Squamous Cell Carcinoma

    PubMed Central

    Ow, Thomas J.

    2011-01-01

    The oral cavity is the most common site of head and neck squamous cell carcinoma, a disease which results in significant morbidity and mortality worldwide. Though the primary modality of treatment for patients with oral cavity cancer remains surgical resection, many patients present with advanced disease and are thus treated using a multi-disciplinary approach. Patients with extracapsular spread of lymphatic metastasis and surgical margins that remain positive have been found to be at high risk for local-regional recurrence and death from disease, and are most often recommended to receive both post-operative radiation as well as systemic chemotherapy. The basis for this approach, as well as scientific developments that underly future trials of novels treatments for patients with high-risk oral cavity cancer are reviewed. PMID:21461056

  10. Lenvatinib: a potential breakthrough in advanced hepatocellular carcinoma?

    PubMed

    Oikonomopoulos, Georgios; Aravind, Preetha; Sarker, Debashis

    2016-02-01

    Treatment of advanced hepatocellular carcinoma (HCC) has reached a plateau after the approval of sorafenib in 2007. Several molecularly targeted therapies have failed to show significant improvement in survival outcomes compared with sorafenib, due to flaws in the design of clinical trials or failure to understand and correct for the competing co-morbidity of liver dysfunction. Lenvatinib is a multitargeted tyrosine kinase inhibitor with potent antiangiogenic effects, and has recently been approved for differentiated thyroid cancer. Lenvatinib has shown highly promising response data in Phase I/II clinical trials in HCC, although with some concerns regarding its toxicity profile. The pivotal Phase III REFLECT trial comparing lenvatinib to sorafenib has been completed, and the results of this trial will determine whether lenvatinib represents a breakthrough in the current crisis affecting HCC drug development.

  11. Thymostimulin in advanced hepatocellular carcinoma: A phase II trial

    PubMed Central

    Dollinger, Matthias M; Behrens, Christa M; Lesske, Joachim; Behl, Susanne; Behrmann, Curd; Fleig, Wolfgang E

    2008-01-01

    Background Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma in vitro. In a phase II trial, we investigated safety and efficacy including selection criteria for best response in advanced or metastasised hepatocellular carcinoma. Methods 44 patients (84 % male, median age 69 years) not suitable or refractory to conventional therapy received thymostimulin 75 mg subcutaneously five times per week for a median of 8.2 months until progression or complete response. 3/44 patients were secondarily accessible to local ablation or chemoembolisation. Primary endpoint was overall survival, secondary endpoint tumor response or progression-free survival. A multivariate Cox's regression model was used to identify variables affecting survival. Results Median survival was 11.5 months (95% CI 7.9–15.0) with a 1-, 2- and 3-year survival of 50%, 23% and 9%. In the univariate analysis, a low Child-Pugh-score (p = 0.01), a low score in the Okuda- and CLIP-classification (p < 0.001) or a low AFP-level (p < 0.001) were associated with better survival, but not therapy modalities other than thymostimulin (p = 0.1) or signs of an invasive HCC phenotype such as vascular invasion (p = 0.3) and metastases (p = 0.1). The only variables independently related to survival in the Cox's regression model were Okuda stage and presence of liver cirrhosis (p < 0.01) as well as response to thymostimulin (p < 0.05). Of 39/44 patients evaluable for response, two obtained complete responses (one after concomitant radiofrequency ablation), five partial responses (objective response 18%), twenty-four stable disease (tumor control rate 79%) and eight progressed. Median progression-free survival was 6.4 months (95% CI 0.8–12). Grade 1 local reactions following injection were the only side effects. Conclusion Outcome in our study rather depended on liver function and intrahepatic tumor growth (presence of liver cirrhosis and Okuda stage) in addition

  12. Hepatocellular carcinoma: Advances in diagnosis, management, and long term outcome.

    PubMed

    Bodzin, Adam S; Busuttil, Ronald W

    2015-05-28

    Hepatocellular carcinoma (HCC) remains a common and lethal malignancy worldwide and arises in the setting of a host of diseases. The incidence continues to increase despite multiple vaccines and therapies for viruses such as the hepatitis B and C viruses. In addition, due to the growing incidence of obesity in Western society, there is anticipation that there will be a growing population with HCC due to non-alcoholic fatty liver disease. Due to the growing frequency of this disease, screening is recommended using ultrasound with further imaging using magnetic resonance imaging and multi-detector computed tomography used for further characterization of masses. Great advances have been made to help with the early diagnosis of small lesions leading to potential curative resection or transplantation. Resection and transplantation maybe used in a variety of patients that are carefully selected based on underlying liver disease. Using certain guidelines and clinical acumen patients may have good outcomes with either resection or transplantation however many patients are inoperable at time of presentation. Fortunately, the use of new locoregional therapies has made down staging patients a potential option making them potential surgical candidates. Despite a growing population with HCC, new advances in viral therapies, chemotherapeutics, and an expanding population of surgical and transplant candidates might all contribute to improved long-term survival of these patients.

  13. Hepatocellular carcinoma: Advances in diagnosis, management, and long term outcome

    PubMed Central

    Bodzin, Adam S; Busuttil, Ronald W

    2015-01-01

    Hepatocellular carcinoma (HCC) remains a common and lethal malignancy worldwide and arises in the setting of a host of diseases. The incidence continues to increase despite multiple vaccines and therapies for viruses such as the hepatitis B and C viruses. In addition, due to the growing incidence of obesity in Western society, there is anticipation that there will be a growing population with HCC due to non-alcoholic fatty liver disease. Due to the growing frequency of this disease, screening is recommended using ultrasound with further imaging using magnetic resonance imaging and multi-detector computed tomography used for further characterization of masses. Great advances have been made to help with the early diagnosis of small lesions leading to potential curative resection or transplantation. Resection and transplantation maybe used in a variety of patients that are carefully selected based on underlying liver disease. Using certain guidelines and clinical acumen patients may have good outcomes with either resection or transplantation however many patients are inoperable at time of presentation. Fortunately, the use of new locoregional therapies has made down staging patients a potential option making them potential surgical candidates. Despite a growing population with HCC, new advances in viral therapies, chemotherapeutics, and an expanding population of surgical and transplant candidates might all contribute to improved long-term survival of these patients. PMID:26019732

  14. Laryngeal Paralyses: Theoretical Considerations and Effects on Laryngeal Vibration.

    ERIC Educational Resources Information Center

    Smith, Marshall E.; And Others

    1992-01-01

    A theoretical four-mass model of the larynx was developed to simulate laryngeal biomechanical behavior and used to evaluate states of asymmetric laryngeal vibration. Simulations of laryngeal paralyses were compared with data on glottal vibration in observed laryngeal function. (Author/JDD)

  15. Docetaxel as neoadjuvant chemotherapy in patients with advanced cervical carcinoma.

    PubMed

    Vallejo, Carlos T; Machiavelli, Mario R; Pérez, Juan E; Romero, Alberto O; Bologna, Fabrina; Vicente, Hernán; Lacava, Juan A; Ortiz, Eduardo H; Cubero, Alberto; Focaccia, Guillermo; Suttora, Guillermo; Scenna, Mirna; Boughen, José M; Leone, Bernardo A

    2003-10-01

    The purpose of this study was to evaluate the efficacy and toxicity of docetaxel as single-agent neoadjuvant chemotherapy in locoregionally advanced cervical carcinoma. Between April 1998 and August 2000, 38 untreated patients with International Federation of Gynecology and Obstetrics stages IIB to IVA were entered onto this study. The median age was 44 years (range: 25-66 years). Stages: IIB 22 patients, IIIB 15 patients, and IVA 1 pt. Treatment consisted of docetaxel 100 mg/m2 IV infusion during 1 hour. Standard premedication with dexamethasone, diphenhydramine, and ranitidine was used. Cycles were repeated every 3 weeks for three courses, followed by radical surgery when it was judged appropriate, or definitive radiotherapy. Both staging and response assessment were performed by a multidisciplinary team. 106 cycles of therapy were administered; all patients were evaluable for TX, whereas 35 were evaluable for response (3 patients refused further treatment after the first cycle of therapy). Complete response (CR): 1 patient (3%); partial response: 11 patients (31%), for an overall objective response rate of 34% (95% CI: 15-53%); no change (NC): 16 patients (46%); and progressive disease: 7 patients (20%). Six patients (17%) underwent surgery and a pathologic CR was confirmed in 1 of them. The median time to treatment failure and the median survival have not been reached yet. The limiting toxicity was leukopenia in 25 patients (69%) (G1-G2: 14 patients, G3: 10 patients, and G4: 1 patient). Neutropenia: 28 patients (78%) (G1-G2: 10 patients, G3: 8 and G4: 10). Myalgias: 17 patients (47%) (G1-G2: 15 patients and G3: 2 patients). Emesis: 21 patients (55%) (G1-G2: 19 patients and G3: 2 patients). Alopecia G3: 13 patients (36%); rash cutaneous 26 patients (68%) (G1-G2: 22 patients and G3: 4 patients). There were no hypersensitivity reactions or fluid-retention syndrome. The received dose intensity was 91% of that projected. Docetaxel is an active drug against advanced

  16. Laryngeal cryptococcus: a rare cause of hoarseness in renal allograft recipient

    PubMed Central

    Sandhu, Jashan; Sandhu, Jasvinder Singh; Kaur Puri, Harpreet; Munjal, Manish

    2017-01-01

    Cryptococcosis commonly involves central nervous system and lungs in organ transplant recipients. Isolated laryngeal infection is extremely rare. We report a rare case of cryptococcus in a renal allograft recipient that clinically presented with hoarseness of voice and mimicked laryngeal carcinoma on examination. PMID:28197527

  17. Fisetin inhibits laryngeal carcinoma through regulation of AKT/NF-κB/mTOR and ERK1/2 signaling pathways.

    PubMed

    Zhang, Xi-Jun; Jia, Shen-Shan

    2016-10-01

    Targeting cancer cells is crucial for improving the efficiency of laryngeal cancer treatment. However, the signaling pathway and therapeutic strategy, related to the tumor, still need further research. Dietary flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) found in many fruits and vegetables has been shown in preclinical studies to inhibit cancer growth through regulating cell cycle, apoptosis, angiogenesis, invasion and metastasis without causing any toxicity to normal cells. PI3K/AKT and ERK1/2 have been known as essential signaling pathways to modulate cell proliferation, apoptosis as well as autophagy via mTOR, Caspase-3 and NF-κB signals. In our study, flow cytometry and western blot assays suggested that apoptosis was induced by fisetin administration, promoting Caspase-3 expressions by regulating PI3K/AKT/NF-κB. Additionally, fisetin suppressed TU212 cells proliferation, which was linked with ERK1/2 inactivation. Further, the activation of PI3K/AKT-regulated mTOR was inhibited by fisetin, leading to transcription suppression and proliferation inhibition of TU212 cells. In vivo studies also showed that the tumor volume and weight of nude mice were reduced for fisetin use with KI-67 decrease and LC3II increase in tumor tissue samples. Together, our data indicated that fisetin had a potential role in controlling human laryngeal cancer through inhibiting tumor cell proliferation, inducing apoptosis and autophagy regulated by ERK1/2 and AKT/NF-κB/mTOR signaling pathways, which might provide a therapeutic strategy for laryngeal cancer inhibition in future.

  18. Lenvatinib in Advanced, Radioactive Iodine-Refractory, Differentiated Thyroid Carcinoma.

    PubMed

    Yeung, Kay T; Cohen, Ezra E W

    2015-12-15

    Management options are limited for patients with radioactive iodine refractory, locally advanced, or metastatic differentiated thyroid carcinoma. Prior to 2015, sorafenib, a multitargeted tyrosine kinase inhibitor, was the only approved treatment and was associated with a median progression-free survival (PFS) of 11 months and overall response rate (ORR) of 12% in a phase III trial. Lenvatinib, a multikinase inhibitor with high potency against VEGFR and FGFR demonstrated encouraging results in phase II trials. Recently, the pivotal SELECT trial provided the basis for the FDA approval of lenvatinib as a second targeted therapy for these patients. Median PFS of 18.3 months in the lenvatinib group was significantly improved from 3.6 months in the placebo group, with an HR of 0.21 (95% confidence interval, 0.4-0.31; P < 0.0001). ORR was also significantly increased in the lenvatinib arm (64.7%) compared with placebo (1.5%). In this article, we will review the molecular mechanisms of lenvatinib, the data from preclinical studies to the recent phase III clinical trial, and the biomarkers being studied to further guide patient selection and predict treatment response.

  19. Strong Expression of Chemokine Receptor CXCR4 by Renal Cell Carcinoma Correlates with Advanced Disease

    PubMed Central

    Wehler, Thomas C.; Graf, Claudine; Biesterfeld, Stefan; Brenner, Walburgis; Schadt, Jörg; Gockel, Ines; Berger, Martin R.; Thüroff, Joachim W.; Galle, Peter R.; Moehler, Markus; Schimanski, Carl C.

    2008-01-01

    Diverse chemokines and their receptors have been associated with tumor growth, tumor dissemination, and local immune escape. In different tumor entities, the level of chemokine receptor CXCR4 expression has been linked with tumor progression and decreased survival. The aim of this study was to evaluate the influence of CXCR4 expression on the progression of human renal cell carcinoma. CXCR4 expression of renal cell carcinoma was assessed by immunohistochemistry in 113 patients. Intensity of CXCR4 expression was correlated with both tumor and patient characteristics. Human renal cell carcinoma revealed variable intensities of CXCR4 expression. Strong CXCR4 expression of renal cell carcinoma was significantly associated with advanced T-status (P = .039), tumor dedifferentiation (P = .0005), and low hemoglobin (P = .039). In summary, strong CXCR4 expression was significantly associated with advanced dedifferentiated renal cell carcinoma. PMID:19266088

  20. Long-term follow-up after transoral laser microsurgery and adjuvant radiotherapy for advanced recurrent squamous cell carcinoma of the head and neck

    SciTech Connect

    Christiansen, Hans . E-mail: hchrist@gwdg.de; Hermann, Robert Michael; Martin, Alexios; Florez, Rodrigo; Kahler, Elke; Nitsche, Mirko; Hille, Andrea; Steiner, Wolfgang; Hess, Clemens F.; Pradier, Olivier

    2006-07-15

    Purpose: The aim of this study was to evaluate the efficacy of adjuvant radiotherapy after transoral laser microsurgery for advanced recurrent head-and-neck squamous cell carcinoma (HNSCC). Patients and Methods: Between 1988 and 2000, 37 patients with advanced local recurrences (23 local and 14 locoregional recurrences) of HNSCC without distant metastases were treated in curative intent with organ-preserving transoral laser microsurgery and adjuvant radiotherapy (before 1994 split-course radiotherapy with carboplatinum, after 1994 conventional radiotherapy). Initial therapy of the primary (8.1% oral cavity, 35.1% oropharynx, 13.5% hypopharynx, and 43.3% larynx) before relapse was organ-preserving transoral laser microsurgery without any adjuvant therapy. Results: After a median follow-up of 124 months, the 5-year overall survival rate was 21.3%, the loco-regional control rate 48.3%, respectively. In multivariate analysis, stage of original primary tumor (Stage I/II vs. Stage III/IV), and patient age (<58 years vs. {>=}58 years) showed statistically significant impact on prognosis. In laryngeal cancer, larynx preservation rate after treatment for recurrent tumor was 50% during follow-up. Conclusion: Our data show that organ-preserving transoral laser microsurgery followed by adjuvant radiotherapy is a curative option for patients who have advanced recurrence after transoral laser surgery and is an alternative to radical treatment.

  1. Diversified expression of aryl hydrocarbon receptor dependent genes in human laryngeal squamous cell carcinoma cell lines treated with β-naphthoflavone.

    PubMed

    Brauze, Damian; Fijalkiewicz, Katarzyna; Szaumkessel, Marcin; Kiwerska, Katarzyna; Bednarek, Kinga; Rydzanicz, Malgorzata; Richter, Julia; Grenman, Reidar; Jarmuz-Szymczak, Malgorzata

    2014-11-18

    The aryl hydrocarbon receptor (AhR) mediates a variety of biological responses to ubiquitous environmental pollutants. In this study the effect of administration of β-naphthoflavone (BNF), potent AhR ligand, on the expression of AhR, AhRR, CYP1A1, CYP1A2, CYP1B1, NQO1, GSTA1, ALDH3A1 and UGT1A genes encoding the enzymes controlled by AhR were examined in thirteen laryngeal tumor cell lines and in HepaRG cell line. The analyzed cell lines were derived from patients with squamous laryngeal cancer, with history of cigarette smoking and without signs of human papillomavirus types 16 and 18 infection in investigated cells. Quantitative real-time RT-PCR analysis revealed huge interindividual differences in expression of genes from AhR regulatory network. Our results strongly suggest predominant effect of DNA methylation on induction of CYP1A1 expression by AhR ligands as well. Our results indicate that differentiated HepaRG cell line appeared to be very good substitute for human liver in studies on xenobiotic metabolism by AhR regulated enzymes.

  2. Cyberknife treatment for advanced or terminal stage hepatocellular carcinoma

    PubMed Central

    Kato, Hiroyuki; Yoshida, Hideo; Taniguch, Hiroyoshi; Nomura, Ryutaro; Sato, Kengo; Suzuki, Ichiro; Nakata, Ryo

    2015-01-01

    AIM: To investigate the safety and efficacy of the Cyberknife treatment for patients with advanced or terminal stage hepatocellular carcinoma (HCC). METHODS: Patients with HCC with extrahepatic metastasis or vascular or bile duct invasion were enrolled between May 2011 and June 2015. The Cyberknife was used to treat each lesion. Treatment response scores were based on Response Evaluation Criteria in Solid Tumors v1.1. The trends of tumor markers, including alpha fetoprotein (AFP) and proteins induced by vitamin K absence II (PIVKA II) were assessed. Prognostic factors for tumor response and tumor markers were evaluated with Fisher’s exact test and a logistic regression model. Survival was evaluated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Sixty-five patients with 95 lesions were enrolled. Based on the Barcelona Clinic Liver Cancer classification, all patients were either in the advanced or terminal stage of the disease. The target lesions were as follows: 52 were bone metastasis; 9, lung metastasis; 7, brain metastasis; 9, portal vein invasion; 4, hepatic vein invasion; 4, bile duct invasion; and 10 other lesion types. The response rate and disease control rate were 34% and 53%, respectively. None of the clinical factors correlated significantly with tumor response. Fiducial marker implantation was associated with better control of both AFP (HR = 0.152; 95%CI: 0.026-0.887; P = 0.036) and PIVKA II (HR = 0.035; 95%CI: 0.003-0.342; P = 0.004). The median survival time was 9 mo (95%CI: 5-15 mo). Terminal stage disease (HR = 9.809; 95%CI: 2.589-37.17, P < 0.001) and an AFP of more than 400 ng/mL (HR = 2.548; 95%CI: 1.070-6.068, P = 0.035) were associated with worse survival. A radiation dose higher than 30 Gy (HR = 0.274; 95%CI: 0.093-0.7541, P = 0.012) was associated with better survival. In the 52 cases of bone metastasis, 36 patients (69%) achieved pain relief. One patient had cerebral

  3. MLN0264 in Previously Treated Asian Participants With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C

    ClinicalTrials.gov

    2017-02-08

    Advanced Gastrointestinal Carcinoma; Gastroesophageal Junction Adenocarcinoma; Recurrent Gastric Adenocarcinoma; Recurrent Gastroesophageal Junction Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Recurrent Gastrointestinal Carcinoma

  4. A Challenging Surgical Approach to Locally Advanced Primary Urethral Carcinoma

    PubMed Central

    Lucarelli, Giuseppe; Spilotros, Marco; Vavallo, Antonio; Palazzo, Silvano; Miacola, Carlos; Forte, Saverio; Matera, Matteo; Campagna, Marcello; Colamonico, Ottavio; Schiralli, Francesco; Sebastiani, Francesco; Di Cosmo, Federica; Bettocchi, Carlo; Di Lorenzo, Giuseppe; Buonerba, Carlo; Vincenti, Leonardo; Ludovico, Giuseppe; Ditonno, Pasquale; Battaglia, Michele

    2016-01-01

    Abstract Primary urethral carcinoma (PUC) is a rare and aggressive cancer, often underdetected and consequently unsatisfactorily treated. We report a case of advanced PUC, surgically treated with combined approaches. A 47-year-old man underwent transurethral resection of a urethral lesion with histological evidence of a poorly differentiated squamous cancer of the bulbomembranous urethra. Computed tomography (CT) and bone scans excluded metastatic spread of the disease but showed involvement of both corpora cavernosa (cT3N0M0). A radical surgical approach was advised, but the patient refused this and opted for chemotherapy. After 17 months the patient was referred to our department due to the evidence of a fistula in the scrotal area. CT scan showed bilateral metastatic disease in the inguinal, external iliac, and obturator lymph nodes as well as the involvement of both corpora cavernosa. Additionally, a fistula originating from the right corpus cavernosum extended to the scrotal skin. At this stage, the patient accepted the surgical treatment, consisting of different phases. Phase I: Radical extraperitoneal cystoprostatectomy with iliac-obturator lymph nodes dissection. Phase II: Creation of a urinary diversion through a Bricker ileal conduit. Phase III: Repositioning of the patient in lithotomic position for an overturned Y skin incision, total penectomy, fistula excision, and “en bloc” removal of surgical specimens including the bladder, through the perineal breach. Phase IV: Right inguinal lymphadenectomy. The procedure lasted 9-and-a-half hours, was complication-free, and intraoperative blood loss was 600 mL. The patient was discharged 8 days after surgery. Pathological examination documented a T4N2M0 tumor. The clinical situation was stable during the first 3 months postoperatively but then metastatic spread occurred, not responsive to adjuvant chemotherapy, which led to the patient's death 6 months after surgery. Patients with advanced stage tumors of

  5. Lenalidomide and Cetuximab in Treating Patients With Advanced Colorectal Cancer or Head and Neck Cancer

    ClinicalTrials.gov

    2017-01-31

    Recurrent Colon Carcinoma; Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Rectal Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IVA Colon Cancer; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVA Major Salivary Gland Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Verrucous Carcinoma; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVB Major Salivary Gland Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oral Cavity Verrucous Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVB Rectal Cancer; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Verrucous Carcinoma; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVC Major Salivary Gland Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Oral Cavity Verrucous Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma; Tongue Carcinoma; Untreated Metastatic Squamous Cell Carcinoma to Neck

  6. Prometheus' spirit: quality survival in advanced hepatocellular carcinoma after gemcitabine and cisplatin-based chemotherapy.

    PubMed

    Doval, D C; Pande, S B; Sharma, J B; Pavithran, K; Jena, A; Vaid, A K

    2008-10-01

    In advanced virus-induced hepatocellular carcinoma (HCC) associated with cirrhosis, the average survival is four months. We report a 56-year-old man with a large-volume advanced HCC, in whom gemcitabine and cisplatin-based chemotherapy resulted in near-complete regression, and quality survival of 24 months.

  7. Recent advances in the management of renal cell carcinoma

    PubMed Central

    Molina, Ana M.; Nanus, David M.

    2016-01-01

    Therapeutic options for patients with metastatic renal cell carcinoma have significantly improved over the past few years with the recent approval of two new agents resulting in prolonged progression-free and overall survival. PMID:27019698

  8. Imaging of laryngeal trauma.

    PubMed

    Becker, Minerva; Leuchter, Igor; Platon, Alexandra; Becker, Christoph D; Dulguerov, Pavel; Varoquaux, Arthur

    2014-01-01

    External laryngeal trauma is a rare but potentially life-threatening situation in the acutely injured patient. Trauma mechanism and magnitude, maximum focus of the applied force, and patient related factors, such as age and ossification of the laryngeal cartilages influence the spectrum of observed injuries. Their correct diagnosis and prompt management are paramount in order to avoid patient death or long-term impairment of breathing, swallowing and speaking. The current review provides a comprehensive approach to the radiologic interpretation of imaging studies performed in patients with suspected laryngeal injury. It describes the key anatomic structures that are relevant in laryngeal trauma and discusses the clinical role of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) in the acute emergency situation. The added value of two-dimensional multiplanar reconstructions (2D MPR), three-dimensional volume rendering (3D VR) and virtual endoscopy (VE) for the non-invasive evaluation of laryngeal injuries and for treatment planning is discussed. The clinical presentation, biomechanics of injury, diagnostic pitfalls and pearls, common and uncommon findings are reviewed with emphasis of fracture patterns, involvement of laryngeal joints, intra- and extralaryngeal soft tissue injuries, and complications seen in the acute emergency situation. The radiologic appearance of common and less common long-term sequelae, as well as treatment options are equally addressed.

  9. Treatment of advanced renal cell carcinoma: recent advances and current role of immunotherapy, surgery, and cryotherapy.

    PubMed

    Mennitto, Alessia; Verzoni, Elena; Calareso, Giuseppina; Spreafico, Carlo; Procopio, Giuseppe

    2017-01-21

    Renal cell carcinoma (RCC) is the 10th most common cancer in Western countries. The prognosis of metastatic disease is unfavorable but may be different according to several risk factors, such as histology and clinical features (Karnofsky performance status, time from nephrectomy, hemoglobin level, neutrophils and thrombocytes count, lactate dehydrogenase and calcium serum value, sites and extension of the disease). In this review, we focused on some recent developments in the use of immunotherapy, surgery and cryotherapy in the treatment of advanced disease. While RCC is unresponsive to chemotherapy, recent advances have emerged with the development of targeted agents and innovative immunotherapy-based treatments. Surgical resection remains the standard of care for patients with small renal lesions but in patients with significant comorbidities ablative therapies such as cryoablation and radiofrequency ablation may lead to local cancer control and avoid surgical complications and morbidity. In the setting of metastatic RCC, radical nephrectomy, or cytoreductive nephrectomy, is considered a palliative surgery, usually part of a multimodality treatment approach that requires systemic treatments.

  10. Laryngeal cancer in acquired immunodeficiency syndrome.

    PubMed

    Shushan, S; Cinamon, U; Levy, D; Sokolov, M; Roth, Y

    2009-08-01

    With improved survival, more AIDS patients, especially heavy smokers and alcohol abusers, may be confronted with laryngeal squamous cell carcinoma. Since curative treatment may require aggressive combined therapy, these patients, often suffering from immunosupression and poor general condition, present unique therapeutic challenges. The objective of the study was to describe treatment dilemmas. This case report presents a detailed description of an AIDS patient with carcinoma of the larynx. A patient with T3N0M0 laryngeal carcinoma and AIDS underwent tracheotomy and biopsy, followed by severe neck and pulmonary infection. After convalescence, radiotherapy was administered, with no evidence of a disease during a 3.5-year follow-up. During his remaining life, the patient developed severe psychoaffective disorder, his immune state deteriorated until he demised from sepsis. In conclusion, patients with HIV infection, especially having a history of tobacco or alcohol abuse, should be carefully examined for head and neck carcinoma that is likely to be more aggressive. Following surgery, AIDS patients may have worse wound healing and a greater tendency to contract infections. Radiotherapy and especially chemotherapy may cause life-threatening complications. Although early detection may increase survival, curative treatment should involve many disciplines and extra caution.

  11. Long-term outcomes of type I thyroplasty with silicone implantation: Assessment of excised laryngeal tissue from a patient with secondary hypopharyngeal carcinoma.

    PubMed

    Adachi, Kazuo; Umezaki, Toshiro; Nishijima, Toshimitsu; Yamamoto, Hidetaka; Oda, Yoshinao

    2017-04-01

    Here we describe the long-term outcomes of type I thyroplasty (TP-I) with silicone block implantation through histopathological assessments in a male patient who underwent pharyngolaryngectomy for secondary hypopharyngeal carcinoma 7 years after silicone implantation. A 66-year-old man presented with esophageal carcinoma and underwent subtotal esophagotomy. Subsequently, his left vocal fold exhibited fixation in a paramedian position, and he underwent TP-I with silicone block implantation 2 years after the primary esophageal surgery. His voice quality improved; however, he developed glottic carcinoma in the right vocal fold 6 months after TP-I and underwent laser cordectomy. Glottic carcinoma recurred 21 months later, and he underwent laser cordectomy again. Five years after the second laser surgery, he underwent pharyngolaryngectomy and neck dissection for hypopharyngeal carcinoma detected in the right pyriform sinus. We histopathologically examined a horizontal section of the resected larynx to assess silicone implant-related changes. Although migration of the silicone implant was not observed, a very mild foreign body reaction occurred around the implant. The patient is currently in remission. Our findings suggest that silicone implants are suitable for TP-I due to their remarkable affinity for human tissue and the low risk of a tissue reaction.

  12. Optical diagnosis of mammary ductal carcinoma using advanced optical technology

    NASA Astrophysics Data System (ADS)

    Wu, Yan; Fu, Fangmeng; Lian, Yuane; Nie, Yuting; Zhuo, Shuangmu; Wang, Chuan; Chen, Jianxin

    2015-02-01

    Clinical imaging techniques for diagnosing breast cancer mainly include X-ray mammography, ultrasound, and magnetic resonance imaging (MRI), which have respective drawbacks. Multiphoton microscopy (MPM) has become a potentially attractive optical technique to bridge the current gap in clinical utility. In this paper, MPM was used to image normal and ductal cancerous breast tissues, based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). Our results showed that MPM has the ability to exhibit the microstructure of normal breast tissue, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) lesions at the molecular level comparable to histopathology. These findings indicate that, with integration of MPM into currently accepted clinical imaging system, it has the potential to make a real-time histological diagnosis of mammary ductal carcinoma in vivo.

  13. Chemotherapy With or Without Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2017-04-12

    Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Major Salivary Gland Cancer AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Major Salivary Gland Cancer AJCC v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Verrucous Carcinoma; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Major Salivary Gland Cancer AJCC v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oral Cavity Verrucous Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Verrucous Carcinoma; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Major Salivary Gland Cancer AJCC v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Oral Cavity Verrucous Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7; Tongue Carcinoma; Untreated Metastatic Squamous Cell Carcinoma to Neck With Occult Primary

  14. Hedgehog pathway inhibition in advanced basal cell carcinoma: latest evidence and clinical usefulness

    PubMed Central

    Silapunt, Sirunya; Chen, Leon; Migden, Michael R.

    2016-01-01

    Treatment of locally advanced basal cell carcinomas (laBCCs) with large, aggressive, destructive, and disfiguring tumors, or metastatic disease is challenging. Dysregulation of the Hedgehog (Hh) signaling pathway has been identified in the vast majority of basal cell carcinomas (BCCs). There are two United States Food and Drug Administration (US FDA)-approved Hh pathway inhibitors (HPIs) that exhibit antitumor activity in advanced BCC with an acceptable safety profile. Common adverse effects include muscle spasms, dysgeusia, alopecia, fatigue, nausea and weight loss. PMID:27583029

  15. Usefulness and efficiency of formalin-fixed paraffin-embedded specimens from laryngeal squamous cell carcinoma in HPV detection by IHC and PCR/DEIA.

    PubMed

    Morshed, Kamal; Polz-Dacewicz, Małgorzata; Szymański, Marcin; Smoleń, Agata

    2010-09-30

    The use of formalin-fixed paraffin-embedded (FFPE) tissues for HPV DNA detection by PCR from biopsy materials is not entirely clear in retrospective studies. The aim of our study was to evaluate the usefulness and efficiency of FFPE tissues from laryngeal cancer (LSCC) in HPV detection by immunohistochemistry reaction (IHC) and PCR-DNA enzyme immunoassay method (PCR/DEIA) and to compare with HPV detection from DFT. HPV-DNA was amplified from 54 FFPE tissues from LSCC specimens by the short PCR fragment (SPF10) primer set using PCR/DNA method and monoclonal anti Human Papillomavirus antibodies in IHC. In the same patients 54 specimens were collected and immediately deep-frozen and stored at (-70°C) to (-80°C). All the FFPE and deep-frozen tissue (DFT) specimens were positive for β-globin amplification. HPV was detected by two methods (SPF10 PCR/DEIA and IHC) in 14 (25.92%) out of 54 specimens from FFPE. Significant differences were found between the HPV detection using PCR/DEIA method and IHC method in FFPE tissues. The comparative analysis of the 54 samples after assuming PCR method in FFPE tissues showed accuracy of 92.6%, sensitivity of 90.5% and specificity of 93.9%. The FFPE tissues method has high sensitivity, specificity and accuracy when used to detect HPV DNA by PCR reaction and it is comparable to DFT results. DNA quality of FFPE samples is adequate and it can be used in HPV-DNA detection and in retrospective studies on LSCC.

  16. Vismodegib: a guide to its use in locally advanced or metastatic basal cell carcinoma.

    PubMed

    Lyseng-Williamson, Katherine A; Keating, Gillian M

    2013-02-01

    Vismodegib is the first Hedgehog pathway inhibitor to be approved in the USA, where it is indicated for the treatment of adults with metastatic basal cell carcinoma (BCC), or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation. In an ongoing, noncomparative, phase II trial, oral vismodegib was effective in and had an acceptable tolerability profile in the treatment of patients with locally advanced or metastatic BCC.

  17. A Novel Inflammation- and Nutrition-Based Prognostic System for Patients with Laryngeal Squamous Cell Carcinoma: Combination of Red Blood Cell Distribution Width and Body Mass Index (COR-BMI)

    PubMed Central

    Chen, Shiqi; Yang, Ankui; Zhang, Quan

    2016-01-01

    Background Laryngeal squamous cell carcinoma (LSCC) is a head and neck cancer type. In this study, we introduced a novel inflammation- and nutrition-based prognostic system, referred to as COR-BMI (Combination of red blood cell distribution width and body mass index), for LSCC patients. Methods A total of 807 LSCC patients (784 male and 23 female, 22–87 y of age) who underwent surgery were enrolled in this retrospective cohort study. The patients were stratified by COR-BMI into three groups: COR-BMI (0) (RDW ≤ 13.1 and BMI ≥ 25); COR-BMI (1) (RDW ≤ 13.1 and BMI < 18.5 or 18.5 ≤ BMI < 25; RDW > 13.1 and 18.5 ≤ BMI < 25 or BMI ≥ 25); or COR-BMI (2) (RDW > 13.1 and BMI < 18.5). Cox regression models were used to investigate the association between COR-BMI and cancer-specific survival (CSS) rate among LSCC patients. Results The 5-y, 10-y, and 15-y CSS rates were 71.6%, 60.1%, and 55.4%, respectively. There were significant differences among the COR-BMI groups in age (< 60 versus ≥ 60 y; P = 0.005) and T stage (T1, T2, T3, or T4; P = 0.013). Based on the results, COR-BMI (1 versus 0: HR = 1.76; 95% CI = 0.98–3.15; 2 versus 0: HR = 2.91; 95% CI = 1.53–5.54, P = 0.001) was a significant independent predictor of CSS. Conclusion COR-BMI is a novel inflammation- and nutrition-based prognostic system, which could predict long-term survival in LSCC patients who underwent surgery. PMID:27658208

  18. Weekly Low-Dose Docetaxel-Based Chemoradiotherapy for Locally Advanced Oropharyngeal or Hypopharyngeal Carcinoma: A Retrospective, Single-Institution Study

    SciTech Connect

    Fukada, Junichi; Shigematsu, Naoyuki; Takeda, Atsuya; Ohashi, Toshio; Tomita, Toshiki; Shiotani, Akihiro; Kunieda, Etsuo; Kawaguchi, Osamu; Fujii, Masato; Kubo, Atsushi

    2010-02-01

    Purpose: To retrospectively assess the efficacy, toxicity, and prognostic factors of weekly low-dose docetaxel-based chemoradiotherapy for Stage III/IV oropharyngeal or hypopharyngeal carcinoma. Methods and Materials: Between 2001 and 2005, 72 consecutive patients with locally advanced oropharyngeal or hypopharyngeal carcinoma were treated with concurrent chemoradiotherapy (CCR; radiation at 60 Gy plus weekly docetaxel [10 mg/m{sup 2}]). Thirty of these patients also received neoadjuvant chemotherapy (NAC; docetaxel, cisplatin, and 5-fluorouracil) before concurrent chemoradiotherapy. Survival was calculated according to the Kaplan-Meier method. The prognostic factors were evaluated by univariate and multivariate analyses. Results: The median follow-up was 33 months, with overall survival, disease-free survival, and locoregional control rates at 3 years of 59%, 45%, and 52%, respectively. Thirty-six patients (50%) experienced more than one Grade 3 to 4 acute toxicity. Grade 3 mucositis occurred in 32 patients (44%), Grade 4 laryngeal edema in 1 (1%). Grade >=3 severe hematologic toxicity was observed in only 2 patients (3%). Grade 3 dysphagia occurred as a late complication in 2 patients (3%). Multivariate analyses identified age, T stage, hemoglobin level, and completion of weekly docetaxel, but not NAC, as significant factors determining disease-free survival. Conclusions: Docetaxel is an active agent used in both concurrent and sequential chemoradiotherapy regimens. Mucositis was the major acute toxicity, but this was well tolerated in most subjects. Anemia was the most significant prognostic factor determining survival. Further studies are warranted to investigate the optimal protocol for integrating docetaxel into first-line chemoradiotherapy regimens, as well as the potential additive impact of NAC.

  19. Managing patients receiving sorafenib for advanced hepatocellular carcinoma: a case study.

    PubMed

    Hull, Diana; Armstrong, Ceri

    2010-05-01

    Despite improvements in cytotoxic chemotherapy agents over the last 50 years, the outlook for patients with many of the most common solid tumours has remained poor. However, in recent years a number of targeted therapies have been licensed in the European Union for use in these cancer types. One such therapy, a tyrosine kinase inhibitor (sorafenib) is now used to treat patients with advanced hepatocellular carcinoma (HCC) and metastatic renal cell carcinoma. This article will explore the role of the oncology nurse in managing patients receiving sorafenib for advanced HCC. A brief overview of sorafenib as a current treatment approved for advanced HCC in the palliative setting is presented. This is followed by a case study-based discussion with particular reference to some of the key care coordination challenges facing the oncology nurse. The management of treatment-related adverse events and the importance of using a multidisciplinary team approach is also reviewed.

  20. Stereotactic Body Radiation Therapy in Treating Patients With High Risk Locally Advanced Head and Neck Cancer

    ClinicalTrials.gov

    2017-03-07

    Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Recurrent Oral Cavity Squamous Cell Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Stage II Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage III Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Hypopharyngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IVC Oral Cavity Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma

  1. Nab-paclitaxel as alternative treatment regimen in advanced cholangiocellular carcinoma

    PubMed Central

    Unseld, Matthias; Scheithauer, Werner; Weigl, Roman; Kornek, Gabriela; Stranzl, Nadja; Bianconi, Daniela; Brunauer, Georg; Steger, Guenther; Zielinski, Christoph C.

    2016-01-01

    Background Advanced cholangiocellular carcinoma has a poor prognosis with limited therapeutic options. Nab-paclitaxel has recently been described to be beneficial in metastatic pancreatic cancer improving overall and progression free survival (PFS). The potential antitumor activity of nab-paclitaxel in cholangiocellular carcinoma is hitherto unknown. Methods We retrospectively analyzed an institutional cholangiocellular carcinoma registry to determine the potential biological activity of nab-paclitaxel in advanced intrahepatic cholangiocellular carcinoma. Disease control rate (DCR), PFS and overall survival (OS) upon nab-paclitaxel based treatment, after failure of platinum-containing first-line combination chemotherapy, was assessed. Results Twelve patients were identified. Five of 12 patients (42%) received nab-paclitaxel as second line, and 7 patients (56%) as third-line treatment. The objective DCR with nab-paclitaxel was 83% (10/12 patients). One patient had a complete remission (CR), two patients had a partial remission (PR) and 7 patients had stable disease (SD). Disease was rated progressive in two patients. In all 12 patients receiving nab-paclitaxel the median time to progression was 6 months (range, 2.1–19.5 months). Median OS after initiation of nab-paclitaxel treatment was 9 months (2.1–28.4 months). The median time of survival after diagnosis of advanced disease was 21.5 months, whereby 3 patients were alive at the date of censoring (04/01/2015). Conclusions This is the first report suggesting substantial antitumor activity of nab-paclitaxel in advanced cholangiocellular carcinoma. In this small series, nab-paclitaxel based salvage chemotherapy appears to have a biological activity by controlling the disease and positively affecting survival. Randomized trials in this disease entity and subgroup of patients are urged. PMID:27563449

  2. Virilizing Adrenocortical Carcinoma Advancing to Central Precocious Puberty after Surgery

    PubMed Central

    Kim, Min Sun; Yang, Eu Jeen; Cho, Dong Hyu; Hwang, Pyung Han

    2015-01-01

    Adrenocortical carcinoma (ACC) in pediatric and adolescent patients is rare, and it is associated with various clinical symptoms. We introduce the case of an 8-year-old boy with ACC who presented with peripheral precocious puberty at his first visit. He displayed penis enlargement with pubic hair and facial acne. His serum adrenal androgen levels were elevated, and abdominal computed tomography revealed a right suprarenal mass. After complete surgical resection, the histological diagnosis was ACC. Two months after surgical removal of the mass, he subsequently developed central precocious puberty. He was treated with a gonadotropin-releasing hormone agonist to delay further pubertal progression. In patients with functioning ACC and surgical removal, clinical follow-up and hormonal marker examination for the secondary effects of excessive hormone secretion may be a useful option at least every 2 or 3 months after surgery. PMID:26019766

  3. Virilizing adrenocortical carcinoma advancing to central precocious puberty after surgery.

    PubMed

    Kim, Min Sun; Yang, Eu Jeen; Cho, Dong Hyu; Hwang, Pyung Han; Lee, Dae-Yeol

    2015-05-01

    Adrenocortical carcinoma (ACC) in pediatric and adolescent patients is rare, and it is associated with various clinical symptoms. We introduce the case of an 8-year-old boy with ACC who presented with peripheral precocious puberty at his first visit. He displayed penis enlargement with pubic hair and facial acne. His serum adrenal androgen levels were elevated, and abdominal computed tomography revealed a right suprarenal mass. After complete surgical resection, the histological diagnosis was ACC. Two months after surgical removal of the mass, he subsequently developed central precocious puberty. He was treated with a gonadotropin-releasing hormone agonist to delay further pubertal progression. In patients with functioning ACC and surgical removal, clinical follow-up and hormonal marker examination for the secondary effects of excessive hormone secretion may be a useful option at least every 2 or 3 months after surgery.

  4. Laryngitis: types, causes, and treatments.

    PubMed

    Dworkin, James Paul

    2008-04-01

    Inflammatory processes that affect the unified airway can concurrently exert significant influence on the larynx and surrounding mucosal surfaces. Laryngeal inflammation can be present secondary to direct effects of irritants, toxins, and antigens, but can also involve mechanical and infectious effects as well as secondary inflammation from behavioral mechanisms. This review examines laryngeal inflammation in the context of the unified airway and discusses pathophysiologic mechanisms that are central to the development of acute and chronic laryngitis.

  5. Laryngeal hypersensitivity in chronic cough.

    PubMed

    Hull, J H; Menon, A

    2015-12-01

    Patients with chronic cough often report symptoms arising in the throat, in response to non-specific stimuli. Accordingly, the concept of a 'hypersensitivity' of the larynx in chronic cough has evolved over the past ten years. Patients with cough and laryngeal hypersensitivity frequently report features that overlap other laryngeal dysfunction syndromes, including a tendency for the vocal cords to inappropriately adduct. The mechanisms underlying laryngeal hypersensitivity in chronic cough are currently unclear, however recent studies provide new clinical and physiological techniques to aid detection and monitoring of laryngeal hypersensitivity. This review provides an overview of the current state of knowledge in this field.

  6. Organ preservation surgery for laryngeal cancer

    PubMed Central

    Chawla, Sharad; Carney, Andrew Simon

    2009-01-01

    The principles of management of the laryngeal cancer have evolved over the recent past with emphasis on organ preservation. These developments have paralleled technological advancements as well as refinement in the surgical technique. The surgeons are able to maintain physiological functions of larynx namely speech, respiration and swallowing without compromising the loco-regional control of cancer in comparison to the more radical treatment modalities. A large number of organ preservation surgeries are available to the surgeon; however, careful assessment of the stage of the cancer and selection of the patient is paramount to a successful outcome. A comprehensive review of various organ preservation techniques in vogue for the management of laryngeal cancer is presented. PMID:19442314

  7. Advanced oxidation protein products and total antioxidant activity in colorectal carcinoma.

    PubMed

    Avinash, S S; Anitha, M; Vinodchandran; Rao, Gayathri M; Sudha, K; Shetty, Beena V

    2009-01-01

    The present study was designed to assess the levels of advanced oxidation protein products (AOPP) and percent hemolysis (that indirectly indicates the degree of membrane damage secondary to lipid peroxidation) in colorectal carcinoma. Glutathione (GSH), total thiols and albumin were measured to determine the antioxidant status. Considering the dynamic interaction between various antioxidants in the body, we measured the total antioxidant activity (AOA). Globulin was measured to assess the inflammatory response secondary to oxidative stress. Investigations were conducted in 45 cases of recently diagnosed primary colorectal adenocarcinoma. As control, 45 age and sex matched healthy persons were chosen. GSH was estimated in whole blood, percent hemolysis in RBC suspension and other parameters in plasma. We observed a very high significant increase (P<0.001) in AOPP, percent hemolysis and a highly significant increase (P<0.01) in globulin in colorectal carcinoma. We observed a very high significant decrease (P<0.001) in whole blood GSH, total thiols, albumin, AOA and a significant decrease (P<0.05) in plasma GSH in colorectal carcinoma. A very high significant negative correlation between percent hemolysis and AOA and an apparent negative correlation between total thiols and AOPP was seen in colorectal carcinoma. This demonstrated oxidative stress, decreased antioxidant status and secondary inflammatory response in colorectal carcinoma.

  8. Angiogenesis-Related Gene Expression Profile with Independent Prognostic Value in Advanced Ovarian Carcinoma

    PubMed Central

    Redondo, Andrés; Mariño-Enríquez, Adrián; Madero, Rosario; Espinosa, Enrique; Vara, Juan Ángel Fresno; Sánchez-Navarro, Iker; Hernández-Cortes, Ginés; Zamora, Pilar; Pérez-Fernández, Elia; Miguel-Martín, María; Suárez, Asunción; Palacios, José; González-Barón, Manuel; Hardisson, David

    2008-01-01

    Background Ovarian carcinoma is the most important cause of gynecological cancer-related mortality in Western societies. Despite the improved median overall survival in patients receiving chemotherapy regimens such as paclitaxel and carboplatin combination, relapse still occurs in most advanced diseased patients. Increased angiogenesis is associated with rapid recurrence and decreased survival in ovarian cancer. This study was planned to identify an angiogenesis-related gene expression profile with prognostic value in advanced ovarian carcinoma patients. Methodology/Principal Findings RNAs were collected from formalin-fixed paraffin-embedded samples of 61 patients with III/IV FIGO stage ovarian cancer who underwent surgical cytoreduction and received a carboplatin plus paclitaxel regimen. Expression levels of 82 angiogenesis related genes were measured by quantitative real-time polymerase chain reaction using TaqMan low-density arrays. A 34-gene-profile which was able to predict the overall survival of ovarian carcinoma patients was identified. After a leave-one-out cross validation, the profile distinguished two groups of patients with different outcomes. Median overall survival and progression-free survival for the high risk group was 28.3 and 15.0 months, respectively, and was not reached by patients in the low risk group at the end of follow-up. Moreover, the profile maintained an independent prognostic value in the multivariate analysis. The hazard ratio for death was 2.3 (95% CI, 1.5 to 3.2; p<0.001). Conclusions/Significance It is possible to generate a prognostic model for advanced ovarian carcinoma based on angiogenesis-related genes using formalin-fixed paraffin-embedded samples. The present results are consistent with the increasing weight of angiogenesis genes in the prognosis of ovarian carcinoma. PMID:19112514

  9. Effective multimodality treatment for advanced epidermoid carcinoma of the female genital tract

    SciTech Connect

    Kalra, J.; Cortes, E.; Chen, S.; Krumholz, B.; Rovinsky, J.J.; Molho, L.; Seltzer, V.; Papantoniou, P.; Lee, J.Y.

    1985-07-01

    Fifteen patients with advanced or recurrent squamous-cell carcinoma of the cervix, vulva, vagina, and urethra were treated with simultaneous combination chemotherapy (5-fluorouracil infusion and mitomycin C) and radiotherapy (3,000 rad for a period of three weeks). Three to four weeks after completion of radiotherapy, 13 of 15 patients achieved partial or complete tumor shrinkage. Nine of 15 patients are alive, eight of whom (at a median follow-up time of 24 months) have no evidence of disease. The longest survival time was 45 + months. There was minimal toxicity associated with this therapy. The results of this pilot study suggest that the simultaneous administration of radiation and chemotherapy is an effective method of treatment of advanced female genital tract carcinoma.

  10. [Laparoscopic abdominoperineal resection after preoperative chemoradiotherapy for advanced carcinoma associated with anal fistula].

    PubMed

    Morikawa, Takashi; Yamashita, Kimihiro; Sumi, Yasuo; Kanemitsu, Kiyonori; Yamamoto, Masashi; Kanaji, Shingo; Imanishi, Tatsuya; Nakamura, Tetsu; Suzuki, Satoshi; Tanaka, Kenichi; Kakeji, Yoshihiro

    2014-11-01

    The patient was a 71-year-old man who was diagnosed with anal fistula 50 years previously. He complained of mucous and bloody stools. He was diagnosed with a carcinoma associated with anal fistula after biopsy. Image examination showed that the tumor was filled with mucinous substances and that it had invaded the levator ani muscle, with left external iliac and left inguinal lymph node metastases. Therefore, preoperative chemoradiotherapy for locally advanced cancer was administered. After chemoradiotherapy, the tumor and metastatic lymph nodes reduced in size. We performed laparoscopic abdominoperineal resection. Histopathologically, the tumor was revealed as a mucinous adenocarcinoma, but no cancer cells were present on the surgical margin. This case suggested that preoperative chemoradiotherapy could be effective for locally advanced carcinoma associated with anal fistula.

  11. Combined chemotherapy and radiation therapy for advanced carcinoma of the cervix

    SciTech Connect

    Lipsztein, R.; Kredentser, D.; Dottino, P.; Goodman, H.M.; Dalton, J.F.; Bloomer, W.D.; Cohen, C.

    1987-12-01

    Ten patients with advanced squamous cell carcinoma of the uterine cervix received induction chemotherapy with cis-platinum, mitomycin-C, vincristine, and bleomycin (BOMP) over a 5 week period, followed by radiotherapy with concomitant weekly cisplatinum. Two patients were FIGO stage I-B barrel-shaped, five were stage II-B, and three were III-B. All patients responded to induction chemotherapy with five complete and five partial responses. At the completion of radiation therapy, nine patients had negative biopsies. One patient never reached a complete response and died of distant metastasis. Another underwent total exenteration for a central recurrence and was found to have microscopic paraaortic lymph node involvement. A third recurred in the parametrium. Two patients with barrel-shaped tumors underwent extrafascial hysterectomies; both had negative specimens and tolerated surgery well. Although follow-up is short, this new approach for advanced carcinoma of the cervix yielded excellent results and was well tolerated.

  12. Pilot study with pegylated liposomal doxorubicin for advanced or unresectable hepatocellular carcinoma

    PubMed Central

    Schmidinger, M; Wenzel, C; Locker, G J; Muehlbacher, F; Steininger, R; Gnant, M; Crevenna, R; Budinsky, A C

    2001-01-01

    We performed a pilot-study on pegylated liposomal doxorubicin (PLD) for advanced hepatocellular carcinoma. Seventeen patients received 40 mg/m2 PLD intravenously every 4 weeks. A clinical benefit response was achieved in 50% (complete remission 7%, minor remission 7%, stable disease 36%). Toxicities were moderate. In view of these encouraging findings, further studies appear warranted. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11747325

  13. Yttrium-90 Radioembolization of Hepatocellular Carcinoma-Performance, Technical Advances, and Future Concepts.

    PubMed

    Molvar, Christopher; Lewandowski, Robert

    2015-12-01

    Hepatocellular carcinoma (HCC) is a lethal tumor, claiming over half a million lives per year. Treatment of HCC is commonly performed without curative intent, and palliative options dominate, including catheter-based therapies, namely, transarterial chemoembolization and yttrium-90 ((90)Y) radioembolization. This review will showcase the performance of (90)Y radioembolization for the treatment of HCC, focusing on recent seminal data and technical advances. In particular, novel radioembolization treatment concepts are discussed and compared with conventional HCC therapy.

  14. Adjuvant radiotherapy for locally advanced upper tract urothelial carcinoma

    PubMed Central

    Huang, Yun-Ching; Chang, Ying-Hsu; Chiu, Kuo-Hsiung; Shindel, Alan W.; Lai, Chia-Hsuan

    2016-01-01

    There is relatively little literature on adjuvant radiotherapy after radical nephroureterectomy with bladder cuff excision (RNU) for patients with upper tract urothelial carcinoma (UTUC). This study was designed to determine the efficacy of adjuvant radiotherapy for patients with pT3N0M0 UTUC. We retrospectively reviewed 198 patients treated with RNU between December 2001 and January 2015. Postoperative radiotherapy was administered in 40 (20.2%) of patients. Patients who received radiotherapy were younger than those that did not (65.2 vs. 70.5 years, p = 0.023). With median follow up of 29.1 months, Kaplan-Meier analysis with the log-rank test demonstrated no significant differences between those omitting vs receiving adjuvant radiotherapy in regards to 2-year rates of overall survival (72.0% vs. 73.4%, p = 0.979), cancer-specific survival (73.2% vs. 75.3%, p = 0.844), and recurrence-free survival (61.2% vs. 66.3%, p = 0.742). However, in multivariable analysis with Cox regression, young age, absence of chronic kidney disease, negative lymphovascular invasion, negative surgical margin, and adjuvant chemotherapy were also associated with better cancer-specific survival. In conclusion, adjuvant radiotherapy did not offer any significant benefit in terms of overall, cancer-specific, and recurrence-free survivals in patients with pT3N0M0 UTUC after RNU. More effective systemic adjuvant chemotherapy is necessary to improve the outcome of these patients. PMID:27910890

  15. Phase II Study of Concurrent Chemoradiation in Combination With Erlotinib for Locally Advanced Esophageal Carcinoma

    SciTech Connect

    Li Gang; Hu Wei; Wang Jianhua; Deng Xia; Zhang Ping; Zhang Xuebang; Xie Congyin; Wu Shixiu

    2010-12-01

    Purpose: To investigate the feasibility and efficacy of concurrent chemoradiation in combination with erlotinib for locally advanced esophageal carcinoma. Methods and Materials: Twenty-four patients with locally advanced esophageal carcinoma were treated with concurrent chemoradiotherapy. A daily fraction of 2.0 Gy was prescribed to a total dose of 60 Gy over 6 weeks. Concurrent paclitaxel (135 mg/m{sup 2}, d{sub 1}) and cisplatin (20 mg/m{sup 2}, d{sub 1-3}) were administered on Day 1 and Day 29 of the radiotherapy. Erlotinib, an oral epidermal growth factor receptor-tyrosine kinase inhibitor, was taken by every patient at the dose of 150 mg daily during the chemoradiotherapy. Results: The median follow-up of the 24 patients was 18.6 months (range, 7.1-29.6 months). The 2-year overall survival, local-regional control, and relapse-free survival were 70.1% (95% CI, 50.4-90%), 87.5% (95% CI, 73.5-100%), and 57.4% (95% CI, 36.3-78.7%), respectively. During the chemoradiotheapy, the incidences of acute toxicities of Grade 3 or greater, such as leucopenia and thrombocytopenia, were 16.7 % (4/24) and 8.3% (2/24). Conclusions: Application of concurrent chemoradiotherapy in combination with erlotinib for locally advanced esophageal carcinoma yielded satisfactory 2-year overall survival and local-regional control. The toxicities were well tolerated.

  16. Phase 1 Study of Erlotinib Plus Radiation Therapy in Patients With Advanced Cutaneous Squamous Cell Carcinoma

    SciTech Connect

    Heath, C. Hope; Deep, Nicholas L.; Nabell, Lisle; Carroll, William R.; Desmond, Renee; Clemons, Lisa; Spencer, Sharon; Magnuson, J. Scott; Rosenthal, Eben L.

    2013-04-01

    Purpose: To assess the toxicity profile of erlotinib therapy combined with postoperative adjuvant radiation therapy in patients with advanced cutaneous squamous cell carcinoma. Methods and Materials: This was a single-arm, prospective, phase 1 open-label study of erlotinib with radiation therapy to treat 15 patients with advanced cutaneous head-and-neck squamous cell carcinoma. Toxicity data were summarized, and survival was analyzed with the Kaplan-Meier method. Results: The majority of patients were male (87%) and presented with T4 disease (93%). The most common toxicity attributed to erlotinib was a grade 2-3 dermatologic reaction occurring in 100% of the patients, followed by mucositis (87%). Diarrhea occurred in 20% of the patients. The 2-year recurrence rate was 26.7%, and mean time to cancer recurrence was 10.5 months. Two-year overall survival was 65%, and disease-free survival was 60%. Conclusions: Erlotinib and radiation therapy had an acceptable toxicity profile in patients with advanced cutaneous squamous cell carcinoma. The disease-free survival in this cohort was comparable to that in historical controls.

  17. Photodynamic therapy (PDT) in advanced inoperable bronchial carcinoma

    NASA Astrophysics Data System (ADS)

    Moghissi, Keyvan; Dixon, Kate; Stringer, Mark R.; Brown, Stanley B.

    1996-12-01

    Objective: To assess the efficacy of PDT to: Palliate symptoms, control disease and extend survival in patients with advanced inoperable cancer. Subject and Method: 55 Males and 23 females aged between 45-81 years (mean 66 years) with inoperable and advanced lung cancer with > 5O. obstructive lesions of the main, lobar or segmental bronchi. Patients had pre-treatment routine clinical radiological, functional and endoscopic assessment with proven histological diagnosis. Protocol of PDT was; Intravenous injection of 2 mg/Kg bodyweight Polyhaematoporphyrin (equivalent to Photofrin) or Photofrin followed 24-72 hours later by illumination of tumour using 630 nm light (Oxford Laser) delivered via an optical fibre with end diffuser. Treatments were carried out under general anaesthesia as a day case procedure. Patients were rebronchoscoped for debridement/retreatment 4-7 days later. Results: There was no treatment related mortality. Two patients developed mild photosensitivity reaction. All patients showed symptomatic improvement with good initial functional and radiological amelioration. Every patient responded to treatment. Seven patients had complete response and negative histology for 3-12 months. After the first treatment average Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1) improvement was 0.5 litres and 0.4 litres respectively. Twenty five percent of patients (nr 19) survived more than 2 years, 10'. (nr=8) between 1-2 years and the remaining 51 patients less than a year. Conclusion: PDT should be considered as a therapeutic modality for all stages of lung cancer and is an excellent treatment modality for palliation in advanced bronchial malignancies.

  18. Bilateral Blindness Following Chemoradiation for Locally Advanced Oropharyngeal Carcinoma

    PubMed Central

    Zeng, K. Liang; Kuruvilla, Sara; Sanatani, Michael

    2015-01-01

    Wernicke's encephalopathy is a life-threatening neurologic complication of thiamine deficiency. Though the presentation of symptoms can vary widely, the classical triad is founded on ophthalmoplegia, alteration of mental status, and gait disturbance. We describe a case of Wernicke's encephalopathy in an oncology patient shortly after concurrent 5-fluorouracil, carboplatin, and radiotherapy for locally advanced oropharyngeal cancer, presenting as complete bilateral blindness, ataxia, nystagmus, and confusion. Thiamine was given based on clinical suspicion and rapid improvement of clinical findings occurred. An MRI performed later supported the diagnosis of Wernicke's encephalopathy. A multifactorial etiology of thiamine deficiency from nutritional deficits and neurotoxic effects of chemotherapy are hypothesized. PMID:26623207

  19. Sonidegib, a novel smoothened inhibitor for the treatment of advanced basal cell carcinoma.

    PubMed

    Doan, Hung Q; Silapunt, Sirunya; Migden, Michael R

    2016-01-01

    Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. If left untreated, BCCs can become locally aggressive or even metastasize. Currently available treatments include local destruction, surgery, and radiation. Systemic options for advanced disease are limited. The Hedgehog (Hh) pathway is aberrantly activated in a majority of BCCs and in other cancers. Hh pathway inhibitors are targeted agents that inhibit the aberrant activation of the Hh pathway, with smoothened being a targeted component. Sonidegib is a novel smoothened inhibitor that was recently approved by the US Food and Drug Administration. This review focuses on BCC pathogenesis and the clinical efficacy of sonidegib for the treatment of advanced BCC.

  20. Sonidegib, a novel smoothened inhibitor for the treatment of advanced basal cell carcinoma

    PubMed Central

    Doan, Hung Q; Silapunt, Sirunya; Migden, Michael R

    2016-01-01

    Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. If left untreated, BCCs can become locally aggressive or even metastasize. Currently available treatments include local destruction, surgery, and radiation. Systemic options for advanced disease are limited. The Hedgehog (Hh) pathway is aberrantly activated in a majority of BCCs and in other cancers. Hh pathway inhibitors are targeted agents that inhibit the aberrant activation of the Hh pathway, with smoothened being a targeted component. Sonidegib is a novel smoothened inhibitor that was recently approved by the US Food and Drug Administration. This review focuses on BCC pathogenesis and the clinical efficacy of sonidegib for the treatment of advanced BCC. PMID:27695345

  1. Advanced carcinoma of the stomach treated with definitive proton therapy

    SciTech Connect

    Koyama, S.; Kawanishi, N.; Fukutomi, H.; Osuga, T.; Iijima, T.; Tsujii, H.; Kitagawa, T. )

    1990-04-01

    We report the case of a 72-yr-old man who suffered from severe chronic emphysema with poor pulmonary function, and who had advanced cancer of the stomach. Proton beam radiotherapy was applied to the lesion, since surgery was contraindicated. The total dose to the stomach lesion was 61 Gy in 7 wk. The tumor on the stomach regressed, with flattening of the round wall of the lesion. The reactive changes of the proton beam radiotherapy, based on the histopathological examination, revealed extensive tumor necrosis and sparing of vital architecture of normal tissue around the irradiated tumor tissue. Only small clusters of vital or devitalized tumor cells with less than approximately 5% of the whole tumor tissue remained after treatment. We suggest that a high dose of radiation delivered by well-defined proton field could result in an improved therapeutic outcome without undue risk of injury to normal tissue.

  2. Gemcitabine and oxaliplatin in advanced biliary tract carcinoma: a phase II study

    PubMed Central

    André, T; Reyes-Vidal, J M; Fartoux, L; Ross, P; Leslie, M; Rosmorduc, O; Clemens, M R; Louvet, C; Perez, N; Mehmud, F; Scheithauer, W

    2008-01-01

    Advanced biliary tract carcinomas (BTCs) are often diagnosed at an advanced/metastatic stage and have a poor prognosis. The combination of gemcitabine and oxaliplatin (GEMOX) has shown promising activity in this setting. This international phase II study evaluated the efficacy and safety of GEMOX as first-line therapy in patients with advanced BTCs. Eligible patients with previously untreated locally advanced or metastatic BTC received gemcitabine 1000 mg m−2 (day 1) and oxaliplatin 100 mg m−2 (day 2), every 2 weeks. Seventy patients were enroled; 72.9% had metastatic disease. Sixty-seven patients were treated. There were 10 confirmed partial responses (14.9%; 95% confidence interval (CI), 7.4–25.7%) in the treated population (RECIST). Twenty-four patients (35.8 %) had stable disease. The objective response rate was 20.5% in patients with non-gallbladder cancers (9/44 patients) and 4.3% in patients with gallbladder cancers (1/23). Median overall survival for the intent-to-treat population was 8.8 months (95% CI, 6.9–11.1%) and progression-free survival was 3.4 months (95% CI, 2.5–4.6%). Grade 3/4 toxicities included thrombocytopenia (14.9% of patients), alanine aminotransferase elevation (13.4%), anaemia (10.4%), neutropenia (11.9%) and pain (11.9%). In this study, GEMOX demonstrated activity in non-gallbladder carcinoma, but poor activity in gallbladder carcinoma. GEMOX is well tolerated in advanced BTCs. PMID:19238628

  3. High dose intensity combination chemotherapy for advanced epithelial ovarian carcinoma: results of a pilot study.

    PubMed Central

    Sweetenham, J. W.; McKendrick, J. J.; Jones, D. H.; Whitehouse, J. M.; Williams, C. J.

    1990-01-01

    Retrospective studies have recently demonstrated a significant correlation between dose intensity of chemotherapy and response rates and survival in various diseases including epithelial ovarian carcinoma. As part of a proposed randomised trial to assess the effect of dose intensity on outcome in ovarian carcinoma, a pilot study has been undertaken to determine the toxicity and efficacy of the high intensity therapy. Nineteen patients with advanced ovarian carcinoma received initial treatment with cisplatin 120 mg m-2 i.v. day 1, and cyclophosphamide 1,000 mg-2 i.v. day 1, given at 21-day intervals for six cycles. The average relative dose intensity of this therapy is 1.14 when compared with the CHAP regimen. Severe toxicity was experienced by most patients. The median received average relative dose intensity was 0.90, with only one patient receiving treatment to the proposed intensity. Randomised studies of the effect of dose intensity in ovarian carcinoma are essential, but an initial step must be to assess whether the proposed high dose treatment can be delivered. PMID:2155645

  4. Stereotactic ablative radiotherapy with CyberKnife for advanced thymic carcinoma: a case report.

    PubMed

    Fan, C Y; Huang, W Y; Jen, Y M; Lin, M J; Lin, K T

    2015-10-01

    Thymic carcinoma is a rare but lethal mediastinal cancer. The optimal treatment for advanced thymic carcinoma is not yet established. This report is the first known of stereotactic ablative radiotherapy (sabr) with CyberKnife (Accuray, Sunnyvale, CA, U.S.A.) as definitive therapy for thymic carcinoma. The patient, a 70-year-old woman with thymic carcinoma, invasion into neighboring organs, and pleural metastases-underwent CyberKnife sabr at 40 Gy in 5 fractions for two lesions, one in the thymus and one in the right paraspinal pleura. After 61 months of observation, a partial response was observed in the irradiated fields. However, disease progression in the non-irradiated pleura was noted. The patient underwent salvage CyberKnife sabr for the four initially nonirradiated pleural lesions. Computed tomography images obtained 10 months after the salvage therapy revealed a partial response. The patient is living, with progression-free irradiated lesions and no radiation-related toxicity. CyberKnife sabr is feasible for patients who are unable to undergo either surgery or conventionally fractionated radiation therapy.

  5. Role of HERG1 potassium channel in both malignant transformation and disease progression in head and neck carcinomas.

    PubMed

    Menéndez, Sofía T; Rodrigo, Juan P; Alvarez-Teijeiro, Saúl; Villaronga, M Ángeles; Allonca, Eva; Vallina, Aitana; Astudillo, Aurora; Barros, Francisco; Suárez, Carlos; García-Pedrero, Juana M

    2012-08-01

    Evidence indicates that human ether à-go-go-related gene 1 (HERG1) voltage-gated potassium channels could represent new valuable membrane therapeutic targets and diagnostic/prognostic biomarkers in various cancers. This study is the first to investigate the expression pattern of HERG1 potassium channel subunit in both primary tumors and precancerous lesions to establish its clinical and biological role during the development and progression of head and neck squamous cell carcinomas. HERG1 protein expression was evaluated by immunohistochemistry in paraffin-embedded tissue specimens from 133 patients with laryngeal/hypopharyngeal squamous cell carcinomas and 75 patients with laryngeal dysplasia, and correlated with clinical data. Our findings demonstrate that HERG1 is frequently aberrantly expressed in a high percentage of primary tumors (87%), whereas expression was negligible in both stromal cells and normal-adjacent epithelia. HERG1 expression increased during head and neck squamous cell carcinoma progression and was significantly associated with lymph node metastasis (P=0.04), advanced disease stages (P<0.001), regional tumor recurrence (P=0.004), distant metastasis (P=0.03) and reduced disease-specific survival (P=0.012, log-rank test). HERG1-positive expression was also detected in 31 (41%) of 75 laryngeal dysplasias. Interestingly, HERG1 expression increased with the grade of dysplasia; however, HERG1 expression but not histology correlated significantly with increased laryngeal cancer risk (P=0.007). In addition, functional studies in head and neck squamous cell carcinoma-derived cell lines further revealed that HERG1 expression promotes anchorage-dependent and -independent cell growth and invasive capability, although independently of its ion-conducting function. Our data demonstrate that HERG1 expression is a biologically and clinically relevant feature in head and neck squamous cell carcinoma progression and also during malignant transformation, and a

  6. Patient Reflections on Decision Making for Laryngeal Cancer Treatment.

    PubMed

    Shuman, Andrew G; Larkin, Knoll; Thomas, Dorothy; Palmer, Frank L; Fins, Joseph J; Baxi, Shrujal S; Lee, Nancy; Shah, Jatin P; Fagerlin, Angela; Patel, Snehal G

    2017-02-01

    Objective To describe the reflections of patients treated for laryngeal cancer with regard to treatment-related decision making. Study Design Cross-sectional survey-based pilot study. Setting Single-institution tertiary care cancer center. Subjects/Methods Adults with laryngeal carcinoma were eligible to participate (N = 57; 46% treated surgically, 54% nonsurgically). Validated surveys measuring decisional conflict and regret explored patients' reflections on their preferences and priorities regarding treatment-related decision making for laryngeal cancer and how patient-reported functional outcomes, professional referral patterns, and desired provider input influenced these reflections. Results When considering the level of involvement of surgeons, radiation oncologists, and medical oncologists in their care, patients were more likely to believe that the specialist whom they saw first was the most important factor in deciding how to treat their cancer (Fisher's exact, ~χ(2) = 16.2, df = 6, P = .02). Patients who were treated for laryngeal cancer who reported worse voice-related quality of life recalled more decisional conflict ( P = .01) and experienced more decisional regret ( P < .001). Of the patients for whom speech was a top priority prior to treatment, better voice-related quality of life overall scores were correlated with less decision regret about treatment decisions ( P < .02). Of the patients for whom eating and drinking were top priorities prior to treatment, better MD Anderson Dysphagia Inventory global scores were correlated with less decision regret about treatment decisions ( P < .002). Conclusion Patient priorities and attitudes, coupled with functional outcomes and professional referral patterns, influence how patients reflect on their choices regarding management of laryngeal cancer. Better understanding of these variables may assist in ensuring that patients' voices are integrated into individualized laryngeal cancer treatment planning.

  7. Immunotherapy for patients with advanced pancreatic carcinoma: a promising treatment

    PubMed Central

    Liu, Jing; Lian, Zhouyang; Liang, Long; Chen, Wenbo; Luo, Xiaoning; Pei, Shufang; Mo, Xiaokai; Zhang, Lu; Huang, Wenhui; Ouyang, Fusheng; Guo, Baoliang; Liang, Changhong; Zhang, Shuixing

    2017-01-01

    There are limited data on the safety and efficacy of immunotherapy for patients with advanced pancreatic cancer (APC). A meta-analysis of single-arm trials is proposed to assess the efficacy and safety of immunotherapy for APC. Eighteen relevant studies involving 527 patients were identified. The pooled disease control rate (DCR), overall survival (OS), progression free survival (PFS), and 1-year survival rate were estimated as 59.32%, 7.90 months, 4.25 months, and 30.12%, respectively. Subgroup analysis showed that the pooled OS, PFS, and 1-year survival rate were significantly higher for autologous activated lymphocyte therapy compared with peptide-based vaccine therapy (OS: 8.28 months vs. 7.40 months; PFS: 6.04 months vs. 3.86 months; 1-year survival rate: 37.17% vs. 19.74%). Another subgroup analysis demonstrated that the pooled endpoints were estimated as obviously higher for immunotherapy plus chemotherapy compared with immunotherapy alone (DCR: 62.51% vs. 47.63%; OS: 8.67 months vs. 4.91 months; PFS: 4.91 months vs. 3.34 months; 1-year survival rate: 32.32% vs. 21.43%). Of the included trials, seven trials reported no treatment related adverse events , five trials reported (16.6 3.9) % grade 3 adverse events and no grade 4 adverse events. In conclusion, immunotherapy is safe and effective in the treatment of APC. PMID:27992378

  8. Histoplasmosis laryngeal: report first case in Colombia.

    PubMed

    Moriones Robayo, Carlos Alberto; Guerra Ortiz, Claudia Patricia

    2014-01-01

    Laryngeal histoplasmosis is a fungal infection that is frequent in Colombia. Laryngeal histoplasmosis usually occurs in immunocompromised patients through the dissemination of the fungus from the lungs to other organs. Histoplasmosis isolated laryngeal (primary) is rare. If a patient presents with a history of immunosuppression by renal transplant, primary laryngeal histoplasmosis with supraglottic granulomatous inflammation that was treated with amphotericin B and Itraconazole, with complete resolution of laryngeal lesions.

  9. Third generation tyrosine kinase inhibitors and their development in advanced renal cell carcinoma.

    PubMed

    Bukowski, Ronald M

    2012-01-01

    Angiogenesis in general and the vascular endothelial growth factor (VEGF) signaling axis in particular is a validated target in renal cell carcinoma (RCC). Clear-cell carcinoma of the kidney is now recognized as a malignancy that is sensitive to inhibitors of the VEGF pathway. Treatment options for patients with metastatic renal cell carcinoma have evolved in dramatic fashion over the past 6 years, and a new paradigm has developed. The cytokines interferon-α and interleukin-2 were previously utilized for therapy, but since December 2005, six new agents have been approved in the United States for the treatment of advanced RCC. Two are tyrosine kinase inhibitors (TKI's) including sunitinib and recently pazopanib, and the multikinase inhibitor sorafenib. The current review examines the evolving data with the next generation of TKI's, axitinib and tivozanib being developed for the treatment of advanced RCC. These agents were synthesized to provide increased target specificity and enhanced target inhibition. The preclinical and clinical data are examined, an overview of the development of these TKI's is provided, and discussion plus speculation concerning their potential roles as RCC therapy is provided.

  10. Prognostic significance of lymphangiogenesis in pharyngolaryngeal carcinoma patients

    PubMed Central

    2010-01-01

    Background Lymphatic vessel spread is considered a major route for head and neck squamous cell carcinoma metastasis. Formation of new lymphatic vessels could facilitate the process, raising the malignant potential of these tumours. Recent identification of lymphatic markers allows the study of the lymphangiogenesis phenomenon. We searched for molecular events involved in the lymphangiogenic process that could have prognostic value in laryngeal/pharyngeal carcinoma patients. Methods 104 paraffin-embedded pharyngeal/laryngeal tumour samples were studied. Immunohistochemical analysis of podoplanin and double immunofluorescence analysis of Ki-67 and D2-40 were performed. Lymph vessel density (inside the tumour mass, at its periphery or considered as a whole) and the presence of tumour emboli inside lymphatics were recorded. The proliferative state of endothelial lymphatic cells was evaluated. Results Lymphatic vessels were detected inside the tumour mass (75%) and in the surrounding tissue (80%); some of them in a proliferative state. Tumour emboli were detected in a high proportion of the cases (45%). Lymphatic vessel density was higher in the pharyngeal cases (p = 0.0029), in greater size (p = 0.039), more advanced stage primary tumours (p = 0.006) and in carcinomas of patients with affected nodes (p = 0.019). The presence of tumour emboli and a high global vessel density were indicators of poor prognosis (recorded as death from tumour) in the laryngeal group (p = 0.015 and p = 0.027, respectively), but notably not in the pharyngeal one. Interestingly, high global vessel density showed a negative prognostic value among pathologically staged N0 laryngeal carcinomas (p = 0.03). Conclusions The lymphangiogenic process correlated with aggressive tumour features (pN category, tumour size, tumour stage), but might play different roles in tumours arising from different anatomic sites. Our results suggest that detection of tumour emboli and assessment of global vessel

  11. Vismodegib: the first drug approved for advanced and metastatic basal cell carcinoma.

    PubMed

    Dubey, A K; Dubey, S; Handu, S S; Qazi, M A

    2013-01-01

    Treatment of basal cell carcinoma (BCC) usually involves surgical interventions and laser ablation, but in locally advanced BCC, which arise either from earlier untreated lesions or from recurrence of aggressive BCC, surgery and radiotherapy are not helpful. Vismodegib, the first oral-targeted therapy for locally advanced and metastatic BCC, unsuitable for surgery or radiotherapy, was recently approved by US Food and Drug Administration (FDA). The drug was under the priority review program of FDA and was approved on the basis of promising results of phase II trial. Vismodegib acts by targeting the hedgehog pathway, which is activated abnormally in most BCCs. Approval of vismodegib is a big step ahead in the treatment of advanced BCC, where there was no other effective drug therapy till now.

  12. Functional organ preservation in laryngeal and hypopharyngeal cancer

    PubMed Central

    Ambrosch, Petra; Fazel, Asita

    2012-01-01

    The principles of open versus laser microsurgical approaches for partial resections of the larynx are described, oncologic as well as functional results discussed and corresponding outcomes following primary radiotherapy are opposed. Over the last decade, the endoscopic partial resection of the larynx has developed to an accepted approach in the treatment of early glottic and supraglottic carcinomas thus leading to a remarkable decline in the use of open surgery. Comparing the various surgical approaches of laryngeal partial resections, the oncological outcome of the patients, as far as survival and organ preservation are concerned, are comparable, whereas functional results of the endoscopic procedures are superior with less morbidity. The surgical procedures put together, are all superior to radiotherapy concerning organ preservation. Transoral laser microsurgery has been used successfully for vocal cord carcinomas with impaired mobility or fixation of the vocal cord, supraglottic carcinomas with infiltration of the pre- and/or paraglottic space as well as for selected hypopharyngeal carcinomas. It has been well documented that laser microsurgery achieves good oncological as well as functional results with reasonable morbidity. However, patients with those tumours have been successfully treated by open partial resections of the larynx at medical centres with appropriate expertise. The initially enthusiastic assessment of study results concerning the efficacy of various protocols of chemoradiation with the intent of organ preservation for laryngeal and hypopharyngeal carcinomas are judged more cautious, today, due to recent reports of rather high rates of late toxicity complications. PMID:22558052

  13. Management of laryngeal radionecrosis: Animal and clinical experience

    SciTech Connect

    Oppenheimer, R.W.; Krespi, Y.P.; Einhorn, R.K.

    1989-05-01

    Radiation necrosis of the laryngeal cartilages is an uncommon complication of radiotherapy for laryngeal carcinoma. It is a devastating process for which there is no one acceptable treatment. Medical management offers only temporary, symptomatic relief, which further necessitates surgical treatment. Surgical management may start with a tracheotomy; however, it often ends with a total laryngectomy. Physiologically, the necrotic cartilages are the source of the problem. It is a general surgical principle that nonviable tissue must be excised to promote healing. Therefore, if the affected laryngeal cartilages were removed, the larynx should heal. Total or near total removal of the thyroid and cricoid cartilages with preservation of the endolaryngeal soft tissues has not been reported in the literature. Theoretically, if the entire cartilaginous framework is removed, there would be no structural support for the airway. We have found using animal models, that submucosal resection of the laryngeal cartilages, leaving the perichondrium and endolaryngeal soft tissues intact can result in a competent airway. Animal and clinical experience will be presented.

  14. Oncology Gold Standard™ practical consensus recommendations 2016 for treatment of advanced clear cell renal cell carcinoma

    PubMed Central

    Batra, U; Parikh, PM; Prabhash, K; Tongaonkar, HB; Chibber, P; Dabkara, D; Deshmukh, C; Ghadyalpatil, N; Hingmire, S; Joshi, A; Raghunath, SK; Rajappa, S; Rajendranath, R; Rawal, SK; Singh, Manisha; Singh, R; Somashekhar, SP; Sood, R

    2016-01-01

    The Oncology Gold Standard (OGS) Expert Group on renal cell carcinoma (RCC) developed the consensus statement to provide community oncologists practical guidelines on the management of advanced clear cell (cc) RCC using published evidence, practical experience of experts in real life management, and results of a nationwide survey involving 144 health-care professionals. Six broad question categories containing 33 unique questions cover major situations in the routine management of RCC. This document serves as a ready guide for the standard of care to optimize outcome. The table of “Take Home Messages” at the end is a convenient tool for busy practitioners. PMID:28032079

  15. [Open and closed laryngeal injuries].

    PubMed

    Bartnik, Władysław; Bartnik-Krystalska, Alicja

    2003-01-01

    Treatment and results of 13 laryngeal and trachea traumas have been presented. All patients were operated in 24 hours after the injury. We had good results, only two patients had vocal chord paralysis. After phoniatric rehabilitation they regained good voice.

  16. Interrelation of mandibular laryngeal functions.

    PubMed

    Cookman, S; Verdolini, K

    1999-03-01

    The purpose of the experiment was to explore relations between jaw and laryngeal functions. The general question was whether laryngeal adduction was affected by jaw opening or by jaw biting. Twelve untrained, vocally healthy male and female adults participated as subjects. Subjects produced repeated tokens of /uh/ in each of 12 experimental conditions involving combinations of 3 jaw openings (10 mm, 25 mm, 40 mm), 2 jaw biting pressures (10 kPa, 200 kPa), and 2 fundamental frequencies (conversational and high). For each token, laryngeal adduction was estimated from the electroglottographic closed quotient. The most straightforward results were that (1) laryngeal adduction increased as jaw opening increased at the conversational pitch, for all subjects, independent of biting pressure, and (2) laryngeal adduction increased as biting pressure increased, at the conversational pitch, for males, independent of jaw opening. Other relations between estimated laryngeal adduction and jaw manipulations were more complex, varying with fundamental frequency and gender. Speculations are made about possible biomechanical and neurological explanations for the findings.

  17. Cixutumumab, Everolimus, and Octreotide Acetate in Treating Patients With Advanced Low to Intermediate Grade Neuroendocrine Carcinoma

    ClinicalTrials.gov

    2016-07-14

    Gastrin-Producing Neuroendocrine Tumor; Lung Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Pancreatic Glucagonoma; Pancreatic Insulinoma; Pancreatic Polypeptide Tumor; Paraganglioma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Merkel Cell Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Somatostatin-Producing Neuroendocrine Tumor; Stage III Merkel Cell Carcinoma; Stage IV Merkel Cell Carcinoma; Thyroid Gland Medullary Carcinoma

  18. Survival among patients with advanced renal cell carcinoma in the pretargeted versus targeted therapy eras.

    PubMed

    Li, Pengxiang; Wong, Yu-Ning; Armstrong, Katrina; Haas, Naomi; Subedi, Prasun; Davis-Cerone, Margaret; Doshi, Jalpa A

    2016-02-01

    Between December 2005 and October 2009, FDA approved six targeted therapies shown to significantly extend survival for advanced renal cell carcinoma (RCC) patients in clinical trials. This study aimed to examine changes in survival between the pretargeted and targeted therapy periods in advanced RCC patients in a real-world setting. Utilizing the 2000-2010 SEER Research files, a pre-post study design with a contemporaneous comparison group was employed to examine differences in survival outcomes for patients diagnosed with advanced RCC (study group) or advanced prostate cancer (comparison group, for whom no significant treatment innovations happened during this period) across the pretargeted therapy era (2000-2005) and the targeted therapy era (2006-2010). RCC patients diagnosed in the targeted therapy era (N = 6439) showed improved survival compared to those diagnosed in the pretargeted therapy era (N = 7231, hazard ratio (HR) for all-cause death: 0.86, P < 0.01), while the change between the pre-post periods was not significant for advanced prostate cancer patients (HR: 0.97, P = 0.08). Advanced RCC patients had significantly larger improvements in overall survival compared to advanced prostate cancer patients (z = 4.31; P < 0.01). More detailed year-to-year analysis revealed greater survival improvements for RCC in the later years of the posttargeted period. Similar results were seen for cause-specific survival. Subgroup analyses by nephrectomy status, age, and gender showed consistent findings. Patients diagnosed with advanced RCC during the targeted therapy era had better survival outcomes than those diagnosed during the pretargeted therapy era. Future studies should examine the real-world survival improvements directly associated with targeted therapies.

  19. Percutaneous Irreversible Electroporation of Locally Advanced Pancreatic Carcinoma Using the Dorsal Approach: A Case Report

    SciTech Connect

    Scheffer, Hester J. Melenhorst, Marleen C. A. M.; Vogel, Jantien A.; Tilborg, Aukje A. J. M. van; Nielsen, Karin Kazemier, Geert; Meijerink, Martijn R.

    2015-06-15

    Irreversible electroporation (IRE) is a novel image-guided ablation technique that is increasingly used to treat locally advanced pancreatic carcinoma (LAPC). We describe a 67-year-old male patient with a 5 cm stage III pancreatic tumor who was referred for IRE. Because the ventral approach for electrode placement was considered dangerous due to vicinity of the tumor to collateral vessels and duodenum, the dorsal approach was chosen. Under CT-guidance, six electrodes were advanced in the tumor, approaching paravertebrally alongside the aorta and inferior vena cava. Ablation was performed without complications. This case describes that when ventral electrode placement for pancreatic IRE is impaired, the dorsal approach could be considered alternatively.

  20. Complete Remission of Locally Advanced Penile Squamous Cell Carcinoma after Multimodality Treatment

    PubMed Central

    Meng, Yifan; Bernie, Helen Levey; Weng, Tzu-Hua; Ling, Dean-An; Messing, Edward M.; Guancial, Elizabeth

    2016-01-01

    Treatment of locally advanced penile squamous cell carcinoma (pSCC) remains highly controversial secondary to disease rarity and lack of prospective randomized controlled trials. The current mainstays of care are multi-modality treatment with neoadjuvant chemotherapy and surgery. However, clinicians often have difficulty making recommendations for patients unable to tolerate chemotherapy or surgery due to scarcity of data to guide clinical decision-making. We report two cases of locally advanced pSCC that achieved complete remission after treatment with cisplatin-based neoadjuvant chemotherapy and surgery in one case, and concurrent cisplatin chemoradiation in a second, supporting the use of chemotherapy as part of first-line multimodal therapy. We also discuss additional treatment options for patients unable to tolerate traditional chemotherapy regimens. PMID:28191294

  1. Uncommon gastrointestinal bleeding during targeted therapy for advanced renal cell carcinoma: A report of four cases

    PubMed Central

    FUJIHARA, SHINTARO; MORI, HIROHITO; KOBARA, HIDEKI; NISHIYAMA, NORIKO; AYAKI, MAKI; OHATA, RYO; UEDA, NOBUFUMI; SUGIMOTO, MIKIO; KAKEHI, YOSHIYUKI; MASAKI, TSUTOMU

    2015-01-01

    Clinically available targeted agents to treat advanced renal cell carcinoma (RCC) include sunitinib, sorafenib and temsirolimus. Sorafenib and sunitinib have been associated with bleeding in selected trials, but clinical and endoscopic characteristics of gastrointestinal bleeding are not well described. Herein, we report four cases of advanced RCC in which endoscopic hemostasis effectively resolved high-grade, life-threatening gastrointestinal bleeding that occurred during targeted therapy. Although stomatitis and mucositis have occurred during targeted therapies, life-threatening gastrointestinal bleeding is less common. In these four patients, the origins of gastrointestinal bleeding were identified, and complete endoscopic hemostasis was achieved. Endoscopies revealed variable characteristics including angiodysplasia, multiple gastric ulcers and oozing bleeding of the normal mucosa. Although the most effective diagnostic and treatment strategies are disputed, endoscopic examinations are best performed before starting targeted therapies. Additionally, these patients should be monitored even for rare life-threatening events. PMID:26722259

  2. Identifying locally advanced basal cell carcinoma eligible for treatment with vismodegib: an expert panel consensus.

    PubMed

    Peris, Ketty; Licitra, Lisa; Ascierto, Paolo A; Corvò, Renzo; Simonacci, Marco; Picciotto, Franco; Gualdi, Giulio; Pellacani, Giovanni; Santoro, Armando

    2015-01-01

    Basal cell carcinoma (BCC) is the most common skin cancer worldwide. Most occur on the head and neck, where cosmetic and functional outcomes are critical. BCC can be locally destructive if not diagnosed early and treated appropriately. Surgery is the treatment of choice for the majority of high-risk lesions. Aggressive, recurrent or unresectable tumors can be difficult to manage. Until recently, no approved systemic therapy was available for locally advanced or metastatic BCC inappropriate for surgery or radiotherapy. Vismodegib provides a systemic treatment option. However, a consensus definition of advanced BCC is lacking. A multidisciplinary panel with expertise in oncology, dermatology, dermatologic surgery and radiation oncology proposes a consensus definition based on published evidence and clinical experience.

  3. Advanced primary pulmonary lymphoepithelioma-like carcinoma: clinical manifestations, treatment, and outcome

    PubMed Central

    Lin, Chun-Yu; Chen, Ying-Jen; Hsieh, Meng-Heng; Wang, Chih-Wei

    2017-01-01

    Background Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is rare, with better clinical outcomes than other lung cancers. However, reports on advanced LELC characteristics and prognosis are lacking. Methods This retrospective study included adults diagnosed with advanced LELC (at least stage IIIA) between January 2003 and December 2015. Clinical characteristics, treatment modalities, and outcomes were recorded. Results Study population comprised 23 patients with a mean age of 63.7±10.6 years. The Eastern Cooperative Oncology Group status on diagnosis was 0 in five patients and 1 in the others. Most patients received multimodality treatment and all received cisplatin-based chemotherapy. Median follow-up duration was 28.8 months. The median progression free survival (PFS) was 14.6 months in patients received palliative chemotherapy. There were nine (39.1%) deaths. The median overall survival (OS) was not achieved. Until July 31, 2016, median OS was 54.1 months for stage IIIB and 27.6 months for stage IV. There was no significant difference in OS among all stages. No prognostic factors were found. Conclusions Advanced LELC responded well to cisplatin-based chemotherapy and/or radiotherapy. Main tumor resection is probably beneficial for advanced LELC. Long-term survival is possible for advanced LELC after multimodality treatment. PMID:28203414

  4. Sorafenib for the treatment of advanced hepatocellular carcinoma with extrahepatic metastasis: a prospective multicenter cohort study.

    PubMed

    Nakano, Masahito; Tanaka, Masatoshi; Kuromatsu, Ryoko; Nagamatsu, Hiroaki; Tajiri, Nobuyoshi; Satani, Manabu; Niizeki, Takashi; Aino, Hajime; Okamura, Shusuke; Iwamoto, Hideki; Shimose, Shigeo; Shirono, Tomotake; Koga, Hironori; Torimura, Takuji

    2015-12-01

    Sorafenib, an oral multikinase inhibitor, is approved for advanced hepatocellular carcinoma (HCC) treatment. However, its therapeutic effect in advanced HCC patients with extrahepatic metastasis remains uncertain. This study aimed to prospectively assess the efficacy, safety, and survival risk factors and evaluate the prognostic impact of sorafenib treatment in advanced HCC patients with or without extrahepatic metastasis. Between May 2009 and March 2014, 312 consecutive advanced HCC patients who received sorafenib were enrolled in this study. We evaluated their characteristics and compared the clinical outcomes of those with and without extrahepatic metastasis. Of the enrolled patients, 245 (81%) received sorafenib treatment for more than 1 month, with a median duration of 3.6 months. Eighteen patients demonstrated partial response to sorafenib therapy, 127 had stable disease, and 134 had progressive disease at the first radiologic assessment. The median survival time (MST) and progression-free survival (PFS) were 10.3 and 3.6 months, respectively. Multivariate analysis identified gender, Child-Pugh class, baseline serum des-gamma-carboxy prothrombin level, and treatment duration as independent risk factors for survival. Extrahepatic metastasis was detected in 178 patients. However, the MST, PFS, and therapeutic effect were comparable between patients with and without extrahepatic metastasis. The independent risk factors for decreased overall survival in patients with extrahepatic metastasis were similar to those affecting all patients. Our results indicated that sorafenib could be administered for hepatic reserve and as long-term treatment for advanced HCC patients regardless of their extrahepatic metastasis status.

  5. The effect of locoregional therapies in patients with advanced hepatocellular carcinoma treated with sorafenib

    PubMed Central

    Sarpel, Umut; Spivack, John H.; Berger, Yaniv; Heskel, Marina; Aycart, Samantha N.; Sweeney, Robert; Edwards, Martin P.; Labow, Daniel M.; Kim, Edward

    2016-01-01

    Background & aims It is unknown whether the addition of locoregional therapies (LRTx) to sorafenib improves prognosis over sorafenib alone in patients with advanced hepatocellular carcinoma (HCC). The aim of this study was to assess the effect of LRTx in this population. Methods A retrospective analysis was performed of patients with advanced HCC as defined by extrahepatic metastasis, lymphadenopathy >2 cm, or gross vascular invasion. Sorafenib therapy was required for inclusion. Survival of patients who received LRTx after progression to advanced stage was compared to those who did not receive LRTx. Results Using an intention to treat analysis of 312 eligible patients, a propensity weighted proportional hazards model demonstrated LRTx as a predictor of survival (HR = 0.505, 95% CI: 0.407–0.628; P < 0.001). The greatest benefit was seen in patients with the largest tumor burden (HR = 0.305, 95% CI: 0.236–0.393; P < 0.01). Median survival in the sorafenib arm was 143 days (95% CI: 118–161) vs. 247 days (95% CI: 220–289) in the sorafenib plus LRTx arm (P < 0.001). Conclusions These results demonstrate a survival benefit with the addition of LRTx to sorafenib for patients with advanced HCC. These findings should prompt a prospective clinical trial to further assess the role of LRTx in patients with advanced HCC. PMID:27154804

  6. Cetuximab concurrent with IMRT versus cisplatin concurrent with IMRT in locally advanced nasopharyngeal carcinoma

    PubMed Central

    Wu, Xin; Huang, Jingwen; Liu, Lei; Li, Hongmei; Li, Ping; Zhang, Jing; Xie, Li

    2016-01-01

    Abstract To evaluate the treatment efficacies and toxicities of concurrent cetuximab-based bioradiotherapy (BRT) or cisplatin-based chemoradiotherapy (CRT) in locally advanced nasopharyngeal carcinoma. :Patients with previously untreated locally advanced nasopharyngeal carcinoma were matched into pairs, and enrolled into the study. All patients were given either BRT or CRT. Survival outcomes, toxicities, and prognostic factors were evaluated. :A total of 112 patients were enrolled. The 5-year overall survival was 79.3% and 79.5% in CRT and BRT arm, respectively (P = 0.797) and the 5-year DFS was 73.5% and 74.6%, respectively (P = 0.953). In toxicity analysis, CRT arm had more significant decrease in white blood cell, platelet, hemoglobin, and severe vomiting, while more severe skin reactions and mucositis were shown in BRT arm. :BRT was not less efficacious than traditional CRT. They lead to different aspects of toxicities. If patients cannot stand more severe toxicities caused by CRT, BRT could be an ideal alternative. PMID:27684830

  7. Salvage surgery for locoregional recurrences of advanced pharyngolaryngeal squamous cell carcinoma after organ preservation failure.

    PubMed

    López Delgado, I; Riestra Ayora, J; Arenas Brítez, O; García López, I; Martínez Guirado, T; Scola Yurrita, B

    2014-12-01

    Organ preservation treatment for advanced head and neck squamous cell carcinoma is associated with poor outcomes due to locoregional recurrences. Salvage surgery is the main therapeutic option for some of these patients. The aim of this study was to analyse the results of salvage surgery for advanced pharyngolaryngeal squamous cell carcinoma previously treated with radiochemotherapy. We performed a retrospective study on 38 patients (36 men, 2 women). The median age at diagnosis was 60 years with a mean follow-up period of 49.8 months. Recurrences were diagnosed at a mean of 395 days after finalising organ preservation treatment. Patients went under different salvage surgeries, including 22 total laryngectomies, 6 partial laryngectomies (3 transoral laser surgeries and 3 opened surgeries), 8 functional neck dissections and 2 tongue base surgeries. Nineteen patients had no postoperative complications after a mean hospital stay of 2 weeks. However, 5 patients died of significant recurrent bleedings. There were 4 salivary fistulas that responded to conservative management, while 7 patients had important pharyngostomas that required reconstruction with either regional or free flaps. The mean hospital stay was of 61.60 days for all patients. Five-year overall survival from diagnosis, overall survival after salvage surgery and survival after salvage surgery were 44.20, 37.90 and 45.70%, respectively. In summary, we conclude that salvage surgery is an optimal treatment for pharyngolaryngeal and regional recurrences and provides improvement in locoregional control and survival, despite the severe complications.

  8. Preoperative radiotherapy followed by radical vulvectomy with inguinal lymphadenectomy for advanced vulvar carcinomas

    SciTech Connect

    Rotmensch, J.; Rubin, S.J.; Sutton, H.G.; Javaheri, G.; Halpern, H.J.; Schwartz, J.L.; Stewart, M.; Weichselbaum, R.R.; Herbst, A.L. )

    1990-02-01

    A therapeutic alternative to exenteration for large locally advanced vulvar carcinoma involving the rectum, anus, or vagina is the use of preoperative radiation followed by radical surgery. Between 1980 and 1988, 13 patients with Stage III and 3 with Stage IV vulvar carcinoma involving the rectum/anus, urethra, or vagina were treated with 4000 rad to the vulva and 4500 rad to the inguinal and pelvic nodes followed by a radical vulvectomy and inguinal lymphadenectomy 4 weeks later. The overall 5 year cumulative survival was 45%. Twelve tumors regressed after radiation with 62.5% of the patients having visceral preservation while in 4 patients there was no major response to radiation and urinary or fecal diversion was required. Of the 6 recurrences 4 were central and 2 distant. Three patients with central recurrences had tumor within 1 cm of the vulvectomy margin. Complications included wet desquamation, inguinal wound separation, lymphedema, and urethral strictures. There were no operative deaths. It is concluded that the use of preoperative radiation followed by radical vulvectomy may be an alternative to pelvic exenteration in selected patients with advanced vulvar lesions.

  9. Detection of Early Tumor Response to Axitinib in Advanced Hepatocellular Carcinoma by Dynamic Contrast Enhanced Ultrasound.

    PubMed

    Lo, Glen M; Al Zahrani, Hassan; Jang, Hyun Jung; Menezes, Ravi; Hudson, John; Burns, Peter; McNamara, Mairéad G; Kandel, Sonja; Khalili, Korosh; Knox, Jennifer; Rogalla, Patrik; Kim, Tae Kyoung

    2016-06-01

    This study aimed to evaluate the utility of dynamic contrast-enhanced ultrasound (DCE-US) in measuring early tumor response of advanced hepatocellular carcinoma to axitinib. Twenty patients were enrolled (aged 18-78 y; median 65). DCE-US was performed with bolus injection and infusion/disruption replenishment. Median overall survival was 7.1 mo (1.8-27.3) and progression free survival was 3.6 mo (1.8-17.4). Fifteen patients completed infusion scans and 12 completed bolus scans at 2 wk. Among the perfusion parameters, fractional blood volume at infusion (INFBV) decreased at 2 wk in 10/15 (16%-81% of baseline, mean 47%) and increased in 5/15 (116%-535%, mean 220%). This was not significantly associated with progression free survival (p = 0.310) or progression at 16 wk (p = 0.849), but was borderline statistically significant (p = 0.050) with overall survival, limited by a small sample size. DCE-US is potentially useful in measuring early tumor response of advanced hepatocellular carcinoma to axitinib, but a larger trial is needed.

  10. [A Case of Successful Curative Resection Following Downsizing Chemotherapy in Initially Unresectable Locally Advanced Gallbladder Carcinoma].

    PubMed

    Shinmura, Kazuyasu; Kaiho, Takashi; Yanagisawa, Shinji; Okamoto, Ryo; Nishimura, Masaki; Kobayashi, Soichi; Okaniwa, Akira; Mun, Yangi; Tsuchiya, Shunichi; Chiba, Ryoji

    2015-11-01

    A 58-year-old woman was referred to our hospital with high fever and right upper abdominal pain. Abdominal computed tomography (CT) revealed a bulky tumor of the gallbladder with liver invasion, metastases to para-aortic lymph nodes, and extensive infiltration to Glisson's sheath. The tumor was initially considered to be unresectable locally advanced gallbladder carcinoma with inflammation, and she received 6 courses of chemotherapy with gemcitabine plus cisplatin. Subsequently, the inflammation was extinguished, and CT showed the main tumor shrunk and the Glisson's sheath infiltration disappeared; however, a liver metastasis existed in segment 5. Thus, S4a plus S5 hepatic segmentectomy with extrahepatic bile duct resection and regional and para-aortic lymphadenectomy was performed. The pathological diagnosis was pT3a, pN1, pM1 (Hep, LYM), fStage ⅣB. Curative resection was then performed. If selected according to their response to downsizing chemotherapy, conversion therapy might therefore be an effective multidisciplinary treatment for patients with initially unresectable locally advanced gallbladder carcinoma.

  11. High expression of Wls is associated with lymph node metastasis and advanced TNM stage in gastric carcinomas.

    PubMed

    Zhang, Wei; Tao, Hong; Chen, Xiao; Sugimura, Haruhiko; Wang, Jiandong; Zhou, Ping

    2017-03-01

    The roles of Wnt protein in carcinogenesis have been well documented in human cancers. Wls is a key modulator for the secretion of Wnt protein. We previously found that Wls was aberrantly expressed in colorectal carcinomas. Studies have revealed that dysregulation of Wnt signal transduction plays an important role in gastric carcinoma. We hypothesized that Wls may play a role in the development and progression of gastric carcinoma. In this study, three gastric cancer cell lines MGC-803, SGC-7901, and AGS, and a set of gastric carcinoma tissue specimens were subjected to immunohistochemistry. The relationship between the expression of Wls and clinicopathological parameters was analyzed. Wls was negatively detected in MGC-803, positively detected in SGC-7901 and AGS cell lines. Wls was weakly expressed in 9.7% (15/154), moderately in 33.1% (51/154), and strongly in 57.1% (88/154) of tested gastric carcinoma specimens. High expression of Wls was positively associated with well and moderately differentiated tumors (P = 0.035, rs  = 0.170), lymph node metastasis (P = 0.001, rs  = 0.276), and advanced TNM stage (P = 0.006, rs  = 0.219). Our data suggest that Wls protein is related to tumor metastasis and advanced TNM stage, and may be used as a new marker for prognosis of gastric carcinoma.

  12. Advanced basal cell carcinoma, the hedgehog pathway, and treatment options – role of smoothened inhibitors

    PubMed Central

    Fecher, Leslie A; Sharfman, William H

    2015-01-01

    Cutaneous basal cell carcinoma (BCC) is the most common human cancer and its incidence is rising worldwide. Ultraviolet radiation exposure, including tanning bed use, as well as host factors play a role in its development. The majority of cases are treated and cured with local therapies including surgery. Yet, the health care costs of diagnosis and treatment of BCCs in the US is substantial. In the United States, the cost of nonmelanoma skin cancer care in the Medicare population is estimated to be US$426 million per year. While rare, locally advanced BCCs that can no longer be controlled with surgery and/or radiation, and metastatic BCCs do occur and can be associated with significant morbidity and mortality. Vismodegib (GDC-0449), a smoothened inhibitor targeted at the hedgehog pathway, is the first US Food and Drug Association (FDA)-approved agent in the treatment of locally advanced, unresectable, and metastatic BCCs. This class of agents appears to be changing the survival rates in advanced BCC patients, but appropriate patient selection and monitoring are important. Multidisciplinary assessments are essential for the optimal care and management of these patients. For some patients with locally advanced BCC, treatment with a hedgehog inhibitor may eliminate the need for an excessively disfiguring or morbid surgery. PMID:26604681

  13. Challenges and new horizons in the management of advanced basal cell carcinoma: a UK perspective

    PubMed Central

    Lear, J T; Corner, C; Dziewulski, P; Fife, K; Ross, G L; Varma, S; Harwood, C A

    2014-01-01

    Basal cell carcinoma (BCC) is a common malignancy with a good prognosis in the majority of cases. However, some BCC patients develop a more advanced disease that poses significant management challenges. Such cases include locally advanced, recurrent or metastatic BCC, or tumours that occur in anatomical sites where surgical treatment would result in significant deformity. Until recently, treatment options for these patients have been limited, but increased understanding of the molecular basis of BCC has enabled potential therapies, such as hedgehog signalling pathway inhibitors, to be developed. A clear definition of advanced BCC as a distinct disease entity and formal management guidelines have not previously been published, presumably because of the rarity, heterogeneity and lack of treatment options available for the disease. Here we provide a UK perspective from a multidisciplinary group of experts involved in the treatment of complex cases of BCC, addressing the key challenges associated with the perceived definition and management of the disease. With new treatments on the horizon, we further propose a definition for advanced BCC that may be used as a guide for healthcare professionals involved in disease diagnosis and management. PMID:25211660

  14. Clinical outcomes of advanced-stage glassy cell carcinoma of the uterine cervix: a need for reappraisal

    PubMed Central

    Yoon, Nara; Kim, Ji-Ye; Kim, Hyun-Soo

    2016-01-01

    We performed a retrospective analysis of the clinical features and patient outcomes for advanced-stage glassy cell carcinoma of the uterine cervix. The study was restricted to cases in which the glassy cell features constituted at least 95% of the biopsied specimen. During the study period, 675 patients were diagnosed with primary cervical carcinoma. Five (0.7%) of the 675 patients had cervical glassy cell carcinoma; of these, three were premenopausal, and two were postmenopausal. Abnormal vaginal bleeding was the most frequent presenting symptom. Glassy cell carcinoma presented as a fungating, exophytic, or infiltrative mass. The greatest tumor dimension ranged from 3 to 9 cm. All patients had parametrial extension. Four patients had stage IIB tumors, and one had a stage IIIB tumor. All patients received concurrent chemoradiation therapy. The patient with a stage IIIB tumor died of hypovolemic shock caused by upper gastrointestinal bleeding during radiation therapy. Three patients with stage IIB tumors survived for more than 8 years without tumor recurrence or metastasis. One of these three patients died of pelvic recurrence 10 years after the initial diagnosis. Cervical glassy cell carcinoma has traditionally been considered an aggressive, highly malignant tumor with poor prognosis, but our data suggest that patient survival is not significantly decreased compared with other histological types of cervical carcinoma. It will be necessary to analyze patient outcomes using a larger number of cervical glassy cell carcinoma cases to confirm our findings. PMID:27793022

  15. Adjuvant radiotherapy after transoral laser microsurgery for advanced squamous carcinoma of the head and neck

    SciTech Connect

    Pradier, Olivier . E-mail: opradier@gwdg.de; Christiansen, Hans; Schmidberger, Heinz; Martin, Alexios; Jaeckel, Martin C.; Steiner, Wolfgang; Ambrosch, Petra; Kahler, Elke; Hess, Clemens F.

    2005-12-01

    Purpose: To evaluate the efficacy of an adjuvant radiotherapy after transoral laser microsurgery for advanced squamous cell carcinoma of the head and neck and to show that a less invasive surgery with organ preservation in combination with radiotherapy is an alternative to a radical treatment. Patients and Methods: Between 1987 and 2000, 208 patients with advanced squamous cell carcinoma of the head and neck were treated with postoperative radiotherapy after surgical CO{sub 2} laser resection. Primary sites included oral cavity, 38; oropharynx, 88; larynx, 36; hypopharynx, 46. Disease stages were as follows: Stage III, 40 patients; Stage IV, 168 patients. Before 1994, the treatment consisted of a split-course radiotherapy with carboplatinum (Treatment A). After 1994, the patients received a conventional radiotherapy (Treatment B). Results: Patients had 5-year locoregional control and disease-specific survival (DSS) rates of 68% and 48%, respectively. The 5-year DSS was 70% and 44% for Stages III and IV, respectively (p = 0.00127). Patients treated with a hemoglobin level greater or equal to 13.5 g/dL before radiotherapy had a 5-year DSS of 55% as compared with 39% for patients treated with a hemoglobin level greater than 13.5 g/dL (p = 0.0054). Conclusion: In this series of patients with advanced head-and-neck tumors, transoral laser surgery in combination with adjuvant radiotherapy resulted in locoregional control and DSS rates similar to those reported for radical surgery followed by radiotherapy. Treatment B has clearly been superior to Treatment A. A further improvement of our treatment regimen might be expected by the combination of adjuvant radiotherapy with concomitant platinum-based chemotherapy.

  16. Oral squamous cell carcinoma among Yemenis: Onset in young age and presentation at advanced stage

    PubMed Central

    Al-Mohaya, Maha; Abdulhuq, Mahmoud; Al-Mandili, Ahmad; Al-Anazi, Yousef

    2012-01-01

    Objectives: Oral cancer represents a health burden worldwide. Up to 90% of oral cancer cases are squamous cell carcinomas (SCC). The data on oral SCC in Yemen are lacking. The objective of this study therefore was to describe and analyze the demographic, clinical and histological characteristics of Yemeni patients with oral SCC. Study Design: In this cross-sectional study, two sets of retrospective data for Yemeni cancer patients were obtained officially by two different registries. Patients with oral SCC were included. Their ages were dichotomized using 40 and 45 years alternately as individual cut-points for young and old patients. The patients` demographic, clinical and histological characteristics were statistically analyzed. Results: There were 457 Yemenis with oral SCC; 253 patients (55.4%) were men. The overall mean age was 58.15±14.11 years. The tongue was the most affected oral sub-site accounting for 53% of the reported cases. The well and moderately differentiated oral SCC accounted for 55.5% and 25.6% of the total cases respectively. Noteworthy, 62 patients (14%) were affected by the age of ?40; this increased to 105 patients (23%) aged ?45 years. Additionally, a high proportion of oral SCC patients (62%, 283) were diagnosed at advanced tumor stages (regional extension or metastasized). The distributions of histological grades and tumor stages in young and old patients were significantly different (P=0.006 and 0.026 respectively). Conclusion: The relative frequency of oral SCC among Yemeni young people is high. Unfortunately, most of oral SCC patients in Yemen were diagnosed at advanced stage. Key words:Oral squamous cell carcinoma, Yemen, young patients, advanced stage. PMID:24558559

  17. Neoadjuvant chemoradiotherapy followed by surgery in locally advanced squamous cell carcinoma of the vulva.

    PubMed

    Gaudineau, A; Weitbruch, D; Quetin, P; Heymann, S; Petit, T; Volkmar, P; Bodin, F; Velten, M; Rodier, J F

    2012-10-01

    Alternative therapies have been sought to alleviate mutilation and morbidity associated with surgery for vulvar neoplasms. Our prime objective was to assess tumor absence in pathological vulvar and nodal specimens following neoadjuvant chemoradiotherapy in locally advanced vulvar neoplasms. Data were retrospectively collected from January 2001 to May 2009 from 22 patients treated with neoadjuvant therapy for locally advanced squamous cell carcinoma of the vulva. Neoadjuvant treatment consisted of inguino-pelvic radiotherapy (50 Gy) in association with chemotherapy when possible. Surgery occurred at intervals of between 5 to 8 weeks. The median age of patients at diagnosis was 74.1 years. All patients were primarily treated with radiotherapy and 15 received a concomitant chemotherapy. Additionally, all patients underwent radical vulvectomy and bilateral inguino-femoral lymphadenectomy. Tumor absence in the vulvar and nodal pathological specimens was achieved for 6 (27%) patients, while absence in the vulvar pathological specimens was only achieved for 10 (45.4%) patients. Postoperative follow-up revealed breakdown of groin wounds, vulvar wounds and chronic lymphedema in 3 (14.3%), 7 (31.8%) and 14 cases (63.6%), respectively. Within a median follow-up time of 2.3 years [interquartile range (IQR), 0.6-4.6], 12 (54.6%) patients experienced complete remission and 6 cases succumbed to metastatic evolution within a median of 2.2 years (IQR, 0.6-4.6), with 1 case also experiencing perineal recurrence. Median survival time, estimated using the Kaplan-Meier method, was 5.1 years (IQR, 1.0-6.8). We suggest that neoadjuvant chemoradiotherapy may represent a reliable and promising strategy in locally advanced squamous cell carcinoma of the vulva.

  18. Neoadjuvant chemoradiotherapy followed by surgery in locally advanced squamous cell carcinoma of the vulva

    PubMed Central

    GAUDINEAU, A.; WEITBRUCH, D.; QUETIN, P.; HEYMANN, S.; PETIT, T.; VOLKMAR, P.; BODIN, F.; VELTEN, M.; RODIER, J.F.

    2012-01-01

    Alternative therapies have been sought to alleviate mutilation and morbidity associated with surgery for vulvar neoplasms. Our prime objective was to assess tumor absence in pathological vulvar and nodal specimens following neoadjuvant chemoradiotherapy in locally advanced vulvar neoplasms. Data were retrospectively collected from January 2001 to May 2009 from 22 patients treated with neoadjuvant therapy for locally advanced squamous cell carcinoma of the vulva. Neoadjuvant treatment consisted of inguino-pelvic radiotherapy (50 Gy) in association with chemotherapy when possible. Surgery occurred at intervals of between 5 to 8 weeks. The median age of patients at diagnosis was 74.1 years. All patients were primarily treated with radiotherapy and 15 received a concomitant chemotherapy. Additionally, all patients underwent radical vulvectomy and bilateral inguino-femoral lymphadenectomy. Tumor absence in the vulvar and nodal pathological specimens was achieved for 6 (27%) patients, while absence in the vulvar pathological specimens was only achieved for 10 (45.4%) patients. Postoperative follow-up revealed breakdown of groin wounds, vulvar wounds and chronic lymphedema in 3 (14.3%), 7 (31.8%) and 14 cases (63.6%), respectively. Within a median follow-up time of 2.3 years [interquartile range (IQR), 0.6–4.6], 12 (54.6%) patients experienced complete remission and 6 cases succumbed to metastatic evolution within a median of 2.2 years (IQR, 0.6–4.6), with 1 case also experiencing perineal recurrence. Median survival time, estimated using the Kaplan-Meier method, was 5.1 years (IQR, 1.0–6.8). We suggest that neoadjuvant chemoradiotherapy may represent a reliable and promising strategy in locally advanced squamous cell carcinoma of the vulva. PMID:23205089

  19. A unique bleeding-related complication of sorafenib, a tyrosine kinase inhibitor, in advanced hepatocellular carcinoma: a case report

    PubMed Central

    2014-01-01

    Introduction Sorafenib, a multikinase inhibitor as a standard of care for advanced hepatocellular carcinoma, may lead endothelial cells to an unstable state by blocking the signaling pathway of vascular endothelial growth factor receptor, which may result in the disruption of the architecture and integrity of the microvasculature, and eventually increase the risk of hemorrhage. Hemobilia is a relatively uncommon condition as a consequence of hepatocellular carcinoma and its risk factors remain uncertain. Case presentation Here we report a unique case of hemobilia occurring in a 55-year-old Korean man with hepatitis B virus-related hepatocellular carcinoma on Barcelona Clinic Liver Cancer advanced stage after seven days of treatment with sorafenib. He had received prior radiation therapy. Endoscopy revealed bleeding from the major duodenal papilla and endoscopic retrograde cholangiography revealed an amorphous filling defect throughout the common bile duct. Blood clots were removed by balloon sweeping and a nasobiliary drainage tube was placed. No further bleeding has been detected as of eight months after discontinuation of sorafenib. Conclusion Sorafenib may increase the risk of biliary bleeding in hepatocellular carcinoma patients who were primed with irradiation, by blocking the signaling pathway of the vascular endothelial growth factor receptor. Therefore, sorafenib should be used with caution in patients with advanced hepatocellular carcinoma, especially when combined with radiation therapy. PMID:24571585

  20. Comprehensive Genomic Profiling of Advanced Penile Carcinoma Suggests a High Frequency of Clinically Relevant Genomic Alterations

    PubMed Central

    Pal, Sumanta K.; Wang, Kai; Palma, Norma A.; Sanford, Eric; Bailey, Mark; He, Jie; Elvin, Julia A.; Chmielecki, Juliann; Squillace, Rachel; Dow, Edward; Morosini, Deborah; Buell, Jamie; Yelensky, Roman; Lipson, Doron; Frampton, Garrett M.; Howley, Peter; Ross, Jeffrey S.; Stephens, Philip J.; Miller, Vincent A.

    2016-01-01

    Background. Advanced penile squamous cell carcinoma (PSCC) is associated with poor survival due to the aggressiveness of the disease and lack of effective systemic therapies. Comprehensive genomic profiling (CGP) was performed to identify clinically relevant genomic alterations (CRGAs). Materials and Methods. DNA was extracted from 40 μm of formalin-fixed, paraffin-embedded sections in patients with advanced PSCC. CGP was performed on hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of 692× for 3,769 exons of 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer. CRGAs were defined as genomic alterations (GAs) linked to targeted therapies on the market or under evaluation in mechanism-driven clinical trials. Results. Twenty male patients with a median age of 60 years (range, 46–87 years) were assessed. Seventeen (85%) cases were stage IV and three cases (15%) were stage III. CGP revealed 109 GAs (5.45 per tumor), 44 of which were CRGAs (2.2 per tumor). At least one CRGA was detected in 19 (95%) cases, and the most common CRGAs were CDKN2A point mutations and homozygous deletion (40%), NOTCH1 point mutations and rearrangements (25%), PIK3CA point mutations and amplification (25%), EGFR amplification (20%), CCND1 amplification (20%), BRCA2 insertions/deletions (10%), RICTOR amplifications (10%), and FBXW7 point mutations (10%). Conclusion. CGP identified CRGAs in patients with advanced PSCC, including EGFR amplification and PIK3CA alterations, which can lead to the rational administration of targeted therapy and subsequent benefit for these patients. Implications for Practice: Few treatment options exist for patients with advanced penile squamous cell carcinoma (PSCC). Outcomes are dismal with platinum-based chemotherapy, with median survival estimated at 1 year or less across multiple series. Biological studies of patients with PSCC to date have principally focused on human papillomavirus status

  1. Advancements in the Management of HPV-Associated Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Zeitlin, Ross; Nguyen, Harrison P.; Rafferty, David; Tyring, Stephen

    2015-01-01

    Head and neck carcinomas have long been linked to alcohol and tobacco abuse; however, within the last two decades, the human papillomavirus (HPV) has emerged as a third etiology and is specifically associated with head and neck squamous cell carcinomas (HNSCC). In this anatomical region, the oncogenic HPV-16 mediates transformation and immortalization of epithelium, most commonly in the oropharynx. Nevertheless, the recent identification of novel HPV mechanisms thought to be specific to oropharyngeal carcinogenesis has coincided with observations that HPV-associated HNSCC has differing clinical behavior—in terms of natural history, therapeutic response, and prognosis—than HPV-negative head and neck tumors. Taken together with the growing incidence of HPV transmission in younger populations, these discoveries have sparked a rapid expansion in both laboratory and clinical studies on the infection and disease. Herein, we review the clinical characteristics of HPV-associated HNSCC, with particular emphasis on recent advancements in our understanding of the management of this infectious malignancy. PMID:26239449

  2. Cabozantinib in the treatment of advanced renal cell carcinoma: clinical trial evidence and experience

    PubMed Central

    Ruiz-Morales, Jose Manuel; Heng, Daniel Y.C.

    2016-01-01

    The treatment of metastatic renal cell carcinoma (mRCC) is rapidly changing. During first-line treatment with targeted therapy, patients ultimately develop resistance to therapy and the disease progresses. Recently, cabozantinib has demonstrated a better response rate, progression-free survival and overall survival compared with everolimus after failure of prior targeted therapy in patients with advanced or metastatic renal cell carcinoma (RCC). Cabozantinib is a small-molecule tyrosine kinase inhibitor (TKI). It exerts inhibition of MET, vascular endothelial growth factor receptor type 2, AXL, and many other receptor tyrosine kinases that are also implicated in tumor pathobiology, including RET, KIT, and FLT3. MET drives tumor survival, invasion, angiogenesis, and metastasis through several downstream signaling pathways. AXL has recently been described as an essential mediator of cancer metastasis that mediates crosstalk and resistance to TKIs. MET and AXL are thought to be anti-vascular endothelial growth factor receptor (VEGF) resistance pathways and thus cabozantinib represents a logical choice after progression on initial VEGF therapy. Subgroup analyses examining those with good performance status or visceral and bone metastases indicate that the hazard ratios may be better when using cabozantinib versus everolimus. However, there were no clear statistically significant differences between any subgroups. PMID:27904650

  3. Safety and efficacy of vismodegib in patients aged ≥65 years with advanced basal cell carcinoma.

    PubMed

    Chang, Anne Lynn S; Lewis, Karl D; Arron, Sarah T; Migden, Michael R; Solomon, James A; Yoo, Simon; Day, Bann-Mo; McKenna, Edward F; Sekulic, Aleksandar

    2016-11-15

    Because many patients with unresectable basal cell carcinoma (BCC) are aged ≥65 years, this study explores the efficacy and safety of vismodegib in these patients with locally advanced (la) or metastatic (m) basal cell carcinoma (BCC) in the ERIVANCE BCC trial and the expanded access study (EAS).We compared patients aged ≥65 years to patients aged <65 years taking vismodegib 150 mg/day, using descriptive statistics for response and safety. Patients aged ≥65 years (laBCC/mBCC) were enrolled in ERIVANCE BCC (33/14) and EAS (27/26). Investigator-assessed best overall response rate in patients ≥65 and <65 years was 46.7%/35.7% and 72.7%/52.6% (laBCC/mBCC), respectively, in ERIVANCE BCC and 45.8%/33.3% and 46.9%/28.6%, respectively, in EAS. These differences were not clinically meaningful. Safety was similar in both groups, although those aged ≥65 years had a higher percentage of grade 3-5 adverse events than those aged <65 years. Vismodegib demonstrated similar clinical activity and adverse events regardless of age.

  4. Safety and efficacy of vismodegib in patients aged ≥65 years with advanced basal cell carcinoma

    PubMed Central

    Chang, Anne Lynn S.; Lewis, Karl D.; Arron, Sarah T.; Migden, Michael R.; Solomon, James A.; Yoo, Simon; Day, Bann-Mo; McKenna, Edward F.; Sekulic, Aleksandar

    2016-01-01

    Because many patients with unresectable basal cell carcinoma (BCC) are aged ≥65 years, this study explores the efficacy and safety of vismodegib in these patients with locally advanced (la) or metastatic (m) basal cell carcinoma (BCC) in the ERIVANCE BCC trial and the expanded access study (EAS).We compared patients aged ≥65 years to patients aged <65 years taking vismodegib 150 mg/day, using descriptive statistics for response and safety. Patients aged ≥65 years (laBCC/mBCC) were enrolled in ERIVANCE BCC (33/14) and EAS (27/26). Investigator-assessed best overall response rate in patients ≥65 and <65 years was 46.7%/35.7% and 72.7%/52.6% (laBCC/mBCC), respectively, in ERIVANCE BCC and 45.8%/33.3% and 46.9%/28.6%, respectively, in EAS. These differences were not clinically meaningful. Safety was similar in both groups, although those aged ≥65 years had a higher percentage of grade 3-5 adverse events than those aged <65 years. Vismodegib demonstrated similar clinical activity and adverse events regardless of age. PMID:27764798

  5. Immune inflammation indicators and implication for immune modulation strategies in advanced hepatocellular carcinoma patients receiving sorafenib

    PubMed Central

    Gardini, Andrea Casadei; Scarpi, Emanuela; Faloppi, Luca; Scartozzi, Mario; Silvestris, Nicola; Santini, Daniele; de Stefano, Giorgio; Marisi, Giorgia; Negri, Francesca V.; Foschi, Francesco Giuseppe; Valgiusti, Martina; Ercolani, Giorgio; Frassineti, Giovanni Luca

    2016-01-01

    We evalueted a systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) with the aim to explored their prognostic value in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. 56 advanced HCC patients receiving sorafenib were available for our analysis. Lymphocyte, neutrophil and platelet were measured before beginning of treatment and after one month. Patient with SII ≥ 360 showed lower median PFS (2.6 vs. 3.9 months, P < 0.026) and OS (5.6 vs. 13.9 months, P = 0.027) with respect to patients with SII < 360. NLR ≥ 3 had a lower median PFS (2.6 vs. 3.3 months, P < 0.049) but not OS (5.6 vs. 13.9 months, P = 0.062) than those with NLR < 3. After adjusting for clinical covariates SII and NLR remained an independent prognostic factor for OS. The SII and NLR represent potential prognostic indicator in patients with advanced HCC treated with sorafenib. PMID:27613839

  6. [Recent advancements in the treatment of renal cell carcinoma--focus on international guidelines].

    PubMed

    Biró, Krisztina; Küronya, Zsófia

    2010-12-01

    Recent advances in understanding the fundamental biology underlying clear-cell RCC have opened the door to a series of targeted agents, such as tyrosine kinase inhibitors (TKIs) or mTOR inhibitors. These new agents have become the standard of care in managing advanced clear-cell RCC. Choice of initial medical management in patients with metastatic clear-cell RCC should be guided by randomised studies. On the evidence available, the first-line therapy in patients with good- or intermediate-risk mRCC should be either sunitinib or pazopanib, or bevacizumab plus interferon. In selected patients sorafenib is an option, as is high-dose interleukin-2 if performance status is good. In patients with poor prognosis, temsirolimus is recommended. In cytokine refractory patients, sorafenib, when patients have progressed on a tyrosine kinase inhibitor everolimus is the agent of choice. Biró K, Küronya Z. Recent advancements in the treatment of renal cell carcinoma - focus on international guidelines.

  7. Chemotherapy and target therapy for hepatocellular carcinoma: New advances and challenges

    PubMed Central

    Deng, Gan-Lu; Zeng, Shan; Shen, Hong

    2015-01-01

    Primary liver cancer is one of the commonest causes of death. Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers. For patients with unresectable or metastatic HCC, conventional chemotherapy is of limited or no benefit. Sorafenib is the only systemic treatment to demonstrate a statistically significant but modest overall survival benefit, leading to an era of targeted agents. Many clinical trials of targeted drugs have been carried out with many more in progress. Some drugs like PTK787 showed potential benefits in the treatment of HCC. Despite these promising breakthroughs, patients with HCC still have a dismal prognosis. Recently, both a phase III trial of everolimus and a phase II clinical trial of trebananib failed to demonstrate effective antitumor activity in advanced HCC. Sorafenib still plays a pivotal role in advanced HCC, leading to further explorations to exert its maximum efficacy. Combinations targeted with chemotherapy or transarterial chemoembolization is now being tested and might bring about advances. New targeted agents such as mammalian target of rapamycin inhibitors are under investigation, as well as further exploration of the mechanism of hepatocarcinogenesis. PMID:25914779

  8. Is Gemcitabine and Cisplatin Induction Chemotherapy Superior in Locoregionally Advanced Nasopharyngeal Carcinoma?

    PubMed Central

    Zheng, Wei; Qiu, Sufang; Huang, Lingling; Pan, Jianji

    2015-01-01

    Objective: To investigate the outcome of locoregionally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy followed by chemoradiotherapy. Methods: Between June 2005 and October 2007, 604 patients with locoregionally advanced NPC were analyzed, of whom 399 and 205 were treated with conventional radiotherapy and intensity-modulated radiotherapy (IMRT) respectively. Meanwhile, 153 patients received concurrent chemotherapy, and 520 were given induction chemotherapy. Results: With a median follow-up time of 65 months, the 3-, and 5-year overall survival (OS), locoregional free survival (LRFS), and distant-metastasis free survival (DMFS) rates were 82.5% vs. 72.6%, 90.6% vs. 87.1%, and 82.5% vs. 81.2%, respectively. Induction chemotherapy was not an independent prognostic factor for OS (P=0.193) or LRFS, but there was a positive tendency for DMFS (P=0.088). GP regimen (gemcitabine + cisplatin) was an independent prognostic factor for OS (P = 0.038) and it had a trend toward improved DMFS (P = 0.109). TP regimen (taxol + cisplatin) was only a significant prognostic factor for DMFS (P =0.038). Conclusions: Adding induction chemotherapy had no survival benefit, but GP regimen benefited overall survival and had a trend toward improved DMFS. GP regimen may be superior to TP/FP regimen (fluorouracil + cisplatin) in treating locoregionally advanced NPC. PMID:26430402

  9. Patterns of treatment and costs of intermediate and advanced hepatocellular carcinoma management in four Italian centers

    PubMed Central

    Colombo, Giorgio Lorenzo; Cammà, Calogero; Attili, Adolfo Francesco; Ganga, Roberto; Gaeta, Giovanni Battista; Brancaccio, Giuseppina; Franzini, Jean Marie; Volpe, Marco; Turchetti, Giuseppe

    2015-01-01

    Background Hepatocellular carcinoma (HCC) is a severe health condition associated with high hospitalizations and mortality rates, which also imposes a relevant economic burden. Purpose The aim of the present survey is to investigate treatment strategies and related costs for HCC in the intermediate and advanced stages of the disease. Patients and methods The survey was conducted in four Italian centers through structured interviews with physicians. Information regarding the stage of disease, treatments performed, and related health care resource consumption was included in the questionnaire. Direct health care cost per patient associated with the most relevant treatments such as sorafenib, transarterial chemoembolization (TACE), and transarterial radioembolization (TARE) was evaluated. Results Between 2013 and 2014, 285 patients with HCC were treated in the four participating centers; of these, 80 were in intermediate stage HCC (Barcelona Clinic Liver Cancer Classification [BCLC] B), and 57 were in the advanced stage of the disease (BCLC C). In intermediate stage HCC, the most frequent first-line treatment was TACE (63%) followed by sorafenib (15%), radiofrequency ablation (14%), and TARE (1.3%). In the advanced stage of HCC, the most frequently used first-line therapy was sorafenib (56%), followed by best supportive care (21%), TACE (18%), and TARE (3.5%). The total costs of treatment per patient amounted to €12,214.54 with sorafenib, €13,418.49 with TACE, and €26,106.08 with TARE. Both in the intermediate and in the advanced stage of the disease, variability in treatment patterns among centers was observed. Conclusion The present analysis raises for the first time the awareness of the overall costs incurred by the Italian National Healthcare System for different treatments used in intermediate and advanced HCC. Further investigations would be important to better understand the effective health care resource usage. PMID:26527877

  10. Systemic treatment and targeted therapy in patients with advanced hepatocellular carcinoma

    PubMed Central

    Tazi, El Mehdi; Essadi, Ismail; M’rabti, Hind; Touyar, Anass; Errihani, PR Hassan

    2011-01-01

    Background: Advanced hepatocellular carcinoma (HCC) is a malignancy of global importance: it is the sixth most common cancer and the third most common cause of cancer-related mortality worldwide. Despite decades of efforts by many investigators, systemic chemotherapy or hormone therapy has failed to demonstrate improved survival in patients with HCC.. Ongoing studies are evaluating the efficacy and tolerability of combining Sorafenib with erlotinib and other targeted agents or chemotherapy. Aims: On the basis of placebo-controlled, randomized phase III trials, Sorafenib has shown improved survival benefits in advanced HCC and has set a new standard for future clinical trials. The successful clinical development of Sorafenib in HCC has ushered in the era of molecularly targeted agents in this disease, which is discussed in this educational review. Material and Methods: Many molecularly targeted agents that inhibit angiogenesis, epidermal growth factor receptor, and mammalian target of rapamycin are at different stages of clinical development in advanced HCC. Future research should continue to unravel the mechanism of hepatocarcinogenesis and to identify key relevant molecular targets for therapeutic intervention. Identification and validation of potential surrogate and predictive biomarkers hold promise to individualize patients’ treatment to maximize clinical benefit and minimize the toxicity and cost of targeted agents. Results: Systemic therapy with various classes of agents, including hormone and cytotoxic agents, has provided no or marginal benefits. Improved understanding of the mechanism of hepatocarcinogenesis, coupled with the arrival of many newly developed molecularly targeted agents, has provided the unique opportunity to study some of these novel agents in advanced HCC. Conclusions: The demonstration of improved survival benefits by Sorafenib in advanced HCC has ushered in the era of molecular-targeted therapy in this disease, with many agents

  11. Diffuse large B-cell lymphoma mimicking advanced basal cell carcinoma.

    PubMed Central

    Akinyemi, Emmanuel; Mai, Le; Matin, Abu; Maini, Archana

    2007-01-01

    Primary cutaneous B-cell lymphomas (PCBCLs) are made up of a heterogenous group of B-cell lymphoproliferative diseases confined to the skin at the time of diagnosis with no evidence of extracutaneous involvement. With early diagnosis and adequate treatment, PCBCLs as a group has excellent prognosis, with about a 95% survival rate at five years. We report a case of diffuse large B-cell lymphoma (DLBCL) in a 52-year-old woman presenting as a fungating skin ulcer mimicking advanced basal cell carcinoma. Review of available literature showed most studies of PCBCLs being done on Europeans with no universally acceptable system of classification. Clinical findings, diagnostic evaluations and treatment outcomes of PCBCLs are discussed with emphasis on comparison of European Organization for Research and Treatment of Cancer (EORTC) and the World Health Organization (WHO) Classification of Neoplasms of the Hematopoietic and Lymphoid Tissue classification systems. Images Figure 1 Figure 2 PMID:17722675

  12. Diffuse large B-cell lymphoma mimicking advanced basal cell carcinoma.

    PubMed

    Akinyemi, Emmanuel; Mai, Le; Matin, Abu; Maini, Archana

    2007-08-01

    Primary cutaneous B-cell lymphomas (PCBCLs) are made up of a heterogenous group of B-cell lymphoproliferative diseases confined to the skin at the time of diagnosis with no evidence of extracutaneous involvement. With early diagnosis and adequate treatment, PCBCLs as a group has excellent prognosis, with about a 95% survival rate at five years. We report a case of diffuse large B-cell lymphoma (DLBCL) in a 52-year-old woman presenting as a fungating skin ulcer mimicking advanced basal cell carcinoma. Review of available literature showed most studies of PCBCLs being done on Europeans with no universally acceptable system of classification. Clinical findings, diagnostic evaluations and treatment outcomes of PCBCLs are discussed with emphasis on comparison of European Organization for Research and Treatment of Cancer (EORTC) and the World Health Organization (WHO) Classification of Neoplasms of the Hematopoietic and Lymphoid Tissue classification systems.

  13. Treatment of advanced squamous cell carcinoma of the lung: a review

    PubMed Central

    Mileham, Kathryn F.; Bonomi, Philip D.; Batus, Marta; Fidler, Mary J.

    2015-01-01

    Lung cancer remains the single deadliest cancer both in the US and worldwide. The great majority of squamous cell carcinoma (SCC) is attributed to cigarette smoking, which fortunately is declining alongside cancer incidence. While we have been at a therapeutic plateau for advanced squamous cell lung cancer patients for several decades, recent observations suggest that we are on the verge of seeing incremental survival improvements for this relatively large group of patients. Current studies have confirmed an expanding role for immunotherapy [including programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibition], a potential opportunity for VEGFR inhibition, and even future targets in fibroblast growth factor receptor (FGFR) and PI3K-AKT that collectively should improve survival as well as quality of life for those affected by squamous cell lung cancer over the next decade. PMID:26629421

  14. A case report of peritoneal tuberculosis with multiple miliary peritoneal deposits mimicking advanced ovarian carcinoma

    PubMed Central

    Yazdani, Shahla; Sadeghi, Mahmod; Alijanpour, Abolhasan; Naeimi-rad, Mojgan

    2016-01-01

    Background: Peritoneal tuberculosis accounts 1-2% of all forms of tuberculosis. Peritoneal tuberculosis is an important differential diagnosis for ovarian cancer in women with ascites, adnexal mass and elevated cancer antigen 125 (CA125) levels. We report a case of a 32- year -old woman with multiple miliary peritoneal deposits mimicking advanced ovarian carcinoma. Case Presentation: A 32-year-old drug addicted woman presented with menometrorrhagia, fever and shivering, ascites and pelvis mass. Ultrasonography revealed a 53×65 mm cyst in left ovary and ascites. Multiple miliary peritoneal deposits were observed during laparatomy without any mass, histologic examination confirmed tuberculosis of uterus, tubes, omentum, liver and external surfaces of small intestine. Finally, the patient recovered with anti-tuberculosis treatment. Conclusion: These findings highlight considering tuberculosis in the differential diagnosis of any patients with adnexal mass, ascitis and elevated serum CA125 even with negative cytology and bacteriology test results. PMID:26958336

  15. Combination chemotherapy for advanced squamous cell carcinoma of the head and neck.

    PubMed

    Coker, D D; Elias, E G; Chretien, P B; Gray, W C; Coleman, J J; Zentai, T A; Didolkar, M S; Morris, D M; Viravathana, T; Hebel, J R

    1981-01-01

    Fifty-one patients (32 previously untreated, 19 previously treated) with advanced squamous cell carcinoma of the head and neck received a single course of combination chemotherapy consisting of high dose cis-platinum (DDP), bleomycin (Bleo), +/- high dose methotrexate (MTX). Thirty-three (65%) patients responded to therapy; 5 (10%) of these patients had a complete response. Previously untreated patients and those who received the three drugs (DDP, Bleo and MTX) had the highest response rates. The duration of response was 8 to 12 weeks. Seven (15%) patients showed a two-year survival rate. All nonresponders were dead of disease within two years. Three (56%) of the five complete-response patients and 4 (21%) of the partial-response patients survived for two years. The role of preoperative chemotherapy in head and neck cancer is yet to be conclusively defined.

  16. Locally advanced and metastatic basal cell carcinoma: molecular pathways, treatment options and new targeted therapies.

    PubMed

    Ruiz Salas, Veronica; Alegre, Marta; Garcés, Joan Ramón; Puig, Lluis

    2014-06-01

    The hedgehog (Hh) signaling pathway has been identified as important to normal embryonic development in living organisms and it is implicated in processes including cell proliferation, differentiation and tissue patterning. Aberrant Hh pathway has been involved in the pathogenesis and chemotherapy resistance of different solid and hematologic malignancies. Basal cell carcinoma (BCC) and medulloblastoma are two well-recognized cancers with mutations in components of the Hh pathway. Vismodegib has recently approved as the first inhibitor of one of the components of the Hh pathway (smoothened). This review attempts to provide current data on the molecular pathways involved in the development of BCC and the therapeutic options available for the treatment of locally advanced and metastatic BCC, and the new targeted therapies in development.

  17. Lenvatinib therapy for the treatment of patients with advanced renal cell carcinoma.

    PubMed

    Glen, Hilary

    2016-10-01

    Despite advances in metastatic renal cell carcinoma (mRCC) treatments, patients eventually progress and develop resistance to therapies targeting a single pathway. Lenvatinib inhibits VEGFR1-3, FGFR1-4, PDGFRβ, RET and KIT proto-oncogenes. In a randomized, Phase II trial evaluating patients with mRCC who had progressed after one prior VEGF-targeted therapy, progression-free survival was significantly improved with lenvatinib alone or in combination with everolimus versus everolimus alone. This review summarizes the clinical development of lenvatinib in mRCC, and how simultaneous targeting of multiple pathways involved in carcinogenesis and/or therapeutic resistance may improve patient outcomes. Lenvatinib plus everolimus may be a promising second-line treatment in patients with mRCC.

  18. Molecularly targeted therapy for advanced hepatocellular carcinoma - a drug development crisis?

    PubMed Central

    Thillai, Kiruthikah; Ross, Paul; Sarker, Debashis

    2016-01-01

    Hepatocellular carcinoma is the fastest growing cause of cancer related death globally. Sorafenib, a multi-targeted kinase inhibitor, is the only drug proven to improve outcomes in patients with advanced disease offering modest survival benefit. Although comprehensive genomic mapping has improved understanding of the genetic aberrations in hepatocellular cancer (HCC), this knowledge has not yet impacted clinical care. The last few years have seen the failure of several first and second line phase III clinical trials of novel molecularly targeted therapies, warranting a change in the way new therapies are investigated in HCC. Potential reasons for these failures include clinical and molecular heterogeneity, trial design and a lack of biomarkers. This review discusses the current crisis in HCC drug development and how we should learn from recent trial failures to develop a more effective personalised treatment paradigm for patients with HCC. PMID:26909132

  19. CEP55 overexpression predicts poor prognosis in patients with locally advanced esophageal squamous cell carcinoma

    PubMed Central

    Jiang, Wenpeng; Wang, Zhou; Jia, Yang

    2017-01-01

    Development of esophageal squamous cell carcinoma (ESCC) involves alterations in multiple genes with corresponding proteins. Recent studies have demonstrated that centrosomal protein 55 (CEP55) shares certain features with oncogenes, and CEP55 overexpression is associated with the development and progression of malignant tumors. The present study aimed to analyze, for the first time, whether CEP55 expression is related to clinicopothalogic features in the esophageal squamous cell carcinoma (ESCC), as well as patient survival. A total of 110 patients with mid-thoracic ESCC who suffered from Ivor-Lewis were enrolled. The CEP55 expression profile of these patients in tumour tissues and corresponding healthy esophageal mucosa (CHEM) was detected by immunohistochemistry and semi-quantitative reverse transcription-polymerase chain reaction analyses. Correlations between CEP55 expression and clinicopathological factors were analyzed using χ2 test. The log-rank test was employed to calculate survival rate. A Cox regression multivariate analysis was performed to determine independent prognostic factors. The results demonstrated that CEP55 expression in ESCC was significantly higher than that of CHEM (P<0.001). Overexpression of CEP55 was significantly associated with differentiation degree (P=0.022), T stage (P=0.019), lymph node metastasis (P=0.033), clinicopathological staging (P=0.002) and tumor recurrence (P=0.021) in locally advanced ESCC patients. In addition, CEP55 overexpression was significantly associated with reduced overall survival of patients after surgery (P=0.012). The 5-year survival rate of patients without CEP55 overexpression was significantly higher than that of patients with CEP55 overexpression (P=0.012). Therefore, these findings suggest that CEP55 overexpression correlates with poor prognosis in locally advanced ESCC patients. PMID:28123547

  20. Teaching laryngeal electromyography.

    PubMed

    Volk, Gerd Fabian; Pototschnig, Claus; Mueller, Andreas; Foerster, Gerhard; Koegl, Sophie; Schneider-Stickler, Berit; Rovo, Laszlo; Nawka, Tadeus; Guntinas-Lichius, Orlando

    2015-07-01

    To achieve consensus in the methodology, interpretation, validity, and clinical application of laryngeal electromyography (LEMG), a working group on neurolaryngology from the European Laryngological Society (ELS) was founded in 2010. The main task of the working group was to teach key techniques like LEMG procedures. The objective of this study was to collect information on the teaching techniques used and describe them. A multicenter registry was created to analyze the data collected from LEMGs in 14 departments. We screened how often different departments participated in teaching events. Teaching events were classified retrospectively: presentations at conferences and meetings; workshops with hands-on training on patients; workshops with hands-on training on animal models; workshops with hands-on training on anatomic specimens; and supervision by experts to perform LEMG together. Both, supervision to perform LEMG together and the total number of PCA-LEMGs (r = 0.713), as well as supervision to perform LEMG together and the PCA/total-number-of-LEMG ratio (r = 0.814) were correlated significantly (p < 0.05). Similarly, the sum of teaching events was correlated significantly with the total number of PCA-LEMGs (r = 0.605), and so did the sum of teaching events with the PCA/total-number-of-LEMG ratio (r = 0.704). Participation in hands-on training in humans was correlated significantly with the PCA/total-number-of-LEMG ratio (r = 0.640). The data presented herein suggest that multimodal teaching techniques are most effective. To promote multimodal learning an interactive webpage ( http://www.lemg.org) providing videos and animations, and the possibility to discuss cases with other experts was established.

  1. Trans-arterial radioembolization in intermediate-advanced hepatocellular carcinoma: systematic review and meta-analyses

    PubMed Central

    Rognoni, Carla; Ciani, Oriana; Sommariva, Silvia; Facciorusso, Antonio; Tarricone, Rosanna; Bhoori, Sherrie; Mazzaferro, Vincenzo

    2016-01-01

    Trans-arterial radioembolization (TARE) is a recognized, although not explicitly recommended, experimental therapy for unresectable hepatocellular carcinoma (HCC). A systematic literature review was performed to identify published studies on the use of TARE in intermediate and advanced stages HCC exploring the efficacy and safety of this innovative treatment. Twenty-one studies reporting data on overall survival (OS) and time to progression (TTP), were included in a meta-analysis. The pooled post-TARE OS was 63% (95% CI: 56-70%) and 27% (95% CI: 21-33%) at 1- and 3-years respectively in intermediate stage HCC, whereas OS was 37% (95% CI: 26-50%) and 13% (95% CI: 9-18%) at the same time intervals in patients with sufficient liver function (Child-Pugh A-B7) but with an advanced HCC because of the presence of portal vein thrombosis. When an intermediate and advanced case-mix was considered, OS was 58% (95% CI: 48-67%) and 17% (95% CI: 12-23%) at 1- and 3-years respectively. As for TTP, only four studies reported data: the observed progression probability was 56% (95% CI: 41-70%) and 73% (95% CI: 56-87%) at 1 and 2 years respectively. The safety analysis, focused on the risk of liver decompensation after TARE, revealed a great variability, from 0-1% to more than 36% events, influenced by the number of procedures, patient Child-Pugh stage and treatment duration. Evidence supporting the use of radioembolization in HCC is mainly based on retrospective and prospective cohort studies. Based on this evidence, until the results of the ongoing randomized trials become available, radioembolization appears to be a viable treatment option for intermediate-advanced stage HCC. PMID:27579537

  2. Cervical metastasis on level IV in laryngeal cancer.

    PubMed

    Furtado de Araújo Neto, V J; Cernea, C R; Aparecido Dedivitis, R; Furtado de Araújo Filho, V J; Fabiano Palazzo, J; Garcia Brandão, L

    2014-02-01

    The presence of cervical metastasis has substantial negative impact on survival of patients with laryngeal cancer. Bilateral elective selective neck dissection of levels II, III and IV is usually the chosen approach in these patients. However, there is significant morbidity associated with level IV dissection, such as phrenic nerve injury and lymphatic fistula. The objective of the present study was to evaluate the frequency of metastatic nodes in level IV in clinically T3/T4N0 patients with laryngeal cancer. The pathological reports of 77 patients with clinically T3/T4N0 laryngeal squamous cell carcinoma were reviewed. Patients underwent bilateral lateral neck dissection from January 2007 to November 2012. The surgical specimens were subdivided in levels before evaluation. There were 12 patients with neck metastasis (15.58%). In 3 cases (3.89%), there were metastatic lymph nodes in level IV, all T4 and with ipsilateral metastasis. In conclusion, the incidence of level IV metastasis was 3.89%, an in all patients was staged as T4.

  3. Impact of histological subtype on survival in patients with locally advanced cervical cancer that were treated with definitive radiotherapy: adenocarcinoma/adenosquamous carcinoma versus squamous cell carcinoma

    PubMed Central

    Kuroda, Hiromasa; Kimura, Tadashi

    2017-01-01

    Objective To compare the survival outcomes of patients with cervical squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) among patients with locally advanced cervical cancer that were treated with definitive radiotherapy. Methods The baseline characteristics and outcome data of patients with locally advanced cervical cancer who were treated with definitive radiotherapy between November 1993 and February 2014 were collected and retrospectively reviewed. A Cox proportional hazards regression model was used to investigate the prognostic significance of AC/ASC histology. Results The patients with AC/ASC of the cervix exhibited significantly shorter overall survival (OS) (p=0.004) and progression-free survival (PFS) (p=0.002) than the patients with SCC of the cervix. Multivariate analysis showed that AC/ASC histology was an independent negative prognostic factor for PFS. Among the patients who displayed AC/ASC histology, larger tumor size, older age, and incomplete response to radiotherapy were found to be independent prognostic factors. PFS was inversely associated with the number of poor prognostic factors the patients exhibited (the estimated 1-year PFS rates; 100.0%, 77.8%, 42.8%, 0.0% for 0, 1, 2, 3 factors, respectively). Conclusion Locally advanced cervical cancer patients with AC/ASC histology experience significantly worse survival outcomes than those with SCC. Further clinical studies are warranted to develop a concurrent chemoradiotherapy (CCRT) protocol that is specifically tailored to locally advanced cervical AC/ASC. PMID:28028992

  4. [Microlaryngoscopy treatment of laryngeal dysplasia with CO2 laser].

    PubMed

    Motta, G; Esposito, E; Motta, S; Testa, D

    2001-02-01

    Classification of laryngeal dysplasia, the most appropriate treatments and criteria for evaluation of the results is still a highly controversial issue. The objectives of the present study on the treatment of laryngeal dysplasia lesions are to: 1) evaluate the relative incidence of the various forms of dysplasia in relation to grading of the histopathological findings; 2) establish the prognosis for the various forms of dysplasia considered; 3) determine the results achieved by the author's treatment protocol according to the characteristics of the dysplasia; 4) critically evaluate the classifications of laryngeal dysplasia found in the literature in view of the results of the present study. The study involved 141 patients with vocal cord dysplasia (134 men, 7 women; mean age: 56.2 years) who had come under observation at the E.N.T. Dept. of the University of Naples "Federico II" between January 1981 and April 1998. In all cases the dysplasia was removed by CO2 laser microlaryngoscopy. Of the 141 patients 89 (63.2%) showed mild dysplasia, 14 (9.9%) moderate dysplasia, 20 (14.2%) severe dysplasia and 18 (12.7%) in situ carcinoma. The five-year survival rate showed an overall actuarial survival of 89.1% for all patients while the corrected actuarial survival was 98.5% and local disease control was 86.1%. In 17 cases (12%) the dysplasia lesion recurred, in 11 (7.8%) an infiltrating carcinoma arose. Recurrences in the dysplasia were encountered in 9% of the patients with mild lesions, 7.1% of those with moderate dysplasia, 15% of the subjects with the severe form and in 27.7% of those with in situ carcinoma. An infiltrating carcinoma arose in 5.6% of the cases of mild lesion, in 7.1% of the medium dysplasias, 5% of the severe forms and in 22.2% of those with in situ carcinoma. The recurrences and infiltrating carcinomas were successfully treated with endoscopic CO2 laser surgery. Only three cases (2.1%) required radical surgery (total laryngectomy): these were patients

  5. Safety and efficacy of sorafenib in patients with Child-Pugh B advanced hepatocellular carcinoma.

    PubMed

    DA Fonseca, Leonardo Gomes; Barroso-Sousa, Romualdo; Bento, Afonso DA Silva Alves; Blanco, Bruna Paccola; Valente, Gabriel Luis; Pfiffer, Tulio Eduardo Flesch; Hoff, Paulo Marcelo; Sabbaga, Jorge

    2015-07-01

    Sorafenib demonstrated a survival benefit in the treatment of advanced hepatocellular carcinoma (HCC) in phase III trials. However, almost all the patients included in those trials exhibited well-preserved liver function (Child-Pugh A). The aim of this study was to describe our experience with sorafenib in Child-Pugh B HCC patients. A database of patients with advanced HCC treated with sorafenib was retrospectively evaluated. The median overall survival of Child-Pugh B patients (n=20) was 2.53 months [95% confidence interval (CI): 0.33-5.92 months] and of Child-Pugh A patients (n=100) 9.71 months (95% CI: 6.22-13.04). Child-Pugh B patients had a significantly poorer survival compared to Child-Pugh A patients (P=0.002). The toxicities were similar between the two groups. Metastasis, vascular invasion and α-fetoprotein level >1,030 ng/ml were not associated with survival among Child-Pugh B patients (P=0.281, 0.189 and 0.996, respectively). Although the survival outcomes were worse in Child-Pugh B patients treated with sorafenib, the toxicity profile was manageable. Therefore, there remains the question of whether to treat this subgroup of patients and more data are required to define the role of sorafenib in the context of liver dysfunction.

  6. Prognosis and value of preoperative radiotherapy in locally advanced rectal signet-ring cell carcinoma

    PubMed Central

    Ling, Chun-Run; Wang, Rui; Wang, Mo-Jin; Ping, Jie; Zhuang, Wen

    2017-01-01

    As well known, signet-ring cell carcinoma (SRCC) is a rare histological subtype of colorectal adenocarcinoma, which has been associated with poor prognosis and resistant to non-surgery therapy compared with common adenocarcinoma. In this study, we assessed the effect of preoperative radiotherapy (PRT) for locally advanced rectal SRCC in a large patient group from the Surveillance, Epidemiology, and End Results program (SEER, 1988–2011) database. SRCC was found in 0.9% (n = 622) rectal cancer (RC) patients in our study. In the PRT setting, SRCC had significantly worse cancer-specific survival than mucinous adenocarcinoma and nonmucinous adenocarcinoma patients (log-rank, P < 0.001). In terms of SRCC, stage III RC patients benefited from PRT (log-rank, P < 0.001) while stage II did not (P = 0.095). The multivariate Cox proportional hazard model showed that PRT was an independent benefit factor in stage III rectal SRCC patients (HR, 0.611; 95% CI, 0.407–0.919; P = 0.018). In conclusion, SRCC was an independent predictor of poor prognosis in stage III RC patients, but not in stage II. In the PRT setting of locally advanced RC, SRCC patients had significantly worse prognosis. PRT was an independent prognostic factor associated with improved survival in stage III rectal SRCC. PMID:28345614

  7. Oesophageal squamous cell carcinoma (ESCC): Advances through omics technologies, towards ESCC salivaomics.

    PubMed

    González-Plaza, Juan José; Hulak, Nataša; García-Fuentes, Eduardo; Garrido-Sánchez, Lourdes; Zhumadilov, Zhaxybay; Akilzhanova, Ainur

    2015-08-01

    Oesophageal Squamous Cell Carcinoma (ESCC) is one of the two main subtypes of oesophageal cancer, affecting mainly populations in Asia. Though there have been great efforts to develop methods for a better prognosis, there is still a limitation in the staging of this affection. As a result, ESCC is detected at advances stages, when the interventions on the patient do not have such a positive outcome, leading in many cases to recurrence and to a very low 5-year survival rate, causing high mortality. A way to decrease the number of deaths is the use of biomarkers that can trace the advance of the disease at early stages, when surgical or chemotherapeutic methodologies would have a greater effect on the evolution of the subject. The new high throughput omics technologies offer an unprecedented chance to screen for thousands of molecules at the same time, from which a new set of biomarkers could be developed. One of the most convenient types of samples is saliva, an accessible body fluid that has the advantage of being non-invasive for the patient, being easy to store or to process. This review will focus on the current status of the new omics technologies regarding salivaomics in ESCC, or when not evaluated yet, the achievements in related diseases.

  8. Hyperbaric oxygen therapy for laryngeal radionecrosis

    SciTech Connect

    Ferguson, B.J.; Hudson, W.R.; Farmer, J.C. Jr.

    1987-01-01

    Radionecrosis of the larynx is a debilitating disease associated with pain, dysphagia, respiratory obstruction, and, in some cases, the need for laryngectomy. Persistent poor wound healing can lead to death. A series of eight patients with advanced (grades III and IV, Chandler classification) radionecrosis of the larynx treated with adjunctive hyperbaric oxygen therapy is presented. Signs and symptoms of radionecrosis were dramatically ameliorated in seven of eight patients, while one patient, despite subjective improvement, eventually required laryngectomy. There were no deaths. These results are compared to previous series on radionecrosis of the larynx in which hyperbaric oxygen was not used. This series indicates that hyperbaric oxygen therapy is a useful and effective adjunctive treatment modality in the management of laryngeal radionecrosis.

  9. Reconstruction With Modified Face Lift and Orbicularis Oculi V-Y Advancement Flap for Sebaceous Carcinoma on Temple Area.

    PubMed

    Lee, Byeong Ho; Kim, Joo Hyun; Park, Seong Hoon; Ahn, Duk Kyun; Suh, In Suck; Jeong, Hii Sun

    2015-09-01

    Extraocular sebaceous carcinoma that occurs on sebaceous gland is a rare malignant cancer with unknown causes and nonspecific clinical characters, but with distinct pathology and immunohistochemical finding. In Kangnam Sacred Heart Hospital, there was a case that the result of preoperative punch biopsy was squamous cell carcinoma and malignant proliferating trichilemmal tumor, but that of postoperative permanent biopsy was sebaceous carcinoma. The type of tumor, differentiation, location, and aesthetic results are considered to get both recurrence-safe and aesthetically pleasing result. Various flaps were considered, and modified face-lift flap, forehead rotation flap, orbicularis oculi V-Y advancement flap were planned. There were no sign of recurrence of cancer or functional and aesthetical deformities 6 months after the surgery.

  10. Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck

    PubMed Central

    Pivot, X; Raymond, E; Laguerre, B; Degardin, M; Cals, L; Armand, J P; Lefebvre, J L; Gedouin, D; Ripoche, V; Kayitalire, L; Niyikiza, C; Johnson, R; Latz, J; Schneider, M

    2001-01-01

    This phase II study determined response rate of patients with locally advanced or metastatic head and neck cancer treated with pemetrexed disodium, a new multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. 35 patients with local or metastatic relapse of squamous cell carcinoma of the head and neck (31 male, 4 female; median age 53 years) were treated with pemetrexed 500 mg m2 administered as a 10-minute infusion on day 1 of a 21-day cycle. Patients received 1 to 8 cycles of therapy. 9 patients (26.5%) had an objective response, with a median response duration of 5.6 months (range 2.9–20 months). 15 (44.1%) had stable disease, and 8 (23.5%) had progressive disease. 2 patients were not assessable for response. Median overall survival was 6.4 months (range 0.7–28.1 months; 95% CI: 3.9–7.7 months). 24 patients (68.6%) experienced grade 3/4 neutropenia, with febrile neutropenia in 4 (11.4%). Grade 3/4 anaemia and thrombocytopenia occurred in 11 (34.3%) and 6 (17.1%) patients, respectively. The most frequent non-haematological toxicity was grade 3/4 mucositis (17.1%; 6 patients). In conclusion, pemetrexed is active in squamous cell carcinoma of the head and neck. Although substantial haematological toxicities were experienced by patients, subsequent studies have shown that these toxicities can be proactively managed by folic acid and vitamin B12 supplementation. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11531245

  11. Effect of multidrug resistance 1/P-glycoprotein on the hypoxia-induced multidrug resistance of human laryngeal cancer cells.

    PubMed

    Li, Dawei; Zhou, Liang; Huang, Jiameng; Xiao, Xiyan

    2016-08-01

    In a previous study, it was demonstrated that hypoxia upregulated the multidrug resistance (MDR) of laryngeal cancer cells to chemotherapeutic drugs, with multidrug resistance 1 (MDR1)/P-glycoprotein (P-gp) expression also being upregulated. The present study aimed to investigate the role and mechanism of MDR1/P-gp on hypoxia-induced MDR in human laryngeal carcinoma cells. The sensitivity of laryngeal cancer cells to multiple drugs and cisplatin-induced apoptosis was determined by CCK-8 assay and Annexin-V/propidium iodide staining analysis, respectively. The accumulation of rhodamine 123 (Rh123) in the cells served as an estimate of drug accumulation and was evaluated by flow cytometry (FCM). MDR1/P-gp expression was inhibited using interference RNA, and the expression of the MDR1 gene was analyzed using reverse transcription-quantitative polymerase chain reaction and western blotting. As a result, the sensitivity to multiple chemotherapeutic agents and the apoptosis rate of the hypoxic laryngeal carcinoma cells increased following a decrease in MDR1/P-gp expression (P<0.05). Additionally, FCM analysis of fluorescence intensity indicated that the downregulated expression of MDR1/P-gp markedly increased intracellular Rh123 accumulation (P<0.05). Such results suggest that MDR1/P-gp serves an important role in regulating hypoxia-induced MDR in human laryngeal carcinoma cells through a decrease in intracellular drug accumulation.

  12. Transcatheter Arterial Chemoembolization for Advanced Hepatocellular Carcinoma with Inferior Vena Cava and Right Atrial Tumors

    SciTech Connect

    Chern, M. C. Chuang, V. P. Cheng, T. Lin, Z. H. Lin, Y. M.

    2008-07-15

    Advanced hepatocelluar carcinoma (HCC) with invasion of venous systems usually indicates not only a poor prognosis but also a contraindication for transcatheter arterial chemoembolization (TACE). This study evaluated the feasibility of TACE for advanced HCC with inferior vena cava (IVC) and right atrium (RA) tumors and, also, to search for the ideal embolization particle size. Twenty-six patients who had HCC invasion into the IVC included five patients with coexistent RA tumors that were treated with TACE. The chemoembolization method was cisplatin, doxorubicin, and mitomycin C mixed with Lipiodol and Ivalon. The selection of Ivalon particles was divided into two groups based on their size: (A) >180 {mu}m, N = 9; and (B) 47-180 {mu}m, N = 17. The overall response rate was 53.8% (14/26). Based on the response to TACE, the median survival period of the entire group was 4.2 months (range, 1.5 to 76.7 months). The median survival period of the 14 responders was 13.5 months (1.5-76.7 months), and that of the 12 nonresponders, 3.3 months (2.1 to 24.3 months) (p < 0.002). Comparing the two Ivalon particle sizes, the response rate was 12.5% (1/9 patients) for group A and 76.5% for group B (13/17 patients) (p < 0.02). No serious complication was observed post-chemoembolization. In conclusion, TACE is a safe and effective treatment for advanced HCC with IVC and RA tumors, and small Ivalon particles (47-180 {mu}m) are superior to large ones (>180 {mu}m).

  13. Efficacy, safety, pharmacokinetics and biomarkers of cediranib monotherapy in advanced hepatocellular carcinoma: A phase II study

    PubMed Central

    Zhu, Andrew X.; Ancukiewicz, Marek; Supko, Jeffrey G.; Sahani, Dushyant V.; Blaszkowsky, Lawrence S.; Meyerhardt, Jeffrey A.; Abrams, Thomas A.; McCleary, Nadine Jackson; Bhargava, Pankaj; Muzikansky, Alona; Sheehan, Susan; Regan, Eileen; Vasudev, Eamala; Knowles, Michelle; Fuchs, Charles S.; Ryan, David P.; Jain, Rakesh K.; Duda, Dan G.

    2013-01-01

    Purpose We performed a single-arm phase II study of cediranib, a pan-VEGFR tyrosine kinase inhibitor, in patients with advanced hepatocellular carcinoma (HCC). Patients and Methods Patients with histologically confirmed measurable advanced HCC and adequate hematologic, hepatic, and renal functions received cediranib 30-mg orally once daily (4 weeks/cycle). The primary endpoint was progression-free survival (PFS) rate at 3 months. Other endpoints included response rates, overall survival (OS), pharmacokinetics (PK) and biomarkers for cediranib. Results Cediranib treatment resulted in an estimated 3-month-PFS rate of 77% [60%, 99%]. Median PFS was 5.3 [3.5,9.7] months, stable disease was seen in 5/17 patients (29%), and median OS was 11.7 [7.5–13.6] months. Grade 3 toxicities included hypertension (29%), hyponatremia (29%) and hyperbilirubinemia (18%). Cediranib PK were comparable to those seen in cancer patients with normal hepatic function. Plasma levels of VEGF and PlGF increased and sVEGFR1, sVEGFR2 and Ang-2 decreased after cediranib treatment. PFS was inversely correlated with baseline levels of VEGF, sVEGFR2, and bFGF and with on-treatment levels of bFGF and IGF-1, and directly associated with on-treatment levels of IFN-γ. OS was inversely correlated with baseline levels of sVEGFR1, Ang-2, TNF-α, CAIX and CD34+CD133+CD45dim circulating progenitor cells and on-treatment levels of sVEGFR2. Conclusions Despite the limitations of primary endpoint selection, cediranib at 30-mg daily showed a high incidence of toxicity and preliminary evidence of antitumor activity in advanced HCC. Hepatic dysfunction did not appear to affect the steady-state PK of cediranib. Exploratory studies suggested pro-angiogenic and inflammatory factors as potential biomarkers of anti-VEGF therapy in HCC. PMID:23362324

  14. Differential pharmacology and clinical utility of sonidegib in advanced basal cell carcinoma

    PubMed Central

    Wahid, Mohd; Jawed, Arshad; Dar, Sajad Ahmad; Mandal, Raju K; Haque, Shafiul

    2017-01-01

    Patients suffering from advanced basal cell carcinoma (BCC) have very limited treatment options. Sonidegib selectively inhibits the growth of Hedgehog pathway-dependent tumors and can treat locally advanced BCC patients who are not candidates for surgery or radiation therapy. The BOLT clinical trials were conducted to evaluate the efficacy/potency of sonidegib in the treatment of advanced BCC or metastatic BCC. The patients were randomized in 1:2 ratios to receive 200 or 800 mg oral sonidegib daily, stratified by disease, histological subtype and geographical region. The primary efficacy analyses showed that 18 patients in the 200 mg group and 35 patients in the 800 mg group show an objective response (Central Review Committee) that corresponds to 43% (95% confidence interval [CI]: 28–59) and 38% (95% CI: 28–48) in their respective categories. Disease control was found in 93% (39 patients) and 80% (74 patients) of the patients administered 200 and 800 mg sonidegib, respectively. The adverse events were assessed by the Central Review Committee as well as the investigator review team as per the guidelines of National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. The most frequently found adverse events reported in BOLT trials were muscle spasms, alopecia, dysgeusia (taste disturbance), nausea, elevated blood creatine kinase and fatigue. Comparatively, the patients administered 200 mg sonidegib showed fewer adverse events than those in the 800 mg sonidegib category. Thus, the benefit of using the 200 mg dose of sonidegib outweighs the associated risks and it can be inferred that it would be judicious to choose doses of lesser strength. PMID:28182134

  15. [Outcome of treatment with surgical resection of the remaining tumor after modified M-VAC treatment for advanced urothelial carcinoma].

    PubMed

    Narita, Shintaro; Nakano, Masahiro; Matsuzaki, Masato; Watanabe, Jyunichi; Morikawa, Hiroshi; Murata, Hirokatsu; Oda, Hiroyuki; Komatsu, Hideki

    2005-03-01

    We retrospectively evaluated the effect of the surgical resection of the remaining tumor after modified M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) (m-M-VAC) treatment for locally advanced or metastatic urothelial carcinoma. In m-M-VAC therapy, methotrexate and vinblastine on 15 and 22 days were omitted from the classical M-VAC to avoid the discontinuation and the dose reduction, and duration of 1 course was shortened to 21 days from 28 days of the classical M-VAC. Seven patients with locally invasive or metastatic carcinoma of the renal pelvis, ureter, and bladder, 6 males and 1 female, with a median age 64.1 years, ranging from 49 to 77 years received m-M-VAC chemotherapy without severe side effects. In all patients, the residual viable carcinoma was completely resected and they achieved complete remission. The median survival time was 20 months (range, 7 to 61). Five of these 7 patients were still alive. Two patients had no recurrence and achieved long-term survival (survival duration; 61 and 39 months). Although further studies and long-term follow up are required, these results suggest that patients who present with locally advanced or metastatic urothelial carcinoma may benefit from surgical resection after m-M-VAC.

  16. [Laryngeal tuberculosis: study of 11 cases].

    PubMed

    Montejo, M; Alonso, M; Aguirrebengoa, K; Moreno, G; Goicoetxea, J; Petreñas, E; Bañuelos, S; Vergez, A

    2001-01-01

    We report 11 patients with laryngeal tuberculosis seen in our hospital, January 1990 to July 2000. Eight were men and all cases presented with dysphonia and/or disphagia. In 8 pulmonary tuberculosis was associated. Mycobacterium tuberculosis was isolated from the sputum in 7 patients. Granulomatous laryngitis was demonstrated in the eight patients with laryngeal biopsy. The evolution with medical treatment was favourable in all patients.

  17. Nonbacterial thrombotic endocarditis with embolic cerebral vascular accidents in a patient with advanced, recurrent clear cell carcinoma of the ovary: A case report.

    PubMed

    Liang, Lusha W; Perez, Alexander R; Cangemi, Nicholas A; Young, Robert J; Makker, Vicky

    2016-04-01

    •Nonbacterial thrombotic endocarditis can occur in ovarian clear cell carcinoma.•We report on NBTE-associated embolic cerebrovascular infarcts in advanced OCCC.•Further NBTE-associated embolic events can be prevented with anticoagulant therapy.

  18. [A new bite block for laryngeal mask].

    PubMed

    Ohe, Y; Ota, M; Tachibana, C; Aoyama, Y

    2001-05-01

    We devised a new bite block made of a used connector of anesthesia machine (ACOMA medical industry CO., LTD.) for laryngeal mask. Fitness for laryngeal mask and strength against patient's biting are the key for its use. Cutting lengthwise the connector (the outside diameter 22 mm, inside diameter 15-19 mm, 55 mm in length) we made a bite block for laryngeal mask. We studied the strength of a new bite block experimentally and recognized its ability to bear the human biting. We conclude a new bite block for laryngeal mask is clinically useful and can be used during anesthesia for its fitness and safety.

  19. Long-Term Results of Concurrent Chemoradiotherapy for Advanced N2-3 Stage Nasopharyngeal Carcinoma

    PubMed Central

    Wang, Xue; Chen, Meng; Wu, Jing; Xu, Jian-Hua; Qian, Pu-Dong; Guo, Wen-Jie; Jiang, Xue-Song; Zhu, Huan-Feng; Gu, Jia-Jia; Wu, Jian-Feng; Zhang, Ye-wei; He, Xia

    2015-01-01

    Background N-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT). Patients and Methods Between April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy. Results With a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3–4 acute toxicities including bone marrow suppression (leukopenia: χ2 = 3.935, P = 0.047; anemia: χ2 = 9.760, P = 0.002; thrombocytopenia: χ2 = 8.821, P = 0.003), and both liver and renal dysfunction (χ2 = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups. Conclusion IMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute

  20. Laryngeal histoplasmosis: an occupational hazard.

    PubMed

    Teoh, Jian Woei; Hassan, Faridah; Mohamad Yunus, Mohd Razif

    2013-10-01

    Isolated laryngeal histoplasmosis is a very rare entity. It has variable clinical presentations that might mimic both benign and malignant lesions, and is usually associated with pulmonary and other disseminated forms of histoplasmosis. Herein, we report a case of primary laryngeal histoplasmosis without the involvement of other systems in a 70-year-old Chinese man, who previously worked as a miner. He presented with a history of hoarseness for two months, with no other associated symptoms. Direct laryngoscopy revealed irregularity of the posterior one-third of both vocal folds. Histopathological examination revealed the presence of Histoplasma capsulatumon periodic acidSchiff and Grocott's methenamine silver staining. The lesion resolved after one month of oral itraconazole treatment. However, the patient had to complete six months of antifungal treatment to prevent recurrence.

  1. Angiogenesis: prognostic significance in laryngeal cancer.

    PubMed

    Beatrice, F; Cammarota, R; Giordano, C; Corrado, S; Ragona, R; Sartoris, A; Bussolino, F; Valente, G

    1998-01-01

    The aim of this study was to evaluate the role of angiogenesis in the progression of laryngeal squamous cell carcinoma (LSCC). We correlated disease-free survival with microvessel count (MC) in the hot spot areas of 97 randomly selected caucasian males with LSCC followed for 60 to 90 months after surgery with or without radiotherapy. The results obtained indicate that: a) MC higher than 130 microvessels/mm2 is a cut-off value that distinguished patients who relapsed during the follow up period; b) multivariated analysis indicates that MC (p < 0.00001) is an independent predictor of disease free-survival; c) multivariated analysis selectively done on cases with relapse demonstrates that MC correlates with the presence of metastasis (or/and M) with local relapse (T). We suggest that MC is useful in the assessment of prognosis in LSCC and probably will permit selection of patients that could benefit from anti-angiogenic therapy associated with chemotherapy and/or radiotherapy.

  2. Advanced hepatocellular carcinoma and sorafenib: Diagnosis, indications, clinical and radiological follow-up

    PubMed Central

    Colagrande, Stefano; Regini, Francesco; Taliani, Gian Giacomo; Nardi, Cosimo; Inghilesi, Andrea Lorenzo

    2015-01-01

    Advanced stage hepatocellular carcinoma (HCC) is a category of disease defined by radiological, clinical and hepatic function parameters, comprehending a wide range of patients with different general conditions. The main therapeutic option is represented by sorafenib treatment, a multi-kinase inhibitor with anti-proliferative and anti-angiogenic effect. Trans-arterial Radio Embolization also represents a promising new approach to intermediate/advanced HCC. Post-marketing clinical studies showed that only a portion of patients actually benefits from sorafenib treatment, and an even smaller percentage of patients treated shows partial/complete response on follow-up examinations, up against relevant costs and an incidence of drug related adverse effects. Although the treatment with sorafenib has shown a significant increase in mean overall survival in different studies, only a part of patients actually shows real benefits, while the incidence of drug related significant adverse effects and the economic costs are relatively high. Moreover, only a small percentage of patients also shows a response in terms of lesion dimensions reduction. Being able to properly differentiate patients who are responding to the therapy from non-responders as early as possible is then still difficult and could be a pivotal challenge for the future; in fact it could spare several patients a therapy often difficult to bear, directing them to other second line treatments (many of which are at the moment still under investigation). For this reason, some supplemental criteria to be added to the standard modified Response Evaluation Criteria in Solid Tumors evaluation are being searched for. In particular, finding some parameters (cellular density, perfusion grade and enhancement rate) able to predict the sensitivity of the lesions to anti-angiogenic agents could help in stratifying patients in terms of treatment responsiveness before the beginning of the therapy itself, or in the first weeks of

  3. Role of transarterial chemoembolization in relation with sorafenib for patients with advanced hepatocellular carcinoma

    PubMed Central

    Ha, Yeonjung; Lee, Danbi; Shim, Ju Hyun; Lim, Young-Suk; Lee, Han Chu; Chung, Young-Hwa; Lee, Yung Sang; Park, Sook Ryun; Ryu, Min-Hee; Ryoo, Baek-Yeol; Kang, Yoon-Koo; Kim, Kang Mo

    2016-01-01

    Background Although sorafenib is considered standard therapy for advanced hepatocellular carcinoma (HCC), actual treatments vary. We evaluated the effects of different treatment strategies on overall survival. Methods A retrospective study of sorafenib-treated patients with advanced HCC was conducted. The primary outcome was overall survival. Prognostic factors were analyzed using multivariate Cox-proportional hazards model. Results A total of 658 patients (mean age, 54.5 years; 83.3% male) were analyzed; 293, 129, and 236 patients were treated with sorafenib, a combination therapy of sorafenib and transarterial chemoembolization (TACE), and TACE followed by sorafenib, respectively. Overall, 51.2% of patients treated under the combination strategy had portal vein invasion, whereas 89.9% of patients receiving sorafenib monotherapy had distant metastasis. Median overall survival durations were comparable (11.8 months for sorafenib, 16.2 months for the combination therapy, and 13.5 months for TACE followed by sorafenib; P = 0.13). However, among portal vein invasion cases, combination (25.7 months, P = 0.002) and TACE followed by sorafenib (14.0 months, P = 0.030) treatments were associated with longer overall survival duration compared with than sorafenib monotherapy (5.5 months). In a multivariate model, sorafenib duration (hazard ratio [HR], 0.96, P < 0.001) and TACE (HR, 0.24, P < 0.001) along with Child-Pugh stage (HR, 1.83, P = 0.005) were associated with better survival. Conclusions In patients with portal vein invasion, TACE performed concurrently with or before sorafenib administration is associated with better survival. PMID:27494871

  4. Combined-modality treatment for advanced oral tongue squamous cell carcinoma

    SciTech Connect

    Fan, K.-H.; Lin, C.-Y. |; Kang, C.-J.; Huang, S.-F.; Chen, I.-H.; Liao, C.-T. |; Wang, H.-M. |; Cheng, A.-J. |; Chang, J.T.-C. ||. E-mail: jtchang@adm.cgmh.org.tw

    2007-02-01

    Purpose: The aim of this study was to investigate prognostic factors in advanced-stage oral tongue cancer treated with postoperative adjuvant therapy and to identify indications for adjuvant concomitant chemoradiotherapy (CCRT). Methods and Materials: We retrospectively reviewed the records of 201 patients with advanced squamous cell carcinoma of the oral tongue managed between January 1995 and November 2002. All had undergone wide excision and neck dissection plus adjuvant radiotherapy or CCRT. Based on postoperative staging, 123 (61.2%) patients had Stage IV and 78 (38.8%) had Stage III disease. All patients were followed for at least 18 months after completion of radiotherapy or until death. The median follow-up was 40.4 months for surviving patients. The median dose of radiotherapy was 64.8 Gy (range, 58.8-72.8 Gy). Cisplatin-based regimens were used for chemotherapy. Results: The 3-year overall survival (OS) and recurrence-free survival (RFS) rates were 48% and 50.8%, respectively. Stage, multiple nodal metastases, differentiation, and extracapsular spread (ECS) significantly affected disease-specific survival on univariate analysis. On multivariate analysis, multiple nodal metastases, differentiation, ECS, and CCRT were independent prognostic factors. If ECS was present, only CCRT significantly improved survival (3-year RFS with ECS and with CCRT = 48.2% vs. without CCRT = 15%, p = 0.038). In the presence of other poor prognostic factors, results of the two treatment strategies did not significantly differ. Conclusions: Based on this study, ECS appears to be an absolute indication for adjuvant CCRT. CCRT can not be shown to be statistically better than radiotherapy alone in this retrospective series when ECS is not present.

  5. Relationship of ethnicity and overall survival in patients treated with sorafenib for advanced hepatocellular carcinoma

    PubMed Central

    Renouf, Daniel J.; Gill, Sharlene; Cheung, Winson Y.; Lim, Howard J.

    2014-01-01

    Background Although both the SHARP and the Asian-Pacific trials showed improved overall survival (OS) for sorafenib, the magnitude of benefit was substantially less for Asians, who have a higher prevalence of hepatitis B viral (HBV) infection. Whether the worse prognosis is related to ethnicity or to the etiology of hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to identify prognostic factors among patients with HCC who received sorafenib in British Columbia (BC), which has a sizeable Asian population. Methods A total of 255 consecutive patients with advanced HCC who initiated sorafenib from January 2008 to February 2013 were identified using our pharmacy database. Clinicopathological variables and outcomes were retrospectively collected. Prognostic factors were assessed by univariate and multivariate analyses. Results Median age was 63 years, 80.2% were men, and 38% were Asian. Among them, 34.5% had HBV and 29.8% had hepatitis C viral (HCV) infection. In addition, 68.6% had cirrhosis and 45.9% had liver-limited disease. Median progression-free and OS were 3.7 [95% confidence interval (CI): 3.3-4.2] and 7.5 months (95% CI: 5.7-9.2), respectively. On multivariate analysis, Eastern Cooperative Oncology Group performance status (ECOG PS) and HCV positivity correlated with better OS (P<0.001 and 0.04, respectively), but ethnicity did not (P=0.622). Conclusions When treated with sorafenib at the same institution, Asians and Caucasians with advanced HCC had similar OS. ECOG PS and HCV were the only significant prognostic factors. A higher proportion of HCV positivity might explain why the SHARP trial achieved better OS when compared to the Asian-Pacific trial. PMID:25083298

  6. Advanced hepatocellular carcinoma and sorafenib: Diagnosis, indications, clinical and radiological follow-up.

    PubMed

    Colagrande, Stefano; Regini, Francesco; Taliani, Gian Giacomo; Nardi, Cosimo; Inghilesi, Andrea Lorenzo

    2015-05-18

    Advanced stage hepatocellular carcinoma (HCC) is a category of disease defined by radiological, clinical and hepatic function parameters, comprehending a wide range of patients with different general conditions. The main therapeutic option is represented by sorafenib treatment, a multi-kinase inhibitor with anti-proliferative and anti-angiogenic effect. Trans-arterial Radio Embolization also represents a promising new approach to intermediate/advanced HCC. Post-marketing clinical studies showed that only a portion of patients actually benefits from sorafenib treatment, and an even smaller percentage of patients treated shows partial/complete response on follow-up examinations, up against relevant costs and an incidence of drug related adverse effects. Although the treatment with sorafenib has shown a significant increase in mean overall survival in different studies, only a part of patients actually shows real benefits, while the incidence of drug related significant adverse effects and the economic costs are relatively high. Moreover, only a small percentage of patients also shows a response in terms of lesion dimensions reduction. Being able to properly differentiate patients who are responding to the therapy from non-responders as early as possible is then still difficult and could be a pivotal challenge for the future; in fact it could spare several patients a therapy often difficult to bear, directing them to other second line treatments (many of which are at the moment still under investigation). For this reason, some supplemental criteria to be added to the standard modified Response Evaluation Criteria in Solid Tumors evaluation are being searched for. In particular, finding some parameters (cellular density, perfusion grade and enhancement rate) able to predict the sensitivity of the lesions to anti-angiogenic agents could help in stratifying patients in terms of treatment responsiveness before the beginning of the therapy itself, or in the first weeks of

  7. Clinical Benefit Assessment of Vismodegib Therapy in Patients With Advanced Basal Cell Carcinoma

    PubMed Central

    Basset-Seguin, Nicole; Caro, Ivor; Yue, Huibin; Schadendorf, Dirk

    2014-01-01

    Purpose. Vismodegib was approved for the treatment of advanced basal cell carcinoma (aBCC) based on the pivotal ERIVANCE BCC study. The primary endpoint (objective response rate [ORR]) was assessed 9 months after the last patient was enrolled. To confirm the clinical benefit of vismodegib, an additional analysis was performed 12 months after the primary analysis. Materials and Methods. ERIVANCE BCC was a multicenter, nonrandomized, two-cohort study of 104 patients with histologically confirmed aBCC. Patients received 150 mg oral vismodegib daily until disease progression, intolerable toxicity, or withdrawal. An independent review panel comprising three expert clinicians reviewed patient photographs individually and as a consensus panel to evaluate baseline disease severity and clinical benefit after vismodegib treatment in 71 patients with locally advanced BCC (laBCC). Results. Sixty-three patients were efficacy evaluable; baseline and postprogression photographs for 61 were available for review. Baseline disease severity was judged as 5 or 4 (very severe or moderately severe) in 71.4%. Clinical benefit was observed in 76.2% (significant: 65.1%; some: 11.1%). Interpanelist agreement (maximum difference ≤1 point among panelists’ scores in 65.1% and 87.3% of patients for clinical benefit and baseline disease severity, respectively) and correlation between individual and panel reviews were strong. Clinical benefit scores showed good concordance with the protocol-specified ORR obtained by an independent review facility and with investigator-assessed response. Conclusion. Clinical benefit assessed by independent review based on expert clinical judgment provides strong evidence that treatment with vismodegib results in clinically meaningful and durable responses in patients with laBCC. PMID:25001266

  8. Non-coding RNAs deregulation in oral squamous cell carcinoma: advances and challenges.

    PubMed

    Yu, T; Li, C; Wang, Z; Liu, K; Xu, C; Yang, Q; Tang, Y; Wu, Y

    2016-05-01

    Oral squamous cell carcinoma (OSCC) is a common cause of cancer death. Despite decades of improvements in exploring new treatments and considerable advance in multimodality treatment, satisfactory curative rates have not yet been reached. The difficulty of early diagnosis and the high prevalence of metastasis associated with OSCC contribute to its dismal prognosis. In the last few decades the emerging data from both tumor biology and clinical trials led to growing interest in the research for predictive biomarkers. Non-coding RNAs (ncRNAs) are promising biomarkers. Among numerous kinds of ncRNAs, short ncRNAs, such as microRNAs (miRNAs), have been extensively investigated with regard to their biogenesis, function, and importance in carcinogenesis. In contrast to miRNAs, long non-coding RNAs (lncRNAs) are much less known concerning their functions in human cancers especially in OSCC. The present review highlighted the roles of miRNAs and newly discovered lncRNAs in oral tumorigenesis, metastasis, and their clinical implication.

  9. Chemotherapies and targeted therapies in advanced hepatocellular carcinoma: from laboratory to clinic.

    PubMed

    Voiculescu, Mihai; Winkler, Robert E; Moscovici, Marius; Neuman, Manuela G

    2008-09-01

    Chronic liver diseases alone or in conjunction with other risk factors result in increased liver damage leading to inflammation and fibrosis of the liver and rising rates of liver cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC). This review will address the determinants of liver injury at the initiation of the tumor and the risk factors for rapid disease progression. Regardless of the etiology, the unifying feature of these tumors are their propensity to arise upon a background of inflammation and fibrosis. Liver disease is often associated with enhanced hepatocyte apoptosis, which is the case in viral and autoimmune hepatitis, cholestatic diseases, and metabolic disorders. Disruption of apoptosis is responsible for HCC. The mechanisms by which apoptosis occurs in the liver might provide insights into HCC and suggest possible treatments. We aim to better understand the factors that distinguish a relatively long course of HCC from one with rapid progression. We will accomplish this task with three integrated ideas: 1 - the role of epidemiology in establishing the risk factors of co-morbidity with alcohol and hepatitis viruses; 2 - the role of apoptosis and anti-apoptotic signals in the progression of HCC; and 3 - the role of new advancements that have emerged in the field of molecular-directed chemotherapeutics in HCC in recent years. This review will also aim to describe the molecular targeted therapies of non-resectable HCC and the ways of effective combination in this otherwise chemo-resistant tumor.

  10. Pazopanib: a multikinase inhibitor with activity in advanced renal cell carcinoma.

    PubMed

    Bukowski, Ronald M

    2010-05-01

    Treatment options for patients with metastatic renal cell carcinoma (RCC) have changed dramatically, and a new paradigm has evolved. IFN-alpha and IL-2 were previously mainstays of therapy, but since December 2005, six new agents have been approved in the USA for the treatment of advanced RCC. Three of these new agents are multitargeted kinase inhibitors, including sunitinib, sorafenib, and recently pazopanib, two target the mTOR (temsirolimus and everolimus), and one is a humanized monoclonal antibody (bevacizumab in combination with IFN-alpha) that targets VEGF. Sunitinib has emerged as the standard of care for treatment-naive RCC patients, with the recently approved bevacizumab and IFN-alpha combination providing an additional option for this population. The recent approval of pazopanib, based on the results from sequential Phase II and III clinical trials demonstrating improved overall response rates and progression-free survival, provides yet another option for front-line therapy. The current article examines the pazopanib preclinical and clinical data, provides an overview of the development of this tyrosine kinase inhibitor, and provides some speculation concerning its role in RCC therapy.

  11. Clinical and molecular comparison between borderline serous ovarian tumors and advanced serous papillary ovarian carcinomas.

    PubMed

    Halperin, R; Zehavi, S; Dar, P; Habler, L; Hadas, E; Bukovsky, I; Schneider, D

    2001-01-01

    The aim of this study was to characterize the clinical and molecular markers of borderline serous ovarian tumors (BSOT), and to study their expression in the progression from benign lesions to advanced serous papillary ovarian carcinomas (SPOC). The clinical records of 20 patients with BSOT and 22 patients with SPOC were reviewed. Specimens from all these cases and from six benign ovarian serous cystadenomas were evaluated for expression of estrogen receptors (ER), progesterone receptors (PR), p53. HER-2/neu and Ki-67 by immunohistochemical techniques. The mean patient age and the age at menarche differed significantly between the compared groups of BSOT and SPOC (p=0.0006 and p=0.0014, respectively). No difference was observed comparing the other clinical parameters. The immunohistochemical analysis demonstrated a significant increase in the expression of ER (100% vs 72.7%), and a significant decrease in the immunoreactivity for p53 (0% vs 45.4%) and Ki-67 (2% vs 26.8%) in cases of BSOT compared with those of SPOC (p=0.007, p=0.0003 and p=0.012, respectively). No significant difference was demonstrated comparing the expression of PR and HER-2/neu. The immunostaining of benign ovarian serous cystadenoma specimens did not differ significantly from immunoreactivity observed in cases of BSOT. According to immunohistochemical analysis, BSOT had much more in common with benign serous tumors than with SPOC. The main difference between BSOT and SPOC was regarding the overexpression of p53 and Ki-67.

  12. Safety and long term efficacy of porfimer sodium photodynamic therapy in locally advanced biliary tract carcinoma

    PubMed Central

    Pereira, Stephen P; Aithal, Guruprasad P; Ragunath, Krish; Devlin, John; Owen, Faye; Meadows, Helen

    2012-01-01

    Background In patients with unresectable cholangiocarcinoma, photodynamic therapy (PDT) with porfimer sodium promotes biliary drainage and may improve survival and quality of life. Aim To prospectively evaluate the safety and efficacy of PDT in patients with locally advanced biliary tract carcinoma. Methods Eligible patients had unresectable, histologically confirmed disease, a Karnofsky performance status of ≥30% and life expectancy >12 weeks. Patients received 2mg/kg i.v. of porfimer sodium, followed by endobiliary laser activation and stent replacement 48 hrs later. Patients were assessed clinically and radiologically before treatment and on day 28, and followed up thereafter at three-monthly intervals until death. Results 36 patients were entered over an 18 months period: 14 males, 22 females, with a median age of 65 (30-79) yr and performance status of 80 (50-100). PDT was technically successful in all cases and was generally well tolerated; there was no grade 4 toxicity and no treatment-associated mortality. The median survival was 12 (1-84) months. Conclusions Porfimer sodium PDT can be delivered safely to patients with biliary tract cancer and is suitable for testing in phase III studies (UKCRN ID 1218). PMID:23200007

  13. Sonidegib: mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas

    PubMed Central

    Jain, Sachin; Song, Ruolan; Xie, Jingwu

    2017-01-01

    The Hedgehog (Hh) pathway is critical for cell differentiation, tissue polarity, and stem cell maintenance during embryonic development, but is silent in adult tissues under normal conditions. However, aberrant Hh signaling activation has been implicated in the development and promotion of certain types of cancer, including basal cell carcinoma (BCC), medulloblastoma, and gastrointestinal cancers. In 2015, the US Food and Drug Administration (FDA) approved sonidegib, a smoothened (SMO) antagonist, for treatment of advanced BCC (aBCC) after a successful Phase II clinical trial. Sonidegib, also named Odomzo, is the second Hh signaling inhibitor approved by the FDA to treat BCCs following approval of the first SMO antagonist vismodegib in 2012. What are the major features of sonidegib (mechanism of action; metabolic profiles, clinical efficacy, safety, and tolerability profiles)? Will the sonidegib experience help other clinical trials using Hh signaling inhibitors in the future? In this review, we will summarize current understanding of BCCs and Hh signaling. We will focus on sonidegib and its use in the clinic, and we will discuss ways to improve its clinical application in cancer therapeutics. PMID:28352196

  14. Induction chemotherapy for the treatment of non-endemic locally advanced nasopharyngeal carcinoma

    PubMed Central

    Zhao, Lina; Xu, Man; Jiang, Wen; Pan, Haitao; Zang, Jian; Luo, Shanquan; Wang, Jianhua; Zhou, Yongchun; Shi, Mei

    2017-01-01

    Background The role of induction chemotherapy is less clear in non-endemic locally advanced nanopharyngeal carcinomas (NPC). Results With a total of 233 eligible patients and a median follow-up of 36 months, 3-year overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease free survival (DFS) were 84.5%, 94.9%, 78.6% and 69.2%, respectively. The overall failure rate was 21.0% and distant metastasis occurred in 17.2% patients. Multivariate analyses showed that retropharyngeal and bilateral neck lymph node metastasis were significant prognostic factors for DFS and OS. Moreover, patients receiving both GP (gemcitabine+cisplatin) and TP (docetaxel+cisplatin) regimes had significantly higher DFS and OS compared with PF (cisplatin+5-FU) regime. GP regimes lead to significantly improved OS than TP/PF in some subgroup of patients. No severe toxicities were observed. Materials and Methods We retrospectively analyzed stage III-IVb NPC patients treated between Jan 2006 and Dec 2014, with induction chemotherapy followed by concurrent chemoradiation (IC-CCRT). Statistical analyses were performed on survival and failure patterns. Conclusions These results suggested IC-CCRT was safe and effective for NPCs from non-endemic region. The choice of induction regimen appeared to affect patient outcomes. PMID:28036270

  15. Advanced imaging techniques in the therapeutic response of transarterial chemoembolization for hepatocellular carcinoma

    PubMed Central

    Yang, Ke; Zhang, Xiao-Ming; Yang, Lin; Xu, Hao; Peng, Juan

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the major causes of morbidity and mortality in patients with chronic liver disease. Transarterial chemoembolization (TACE) can significantly improve the survival rate of patients with HCC and is the first treatment choice for patients who are not suitable for surgical resections. The evaluation of the response to TACE treatment affects not only the assessment of the therapy efficacy but also the development of the next step in the treatment plan. The use of imaging to examine changes in tumor volume to assess the response of solid tumors to treatment has been controversial. In recent years, the emergence of new imaging technology has made it possible to observe the response of tumors to treatment prior to any morphological changes. In this article, the advances in studies reporting the use of computed tomography perfusion imaging, diffusion-weighted magnetic resonance imaging (MRI), intravoxel incoherent motion, diffusion kurtosis imaging, magnetic resonance spectroscopy, magnetic resonance perfusion-weighted imaging, blood oxygen level-dependent MRI, positron emission tomography (PET)/computed tomography and PET/MRI to assess the TACE treatment response are reviewed. PMID:27239110

  16. Nonsurgical treatment options for basal cell carcinoma - focus on advanced disease.

    PubMed

    Goldenberg, Gary; Hamid, Omid

    2013-12-01

    Basal cell carcinoma (BCC) is the most common cancer in the world. It is typically slow growing and usually effectively managed with surgery. However, BCCs in some patients are unsuitable for surgery or the patient may prefer a nonsurgical treatment. Radiotherapy is a nonsurgical option for the primary treatment of either low- or high-risk BCCs. It is associated with high cure rates, albeit somewhat lower than those observed with Mohs micrographic surgery for high-risk BCCs. Not all patients with BCCs are suitable for radiotherapy. Superficial therapies for BCC include topical imiquimod or 5- fluorouracil and photodynamic therapy (PDT). These therapies are generally associated with somewhat lower clearance rates and/or higher recurrence rates than surgery or radiotherapy, although they may be suitable in patients with low-risk BCCs when surgery or radiotherapy are impractical or less appropriate. An appealing feature of PDT is excellent cosmesis, but PDT is not currently approved by the Food and Drug Administration (FDA), and regimens are not well standardized. Vismodegib is a first-in-class hedgehog pathway inhibitor and recent addition to the armamentarium for the treatment of advanced BCC.

  17. Preliminary results of radiation dose escalation for locally advanced nasopharyngeal carcinoma

    SciTech Connect

    Kwong, Dora L.W. . E-mail: dlwkwong@hkucc.hku.hk; Sham, Jonathan S.T.; Leung, Lucullus H.T.; Cheng, Ashley C.K.; Ng, W.M.; Kwong, Philip W.K.; Lui, W.M.; Yau, C.C.; Wu, P.M.; Wei, William; Au, Gordon

    2006-02-01

    Purpose: To study the safety and efficacy of dose escalation in tumor for locally advanced nasopharyngeal carcinoma (NPC). Methods and Materials: From September 2000 to June 2004, 50 patients with T3-T4 NPC were treated with intensity-modulated radiotherapy (IMRT). Fourteen patients had Stage III and 36 patients had Stage IVA-IVB disease. The prescribed dose was 76 Gy to gross tumor volume (GTV), 70 Gy to planning target volume (PTV), and 72 Gy to enlarged neck nodes (GTVn). All doses were given in 35 fractions over 7 weeks. Thirty-four patients also had concurrent cisplatin and induction or adjuvant PF (cisplatin and 5-fluorouracil). Results: The average mean dose achieved in GTV, GTVn, and PTV were 79.5 Gy, 75.3 Gy, and 74.6 Gy, respectively. The median follow-up was 25 months, with 4 recurrences: 2 locoregional and 2 distant failures. All patients with recurrence had IMRT alone without chemotherapy. The 2-year locoregional control rate, distant metastases-free and disease-free survivals were 95.7%, 94.2%, and 93.1%, respectively. One treatment-related death caused by adjuvant chemotherapy occurred. The 2-year overall survival was 92.1%. Conclusions: Dose escalation to 76 Gy in tumor is feasible with T3-T4 NPC and can be combined with chemotherapy. Initial results showed good local control and survival.

  18. Present and future perspectives on immunotherapy for advanced renal cell carcinoma: Going to the core or beating around the bush?

    PubMed Central

    Kimura, Yasunori

    2015-01-01

    Metastatic lesions of renal cell carcinoma (RCC) occasionally regress spontaneously after surgical removal of the primary tumor. Although this is an exceptionally rare occurrence, RCC has thus been postulated to be immunogenic. Immunotherapies, including cytokine therapy, peptide-based vaccines, and immune checkpoint inhibitors have therefore been used to treat patients with advanced, metastatic RCC. We review the history, trends, and recent progress in immunotherapy for advanced RCC and discuss future perspectives, with consideration of our experimental work on galectin 9 and PINCH as promising specific immunotherapy targets.

  19. U.S. Food and Drug Administration approval: vismodegib for recurrent, locally advanced, or metastatic basal cell carcinoma.

    PubMed

    Axelson, Michael; Liu, Ke; Jiang, Xiaoping; He, Kun; Wang, Jian; Zhao, Hong; Kufrin, Dubravka; Palmby, Todd; Dong, Zedong; Russell, Anne Marie; Miksinski, Sarah; Keegan, Patricia; Pazdur, Richard

    2013-05-01

    The data and regulatory considerations leading to the U.S. Food and Drug Administration (FDA) January 30, 2012 approval of Erivedge (vismodegib) capsules for the treatment of patients with recurrent, locally advanced, or metastatic basal cell carcinoma (BCC) are described. The FDA's approval decision was based primarily on the results observed in a single-arm, parallel cohort, international trial of vismodegib, administered orally at 150 mg daily until disease progression, in patients with pathologically confirmed, recurrent, locally advanced basal cell carcinoma (laBCC) or metastatic basal cell carcinoma (mBCC). An independent review committee confirmed an overall response rate (ORR) of 30.3% [95% confidence interval (CI): 15.6-48.2] in 33 patients with mBCC and an ORR of 42.9% (95% CI: 30.5-56.0) in 63 patients with laBCC; median response durations were 7.6 months and 7.6 months for patients with mBCC and laBCC, respectively. The most common adverse reactions were muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, cough, arthralgias, vomiting, headache, ageusia, insomnia, and upper respiratory tract infection. Animal toxicology studies confirmed that vismodegib is a potent teratogenic agent. Approval was based on durable objective tumor responses supported by knowledge of the pathologic role of Hedgehog signaling in BCC and acceptable toxicity in a population without effective alternative therapies.

  20. Concomitant cetuximab and radiation therapy: A possible promising strategy for locally advanced inoperable non-melanoma skin carcinomas

    PubMed Central

    DELLA VITTORIA SCARPATI, GIUSEPPINA; PERRI, FRANCESCO; PISCONTI, SALVATORE; COSTA, GIUSEPPE; RICCIARDIELLO, FILIPPO; DEL PRETE, SALVATORE; NAPOLITANO, ALBERTO; CARRATURO, MARCO; MAZZONE, SALVATORE; ADDEO, RAFFAELE

    2016-01-01

    Non-melanoma skin cancers (NMSCs) include a heterogeneous group of malignancies arising from the epidermis, comprising squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma and more rare entities, including malignant pilomatrixoma and sebaceous gland tumours. The treatment of early disease depends primarily on surgery. In addition, certain patients present with extensive local invasion or metastasis, which renders these tumours surgically unresectable. Improving the outcome of radiotherapy through the use of concurrent systemic therapy has been demonstrated in several locally advanced cancer-treatment paradigms. Recently, agents targeting the human epidermal growth factor receptor (EGFR) have exhibited a consolidated activity in phase II clinical trials and case series reports. Cetuximab is a monoclonal antibody that binds to and completely inhibits the EGFR, which has been revealed to be up-regulated in a variety of SCCs, including NMSCs. The present review aimed to summarize the role of anti-EGFR agents in the predominant types of NMSC, including SCC and BCC, and focuses on the cetuximab-based studies, highlighting the biological rationale of this therapeutic option. In addition, the importance of the association between cetuximab and radiotherapy for locally advanced NMSC is discussed. PMID:27073643

  1. A useful treatment for patients with advanced mixed-type small cell neuroendocrine carcinoma of the prostate: A case report.

    PubMed

    Uemura, Kei-Ichiro; Nakagawa, Go; Chikui, Katsuaki; Moriya, Fukuko; Nakiri, Makoto; Hayashi, Tokumasa; Suekane, Shigetaka; Matsuoka, Kei

    2013-03-01

    Treating extended prostatic small cell neuroendocrine carcinoma (PSCNC) is extremely difficult and no standard treatment has yet been established. We experienced a case of advanced mixed-type PSCNC in which the patient achieved long-term survival and local control following combined therapy. Locally advanced PSCNC causing lower urinary obstruction was detected during androgen-ablation therapy for stage D2 mixed adenocarcinoma PSCNC. The patient was treated with intra-arterial infusion chemotherapy using a reservoir system and external-beam radiotherapy (EBRT) to the whole pelvis and local tumor. After chemoradiotherapy, the patient's lower urinary obstruction was reduced and did not return during the remaining 40 months of the patient's life. The patient survived for 70 months following the start of the androgen-ablation therapy. The present study reports a useful treatment for advanced mixed-type PSCNC, androgen-ablation therapy and chemoradiotherapy. The present results also suggest that the prognostic factors for advanced mixed-type PSCNC are the sensitivity of the conventional adenocarcinoma to androgen-ablation therapy, degree of metastasis and extent of the small cell neuroendocrine carcinoma component.

  2. [Laryngeal and larynx-associated reflexes].

    PubMed

    Ptok, M; Kühn, D; Miller, S; Jungheim, M; Schroeter, S

    2016-06-01

    The laryngeal adductor reflex and the pharyngoglottal closure reflex protect the trachea and lower respiratory tract against the entrance of foreign material. The laryngeal expiration reflex and the cough reflex serve to propel foreign material, which has penetrated in the cranial direction. The inspiration reflex, the sniff reflex, and the swallowing reflex are further larynx-associated reflexes. In patients with dysphagia the laryngeal adductor reflex can be clinically tested with air pulses. The water swallow test serves to show the integrity of the cough reflex. The sniff reflex is useful to test the abduction function of the vocal folds. Future studies should address laryngeal reflexes more specifically, both for a better understanding of these life-supporting mechanisms and to improve diagnostic procedures in patients with impaired laryngeal function.

  3. Effects of an oral iron chelator, deferasirox, on advanced hepatocellular carcinoma

    PubMed Central

    Saeki, Issei; Yamamoto, Naoki; Yamasaki, Takahiro; Takami, Taro; Maeda, Masaki; Fujisawa, Koichi; Iwamoto, Takuya; Matsumoto, Toshihiko; Hidaka, Isao; Ishikawa, Tsuyoshi; Uchida, Koichi; Tani, Kenji; Sakaida, Isao

    2016-01-01

    AIM To evaluate the inhibitory effects of deferasirox (DFX) against hepatocellular carcinoma (HCC) through basic and clinical studies. METHODS In the basic study, the effect of DFX was investigated in three hepatoma cell lines (HepG2, Hep3B, and Huh7), as well as in an N-nitrosodiethylamine-induced murine HCC model. In the clinical study, six advanced HCC patients refractory to chemotherapy were enrolled. The initial dose of DFX was 10 mg/kg per day and was increased by 10 mg/kg per day every week, until the maximum dose of 30 mg/kg per day. The duration of a single course of DFX therapy was 28 consecutive days. In the event of dose-limiting toxicity (according to the Common Terminology Criteria for Adverse Events v.4.0), DFX dose was reduced. RESULTS Administration of DFX inhibited the proliferation of hepatoma cell lines and induced the activation of caspase-3 in a dose-dependent manner in vitro. In the murine model, DFX treatment significantly suppressed the development of liver tumors (P < 0.01), and significantly upregulated the mRNA expression levels of hepcidin (P < 0.05), transferrin receptor 1 (P < 0.05), and hypoxia inducible factor-1α (P < 0.05) in both tumor and non-tumor tissues, compared with control mice. In the clinical study, anorexia and elevated serum creatinine were observed in four and all six patients, respectively. However, reduction in DFX dose led to decrease in serum creatinine levels in all patients. After the first course of DFX, one patient discontinued the therapy. We assessed the tumor response in the remaining five patients; one patient exhibited stable disease, while four patients exhibited progressive disease. The one-year survival rate of the six patients was 17%. CONCLUSION We demonstrated that DFX inhibited HCC in the basic study, but not in the clinical study due to dose-limiting toxicities. PMID:27833388

  4. Analysis of Prognostic Factors After Yttrium-90 Radioembolization of Advanced Hepatocellular Carcinoma

    SciTech Connect

    Inarrairaegui, Mercedes; Martinez-Cuesta, Antonio; Rodriguez, Macarena; Bilbao, J. Ignacio

    2010-08-01

    Purpose: To analyze which patient-, tumor-, and treatment-related factors may influence outcome after {sup 90}Y radioembolization ({sup 90}Y-RE) for hepatocellular carcinoma (HCC). Patients and Methods: Seventy-two consecutive patients with advanced HCC treated with {sup 90}Y-RE were studied to detect which factors may have influenced response to treatment and survival. Results: Median overall survival was 13 months (95% confidence interval, 9.6-16.3 months). In univariate analysis, survival was significantly better in patients with one to five lesions (19 vs. 8 months, p = 0.001) and in patients with alpha-fetoprotein <52 UI/mL (24 vs. 11 months, p = 0.002). The variation in target tumor size and the appearance of new lesions were analyzed among 50 patients with measurable tumors. A decrease in target tumor size was observed in most patients, and the intensity of such decrease was not associated with any of the factors under study. Patients who developed new lesions in the treated liver (and also in the nontargeted liver) at month 3 more frequently had more than five nodules, bilobar disease, and alpha-fetoprotein >52 UI/mL, and their survival in the multivariate analysis was significantly worse (hazard ratio, 4.7; 95% confidence interval, 13-1.73) (p = 0.002). Conclusions: Yttrium-90 radioembolization results in control of target lesions in the majority of patients with HCC but does not prevent the development of new lesions. Survival of patients treated with {sup 90}Y-RE seems to depend largely on factors related to the aggressiveness of the disease (number of nodules, levels of alpha-fetoprotein, and presence of microscopic disease).

  5. Critical appraisal of pazopanib as treatment for patients with advanced metastatic renal cell carcinoma.

    PubMed

    Bukowski, Ronald M

    2011-01-01

    The management of renal cell carcinoma (RCC) has undergone significant changes during the past 10 years, with the treatment of metastatic RCC undergoing the most radical changes. These developments reflect an enhanced understanding of this tumor's underlying biology, which was then translated into the development of a new treatment paradigm. Current therapeutic approaches for the management of patients with metastatic RCC utilize knowledge of histology, molecular abnormalities, clinical prognostic factors, the natural history of this malignancy, and the treatment efficacy and toxicity of available agents. The treatment options available for patients with metastatic RCC have changed dramatically over the past 6 years. Interferon-α and interleukin-2 were the previous mainstays of therapy, but since December 2005, six new agents have been approved in the US for the treatment of advanced RCC. Three are multi-targeted tyrosine kinase inhibitors (TKI) including sunitinib, sorafenib, and pazopanib, two target the mammalian target of rapamycin (temsirolimus and everolimus), and one is a humanized monoclonal antibody (bevacizumab in combination with interferon-α). The current review focuses on the newest TKI available to treat patients with metastatic RCC, pazopanib. The development of this agent both preclinically and clinically is reviewed. The efficacy and safety data from the pivotal clinical trials are discussed, and the potential role of pazopanib in the treatment of patients with metastatic RCC in comparison to other treatment alternatives is critically appraised. This agent has a favorable overall risk benefit, and the available data demonstrate efficacy in patients with metastatic RCC who are either treatment-naïve or cytokine refractory. It therefore represents another alternative for treatment of metastatic RCC patients.

  6. A Single-institution Experience with Open Irreversible Electroporation for Locally Advanced Pancreatic Carcinoma

    PubMed Central

    Yan, Li; Chen, Yong-Liang; Su, Ming; Liu, Tian; Xu, Kai; Liang, Feng; Gu, Wan-Qing; Lu, Shi-Chun

    2016-01-01

    Background: Locally advanced pancreatic carcinoma (LAPC) is characterized by poor prognosis despite recommended concurrent chemoradiotherapy. Irreversible electroporation (IRE) has emerged as a potential option for the management of unresectable pancreatic cancer. This study was conducted to evaluate the safety and short-term efficacy of open IRE for the treatment of LAPC. Methods: Retrospective data of 25 consecutive patients receiving IRE for T3 lesions from July 2015 to June 2016 at a single center were analyzed. The perioperative and long-term IRE-related complications were reviewed to evaluate the safety of the procedure. The tumor reduction and biological response were analyzed through computed tomography/magnetic resonance imaging; the serum level of CA19-9 was measured as a secondary endpoint to evaluate the short-term efficacy of IRE. Results: All patients were successfully treated; the median tumor size was 4.2 cm and the median IRE time was 36 min. Four intraoperative procedure-related complications were observed (16%): two transient hypertensive episodes, one hypotension case, and one transient supraventricular tachycardia case. Nine postoperative complications were described, including three Grade A pancreatic fistulas, three delayed gastric emptying, one acute pancreatitis, one upper gastrointestinal hemorrhage, and one portal vein thrombosis. The overall rate of stable disease was 28%, 36% achieved partial response, and lower serum CA19-9 levels were recorded in all patients at discharge. Conclusions: IRE is feasible for the treatment of LAPC and is a reasonable intervention strategy owing to its combined attributes of safety and efficacy. PMID:27958223

  7. Combined sorafenib and yttrium-90 radioembolization for the treatment of advanced hepatocellular carcinoma

    PubMed Central

    Salman, A.; Simoneau, E.; Hassanain, M.; Chaudhury, P.; Boucher, L.M.; Valenti, D.; Cabrera, T.; Nudo, C.; Metrakos, P.

    2016-01-01

    Background and Aims In this pilot study, we assessed the safety and tolerability of combining sorafenib with 90Y radioembolization for the treatment of unresectable hepatocellular carcinoma (hcc). Methods The study, conducted prospectively during 2009–2012, included eligible patients with unresectable hcc and a life expectancy of at least 12 weeks. Each patient received sorafenib (400 mg twice daily) for 6–8 weeks before 90Y treatment. Safety and tolerability were assessed. Results Of the 40 patients enrolled, 29 completed treatment (combined therapy). In the initial cohort, the most common cause of hcc was hepatitis C (32.5%), and most patients were staged Child A (82.5%). The 29 patients who completed the study had similar baseline characteristics. Grades 1 and 2 toxicities accounted for 77.8% of all adverse events reported. The most common toxicities reported were fatigue (19.0%), alteration in liver function (7.9%), and diarrhea (6.3%). There were 12 grade 3 and 2 grade 4 toxicity events reported. One patient died of liver failure within 30 days after treatment. During the study, the sorafenib dose was reduced in 6 patients (20.7%), and sorafenib had to be interrupted in 4 patients (13.8%) and discontinued in 4 patients (13.8%). The disease control rate was 72.4% per the modified Response Evaluation Criteria in Solid Tumors, and tumour necrosis was observed in 82.8% of patients. Overall survival in patients undergoing combined therapy was 12.4 months. Conclusions Preliminary results demonstrate the safety and tolerability of combining 90Y radioembolization and sorafenib for advanced hcc. A larger prospective study is needed to determine the extent of the survival benefit. PMID:27803608

  8. A Recent Advance in Image-Guided Locoregional Therapy for Hepatocellular Carcinoma

    PubMed Central

    Shi, Yaoping; Zhai, Bo

    2016-01-01

    Background Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer-related deaths. Hepatic resection and liver transplantation are considered to be the preferred treatment for HCC. However, as novel therapeutic options such as image-guided locoregional therapies have emerged and been refined, the manner in which HCC is treated has changed dramatically compared with what it was considered just 2 decades earlier. Summary This study reviews the current results of various image-guided locoregional therapies for treating HCC, especially focusing on thermal ablative and transarterial techniques. Key Message Advances in image-guided locoregional therapies, including local ablative therapy and transarterial therapy, have led to a major breakthrough in the management of HCC. Both survival rates and cure rates of patients with HCC have improved markedly since the introduction of these techniques. Practical Implications Radiofrequency ablation is currently considered as an alternative to surgical resection for patients with early-stage HCC. A newer technique of ablation such as microwave ablation is increasingly being used, especially for large HCC. Transarterial chemoembolization has become a standard care for asymptomatic patients with multinodular tumors in intermediate-stage disease, and transarterial radioembolization has become the method of choice in HCC cases with portal vein thrombosis. Moreover, combination treatment modalities, such as thermal-based ablation combined with transarterial chemoembolization or 125I seed implant brachytherapy, may further broaden their clinical indications for HCC. Moreover, use of localized radiation in combination with thermal ablation has been reported to improve tumor control and long-term survival. PMID:27904861

  9. Hypofractionated Radiation Therapy Followed by Surgery in Treating Patients With Advanced Squamous Cell Carcinoma of the Oral Cavity

    ClinicalTrials.gov

    2017-01-19

    Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

  10. Benefit of percutaneous endoscopic gastrostomy in patients undergoing definitive chemoradiotherapy for locally advanced nasopharyngeal carcinoma

    PubMed Central

    Xu, Yun; Guo, Qiaojuan; Lin, Jin; Chen, Bijuan; Wen, Jiangmei; Lu, Tianzhu; Xu, Yuanji; Zhang, Mingwei; Pan, Jianji; Lin, Shaojun

    2016-01-01

    Background and aim To evaluate the impact of percutaneous endoscopic gastrostomy (PEG) tube on nutritional status, treatment-related toxicity, and treatment tolerance in patients with locally advanced nasopharyngeal carcinoma (NPC) who underwent chemoradiotherapy. Patients and methods We enrolled 133 consecutive non-metastatic NPC (III/IV stage) patients, who were treated with prophylactic PEG feeding before the initiation of concurrent chemoradiotherapy (CCRT) between June 1, 2010 and June 30, 2014. Meanwhile, another 133 non-PEG patients, who were matched for age, gender, and tumor, node, metastases stage, were selected as historical control cohort. Weight and nutritional status changes from pre-radiotherapy to the end of radiotherapy were evaluated, and treatment tolerance and related acute toxicities were analyzed as well. Results We found that significantly more patients (91.73%) in the PEG group could finish two cycles of CCRT, when compared with those in the non-PEG group (57.89%) (P<0.001). We also indicated that more patients (50.38%) in the non-PEG group experienced weight loss of ≥5%, while the phenomenon was only found in 36.09% patients in the PEG group (P=0.019). In addition, the percentage of patients who lost ≥10% of their weight was similar in these two groups. Changes in albumin and prealbumin levels during radiotherapy in the non-PEG group were higher than those obtained for the PEG group with significant differences (P-values of 0.023 and <0.001, respectively). Furthermore, patients in the PEG group had significantly lower incidence of grade III acute mucositis than those in the non-PEG group (22.56% vs 36.84%, P=0.011). Tube-related complications occurred only in 14 (10.53%) patients in the PEG group, including incision infection of various degrees. Conclusion PEG and intensive nutrition support may help to minimize body weight loss, maintain nutritional status, and offer better treatment tolerance for patients with locally advanced NPC who

  11. Sequential chemoradiotherapy with gemcitabine and cisplatin for locoregionally advanced nasopharyngeal carcinoma.

    PubMed

    Gu, Mo-Fa; Liu, Li-Zhi; He, Long-Jun; Yuan, Wen-Xin; Zhang, Rong; Luo, Guang-Yu; Xu, Guo-Liang; Zhang, Hua-Man; Yan, Chao-Xian; Li, Jian-Jun

    2013-01-01

    We investigated a new chemoradiotherapy (CRT) regimen for locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 240 patients were randomly assigned to three different CRT regimens: sequential CRT [1 cycle chemotherapy + Phase I radiotherapy (RT) + 1 cycle chemotherapy + Phase II RT + 2 cycles chemotherapy] with a cisplatin-gemcitabine (GC) regimen (800 mg/m(2) gemcitabine on Days 1 and 8 and 20 mg/m(2) cisplatin on Days 1-5, every 4 weeks) (sGC-RT); sequential chemoradiotherapy with a cisplatin-fluorouracil (PF) regimen (20 mg/m(2) DDP and 500 mg/m(2) 5-FU on Days 1-5, every 4 weeks) (sPF-RT) and cisplatin-based concurrent chemoradiotherapy plus adjuvant PF chemotherapy (Con-RT + PF). The complete response rate was higher in the sGC + RT group than in the other two groups (98.75% vs. 92.50%, p < 0.01). The 3-year overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) rates in the sGC-RT group were significantly higher than those observed in the Con-RT group (OS, 95.0% vs. 76.3%, p < 0.001; DFS, 89.9% vs. 67.5%, p < 0.001; DMFS, 92.5% vs. 76.0%, p = 0.004) and in the sPF + RT group (OS, 95.0% vs. 73.6%, p < 0.001; DFS, 89.9% vs. 63.3%, p < 0.001; DMFS, 92.5% vs. 74.7%, p = 0.002). There were no significant differences in 3-year OS, DFS and MFS rates between the Con-RT and the sPF-RT groups. The GC-RT group experienced more hematologic toxicity, constipation and rash; however, there were no differences in late RT toxicity between the groups. These results demonstrate that a sGC-RT regimen is effective and well tolerated in patients with locoregionally advanced NPC.

  12. A Challenging Surgical Approach to Locally Advanced Primary Urethral Carcinoma: A Case Report and Literature Review.

    PubMed

    Lucarelli, Giuseppe; Spilotros, Marco; Vavallo, Antonio; Palazzo, Silvano; Miacola, Carlos; Forte, Saverio; Matera, Matteo; Campagna, Marcello; Colamonico, Ottavio; Schiralli, Francesco; Sebastiani, Francesco; Di Cosmo, Federica; Bettocchi, Carlo; Di Lorenzo, Giuseppe; Buonerba, Carlo; Vincenti, Leonardo; Ludovico, Giuseppe; Ditonno, Pasquale; Battaglia, Michele

    2016-05-01

    Primary urethral carcinoma (PUC) is a rare and aggressive cancer, often underdetected and consequently unsatisfactorily treated. We report a case of advanced PUC, surgically treated with combined approaches.A 47-year-old man underwent transurethral resection of a urethral lesion with histological evidence of a poorly differentiated squamous cancer of the bulbomembranous urethra. Computed tomography (CT) and bone scans excluded metastatic spread of the disease but showed involvement of both corpora cavernosa (cT3N0M0). A radical surgical approach was advised, but the patient refused this and opted for chemotherapy. After 17 months the patient was referred to our department due to the evidence of a fistula in the scrotal area. CT scan showed bilateral metastatic disease in the inguinal, external iliac, and obturator lymph nodes as well as the involvement of both corpora cavernosa. Additionally, a fistula originating from the right corpus cavernosum extended to the scrotal skin. At this stage, the patient accepted the surgical treatment, consisting of different phases. Phase I: Radical extraperitoneal cystoprostatectomy with iliac-obturator lymph nodes dissection. Phase II: Creation of a urinary diversion through a Bricker ileal conduit. Phase III: Repositioning of the patient in lithotomic position for an overturned Y skin incision, total penectomy, fistula excision, and "en bloc" removal of surgical specimens including the bladder, through the perineal breach. Phase IV: Right inguinal lymphadenectomy.The procedure lasted 9-and-a-half hours, was complication-free, and intraoperative blood loss was 600 mL. The patient was discharged 8 days after surgery. Pathological examination documented a T4N2M0 tumor. The clinical situation was stable during the first 3 months postoperatively but then metastatic spread occurred, not responsive to adjuvant chemotherapy, which led to the patient's death 6 months after surgery.Patients with advanced stage tumors of the

  13. Prevention of Hepatitis B Virus Reactivation With Lamivudine in a Patient With Advanced Renal Cell Carcinoma Treated With Everolimus.

    PubMed

    D'Aniello, Carmine; Maruzzo, Marco; Basso, Umberto

    2016-01-01

    Anticancer agents may trigger reactivation of hepatitis B virus infection ensuing in asymptomatic to severe liver damage. Preemptive administration of antiviral agents such as lamivudine to patients receiving cytotoxic chemotherapy has been shown to inhibit viral replication and prevent such events. No data are available so far concerning the coadministration of antiviral agents and everolimus, an oral mammalian target of rapamycin inhibitor recently approved for the treatment of advanced renal cell carcinoma. We present in this study the first case to our knowledge of a hepatitis B surface antigen-positive patient with metastatic renal cell carcinoma who has been successfully treated with prophylactic lamivudine and everolimus. Long-term depletion of viral replication was obtained along with stabilization of lung and bone metastases. Hepatitis B surface antigen positivity may be found in up to 10% of cancer patients but should not be considered a contraindication to treatment with everolimus.

  14. Thyroid Gland Involvement in Carcinoma Larynx and Hypopharynx-Predictive Factors and Prognostic Significance

    PubMed Central

    Iype, Elizabeth Mathew; Jagad, Vijay; Varghese, Bipin T.; Sebastian, Paul

    2016-01-01

    Introduction Intraoperative management of thyroid gland in laryngeal and hypopharyngeal cancer is controversial. Aim The objectives of this study were to determine the incidence of thyroid gland invasion in patients undergoing surgery for laryngeal or hypopharyngeal carcinoma, to assess predictive factors and to assess the prognosis in patients with and without thyroid gland invasion. Materials and Methods One hundred and thirty-three patients who underwent surgery for carcinoma larynx and hypopharynx from 2006 to 2010 were reviewed retrospectively. Surgical specimens were examined to determine the incidence of thyroid gland invasion and predictive factors were analysed. The recurrence rate and the survival in patients with and without thyroid gland invasion were also analysed. Results Out of the 133 patients with carcinoma larynx and hypopharynx who underwent surgery, histological thyroid gland invasion was observed in 28/133 (21%) patients. Significant relationship was found between histological thyroid gland invasion and preoperative evidence of thyroid cartilage erosion by CT scan and also when gross thyroid gland involvement observed during surgery. There is significant association between thyroid gland invasion when there is upper oesophageal or subglottic involvement. Conclusion After analysing the retrospective data from our study, we would like to suggest that thyroid gland need not be removed routinely in all laryngectomies, unless there is advanced disease with thyroid cartilage erosion and gross thyroid gland involvement or disease with significant subglottic or oesophageal involvement. PMID:27042568

  15. [Pretherapeutic and posttherapeutic laryngeal imaging].

    PubMed

    Becker, M; Burkhardt, K; Allal, A S; Dulguerov, P; Ratib, O; Becker, C D

    2009-01-01

    Cross-sectional imaging with CT, MRI and more recently PET CT plays an indispensable complementary role to endoscopy in the pretherapeutic diagnostic and staging of laryngeal neoplasms and in the evaluation of the operated or irradiated larynx. Adequate interpretation of the CT, PET CT and MR images requires a thorough knowledge of the patterns of submucosal spread and familiarity with the diagnostic signs of neoplastic invasion as seen with each modality. In addition, one should be aware of the implications of imaging for staging and treatment. Both CT and MR imaging are highly sensitive for the detection of neoplastic invasion of the preepiglottic and paraglottic spaces, subglottic region and cartilage. The high negative predictive value of both CT and MRI allows a relatively reliable exclusion of neoplasm cartilage invasion. The specificity of both CT and MRI is, however, moderately high and both methods may, therefore, overestimate the extent of tumor spread. However, recent investigations have shown that the specificity of MRI may be significantly improved by using new diagnostic criteria which allow differentiation of tumor from peritumoral inflammation in many instances. Both cross-sectional imaging methods also significantly improve the pretherapeutic staging accuracy of laryngeal tumors if used in addition to clinical examination and endoscopic biopsy. In the presence of a submucosal mass, CT and MRI play a key role for the diagnosis, as they may characterize the lesion, reliably depict its submucosal extent and guide the endoscopist to perform deep biopsies which allow the definitive histological diagnosis. Cross-sectional imaging also plays a key role in the evaluation of laryngoceles, recurrent laryngeal nerve paralysis and fractures.

  16. Chinese Herbal Formulation PHY906 and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer

    ClinicalTrials.gov

    2017-03-08

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Advanced Adult Hepatocellular Carcinoma; BCLC Stage B Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma

  17. Occupational risk for laryngeal cancer.

    PubMed

    Flanders, W D; Rothman, K J

    1982-04-01

    In a case-control analysis, we studied the effects of type of employment on laryngeal cancer risk using the interview data from the Third National Cancer Survey. Effects were measured relative to the risk for those employed in a group of arbitrarily defined industries and occupations with low risk. We excluded females and controlled for age, tobacco use, alcohol use, and race in the analysis. We found ratio estimates above 3.0 for workers in the railroad industry and the lumber industry; and for sheetmetal workers, grinding wheel operators, and automobile mechanics.

  18. [Diagnostic and prognostic value of p53 oncogene and the selected neoplastic markers (Ki67, PCNA, DNA ploidy) of the ultrastructure in patients with laryngeal cancer].

    PubMed

    Golusiński, W; Szmeja, Z; Olofsson, J; Biczysko, W; Krygier-Stojałowska, A; Majewski, P

    1996-01-01

    A comparison was performed of staining intensity of immunohistochemical proliferating antigens (p53, PCNA, Ki67), DNA flow cytometry and ultrastructure of the carcinoma cells in 120 cases of laryngeal cancer. Clinically very advanced tumors were in majority (T3 - 43%, T4 - 18%). A 5 graded scale was adapted to evaluate the level of immunohistochemical staining of the carcinoma cell nuclei. A positive staining was obtained in 70% for p53, 57% for Ki67 and in 80(2/3) for PCNA. 62% of the cases were DNA diploid and 38% DNA aneuploid. The DNA diploid carcinomas were accompanied by the enlargement of the cell nuclei, preserving of the nuclei's wide margins of heterochromatine, enlargement of the nuclear area and increase of the number of nuclei. In the aneuploid-polyploid cancer the nuclei had a substantial polymorphism with large cleaved nuclei and with significant variation in size, and with nuclear envelope. A frequent finding was euchromatization of chromatine. Dense chromatine appeared in the form of small clumps spread over the whole area of these irregular nuclei. Enlargement and activation of nucleoli occurred. There was a positive correlation (Chi-square) between T- and N-stage and immunohistochemical staining. There was also a positive correlation in staining intensity between p53, Ki67 and PCNA. There is also strong correlation between these markers of proliferative activity and the degree of aggressiveness of the tumour.

  19. Inhibition of HAX-1 by miR-125a reverses cisplatin resistance in laryngeal cancer stem cells

    PubMed Central

    Liu, Jiajia; Tang, Qinglai; Li, Shisheng; Yang, Xinming

    2016-01-01

    Chemoresistance is a major obstacle in chemotherapy of laryngeal carcinoma. Recently, studies indicate that cancer stem cells are responsible for chemotherapy failure. In addition, microRNAs play important roles in tumor initiation, development and multidrug resistance. In the present study, we found that the expression of microRNA-125a was decreased in laryngeal carcinoma tissues and Hep-2 laryngeal cancer stem cells (Hep-2-CSCs). MicroRNA-125a gain-of-function significantly increased the sensitivity of Hep-2-CSCs to cisplatin in vitro and in vivo. Combination with microRNA-125a mimics can decrease the half maximal inhibitory concentration of Hep-2-CSCs to cisplatin. Mechanically, we found that microRNA-125a reverses cisplatin resistance in Hep-2-CSCs by targeting Hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1). Inhibition of HAX-1 by microRNA-125a significantly promotes the cisplatin-induced apoptosis in Hep-2-CSCs through mitochondrial pathway. In addition, multidrug resistance of Hep-2-CSCs to vincristine, etoposide and doxorubicin was greatly improved after the cells were transfected with microRNA-125a mimics. These dates strongly suggested the promotion of microRNA-125a/HAX-1 axis on chemotherapy of laryngeal carcinoma. PMID:27880721

  20. Isolated laryngeal myasthenia gravis for 26 years.

    PubMed

    Renard, Dimitri; Hedayat, Amir; Gagnard, Corinne

    2015-02-01

    Laryngeal myasthenia gravis is a relatively rare variant of myasthenia gravis. A vast portion of patients with initial laryngeal myasthenia gravis develop involvement of ocular and/or extra-ocular muscles during the years after symptom onset although a minority of laryngeal myasthenia gravis patients continues to have isolated laryngeal muscle involvement for several years. We present a 58-year-old woman with recurrent episodic isolated dysphonia (associated with diffuse bilateral vocal cord paresis on laryngoscopy) since the age of 32. Dysphonia became permanent since 6 months. A diagnosis of laryngeal myasthenia gravis was made based on abnormal single-fiber electromyography and spectacular response to pyridostigmine treatment. Repetitive nerve stimulation was normal and anti-acetylcholine receptor and anti-muscle specific tyrosine kinase antibodies were absent. This case shows that laryngeal myasthenia gravis can be isolated during 26 years of follow-up. We propose that even when myasthenia gravis seems unlikely as underlying mechanism of isolated dysphonia (because of lack of antibodies, normal repetitive nerve stimulation, and absence of extra-laryngeal involvement after years of follow-up), single-fiber electromyography should be performed and myasthenia gravis treatment should be tried.

  1. A case of polypoid and papillary cystitis mimicking an advanced bladder carcinoma with invasion of perivesical fat.

    PubMed

    Ozaki, Kumi; Kitagawa, Kiyohide; Gabata, Toshifumi; Matsui, Osamu

    2014-01-01

    A rare case of polypoid and papillary cystitis without a history of catheterization is reported. A 69-year-old man was admitted to our hospital because of pain during urination and gross hematuria. The cystscopic and imaging findings including ultrasound, CT, and MR image showed an irregular wall thickening and stranding in the perivesical fat, which indicated an advanced bladder carcinoma, but histopathological findings obtained by transurethral resection revealed polypoid and papillary cystitis. Such benign lesions need to be discussed in the differential diagnosis of patients with bladder tumor to avoid excessive resection.

  2. A case of polypoid and papillary cystitis mimicking an advanced bladder carcinoma with invasion of perivesical fat

    PubMed Central

    Ozaki, Kumi; Kitagawa, Kiyohide; Gabata, Toshifumi; Matsui, Osamu

    2014-01-01

    A rare case of polypoid and papillary cystitis without a history of catheterization is reported. A 69-year-old man was admitted to our hospital because of pain during urination and gross hematuria. The cystscopic and imaging findings including ultrasound, CT, and MR image showed an irregular wall thickening and stranding in the perivesical fat, which indicated an advanced bladder carcinoma, but histopathological findings obtained by transurethral resection revealed polypoid and papillary cystitis. Such benign lesions need to be discussed in the differential diagnosis of patients with bladder tumor to avoid excessive resection. PMID:24669128

  3. Locally Advanced Stage High-Grade Mucoepidermoid Carcinoma of Salivary Gland in a 9-Year-Old Girl: The Controversy of Adjuvant Therapy.

    PubMed

    Martínez, Olga Micol; Dorado, Elena Daghoum; García, María Dolores Amorós; Ramírez, María Isabel Oviedo; de la Fuente Muñoz, Isabel; Soler, Jose Luis Fuster

    2016-09-05

    Malignant salivary gland tumors are rare in children, mostly represented by low-grade mucoepidermoid carcinomas. For these patients, long-term survival rates above 95% are reported after surgical resection. Here we report a case of a 9-year-old girl with a high grade locally advanced mucoepidermoid carcinoma undergoing adjuvant radiotherapy and chemotherapy after surgery. We emphasize the controversy and lack of evidence-based indication for these highly toxic adjuvant therapy modalities in children.

  4. Locally Advanced Stage High-Grade Mucoepidermoid Carcinoma of Salivary Gland in a 9-Year-Old Girl: The Controversy of Adjuvant Therapy

    PubMed Central

    Martínez, Olga Micol; Dorado, Elena Daghoum; García, María Dolores Amorós; Ramírez, María Isabel Oviedo; de la Fuente Muñoz, Isabel; Soler, Jose Luis Fuster

    2016-01-01

    Malignant salivary gland tumors are rare in children, mostly represented by low-grade mucoepidermoid carcinomas. For these patients, long-term survival rates above 95% are reported after surgical resection. Here we report a case of a 9-year-old girl with a high grade locally advanced mucoepidermoid carcinoma undergoing adjuvant radiotherapy and chemotherapy after surgery. We emphasize the controversy and lack of evidence-based indication for these highly toxic adjuvant therapy modalities in children. PMID:27746885

  5. Maintenance Peginterferon Therapy and Other Factors Associated with Hepatocellular Carcinoma in Patients with Advanced Hepatitis C

    PubMed Central

    Lok, Anna S.; Everhart, James E.; Wright, Elizabeth C.; Di Bisceglie, Adrian M.; Kim, Hae-Young; Sterling, Richard K.; Everson, Gregory T.; Lindsay, Karen L.; Lee, William M.; Bonkovsky, Herbert L.; Dienstag, Jules L.; Ghany, Marc G.; Morishima, Chihiro; Morgan, Timothy R.

    2010-01-01

    Background & Aims Interferon reportedly decreases the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. The Hepatitis C anti-viral long-term treatment against cirrhosis (HALT-C) trial showed that 4 years of maintenance therapy with peginterferon does not reduce liver disease progression. We investigated whether peginterferon decreases the incidence of HCC in the HALT-C cohort over a longer post-treatment follow-up period. Methods The study included 1,048 patients with chronic Hepatitis C (Ishak fibrosis scores ≥3) who did not have a sustained virological response (SVR) to therapy. They were randomly assigned to groups given a half-dose of peginterferon or no treatment (controls) for 3.5 years and followed for a median 6.1 (maximum 8.7) years. Results Eighty-eight patients developed HCC (68 definite, 20 presumed): 37/515 that were given peginterferon (7.2%) and 51/533 controls (9.6%; P=0.24). There was a significantly lower incidence of HCC among patients given peginterferon therapy who had cirrhosis, but not fibrosis, based on analysis of baseline biopsy samples. After 7 years, the cumulative incidences of HCC in treated and control patients with cirrhosis were 7.8% and 24.2%, respectively (hazard ratio [HR]=0.45; 95% confidence interval [CI]: 0.24–0.83); in treated and control patients with fibrosis they were 8.3% and 6.8%, respectively (HR=1.44; 95% CI: 0.77–2.69). Treated patients with a ≥2-point decrease in the histologic activity index, based on a follow-up biopsy, had a lower incidence of HCC than those with unchanged or increased scores (2.9% vs. 9.4%; P=0.03). Conclusions Extended analysis of the HALT-C cohort showed that long-term peginterferon therapy does not reduce the incidence of HCC among patients with advanced hepatitis C who did not achieve SVRs. Patients with cirrhosis who received peginterferon treatment had a lower risk for HCC than controls. PMID:21129375

  6. Successful Treatment of Advanced Primary Cutaneous Apocrine Carcinoma on the Scrotum with Systemic Chemotherapy and Radiotherapy Followed by Denosumab

    PubMed Central

    Furudate, Sadanori; Fujimura, Taku; Tsukada, Akira; Sato, Yota; Hidaka, Takanori; Tanita, Kayo; Kambayashi, Yumi; Haga, Takahiro; Hashimoto, Akira; Aiba, Setsuya

    2017-01-01

    Primary cutaneous apocrine carcinoma (PCAC) is a rare and highly aggressive cutaneous adnexal type of tumor that has a high metastasis rate and a poor prognosis. Although there are several case reports describing the successful treatment of PCAC with chemoradiotherapy or molecular targeting therapy, no standard therapy for the treatment of advanced PCAC has been established yet. Since receptor activator of nuclear factor kappa-B ligand (RANKL) is expressed in cancers of apocrine origin, leading to immunosuppression at the tumor site, we hypothesized that targeting RANKL with denosumab might be useful for the treatment of PCAC. In this report, we describe a case with advanced PCAC on the scrotum successfully treated with systemic chemotherapy using carboplatin and paclitaxel, and radiotherapy followed by denosumab. PMID:28203164

  7. Alternative treatments in advanced hepatocellular carcinoma patients with progressive disease after sorafenib treatment: a prospective multicenter cohort study

    PubMed Central

    Nakano, Masahito; Tanaka, Masatoshi; Kuromatsu, Ryoko; Nagamatsu, Hiroaki; Satani, Manabu; Niizeki, Takashi; Okamura, Shusuke; Iwamoto, Hideki; Shimose, Shigeo; Shirono, Tomotake; Noda, Yu; Koga, Hironori; Torimura, Takuji

    2016-01-01

    Sorafenib is an oral multikinase inhibitor that has been approved to treat advanced hepatocellular carcinoma (HCC), though it is unclear how much benefit advanced HCC patients with progressive disease (PD) derive from sorafenib treatment. This study aimed to assess survival risk factors and evaluate therapeutic strategies for advanced HCC patients with PD after sorafenib treatment. We analyzed the clinical data and treatment outcomes for 315 consecutive advanced HCC patients treated with sorafenib. Univariate analyses of overall survival identified therapeutic effect as an independent risk factor in all patients. Among all patients, 141 developed PD. Of those, 58 (41%) were treated with sorafenib monotherapy, 70 (50%) with agents other than sorafenib, and 13 (9%) were not treated at all. The median survival time was 6.1 months for PD patients with sorafenib monotherapy and 12.2 months for those administered alternative treatments (p < 0.0001). Our results indicated that sorafenib treatment may have negative long-term therapeutic effects in advanced HCC patients with PD, and that alternative treatments should be considered for these patients after sorafenib administration. PMID:27462865

  8. Salmonella typhimurium mediated delivery of Apoptin in human laryngeal cancer.

    PubMed

    Guan, Guo-fang; Zhao, Ming; Liu, Li-ming; Jin, Chun-shun; Sun, Kai; Zhang, De-jun; Yu, Duo-jiao; Cao, Hong-wei; Lu, Yan-qing; Wen, Lian-ji

    2013-01-01

    An effective cancer therapeutic should target tumours specifically with limited systemic toxicity. Here, we transformed an attenuated Salmonella typhimurium (S. typhimurium) with an Apoptin expressing plasmid into a human laryngeal carcinoma cell line. The expression of the inserted gene was measured using fluorescence and immunoblotting assays. The attenuated S. typhimurium-mediated Apoptin significantly decreased cytotoxicity and strongly increased cell apoptosis through the activation of caspase-3. The process was mediated by Bax, cytochrome c and caspase-9. A syngeneic nude murine tumour model was used to determine the anti-tumour effects of the recombinant bacteria in vivo. Systemic injection of the recombinant bacteria with and without re-dosing caused significant tumour growth delay and reduced tumour microvessel density, thereby extending host survival. Our findings indicated that the use of recombinant Salmonella typhimurium as an Apoptin expression vector has potential cancer therapeutic benefits.

  9. Laryngeal Reflexes: Physiology, Technique and Clinical Use

    PubMed Central

    Ludlow, Christy L.

    2015-01-01

    This review examines the current level of knowledge and techniques available for the study of laryngeal reflexes. Overall, the larynx is under constant control of several systems (including respiration, swallowing and cough) as well as sensory-motor reflex responses involving glossopharyngeal, pharyngeal, laryngeal and tracheobronchial sensory receptors. Techniques for the clinical assessment of these reflexes are emerging and need to be examined for sensitivity and specificity in identifying laryngeal sensory disorders. Quantitative assessment methods for the diagnosis of sensory reductions as well as sensory hypersensitivity may account for laryngeal disorders such as chronic cough, paradoxical vocal fold disorder and muscular tension dysphonia. The development of accurate assessment techniques could improve our understanding of the mechanisms involved in these disorders. PMID:26241237

  10. Radical irradiation and misonidazole in the treatment of advanced cervical carcinoma: results of a phase II trial

    SciTech Connect

    Girinski, T.; Pejovic, M.H.; Haie, C.; Bonnay, M.; Gerbaulet, A.; Mazeron, J.J.; Malaise, E.; Chassagne, D.

    1985-10-01

    Between February 1979 and January 1982, a Phase II study of misonidazole as a radiosensitizer was performed in 34 patients with advanced carcinoma of the uterine cervix. Twenty-nine patients were treated with conventional fractionated radiation and five patients with a twice daily fractionation schedule, 3 days a week. The total dose to the whole pelvis was 5000 cGy delivered in 5.5 weeks. Intracavitary curietherapy delivered an additional boost to the tumor. Misonidazole was given to all patients during external radiation and to 25 patients during intracavitary treatment for a total dose of 11 to 14 g/mS. All patients were followed for at least 28 months after treatment with a median follow-up of 52 months. Misonidazole toxicity included peripheral neuropathy (18%) and central nervous system toxicity (3%). The 3-year survival rate is 74% and the 3-year disease-free survival is 57%. When compared to our historical group survival, 42 and 12% for Stage III and IV, respectively, our data suggest that there is a probable advantage from using misonidazole in advanced carcinoma of the cervix.

  11. The influence of genetic variants of sorafenib on clinical outcomes and toxic effects in patients with advanced renal cell carcinoma

    PubMed Central

    Qin, Chao; Cao, Qiang; Li, Pu; Wang, Shangqian; Wang, Jian; Wang, Meilin; Chu, Haiyan; Zhou, Liqun; Li, Xuesong; Ye, Dingwei; Zhang, Hailiang; Huang, Yiran; Dong, Baijun; Sun, Xiaofeng; Zou, Qing; Cai, Hongzhou; Sun, Lijiang; Zhu, Jian; Liu, Fade; Ji, Junbiao; Cui, Li; Wang, Xiaoxiang; Zhou, Hai; Zhao, Hu; Wu, Bin; Chen, Jianchun; Jiang, Minjun; Zhang, Zhengdong; Shao, Pengfei; Ju, Xiaobing; Yin, Changjun

    2016-01-01

    The purpose of the present study was to investigate whether genetic variants that influence angiogenesis and sorafenib pharmacokinetics are associated with clinical outcomes and toxic effects in advanced renal cell carcinoma patients treated with this drug. One hundred patients with advanced renal cell carcinoma were enrolled. Forty-two polymorphisms in 15 genes were selected for genotyping and analyzed for associations with progression-free survival, overall survival, and toxic effects. We found that rs1570360 in VEGF and rs2239702 in VEGFR2 were significantly associated with progression-free. Specifically, patients carrying the variant genotypes (AG + AA) of these two polymorphisms both had an unfavorable progression-free. In addition, compared with those with the rs2239702 GG genotype, patients with the AG + AA genotype suffered an unfavorable OS. We found that the VEGF rs2010963 CG + GG genotypes had a significantly increased risk of hand-foot syndrome, and the ABCB1 rs1045642 CT + TT genotypes had an increased risk of high blood pressure. Our results suggest that polymorphisms in VEGF and VEGFR2 are associated with sorafenib clinical outcomes, and polymorphisms in VEGF and ABCB1 are associated with sorafenib-related toxicities. Larger studies are warranted to validate our findings. PMID:26830973

  12. The association of nutritional assessment criteria with health-related quality of life in patients with advanced colorectal carcinoma.

    PubMed

    Thoresen, L; Frykholm, G; Lydersen, S; Ulveland, H; Baracos, V; Birdsell, L; Falkmer, U

    2012-07-01

    Health-related quality of life (QoL) is a goal in nutritional oncology but the association between nutritional status and QoL is rarely explored. The aim of the study was to investigate the association of nutritional assessment criteria with QoL in 50 patients with advanced colorectal carcinoma. A second aim was to investigate changes in body weight and QoL during a 3-month follow-up. Muscle mass, nutritional risk, malnutrition and cachexia according to three different criteria were assessed, as well as health-related QoL. At inclusion, 36 patients experienced weight loss, 10 patients sarcopenia, 25 were at nutritional risk, 16 were malnourished and 11, 14 and 31 patients had cachexia according to different criteria. All nutritional assessment criteria discriminated between groups of patients with worse or better QoL to varying degrees. Malnutrition and cachexia defined by the European Palliative Care Research Collaborative and adjusted for recent gain or stabilisation of body weight discriminated on most QoL scores. Weight loss at follow-up was associated with a decrease in several QoL scores. Recognition of weight loss as well as diagnosing malnutrition and cachexia should be the first steps in an interventional pathway to enhance nutritional status and QoL in patients with advanced colorectal carcinoma.

  13. Treatment Outcomes of Patients with Locally Advanced Synchronous Esophageal and Head/Neck Squamous Cell Carcinoma Receiving Curative Concurrent Chemoradiotherapy

    PubMed Central

    Chen, Yen-Hao; Lu, Hung-I.; Chien, Chih-Yen; Lo, Chien-Ming; Wang, Yu-Ming; Chou, Shang-Yu; Su, Yan-Ye; Shih, Li-Hsueh; Li, Shau-Hsuan

    2017-01-01

    The present study investigated clinical outcomes and prognostic factors of patients with locally advanced synchronous esophageal squamous cell carcinoma (ESCC) and head/neck squamous cell carcinoma (HNSCC) receiving curative concurrent chemoradiotherapy (CCRT), and determined whether synchronous ESCC/HNSCC patients had worse prognosis compared to isolated ESCC patients. Using propensity score matching method, we compared 60 locally advanced synchronous ESCC/HNSCC patients with 60 matched isolated ESCC patients. Compared to 60 matched isolated ESCC patients, synchronous ESCC/HNSCC patients had significantly worse prognosis (13.5 months versus 17.2 months, P = 0.01), more grade 3–4 CCRT toxicity, and higher percentage of CCRT interruption. For synchronous ESCC/HNSCC group, the 1-year and 2-year survival rates were 52% and 13%, respectively. Univariate analysis showed that early ESCC stage, non-T4b disease, and salvage operations were significantly associated with superior survival. In multivariate analysis, ESCC stage represented an independent prognosticator. For chemotherapy regimen during CCRT, cisplatin/5-fluorouracil had significantly more grade 3–4 mucositis/esophagitis and neutropenia than weekly cisplatin. In conclusion, synchronous ESCC/HNSCC patients receiving curative CCRT have worse prognosis and poorer compliance of CCRT compared to isolated ESCC patients. For these patients, ESCC stage and T4b disease were significantly associated with clinical outcomes, and salvage operation may improve overall survival. PMID:28134308

  14. [Pre- and postoperative radiotherapy of oral carcinoma of a locally advanced stage. An analysis of the results and complications].

    PubMed

    Zini, G; Barbieri, E; Campobassi, A; Dallera, P; Emiliani, E; Frezza, G; Marchetti, C; Neri, S; Romagnoli, D; Silvano, M

    1989-01-01

    The combination of radiotherapy and surgery in the treatment of advanced oral carcinoma (T3 and T4 lesions) yields good possibilities of recovery; whether radiotherapy should be given before or after surgery is still debated. Fifty patients with advanced oral carcinomas were analyzed: 24 of them were irradiated before and 26 after surgery; doses ranged from 40 to 56 Gy for the first group of patients, and from 50 to 68 Gy for the second one. The disease-free survival 48 months after the diagnosis was 36% in patients who received preoperative irradiation, and 53.6% in patients who received postoperative radiotherapy; the latter allowed local control of the disease to be significantly improved (chi 2 3.99, 0.01 less than p less than 0.05). The quality of survival was worse in the group receiving preoperative irradiation, because of radiation-induced surgical complications, which were especially observed in patients with diffuse disease. Our findings suggest that postoperative radiotherapy may be advisable if the tumor is resectable, since tolerance and local control rate were acceptable. On the contrary, nearly inoperable masses and massive neck diseases often require preoperative irradiation.

  15. Trends in laryngeal cancer mortality in Europe.

    PubMed

    Bosetti, Cristina; Garavello, Werner; Levi, Fabio; Lucchini, Franca; Negri, Eva; La Vecchia, Carlo

    2006-08-01

    After a steady increase since the 1950s, laryngeal cancer mortality had tended to level off since the early 1980s in men from most European countries. To update trends in laryngeal cancer mortality in Europe, age-standardized (world standard) mortality rates per 100,000 were derived from the WHO mortality database for 33 European countries over the period 1980-2001. Jointpoint analysis was used to identify significant changes in mortality rates. In the European Union (EU) as a whole, male mortality declined by 0.8% per year between 1980 and 1989, by 2.8% between 1989 and 1995, by 5.3% between 1995 and 1998, and by 1.5% thereafter (rates were 5.1/100,000 in 1980-1981 and 3.3/100,000 in 2000-2001). This mainly reflects a decrease in rates in men from western and southern European countries, which had exceedingly high rates in the past. Male laryngeal mortality rose up to the early 1990s, and leveled off thereafter in several countries from central and eastern Europe. In 2000-2001 there was still a 10-15-fold variation in male laryngeal mortality between the highest rates in Croatia (7.9/100,000) and Hungary (7.7/100,000) and the lowest ones in Sweden (0.5/100,000) and Finland (0.8/100,000). Laryngeal cancer mortality was comparatively low in women from most European countries, with stable rates around 0.3/100,000 in the EU as a whole over the last 2 decades. Laryngeal cancer trends should be interpreted in terms of patterns and changes in exposure to alcohol and tobacco. Despite recent declines, the persistence of a wide variability in male laryngeal cancer mortality indicates that there is still ample scope for prevention of laryngeal cancer in Europe.

  16. An Unusual Laryngeal Foreign Body in Adult

    PubMed Central

    Ndiaye, Cire; Ahmed, Houra; Diom, Evelyne Siga; Deguenonvo, Richard Edouard Alain; Mbaye, Aminata; Zemene, Yilkal; Ndiaye, Issa Cheikh

    2016-01-01

    The accidental aspiration of a foreign body is a frequent domestic accident among children but a rare occurrence in adults. The laryngeal impaction of a coin is an unusual accident; only a few cases have been reported in the literature. Diagnosis is mostly achieved by clinicoradiological examinations. The authors report an uncommon case of laryngeal impaction of a coin in a 21-year-old patient, presenting with dysphonia without dyspnea or stridor. The extraction was performed by endoscopy. PMID:27999701

  17. [Severe laryngitis associated to gastroesophageal reflux].

    PubMed

    Botto, Hugo; Antonioli, Cintia; Nieto, Mary; Cocciaglia, Alejandro; Cuestas, Giselle; Roques Revol, Magdalena; López Marti, Jessica; Rodríguez, Hugo

    2014-02-01

    There is a strong association between gastroesophageal reflux and pharyngolaryngeal reflux as factors leading to respiratory disease, manifested as dysphonia, wheezing, coughing, recurrent laryngitis, bronchial obstruction, laryngospasm and apparent life-threatening events (ALTEs). These manifestations can be mild or severe and may sometimes put the patient's life at risk. We present two cases of patients with severe laryngitis who required endotracheal intubation, one of which underwent tracheostomy. The diagnostic methods and their limitations and the patients outcomes are described.

  18. Laryngeal Compensation for Voice Production After CO2 Laser Cordectomy

    PubMed Central

    Soliman, Zakaria; Hosny, Sameh Mohammad; Quriba, Amal Saeed

    2015-01-01

    Objectives Carbon dioxide (CO2) laser cordectomy is considered one of the modalities of choice for treatment of early glottic carcinoma. In addition to its comparable oncological results with radiotherapy and open surgical procedures, it preserves of laryngeal functions including voice production. The aim of this study was to detect how the larynx compensates for voice production after different types of CO2 laser cordectomy for early glottic carcinoma together with assessment of the vocal outcome in each compensation mechanism. Methods One hundred twelve patients treated with CO2 laser cordectomy were classified according to their main postoperative phonatory site. Perceptual analysis of voice samples using GRBAS (grade, roughness, breathiness, asthenia, and strain) scale was done for 88 patients after exclusion of the voice samples of all female patients to make the study population homogenous and the samples of 18 male patients due to bad quality (4 patients) or unavailability (14 patients) of their voice samples and the results were compared with those obtained from control group that included 25 age-matched euphonic male subjects. Results Five types of laryngeal compensation were defined including: vocal fold to vocal fold, vocal fold to vocal neofold, vocal fold to vestibular fold, vestibular fold, to vestibular fold, and arytenoids hyper adduction. Characters changes of voice produced by each compensation type were found to be statistically significant except for breathiness, asthenia and strain changes in vocal fold to vocal fold compensation type. Conclusion The larynx can compensate for voice production after CO2 laser cordectomy by five different compensation mechanisms with none of them producing voice quality comparable with that of controls. PMID:26622962

  19. Sonidegib for the treatment of advanced basal cell carcinoma: a comprehensive review of sonidegib and the BOLT trial with 12-month update.

    PubMed

    Chen, Leon; Silapunt, Sirunya; Migden, Michael R

    2016-09-01

    The Hedgehog inhibitors are promising alternative for patients with advanced basal cell carcinoma that are not amenable to radiotherapy or surgery. Sonidegib, also known as LDE225, is an orally available SMO antagonist that was recently approved by the US FDA for the treatment of patients with locally advanced basal cell carcinoma. This article will provide an overview of the pharmacology and pharmacokinetics of sonidegib and in-depth analysis of the BOLT trial with additional data from the 12-month update. The present challenges associated with Hedgehog inhibitors will also be discussed.

  20. Laryngitis

    MedlinePlus

    ... swelling and irritation (inflammation) of the voice box (larynx). The problem is most often associated with hoarseness ... The voice box (larynx) is located at the top of the airway to the lungs (trachea). The larynx contains the vocal cords. When ...

  1. FDA Approval Summary: Nivolumab in Advanced Renal Cell Carcinoma After Anti-Angiogenic Therapy and Exploratory Predictive Biomarker Analysis.

    PubMed

    Xu, James Xunhai; Maher, V Ellen; Zhang, Lijun; Tang, Shenghui; Sridhara, Rajeshwari; Ibrahim, Amna; Kim, Geoffrey; Pazdur, Richard

    2017-03-01

    On November 23, 2015, the U.S. Food and Drug Administration approved nivolumab (OPDIVO, Bristol-Myers Squibb Company) for patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy. The approval was based on efficacy and safety data demonstrated in an open-label, randomized study of 821 patients with advanced RCC who progressed after at least one anti-angiogenic therapy. Patients were randomized to nivolumab or everolimus and followed for disease progression. The primary end point was overall survival. Subsequent therapies, including everolimus for patients who developed progressive disease on the nivolumab arm, were allowed, but no cross-over was permitted. The median overall survival was 25.0 months on the nivolumab arm and 19.6 months on everolimus arm (hazard ratio: 0.73; 95% confidence interval: 0.60-0.89). The confirmed response rates were 21.5% versus 3.9%; median durations of response were 23.0 versus 13.7 months, and median times to response were 3.0 versus 3.7 months in the nivolumab and everolimus arms, respectively. A statistically significant improvement in progression-free survival was not observed in this trial. The safety profile of nivolumab in renal cell cancer was similar to that in other disease settings. However, the incidence of immune-mediated nephritis appeared to be higher in patients with RCC. The Oncologist 2017;22:311-317 IMPLICATIONS FOR PRACTICE: The overall benefit/risk profile demonstrated in trial CA209025 supported the approval of nivolumab as an additional treatment option for patients with advanced renal cell carcinoma after anti-angiogenic therapy. The use of nivolumab in patients who had received vascular endothelial growth factor-targeted therapy resulted in a 5.4 month improvement in median overall survival compared with the everolimus arm. This difference is statistically significant and clinically meaningful.

  2. HPV Genotypes Predict Survival Benefits From Concurrent Chemotherapy and Radiation Therapy in Advanced Squamous Cell Carcinoma of the Cervix

    SciTech Connect

    Wang, Chun-Chieh; Lai, Chyong-Huey; Huang, Yi-Ting; Chao, Angel; Chou, Hung-Hsueh; Hong, Ji-Hong

    2012-11-15

    Purpose: To study the prognostic value of human papillomavirus (HPV) genotypes in patients with advanced cervical cancer treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Methods and Materials: Between August 1993 and May 2000, 327 patients with advanced squamous cell carcinoma of the cervix (International Federation of Gynecology and Obstetrics stage III/IVA or stage IIB with positive lymph nodes) were eligible for this study. HPV genotypes were determined using the Easychip Registered-Sign HPV genechip. Outcomes were analyzed using Kaplan-Meier survival analysis and the Cox proportional hazards model. Results: We detected 22 HPV genotypes in 323 (98.8%) patients. The leading 4 types were HPV16, 58, 18, and 33. The 5-year overall and disease-specific survival estimates for the entire cohort were 41.9% and 51.4%, respectively. CCRT improved the 5-year disease-specific survival by an absolute 9.8%, but this was not statistically significant (P=.089). There was a significant improvement in disease-specific survival in the CCRT group for HPV18-positive (60.9% vs 30.4%, P=.019) and HPV58-positive (69.3% vs 48.9%, P=.026) patients compared with the RT alone group. In contrast, the differences in survival with CCRT compared with RT alone in the HPV16-positive and HPV-33 positive subgroups were not statistically significant (P=.86 and P=.53, respectively). An improved disease-specific survival was observed for CCRT treated patients infected with both HPV16 and HPV18, but these differenced also were not statistically significant. Conclusions: The HPV genotype may be a useful predictive factor for the effect of CCRT in patients with advanced squamous cell carcinoma of the cervix. Verifying these results in prospective trials could have an impact on tailoring future treatment based on HPV genotype.

  3. PCNA--a cell proliferation marker in vocal chord cancer. Part I: Premalignant laryngeal lesions.

    PubMed

    Pignataro, L D; Broich, G; Lavezzi, A M; Biondo, B; Ottaviani, F

    1995-01-01

    Laryngeal hyperkeratotic lesions can progress to fully developed malignant carcinoma in some cases. These premalignant lesions are proliferative disorders whose potential for further tumour progression is perhaps difficult to assess by mere histology. Immunostaining with PCNA, a protein correlated with cell proliferation, has been used to study tissue behavior in 30 cases of premalignant laryngeal vocal chord lesions treated by epithelial stripping in microlaryngoscopy, 15 of whom had no progression and 15 had recurrence and final development of full malignancy. The results showed a statistically significantly higher PCNA-index in the cases which underwent further tumour progression towards malignancy. PCNA testing may thus be suggested as a marker for tumour progression potential and help in determining clinical treatment choices.

  4. NCCN Task Force Report: Optimizing Treatment of Advanced Renal Cell Carcinoma With Molecular Targeted Therapy

    PubMed Central

    Hudes, Gary R.; Carducci, Michael A.; Choueiri, Toni K.; Esper, Peg; Jonasch, Eric; Kumar, Rashmi; Margolin, Kim A.; Michaelson, M. Dror; Motzer, Robert J.; Pili, Roberto; Roethke, Susan; Srinivas, Sandy

    2015-01-01

    The outcome of patients with metastatic renal cell carcinoma has been substantially improved with administration of the currently available molecularly targeted therapies. However, proper selection of therapy and management of toxicities remain challenging. NCCN convened a multidisciplinary task force panel to address the clinical issues associated with these therapies in attempt to help practicing oncologists optimize patient outcomes. This report summarizes the background data presented at the task force meeting and the ensuing discussion. PMID:21335444

  5. What's New in Laryngeal and Hypopharyngeal Cancer Research and Treatment?

    MedlinePlus

    ... Hypopharyngeal Cancer About Laryngeal and Hypopharyngeal Cancer What’s New in Laryngeal and Hypopharyngeal Cancers Research and Treatment? ... to better tests for early detection and to new targeted treatments. Chemoprevention Chemoprevention is the use of ...

  6. What Are the Key Statistics about Laryngeal and Hypopharyngeal Cancers?

    MedlinePlus

    ... Laryngeal and Hypopharyngeal Cancer What Are the Key Statistics About Laryngeal and Hypopharyngeal Cancers? The American Cancer ... 000 cancers will start in the hypopharynx. Survival statistics for these cancers are discussed in “ Survival rates ...

  7. Improved local control for advanced oropharyngeal carcinoma following twice daily radiation therapy

    SciTech Connect

    Wang, C.C.

    1985-12-01

    This paper presents the results of treatment on 99 patients with squamous cell carcinoma of the oropharynx irradiated by the twice-a-day radiation therapy program at the Massachusetts General Hospital. The program consisted of 1.6 Gy per fraction, two fractions per day with 4 hours between fractions, for 12 days, 5 days a week. After 38.4 Gy, the patients were given a 2 week break and then resumed twice-a-day radiation therapy for a total of 64 Gy and occasionally 67.2 Gy. Fifty-two patients had carcinoma of the faucial tonsil and 47 patients had carcinoma of the base of the tongue. For the entire group of patients, the 36 month actuarial local control rate was 58%, and for the T1-2 and T3-4 lesions, the rates were 77% and 48% respectively. In comparison with patients treated by once-a-day radiation therapy for a few years immediately prior to the twice-a-day program, the local control rates were improved to a statistically significant level. Likewise, the results as compared to those published in the literature were no worse and perhaps superior to those of patients treated by the once-a-day schedule.

  8. Hepatocellular carcinoma.

    PubMed

    Macdonald, G A

    1999-05-01

    Hepatitis C infection is associated with the development of hepatocellular carcinoma, and progress has been made in a number of areas. Transgenic mice lines expressing the hepatitis C core protein develop hepatic steatosis, adenomas, and hepatocellular carcinomas, with no significant hepatitis or fibrosis. This implies that hepatitis C can lead directly to malignant transformation. A new lesion, irregular regeneration, has been described in chronic hepatitis C infection and is associated with a 15-fold increase in the relative risk of developing hepatocellular carcinoma. A minority of patients with hepatitis C-related hepatocellular carcinoma have intense lymphocytic infiltration of the cancer, a feature associated with a better prognosis. Several studies have confirmed the association between large cell dysplasia and hepatocellular carcinoma. However, large cell dysplasia may not be a premalignant lesion and instead may be a marker for premalignant alterations elsewhere in the liver. Oral contraceptives previously have been linked to an increased risk of hepatocellular carcinoma. A large multicenter European case-control study has shown minimal increased risk of hepatocellular carcinoma with use of steroidal contraception. Tamoxifen had shown promise in the management of advanced hepatocellular carcinoma. However, a randomized placebo-controlled study of 477 patients with hepatocellular carcinoma found no benefit from tamoxifen. In a preliminary study, however, octreotide has shown improved survival and quality of life in patients with advanced hepatocellular carcinoma. Finally, interferon treatment continues to be linked to a reduced risk of hepatocellular carcinoma in patients with hepatitis C. These studies generally are not randomized, and a randomized prospective study is required to address this issue.

  9. Induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy for larynx organ preservation in advanced laryngeal and hypopharyngeal cancer offers moderate late toxicity outcome (DeLOS-I-trial).

    PubMed

    Dietz, Andreas; Rudat, Volker; Dreyhaupt, Jens; Pritsch, Maria; Hoppe, Florian; Hagen, Rudolph; Pfreundner, Leo; Schröder, Ursula; Eckel, Hans; Hess, Markus; Schröder, Michael; Schneider, Petra; Jens, Bünzel; Zenner, Hans P; Werner, Jochen A; Engenhardt-Cabillic, Rita; Vanselow, Bernhard; Plinkert, Peter; Niewald, Marcus; Kuhnt, Thomas; Budach, Wilfried; Flentje, Michael

    2009-08-01

    A prospective multicenter phase-II trial (12 centers) was performed by the German larynx organ preservation group (DeLOS) to evaluate the effect of induction chemotherapy (ICHT) with paclitaxel/cisplatin (TP), followed by accelerated-hyperfractionated (concomitant boost) radiotherapy (RT) in responders. The trial was focused on larynx preservation, tumor control, survival, salvage surgery and late toxicity in patients with advanced larynx/hypopharynx carcinoma eligible for total laryngectomy (LE). Seventy-one patients (40 larynx, 87.5% St. III, IV; 31 hypopharynx, 93.4% St. III, IV) were enrolled into the study and treated with ICHT (200 mg/m(2) paclitaxel, 100 mg/m(2) cisplatin; day 1, 22) according to the DeLOS protocol. Patients with complete or partial tumor response proceeded to RT (69.9 Gy in 5.5 weeks). Non-responders received a LE followed by postoperative RT (56-70 Gy in 5.5-7 weeks). The response rate to ICHT for larynx cancer was 69.6% (7.1% complete, 62.5% partial response) and for hypopharyngeal cancer was 84.3% (6.9% complete, 77.4% partial response). Overall survival after 36 months was 60.3% (95% CI, 48.4-72.2%), after 42 months was 56.5% (95% CI, 44.2-68.8%). Laryngectomy-free survival was as follows: after 36 months, 43.0% (95% CI, 30.9-55.0%); after 42 months, 41.3% (95% CI, 29.3-53.3%). Both parameters did not show different outcomes after distinguishing larynx from hypopharynx. LE was indicated in 15 non-responders after ICHT. Five of the 15 non-responders refused the laryngectomy. Two of the five received RT instead and had no evidence of disease 42 months after RT. Late toxicity (dysphagia III, IV LENT SOMA score in laryngectomy-free survivors: after 6 months, 1.8%; 12 months, 11.4%; 18 months, 14.5%; 24 months, 8.1%; 36 months, 16%) and salvage surgery (4 pharyngocutaneous fistulas in 27 operations) were tolerable. In a large portion of patients eligible for LE, the larynx could be preserved with satisfying functional outcome. Good

  10. Treatment Modalities and Outcomes in Patients with Advanced Invasive Thymoma or Thymic Carcinoma: A Retrospective Multicenter Study

    PubMed Central

    Modh, Ankit; Rimner, Andreas; Allen, Pamela K.; Greenfield, Brad; Marom, Edith M.; Rice, David; Huang, James; Rosenzweig, Kenneth E.; Komaki, Ritsuko; Gomez, Daniel R.

    2016-01-01

    Introduction We investigated relationships between treatment characteristics and long-term outcomes in patients with locally advanced thymoma or thymic carcinoma. Methods We retrospectively reviewed 146 patients treated in 1980–2011 at two tertiary cancer care centers, 110 with Masaoka-Koga stage III–IVa invasive thymoma and 36 with stage I–IVa thymic carcinoma. Survival probabilities were estimated with the Kaplan-Meier method. Risk factors related to survival were identified by univariate and multivariate competing risk analysis, with overall survival (OS) as the competing risk. Cox regression analysis was used to identify risk factors for OS. Results Median follow-up time for all patients was 64 months. At 5/10 years, rates of OS and freedom from recurrence (FFR) were 81/58% and 81/65%, respectively. Of patients who underwent surgery, trimodality treatment produced better survival compared to less aggressive treatment among patients with stage III disease (p=0.03). Among patients who underwent trimodality treatment, patients with stage III disease had better OS (p=0.03) and FFR (p<0.001) than those with stage IVA disease. On Cox regression analysis, decreased OS was associated with thymic carcinoma (hazard ratio [HR]=7.36, 95% CI=2.38–22.77, p=0.001), R2/unresectable disease (HR=8.45, 95% CI=1.44–49.42, p=0.02) and an Eastern Cooperative Oncology Group performance score of 1 (HR=8.14, 95% CI=1.55–42.75, p=0.01) or 2–3 (HR=29.60, 95% CI=4.0–218.98, p=0.001) versus 0. Conclusion Aggressive treatment with chemotherapy, surgical resection, and postoperative radiation therapy can produce long-term survival for patients with invasive thymic malignanices. PMID:24390276

  11. Novel Pretreatment Scoring Incorporating C-reactive Protein to Predict Overall Survival in Advanced Hepatocellular Carcinoma with Sorafenib Treatment

    PubMed Central

    Nakanishi, Hiroyuki; Kurosaki, Masayuki; Tsuchiya, Kaoru; Yasui, Yutaka; Higuchi, Mayu; Yoshida, Tsubasa; Komiyama, Yasuyuki; Takaura, Kenta; Hayashi, Tsuguru; Kuwabara, Konomi; Nakakuki, Natsuko; Takada, Hitomi; Ueda, Masako; Tamaki, Nobuharu; Suzuki, Shoko; Itakura, Jun; Takahashi, Yuka; Izumi, Namiki

    2016-01-01

    Objectives This study aimed to build a prediction score of prognosis for patients with advanced hepatocellular carcinoma (HCC) after sorafenib treatment. Methods A total of 165 patients with advanced HCC who were treated with sorafenib were analyzed. Readily available baseline factors were used to establish a scoring system for the prediction of survival. Results The median survival time (MST) was 14.2 months. The independent prognostic factors were C-reactive protein (CRP) <1.0 mg/dL [hazard ratio (HR) =0.51], albumin >3.5 g/dL (HR =0.55), alpha-fetoprotein <200 ng/mL (HR =0.45), and a lack of major vascular invasion (HR =0.39). Each of these factors had a score of 1, and after classifying the patients into five groups, the total scores ranged from 0 to 4. Higher scores were linked to significantly longer survival (p<0.0001). Twenty-nine patients (17.6%) with a score of 4 had a MST as long as 36.5 months, whereas MST was as short as 2.4 and 3.7 months for seven (4.2%) and 22 (13.3%) patients with scores of 0 and 1, respectively. Conclusions A novel prognostic scoring system, which includes the CRP level, has the ability to stratify the prognosis of patients with advanced stage HCC after treatment with sorafenib. PMID:27781198

  12. Phase II clinical trial of cisplatin, 5-fluorouracil, and ifosfamide as treatment for advanced locoregional head and neck carcinoma.

    PubMed

    Sánchez Parra, M; Churruca, C; Paredes, A; Lacasta, A; López de Argumedo, G; Alvárez, I; Abad, T; Egana, L; Guimón, E; Piera, J M

    1999-02-01

    The association of ifosfamide with cisplatin and 5-fluorouracil for the management of advanced squamous cell carcinoma of the head and neck was assessed in this trial. Ifosfamide was given initially to 12 patients in combination with standard fixed doses of cisplatin and 5-fluorouracil, at 1,000 mg/m2 daily on days 2, 3, and 4. Two patients died of neutropenia and severe infection, and the authors recruited seven more patients who were treated with a lower dose of ifosfamide, 800 mg/m2 daily on days 2, 3, and 4. One of the seven patients died of neutropenia and severe infection. Three complete remission were observed in 18 patients evaluable for efficacy. The study was closed early because of the severe toxicity profile demonstrated by this scheme and because of no clear advantage in efficacy versus cisplatin plus 5-fluorouracil combinations.

  13. Effects of carbon dioxide on laryngeal receptors

    SciTech Connect

    Anderson, J.W.; Sant'Ambrogio, F.B.; Orani, G.P.; Sant'Ambrogio, G.; Mathew, O.P. )

    1990-02-26

    Carbon dioxide (CO{sub 2}) either stimulates or inhibits laryngeal receptors in the cat. The aim of this study was to correlate the CO{sub 2} response of laryngeal receptors with their response to other known stimuli (i.e. pressure, movement, cold, water and smoke). Single unit action potentials were recorded from fibers in the superior laryngeal nerve of 5 anesthetized, spontaneously breathing dogs together with CO{sub 2} concentration, esophageal and subglottic pressure. Constant streams of warm, humidified air or 10% CO{sub 2} in O{sub 2} were passed through the functionally isolated upper airway for 60 s. Eight of 13 randomly firing or silent receptors were stimulated by CO{sub 2} (from 0.4{plus minus}0.1 to 1.8{plus minus}0.4 imp.s). These non-respiratory-modulated receptors were more strongly stimulated by solutions lacking Cl{sup {minus}} and/or cigarette smoke. Six of 21 respiratory modulated receptors (responding to pressure and/or laryngeal motion) were either inhibited or stimulated by CO{sub 2}. Our results show that no laryngeal receptor responds only to CO{sub 2}. Silent or randomly active receptors were stimulated most often by CO{sub 2} consistent with the reflex effect of CO{sub 2} in the larynx.

  14. Tumor Volumes and Prognosis in Laryngeal Cancer

    PubMed Central

    Issa, Mohamad R.; Samuels, Stuart E.; Bellile, Emily; Shalabi, Firas L.; Eisbruch, Avraham; Wolf, Gregory

    2015-01-01

    Tumor staging systems for laryngeal cancer (LC) have been developed to assist in estimating prognosis after treatment and comparing treatment results across institutions. While the laryngeal TNM system has been shown to have prognostic information, varying cure rates in the literature have suggested concern about the accuracy and effectiveness of the T-classification in particular. To test the hypothesis that tumor volumes are more useful than T classification, we conducted a retrospective review of 78 patients with laryngeal cancer treated with radiation therapy at our institution. Using multivariable analysis, we demonstrate the significant prognostic value of anatomic volumes in patients with previously untreated laryngeal cancer. In this cohort, primary tumor volume (GTVP), composite nodal volumes (GTVN) and composite total volume (GTVP + GTVN = GTVC) had prognostic value in both univariate and multivariate cox model analysis. Interestingly, when anatomic volumes were measured from CT scans after a single cycle of induction chemotherapy, all significant prognosticating value for measured anatomic volumes was lost. Given the literature findings and the results of this study, the authors advocate the use of tumor anatomic volumes calculated from pretreatment scans to supplement the TNM staging system in subjects with untreated laryngeal cancer. The study found that tumor volume assessment after induction chemotherapy is not of prognostic significance. PMID:26569309

  15. Viscoelastic properties of laryngeal posturing muscles

    NASA Astrophysics Data System (ADS)

    Alipour, Fariborz; Hunter, Eric; Titze, Ingo

    2003-10-01

    Viscoelastic properties of canine laryngeal muscles were measured in a series of in vitro experiments. Laryngeal posturing that controls vocal fold length and adduction/abduction is an essential component of the voice production. The dynamics of posturing depends on the viscoelastic and physiological properties of the laryngeal muscles. The time-dependent and nonlinear behaviors of these tissues are also crucial in the voice production and pitch control theories. The lack of information on some of these muscles such as posterior cricoarytenoid muscle (PCA), lateral cricoarytenoid muscle (LCA), and intraarytenoid muscle (IA) was the major incentive for this study. Samples of PCA and LCA muscles were made from canine larynges and mounted on a dual-servo system (Ergometer) as described in our previous works. Two sets of experiments were conducted on each muscle, a 1-Hz stretch and release experiment that provides stress-strain data and a stress relaxation test. Data from these muscles were fitted to viscoelastic models and Young's modulus and viscoelastic constants are obtained for each muscle. Preliminary data indicates that elastics properties of these muscles are similar to those of thyroarytenoid and cricothyroid muscles. The relaxation response of these muscles also shows some similarity to other laryngeal muscles in terms of time constants.

  16. Diesel exhaust, diesel fumes, and laryngeal cancer.

    PubMed

    Muscat, J E; Wynder, E L

    1995-03-01

    A hospital-based, case-control study of 235 male patients with laryngeal cancer and 205 male control patients was conducted to determine the effects of exposure to diesel engine exhaust and diesel fumes and the risk of laryngeal cancer. All patients were interviewed directly in the hospital with a standardized questionnaire that gathered information on smoking habits, alcohol consumption, employment history, and occupational exposures. Occupations that involve substantial exposure to diesel engine exhaust include mainly truck drivers, as well as mine workers, firefighters, and railroad workers. The odds ratio for laryngeal cancer associated with these occupations was 0.96 (95% confidence interval, 0.5 to 1.8). The odds ratio for self-reported exposure to diesel exhaust was 1.47 (95% confidence interval, 0.5 to 4.1). An elevated risk was found for self-reported exposure to diesel fumes (odds ratio, 6.4; 95% confidence interval, 1.8 to 22.6). No association was observed between jobs that entail exposure to diesel fumes, such as automobile mechanics, and the risk of laryngeal cancer. These results show that diesel engine exhaust is unrelated to laryngeal cancer risk. The different findings for self-reported diesel fumes and occupations that involve exposure to diesel fumes could reflect a recall bias.

  17. Impact of Adding Concomitant Chemotherapy to Hyperfractionated Accelerated Radiotherapy for Advanced Head-and-Neck Squamous Cell Carcinoma

    SciTech Connect

    Nuyts, Sandra Dirix, Piet; Clement, Paul M.J.; Poorten, Vincent Vander; Delaere, Pierre; Schoenaers, Joseph; Hermans, Robert; Bogaert, Walter van den

    2009-03-15

    Purpose: To evaluate the feasibility and efficacy of a hyperfractionated accelerated radiotherapy (RT) schedule combined with concomitant chemotherapy (Cx) in patients with locally advanced head-and-neck squamous cell carcinoma. Methods and Materials: Between 2004 and 2007, a total of 90 patients with locoregionally advanced head-and-neck squamous cell carcinoma underwent irradiation according to a hybrid fractionation schedule consisting of 20 fractions of 2 Gy (once daily) followed by 20 fractions of 1.6 Gy (twice daily) to a total dose of 72 Gy. Concomitant Cx (cisplatinum 100 mg/m{sup 2}) was administered at the start of Weeks 1 and 4. Treatment outcome and toxicity were retrospectively compared with a previous patient group (n = 73) treated with the same schedule, but without concomitant Cx, between 2001 and 2004. Results: The locoregional control (LRC) rate was 70% after 2 years. Two-year overall and 2-year disease-free survival rates were 74% and 60%, respectively. In comparison with the RT-only group, an improvement of 15% in both LRC (p = 0.03) and overall survival (p = 0.09) was observed. All patients were treated to full radiation dose according to protocol, although the Cx schedule had to be adjusted in 12 patients. No acute Grade 4 or 5 toxicity was seen, but incidences of Grade 3 acute mucositis (74.5% vs. 50.7%; p = 0.002) and dysphagia (82.2% vs. 47.9%; p < 0.001) were significantly higher in the chemoradiotherapy group compared with patients treated with RT alone. Conclusion: With this chemoradiotherapy regimen, excellent LRC and survival rates were achieved, with acceptable acute toxicity.

  18. Evaluation of the Efficacy of Combined Continuous Arterial Infusion and Systemic Chemotherapy for the Treatment of Advanced Pancreatic Carcinoma

    SciTech Connect

    Ikeda, O. Kusunoki, S.; Kudoh, K.; Takamori, H.; Tsuji, T.; Kanemitsu, K.; Yamashita, Y.

    2006-06-15

    Purpose. To evaluate the effects of combined continuous transcatheter arterial infusion (CTAI) and systemic chemotherapy in patients with advanced pancreatic carcinoma. Methods. CTAI was performed in 17 patients with stage IV pancreatic cancer with (n = 11) or without (n = 6) liver metastasis. The reservoir was transcutaneously implanted with the help of angiography. The inferior pancreatic artery (IPA) was embolized to achieve delivery of the pancreatic blood supply through only the celiac artery. The systemic administration of gemcitabine was combined with the infusion of 5-fluorouracil via the reservoir. Treatment effects were evaluated based on the primary tumor size, liver metastasis, and survival time and factors such as tumor size, tumor location, and stage of pancreatic carcinoma; the embolized arteries were analyzed with respect to treatment effects and prognosis. Results. A catheter was fixed in the gastroduodenal artery and splenic artery in 10 and 7 patients, respectively. Complete peripancreatic arterial occlusion was successful in 10 patients. CT showed a decrease in tumor size in 6 of 17 (35%) patients and a decrease in liver metastases in 6 of 11 (55%) patients. The survival time ranged from 4 to 18 months (mean {+-} SD, 8.8 {+-} 1.5 months). Complete embolization of arteries surrounding the pancreas was achieved in 10 patients; they manifested superior treatment effects and prognoses (p < 0.05). Conclusion. In patients with advanced pancreatic cancer, long-term CTAI with systemic chemotherapy appeared to be effective not only against the primary tumor but also against liver metastases. Patients with successfully occluded peripancreatic arteries tended to survive longer.

  19. Functional results of endoscopic laser surgery in advanced head and neck tumors

    NASA Astrophysics Data System (ADS)

    Sadick, Haneen; Baker-Schreyer, Antonio; Bergler, Wolfgang; Maurer, Joachim; Hoermann, Karl

    1998-01-01

    Functional results following lasersurgery of minor laryngeal carcinomas were very encouraging. The indication for lasersurgical intervention was then extended to larger carcinomas of the larynx and hypopharynx. The purpose of this study was to assess vocal function and swallowing ability after endoscopic lasersurgery and to compare the results with conventional surgical procedures. From January 1994 to December 1996, 72 patients with advanced squamous cell carcinoma of the larynx and hypopharynx were examined prospectively. The patients underwent endoscopic lasersurgery instead of laryngopharyngectomy. The voice quality was evaluated pre- and postoperatively by subjective assessment, registration of voice parameters and sonegraphic classification. The swallowing ability was judged according to individual scores. The necessity of tracheostomy and nasogastric tube were registered and the duration of hospitalization was documented. The results showed that laryngeal phonation and swallowing ability were significantly better 12 months after lasersurgery compared to the preoperative findings whereas the recurrence rate was similar or even better after conventional pharyngolaryngectomy. Lasersurgery as an alternative surgical procedure to laryngectomy enables patients to retain a sufficient voice function and swallowing ability.

  20. Esophageal squamous cell carcinoma (ESCC): advance in genomics and molecular genetics.

    PubMed

    Chen, J; Kwong, D L; Cao, T; Hu, Q; Zhang, L; Ming, X; Chen, J; Fu, L; Guan, X

    2015-01-01

    Esophageal cancer is aggressive and has poor prognosis. Esophageal squamous cell carcinoma (ESCC) is histologically the most prevalent type of esophageal cancer and ranked as the sixth leading cause of cancer death worldwide. In recent years, cancer has been widely regarded as genetic disease, as well as epigenetic abnormalities including DNA methylation, histone deacetylation, chromatin remodeling, gene imprinting and noncoding RNA regulation. In this review, we will provide a general overview of genes, proteins and microRNAs that are involved in the development of ESCC, which aims to enhance our understanding of molecular mechanisms implicated in ESCC development and progression.

  1. Brachytherapy boost in loco-regionally advanced nasopharyngeal carcinoma: a prospective randomized trial of the International Atomic Energy Agency

    PubMed Central

    2014-01-01

    Abstact Background The purpose was to determine whether a brachytherapy boost improves outcomes in patients with advanced nasopharyngeal carcinoma treated with standard chemo-radiotherapy. Methods Patients with nasopharyngeal carcinoma WHO grades I-III and TNM stages III or non-metastatic stage IV were eligible for this phase III study. Patients were randomized to either arm (A) induction chemotherapy, followed by external beam radiotherapy (EBRT) with concomitant cisplatin (n = 139) or arm (B), the same schedule plus a brachytherapy boost to the nasopharynx (n = 135). The EBRT doses given were 70 Gy to the primary tumour and positive lymph nodes and 46 Gy to the negative neck. The additional brachytherapy boost in arm (B) was given by either low dose-rate (LDR – 11 Gy) or high dose-rate (HDR – 3 fractions of 3.0 Gy) brachytherapy. The primary endpoint was 3-year overall survival (OS) and secondary endpoints were: local control, regional control, distant metastasis and grade 3–4 adverse events. Results 274 patients were randomized between September 2004 and December 2008. The two arms were comparable with regard to age, gender, stage and grade. 273 patients completed treatment. Median follow-up was 29 months (0.2-67 months). The effect of treatment arm, country, age, gender, WHO pathology, stage (T3-4, N2-3 versus other) and chemotherapy on overall survival (OS), disease-free survival (DFS) and local recurrence-free survival (LRFS) was studied. Stage significantly affected OS (p = 0.024) and DFS (p = 0.018) while age significantly affected OS (p = 0.014). None of the other factors studied were significant. The 3-year LRFS was 60.5% and 54.4% in arms A and B respectively (p = 0.647). The 3-year regional control rate in the neck was 59.7% and 54.3% respectively (p = 0.7). Distant metastasis developed in 59.7% of patients in arm A and 55.4% in arm B (p = 0.377). Patients with T1/T2 N + had a 3 year LRFS of 51.8% in Arm A (62 patients) versus 57.9% in Arm B (67

  2. Characterization and Management of Hedgehog Pathway Inhibitor-Related Adverse Events in Patients With Advanced Basal Cell Carcinoma

    PubMed Central

    Dréno, Brigitte; Ascierto, Paolo Antonio; Dummer, Reinhard; Basset-Seguin, Nicole; Fife, Kate; Ernst, Scott; Licitra, Lisa; Neves, Rogerio I.; Peris, Ketty; Puig, Susana; Sokolof, Jonas; Sekulic, Aleksandar; Hauschild, Axel; Kunstfeld, Rainer

    2016-01-01

    Abnormal activation of hedgehog pathway signaling is a key driver in the pathogenesis of basal cell carcinoma (BCC). Vismodegib, a first-in-class small-molecule inhibitor of hedgehog pathway signaling, is approved by regulatory authorities for the treatment of adults who have metastatic BCC or locally advanced BCC that has recurred after surgery, or who are not candidates for surgery and who are not candidates for radiation. A second inhibitor, sonidegib, was also recently approved for the same patient group with locally advanced BCC. Adverse events (AEs) commonly observed in hedgehog pathway inhibitor (HPI)-treated patients include muscle spasms, ageusia/dysgeusia, alopecia, weight loss, and asthenia (fatigue). These AEs are thought to be mechanistically related to inhibition of the hedgehog pathway in normal tissue. Although the severity of the majority of AEs associated with HPIs is grade 1–2, the long-term nature of these AEs can lead to decreased quality of life, treatment interruption, and in some cases discontinuation, all of which might affect clinical outcome. The incidence, clinical presentation, putative mechanisms, and management strategies for AEs related to HPIs in advanced BCC are described. These observations represent the first step toward the development of mechanism-based preventive and management strategies. Knowledge of these AEs will allow health care professionals to provide appropriate counseling and supportive care interventions, all of which will contribute to improved quality of life and optimal benefit from therapy. Implications for Practice: The hedgehog pathway inhibitors (HPIs) vismodegib and sonidegib represent a therapeutic breakthrough for patients with advanced basal cell carcinoma. However, the nature of the low-grade adverse events (AEs) commonly observed in HPI-treated patients, including muscle spasms, ageusia/dysgeusia, alopecia, weight loss, and fatigue, can impact clinical outcomes as a result of decreased quality of life

  3. Radioembolization using 90Y-resin microspheres for patients with advanced hepatocellular carcinoma

    SciTech Connect

    Sangro, Bruno . E-mail: bsangro@unav.es; Bilbao, Jose I.; Boan, Jose; Martinez-Cuesta, Antonio; Benito, Alberto; Rodriguez, Javier; Panizo, Angel; Gil, Belen; Inarrairaegui, Mercedes; Herrero, Ignacio; Quiroga, Jorge; Prieto, Jesus

    2006-11-01

    Purpose: To investigate the antitumor effect of resin microspheres loaded with 90-yttrium against hepatocellular carcinoma and their safety in the setting of liver cirrhosis. Patients and Methods: Data from 24 consecutive patients with hepatocellular carcinoma (HCC) treated by radioembolization in the period from September 2003 to February 2005 were reviewed. Patients received no further antineoplastic therapy. A comprehensive evaluation was performed to prevent the risk of damage due to microsphere misplacing. Patients were discharged the day after microspheres injection. Results: Serious liver toxicity observed among cirrhotic patients in a first period was subsequently prevented by modifying the selection criteria and the method for calculating the activity to be administered. Among 21 patients evaluable for response using Response Evaluation Criteria in Solid Tumors (RECIST) criteria, a reduction in size of target lesions was observed in all but 1 patient. When considering only target lesions, disease control rate and response rate were 100% and 23.8%, respectively. However, 43% of patients progressed in the liver in the form of new lesions appearing a median time of 3 months after radioembolization. Conclusion: Our experience in these series of patients indicates that radioembolization using resin microspheres has a significant antitumor effect against HCC and that using stringent selection criteria and conservative models for calculating Radiation activity to be administered, radioembolization can be performed safely even in cirrhotic patients.

  4. Hepatocellular carcinoma

    SciTech Connect

    Nakashima, T.; Kojiro, M.

    1986-01-01

    With the remarkable recent diagnostic and therapeutic advances and the discovery of a possible pathogenetic role of hepatitis B virus, the study and treatment of hepatocellular carcinoma are entering a new era. Parallel developments in the pathological study of this malignancy are also to be expected. To coincide with this new era, this book presents the authors' accumulated pathomorphological knowledge of hepatocellular carcinoma. The detailed coverage is based on the examination findings of 439 cases of hepatocellular carcinoma autopsied at the authors' department in the last twenty years.

  5. Sorafenib plus hepatic arterial infusion chemotherapy with cisplatin versus sorafenib for advanced hepatocellular carcinoma: randomized phase II trial

    PubMed Central

    Ikeda, M.; Shimizu, S.; Sato, T.; Morimoto, M.; Kojima, Y.; Inaba, Y.; Hagihara, A.; Kudo, M.; Nakamori, S.; Kaneko, S.; Sugimoto, R.; Tahara, T.; Ohmura, T.; Yasui, K.; Sato, K.; Ishii, H.; Furuse, J.; Okusaka, T.

    2016-01-01

    Background Sorafenib (Sor) is acknowledged as a standard therapy for advanced hepatocellular carcinoma (HCC). This trial was conducted to evaluate the effect of addition of hepatic arterial infusion chemotherapy with cisplatin (SorCDDP) to Sor for the treatment of advanced HCC. Patients and methods We conducted a multicenter open-labeled randomized phase II trial in chemo-naïve patients with advanced HCC with Child-Pugh scores of 5–7. Eligible patients were randomly assigned 2:1 to receive SorCDDP (sorafenib: 400 mg bid; cisplatin: 65 mg/m2, day 1, every 4–6 weeks) or Sor (400 mg bid). The primary end point was overall survival. Results A total of 108 patients were randomized (Sor, n = 42; SorCDDP, n = 66). The median survival in the Sor and SorCDDP arms were 8.7 and 10.6 months, respectively [stratified hazard ratio (95% confidence interval), 0.60 (0.38–0.96), P = 0.031]. The median time to progression and the response rate were, respectively, 2.8 months and 7.3% in the Sor arm and 3.1 months and 21.7% in the SorCDDP arm. The adverse events were more frequent in the SorCDDP arm than in the Sor arm, but well-tolerated. Conclusion SorCDDP yielded favorable overall survival when compared with Sor in patients with advanced HCC. Clinical Trial registration UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703. PMID:27573564

  6. Immunohistochemical markers of advanced basal cell carcinoma: CD56 is associated with a lack of response to vismodegib.

    PubMed

    Castillo, Jean-Marie; Knol, Anne-Chantal; Nguyen, Jean-Michel; Khammari, Amir; Saint-Jean, Mélanie; Dreno, Brigitte

    2016-10-01

    Vismodegib is an effective treatment for advanced basal cell carcinoma (BCC), but primary resistance to vismodegib remains to be elucidated. Alternative approaches are warranted to help selecting patients most likely to be responsive to treatment. The identification of immunohistochemical markers may support this perspective, as well as better understanding of resistance mechanisms. To determine the level of expression of CD56, PDGF-R, CD117, MMP9, TIMP3, and CXCR4 in advanced BCC, and explore whether expression levels are associated with non-response to vismodegib. A cross-sectional study was conducted. Immunohistochemical markers were selected based on their roles in tumour proliferation and/or migration in skin tumours. Tissue samples included pretreatment advanced BCC samples from patients treated with vismodegib, with an available response after six months of treatment. Regression optimised models were used to build hypotheses regarding a possible association between expression levels and non-response to vismodegib, which was then tested by logistic regression. Twenty-three patients were included. The percentage of samples expressing markers ranged from 43.5% (CD117) to 91.3% (CXCR4). CD56 expression was significantly associated with an increased risk of non-response to vismodegib (OR = 5.5; CI 95%: 3.4-29.8; p = 0.0488); a similar association was suggested for CXCR4 (p = 0.066), but not identified for other markers. These results provide a better understanding of the expression of immunohistochemical markers in advanced BCC. Further detailed analysis of CD56 expression may provide insights into guiding further investigation of the correlation between this marker and non-response to vismodegib.

  7. Treatment algorithm based on the multivariate survival analyses in patients with advanced hepatocellular carcinoma treated with trans-arterial chemoembolization

    PubMed Central

    Prajapati, Hasmukh J.

    2017-01-01

    Purpose To develop the treatment algorithm from multivariate survival analyses (MVA) in patients with Barcelona clinic liver cancer (BCLC) C (advanced) Hepatocellular carcinoma (HCC) patients treated with Trans-arterial Chemoembolization (TACE). Methods Consecutive unresectable and non-tranplantable patients with advanced HCC, who received DEB TACE were studied. A total of 238 patients (mean age, 62.4yrs) was included in the study. Survivals were analyzed according to different parameters from the time of the 1st DEB TACE. Kaplan Meier and Cox Proportional Hazard model were used for survival analysis. The SS was constructed from MVA and named BCLC C HCC Prognostic (BCHP) staging system (SS). Results Overall median survival (OS) was 16.2 months. In HCC patients with venous thrombosis (VT) of large vein [main portal vein (PV), right or left PV, hepatic vein, inferior vena cava] (22.7%) versus small vein (segmental/subsegmental PV) (9.7%) versus no VT had OSs of 6.4 months versus 20 months versus 22.8 months respectively (p<0.001). On MVA, the significant independent prognostic factors (PFs) of survival were CP class, eastern cooperative oncology group (ECOG) performance status (PS), single HCC<5 cm, site of VT, metastases, serum creatinine and serum alpha-feto protein. Based on these PFs, the BCHP staging system was constructed. The OSs of stages I, II and III were 28.4 months, 11.8 months and 2.4 months accordingly (p<0.001). The treatment plan was proposed according to the different stages. Conclusion On MVA of patients with advanced HCC treated with TACE, significant independent prognostic factors (PFs) of survival were CP class, ECOG PS, single HCC<5 cm or others, site of VT, metastases, serum creatinine and serum alpha-feto protein. New BCHP SS was proposed based on MVA data to identify the suitable advanced HCC patients for TACE treatments. PMID:28170405

  8. [Diagnosis and therapy of laryngitis gastrica].

    PubMed

    Pahn, J; Schlottmann, A; Witt, G; Wilke, W

    2000-07-01

    We treated 64 patients with the diagnosis of laryngitis gastrica with Antra (Omeprazol) in doses of 10, 20, and 40 mg. To determine the success of the therapy, pH monitoring of the esophagus and hypopharynx, the voice status and measurement of vocal penetrating capacity were used. The results prove that a 20-mg dose of Antra is suitable for the therapy of laryngitis gastrica with a high rate of success. Problems which arose during the investigation, consequent changes of the original concept of the project as well as new aspects and questions which resulted from this are discussed with respect to further investigation.

  9. Primary laryngeal lymphoma in a child.

    PubMed

    Rodríguez, Hugo; Cuestas, Giselle; Bosaleh, Andrea; Passali, Desiderio; Zubizarreta, Pedro

    2015-01-01

    Malignant tumors of the larynx are very rare in children. They are often diagnosed late, since the initial symptoms are attributed to the process of larynx development or to other, more common pediatric diseases. Early visualization of the larynx with the aid of flexible or rigid fiberoptic laryngoscopy is essential in children having symptoms suggestive of laryngeal disease. Laryngeal lymphoma in children is exceptionally unusual. The certainty of the diagnosis, which is often very difficult to achieve, is generally confirmed by a tissue biopsy. In the present work, we describe the case of a non-Hodgkin lymphoblastic T-cell lymphoma of the larynx in an eight-year-old boy.

  10. Variations in the origin of superior laryngeal artery

    PubMed Central

    Devadas, Deepa; Sukumaran, Tintu Thottiyil

    2016-01-01

    The superior laryngeal artery is the principal artery supplying the laryngeal mucosa, musculature, and glands. Knowledge of variations in the origin of superior laryngeal artery could prove to be very useful during reconstructive surgeries of the larynx, partial laryngectomy, laryngeal transplantation, and also during procedures like super-selective intra-arterial chemotherapy for laryngeal and hypolaryngeal cancers. However, relatively few studies have been done on the superior laryngeal artery in comparison to its clinical importance. The present study was aimed at documenting the prevalence of variable origin of the superior laryngeal artery within the carotid triangle. Sixty hemi-necks obtained from 30 South Indian cadavers were dissected and studied for variations in the origin of superior laryngeal artery. It was observed that the superior laryngeal artery took origin from superior thyroid in 91.7% cases. Variable origin from the external carotid artery was noted in 5% cases. The superior laryngeal artery was found to arise from the lingual artery in one case alone (1.7%). In addition to the above findings, a very rare variation of superior laryngeal artery arising from the ascending pharyngeal (1.7%) was also observed in the hemi-neck of one cadaver. All the variations that were observed were unilateral and on the left side. These findings may help provide further insight to the anatomists, radiologists and surgeons and can help improve performances during surgical manipulations of the larynx. PMID:28127500

  11. Size, shape, structure, and direction of angiogenesis in laryngeal tumour development

    PubMed Central

    Laitakari, J; Näyhä, V; Stenbäck, F

    2004-01-01

    Aims: Angiogenesis and vessel organisation in laryngeal tumour development and progression were examined to determine characteristics of biological and clinical relevance. Methods: Automated quantitative image analysis was performed on 1451 factor VIII (FVIII) associated blood vessels with regard to occurrence, structure, size, shape, and staining intensity, in addition to vessel direction. Results: Vessel numbers were increased in preneoplastic states and severe dysplasia, in addition to squamous cell carcinomas, being greater in poorly differentiated carcinomas. Small regular vessels predominated in benign conditions and large, irregular vessels in malignant neoplasms. Vessel distribution was related to degree of differentiation in squamous cell carcinomas, with circumferential angiogenesis occurring in well differentiated neoplasms, directional angiogenesis in moderately differentiated tumours, and aberrant angiogenesis in less well differentiated neoplasms. Alterations in vessel shape increased significantly with increasing degree of malignancy. Comparing the characteristics of individual vessels showed vessel shape abnormalities and the intensity of FVIII staining to increase with vessel size. Conclusions: Increased angiogenesis was an early event in laryngeal tumour development, with vessel structure, size, and shape related to the tumour growth pattern and behaviour. PMID:15047744

  12. Comparison of hepatic arterial infusion chemotherapy and sorafenib in elderly patients with advanced hepatocellular carcinoma: A case series.

    PubMed

    Nemoto, Tomoyuki; Matsuda, Hidetaka; Nosaka, Takuto; Saito, Yasushi; Ozaki, Yoshihiko; Hayama, Ryoko; Naito, Tatsushi; Takahashi, Kazuto; Ofuji, Kazuya; Ohtani, Masahiro; Hiramatsu, Katsushi; Suto, Hiroyuki; Nakamoto, Yasunari

    2014-11-01

    Sorafenib and hepatic arterial infusion chemotherapy (HAIC) are both indicated for unresectable hepatocellular carcinoma (HCC). In this study, we compared the efficacy and safety of HAIC to that of sorafenib in elderly patients with HCC. Eligible patients included those aged ≥70 years, with histologically or clinically confirmed advanced HCC. A total of 12 patients received sorafenib (800 mg per day) and 8 patients received HAIC with 5-fluorouracil (300 mg/m(2) on days 1-5 and 8-12) with or without cisplatin (20 mg/m(2) on days 1 and 8), with interferon-α (3 times per week for 4 weeks). The response rate was significantly higher in patients treated with HAIC (37.5%) compared to that in patients treated with sorafenib (no response). The median overall survival (18.6 and 11.7 months) and progression-free survival (4.0 and 5.0 months) were similar between the sorafenib and HAIC groups, respectively. In the sorafenib group, 58.3% of the patients discontinued treatment compared to none in the HAIC group. The most frequent adverse event leading to discontinuation of sorafenib was anorexia. Similar to sorafenib, HAIC appears to be a feasible treatment and may also have the advantage of an adequate safety profile for elderly patients with advanced HCC. Further study of HAIC in a larger population of elderly patients is required to assess its potential as an alternative to sorafenib for HCC.

  13. Anatomic and dosimetric changes during the treatment course of intensity-modulated radiotherapy for locally advanced nasopharyngeal carcinoma.

    PubMed

    Wang, Xin; Lu, Jiade; Xiong, Xiaopeng; Zhu, Guopei; Ying, Hongmei; He, Shaoqin; Hu, Weigang; Hu, Chaosu

    2010-01-01

    Many patients with nasopharyngeal carcinoma (NPC) have marked anatomic change during intensity-modulated radiation therapy (IMRT). In this study, the magnitude of anatomic changes and its dosimetric effects were quantified. Fifteen patients with locally advanced NPC treated with IMRT had repeated computed tomography (CT) after 18 fractions. A hybrid plan was made to the anatomy of the second computed tomography scan. The dose of the original plan, hybrid plan, and new plan were compared. The mean volume of left and right parotid decreased 6.19 mL and 6.44 mL, respectively. The transverse diameters of the upper bound of odontoid process, the center of odontoid process, and the center of C2 vertebral body slices contracted with the mean contraction of 8.2 mm, 9.4 mm, and 7.6 mm. Comparing the hybrid plan with the treatment plan, the coverage of target was maintained while the maximum dose to the brain stem and spinal cord increased by 0.08 to 6.51 Gy and 0.05 to 7.8 Gy. The mean dose to left and right parotid increased by 2.97 Gy and 2.57 Gy, respectively. A new plan reduced the dose of spinal cord, brain stem, and parotids. Measurable anatomic changes occurring during the IMRT for locally advanced NPC maintained the coverage of targets but increased the dose to critical organs. Those patients might benefit from replanning.

  14. MRI-detectable polymeric micelles incorporating platinum anticancer drugs enhance survival in an advanced hepatocellular carcinoma model.

    PubMed

    Vinh, Nguyen Quoc; Naka, Shigeyuki; Cabral, Horacio; Murayama, Hiroyuki; Kaida, Sachiko; Kataoka, Kazunori; Morikawa, Shigehiro; Tani, Tohru

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the most intractable and lethal cancers; most cases are diagnosed at advanced stages with underlying liver dysfunction and are frequently resistant to conventional chemotherapy and radiotherapy. The development of tumor-targeting systems may improve treatment outcomes. Nanomedicine platforms are of particular interest for enhancing chemotherapeutic efficiency, and they include polymeric micelles, which enable targeting of multiple drugs to solid tumors, including imaging and therapeutic agents. This allows concurrent diagnosis, targeting strategy validation, and efficacy assessment. We used polymeric micelles containing the T1-weighted magnetic resonance imaging contrast agent gadolinium-diethylenetriaminpentaacetic acid (Gd-DTPA) and the parent complex of the anticancer drug oxaliplatin [(1,2-diaminocyclohexane)platinum(II) (DACHPt)] for simultaneous imaging and therapy in an orthotopic rat model of HCC. The Gd-DTPA/DACHPt-loaded micelles were injected into the hepatic artery, and magnetic resonance imaging performance and antitumor activity against HCC, as well as adverse drug reactions were assessed. After a single administration, the micelles achieved strong and specific tumor contrast enhancement, induced high levels of tumor apoptosis, and significantly suppressed tumor size and growth. Moreover, the micelles did not induce severe adverse reactions and significantly improved survival outcomes in comparison to oxaliplatin or saline controls. Our results suggest that Gd-DTPA/DACHPt-loaded micelles are a promising approach for effective diagnosis and treatment of advanced HCC.

  15. Results of neoadjuvant therapy followed by esophagectomy for patients with locally advanced thoracic esophageal squamous cell carcinoma

    PubMed Central

    Lin, Dong; Ma, Longfei; Ye, Ting; Pan, Yunjian; Shao, Longlong; Song, Zuodong; Jiang, Shujun

    2017-01-01

    Background For patients diagnosed with locally advanced esophageal cancer, neoadjuvant therapy followed by surgery is the most common approach. However, randomized trials resulted in inconsistent conclusions. We conducted this retrospective study to evaluate the influence of neoadjuvant therapy on postoperative events and the influence on disease-free survival (DFS) and overall survival (OS). Methods We retrospectively reviewed all of the patients underwent surgery following neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC) during January 1st, 2013 and December 31st, 2015 in Fudan University Shanghai Cancer Center (FUSCC). Prognostic factors for DFS and OS were identified by univariate and multivariate analyses. Results A total of fifty patients were included. Regarding postoperative morbidities, pneumonia and leakage occurred in 9 (18.0%) and 6 (12.0%) patients, respectively. For the whole patients, the 1-, 2-, 3-year DFS and OS rates were 57.0%, 48.0%, 42.0% and 86.0%, 73.0%, 62.0%, respectively. Lung metastasis and mediastinal node involvement were the most common relapse patterns. Univariate and multivariate analyses confirmed ypTNM stage as an independent prognostic factor for both DFS and OS; while leakage was an independent prognostic factor for DFS. Conclusions Neoadjuvant therapy did not increase postoperative morbidities but did achieve favorable survival. The ypTNM stage was an independent prognostic factor for both DFS and OS. Long-term survival needs further investigation. PMID:28275480

  16. Anatomic and Dosimetric Changes During the Treatment Course of Intensity-Modulated Radiotherapy for Locally Advanced Nasopharyngeal Carcinoma

    SciTech Connect

    Wang Xin; Lu Jiade; Xiong Xiaopeng; Zhu Guopei; Ying Hongmei; He Shaoqin; Hu Weigang; Hu Chaosu

    2010-07-01

    Many patients with nasopharyngeal carcinoma (NPC) have marked anatomic change during intensity-modulated radiation therapy (IMRT). In this study, the magnitude of anatomic changes and its dosimetric effects were quantified. Fifteen patients with locally advanced NPC treated with IMRT had repeated computed tomography (CT) after 18 fractions. A hybrid plan was made to the anatomy of the second computed tomography scan. The dose of the original plan, hybrid plan, and new plan were compared. The mean volume of left and right parotid decreased 6.19 mL and 6.44 mL, respectively. The transverse diameters of the upper bound of odontoid process, the center of odontoid process, and the center of C2 vertebral body slices contracted with the mean contraction of 8.2 mm, 9.4 mm, and 7.6 mm. Comparing the hybrid plan with the treatment plan, the coverage of target was maintained while the maximum dose to the brain stem and spinal cord increased by 0.08 to 6.51 Gy and 0.05 to 7.8 Gy. The mean dose to left and right parotid increased by 2.97 Gy and 2.57 Gy, respectively. A new plan reduced the dose of spinal cord, brain stem, and parotids. Measurable anatomic changes occurring during the IMRT for locally advanced NPC maintained the coverage of targets but increased the dose to critical organs. Those patients might benefit from replanning.

  17. Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma.

    PubMed

    Trojan, Jörg; Waidmann, Oliver

    2016-01-01

    Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months). Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1) blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC.

  18. Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma

    PubMed Central

    Trojan, Jörg; Waidmann, Oliver

    2016-01-01

    Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months). Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1) blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC. PMID:27703962

  19. "Exploratory" surgery for advanced carcinoma of the larynx: a relatively safe approach.

    PubMed

    Tucker, H M

    1998-05-01

    Between the years 1970 and 1986, the author managed 132 patients with T3 glottic carcinoma. Over half of these patients were explored in an effort to safely perform subtotal laryngectomy. Twenty-seven of them were found to have extension of tumor that required immediate conversion to total laryngectomy. Five-year survival rates were essentially the same for all three groups: immediate total laryngectomy, subtotal laryngectomy, and total laryngectomy following attempted subtotal laryngectomy. I conclude that carefully selected patients with T3 glottic cancer may be candidates for subtotal laryngectomy after surgical exploration, since conversion to total laryngectomy yields local control rates as satisfactory as those of initial total laryngectomy. When subtotal laryngectomy is possible, local control of tumor and recurrence rates are as satisfactory as those of total laryngectomy.

  20. Chemotherapy in locally advanced nasopharyngeal carcinoma: An individual patient data meta-analysis of eight randomized trials and 1753 patients

    SciTech Connect

    Baujat, Bertrand; Audry, Helene; Bourhis, Jean; Chan, Anthony T.C.; Onat, Haluk; Chua, Daniel T.T.; Kwong, Dora L.W.; Al-Sarraf, Muhyi; Chi, K.-H.; Hareyama, Masato; Leung, Sing F.; Thephamongkhol, Kullathorn; Pignon, Jean-Pierre . E-mail: jppignon@igr.fr

    2006-01-01

    Objectives: To study the effect of adding chemotherapy to radiotherapy (RT) on overall survival and event-free survival for patients with nasopharyngeal carcinoma. Methods and Materials: This meta-analysis used updated individual patient data from randomized trials comparing chemotherapy plus RT with RT alone in locally advanced nasopharyngeal carcinoma. The log-rank test, stratified by trial, was used for comparisons, and the hazard ratios of death and failure were calculated. Results: Eight trials with 1753 patients were included. One trial with a 2 x 2 design was counted twice in the analysis. The analysis included 11 comparisons using the data from 1975 patients. The median follow-up was 6 years. The pooled hazard ratio of death was 0.82 (95% confidence interval, 0.71-0.94; p = 0.006), corresponding to an absolute survival benefit of 6% at 5 years from the addition of chemotherapy (from 56% to 62%). The pooled hazard ratio of tumor failure or death was 0.76 (95% confidence interval, 0.67-0.86; p < 0.0001), corresponding to an absolute event-free survival benefit of 10% at 5 years from the addition of chemotherapy (from 42% to 52%). A significant interaction was observed between the timing of chemotherapy and overall survival (p = 0.005), explaining the heterogeneity observed in the treatment effect (p = 0.03), with the highest benefit resulting from concomitant chemotherapy. Conclusion: Chemotherapy led to a small, but significant, benefit for overall survival and event-free survival. This benefit was essentially observed when chemotherapy was administered concomitantly with RT.

  1. Phase I Study of Everolimus in Combination with Gemcitabine and Split-Dose Cisplatin in Advanced Urothelial Carcinoma

    PubMed Central

    Abida, Wassim; Milowsky, Matthew I.; Ostrovnaya, Irina; Gerst, Scott R.; Rosenberg, Jonathan E.; Voss, Martin H.; Apolo, Andrea B.; Regazzi, Ashley M.; McCoy, Asia S.; Boyd, Mariel E.; Bajorin, Dean F.

    2016-01-01

    Background: Cisplatin-based combination chemotherapy is standard first-line treatment for patients with advanced urothelial carcinoma (UC). Molecular profiling studies reveal that the PI3K/AKT/mTOR pathway is altered in a significant percentage of UCs. Objective: We conducted a phase I trial to evaluate the feasibility of combining the mTOR inhibitor everolimus with gemcitabine and split-dose cisplatin (GC) in advanced UC in the first-line setting. Methods: Patients received gemcitabine 800 mg/m2 and cisplatin 35 mg/m2 on days 1 and 8 of 21-day cycles for a total of 6 cycles in combination with everolimus at increasing dose levels (DL1:5 mg QOD, DL2:5 mg daily, DL3:10 mg daily) following a standard 3+3 design. Responses were assessed every 2 cycles. Patients with at least stable disease (SD) continued everolimus until progression. Goals were to establish dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) for the combination. Results: 12 patients were enrolled, 3 at DL1, 3 at DL2, and an additional 6 at DL1 *(DL1 following de-escalation). 3/3 patients at DL2 had DLTs during cycle 1. 2/8 evaluable patients at DL1/DL1 * had DLTs during cycle 1. DLTs were primarily hematologic. Further toxicities, also primarily hematologic, were observed during later treatment cycles, leading to 8 chemotherapy dose reductions overall. Partial responses were observed in 4/10 evaluable patients, and SD in 5/10. Median overall survival was 10.8 months (95% CI 6.9, not reached). Conclusions: The maximum tolerated dose was reached at the lowest dose level, 5 mg QOD, for everolimus in combination with gemcitabine and split-dose cisplatin in advanced UC. The regimen was limited by hematologic toxicity. PMID:27376132

  2. Living Donor Liver Transplantation for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis after Concurrent Chemoradiation Therapy

    PubMed Central

    Han, Dai Hoon; Joo, Dong Jin; Kim, Myoung Soo; Choi, Gi Hong; Choi, Jin Sub; Park, Young Nyun; Seong, Jinsil

    2016-01-01

    Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate <10%. Localized concurrent chemoradiotherapy (CCRT), followed by hepatic arterial infusion chemotherapy (HAIC), was recently introduced in this setting. Here, we report our early experience with living donor liver transplantation (LDLT) in such patients after successful down-staging of HCC through CCRT and HAIC. Between December 2011 and September 2012, eight patients with locally advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3–12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10–22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis. PMID:27401662

  3. Recurrence patterns of locally advanced head and neck squamous cell carcinoma after 3D conformal (chemo)-radiotherapy

    PubMed Central

    2011-01-01

    Background To establish recurrence patterns among locally advanced head and neck non-nasopharyngeal squamous cell carcinoma (HNSCC) patients treated with radical (chemo-) radiotherapy and to correlate the sites of loco-regional recurrence with radiotherapy doses and target volumes Method 151 locally advanced HNSCC patients were treated between 2004-2005 using radical three-dimensional conformal radiotherapy. Patients with prior surgery to the primary tumour site were excluded. The sites of locoregional relapses were correlated with radiotherapy plans by the radiologist and a planning dosimetrist. Results Median age was 59 years (range:34-89). 35 patients had stage III disease, 116 patients had stage IV A/B. 36 patients were treated with radiotherapy alone, 42 with induction chemotherapy, 63 with induction and concomitant chemoradiotherapy and 10 concomitant chemoradiotherapy. Median follow-up was 38 months (range 3-62). 3-year cause specific survival was 66.8%. 125 of 151 (82.8%) achieved a complete response to treatment. Amongst these 125 there were 20 local-regional recurrence, comprising 8 local, 5 regional and 7 simultaneous local and regional; synchronous distant metastases occurred in 7 of the 20. 9 patients developed distant metastases in the absence of locoregional failure. For the 14 local recurrences with planning data available, 12 were in-field, 1 was marginal, and 1 was out-of-field. Of the 11 regional failures with planning data available, 7 were in-field, 1 was marginal and 3 were out-of-field recurrences. Conclusion The majority of failures following non-surgical treatment for locally advanced HNSCC were loco-regional, within the radiotherapy target volume. Improving locoregional control remains a high priority. PMID:21609453

  4. Epidemiological evidence indicates asbestos causes laryngeal cancer

    SciTech Connect

    Smith, A.H.; Handley, M.A.; Wood, R. )

    1990-06-01

    A variety of opinions have been expressed in the literature concerning asbestos and laryngeal cancer. This paper presents an analysis of epidemiological studies based on criteria that prioritized the most heavily exposed cohorts. Emphasis was given to the six cohorts or subcohorts with lung cancer relative risk estimates of 2 or more. The two groups of workers with the highest lung cancer relative risk estimates (4.06 and 3.28) both gave strong support for a causal association of asbestos and laryngeal cancer, with relative risk estimates of 1.91 (90% confidence limits 1.00 to 3.34) and 3.75 (90% confidence limits 1.01 to 9.68), respectively. Confounding with cigarette smoking or alcohol consumption does not explain the findings. Case-control studies gave mixed results, but generally supported the hypothesis. It was concluded that asbestos is a probable cause of laryngeal cancer in view of the reasonable consistency of the studies, the strength of the association in key studies, the evidence for dose-response relationships, and the biological plausibility for asbestos being a cause of laryngeal cancer. 48 references.

  5. Dysphagia Caused by Chronic Laryngeal Edema.

    PubMed

    Delides, Alexander; Sakagiannis, George; Maragoudakis, Pavlos; Gouloumi, Αlina-Roxani; Katsimbri, Pelagia; Giotakis, Ioannis; Panayiotides, John G

    2015-10-01

    A rare case of a young female with chronic diffuse laryngeal edema causing severe swallowing difficulty is presented. The patient was previously treated with antibiotics and steroids with no improvement. Diagnosis was made with biopsy of the epiglottis under local anesthesia in the office.

  6. Atraumatic laser treatment for laryngeal papillomatosis

    NASA Astrophysics Data System (ADS)

    McMillan, Kathleen; Pankratov, Michail M.; Wang, Zhi; Bottrill, Ian; Rebeiz, Elie E.; Shapshay, Stanley M.

    1994-09-01

    Ten to fifteen thousand new cases of recurrent respiratory papillomatosis (RRP) are diagnosed each year in the United States. RRP is caused by the human papillomavirus (HPV) and is characterized by recurrent, non-malignant, proliferative lesions of the larynx. Patients with RRP undergo numerous microsurgical procedures to remove laryngeal papilloma threatening airway patency and interfering with phonation. The standard surgical technique involves CO2 laser vaporization of laryngeal epithelium affected by the lesions, and requires general anesthesia. The pulsed dye laser operating at 585 nm has previously been demonstrated to be effective in clearing HPV lesions of the skin (verrucae). For treatment of RRP, the fiber- compatible pulsed dye laser radiation may be delivered under local anesthesia using a flexible intranasal laryngoscope. Potential advantages of the pulsed dye laser treatment over CO2 laser surgery include (1) reduced morbidity, especially a lower risk of laryngeal scarring; (2) lower cost; (3) reduced technical difficulty; and (4) reduced risk of viral dissemination or transmission. In vivo studies are underway to determine the effect of pulsed dye laser radiation on normal canine laryngeal tissue.

  7. A genetic view of laryngeal cancer heterogeneity

    PubMed Central

    de Miguel-Luken, María José; Chaves-Conde, Manuel; Carnero, Amancio

    2016-01-01

    ABSTRACT During the recent decades significant improvements in the understanding of laryngeal molecular biology allowed a better characterization of the tumor. However, despite increased molecular knowledge and clinical efforts, survival of patients with laryngeal cancer remains the same as 30 years ago. Although this result may not make major conclusions as preservation approaches were not broadly used until the time of database collection, it seems to be clear that there is still window for improvement. Although the cornerstone for laryngeal cancer eradication is to implement smoking cessation programs, survival progresses will be hopefully seen in the future. Introducing molecular biomarkers as predictive factors to determine which patients will benefit of preservation treatments may become one of the next steps to improve survival. Furthermore, the development of new therapeutic modalities joint to biomarkers to selectively apply such new therapy in these patients may help to define new modalities with improved survival. New inhibitors against Notch pathway, EGFR, VRK1 or DNA damage repair may become gold standard if we are able to identify patients that may benefit from them, either on survival or functional larynx preservation. It is the moment for an inflexion point on the way laryngeal cancer is clinically managed. PMID:26940775

  8. Phase II study of the PI3K inhibitor BKM120 in patients with advanced or recurrent endometrial carcinoma: a stratified type I-type II study from the GINECO group.

    PubMed

    Heudel, P-E; Fabbro, M; Roemer-Becuwe, C; Kaminsky, M C; Arnaud, A; Joly, F; Roche-Forestier, S; Meunier, J; Foa, C; You, B; Priou, F; Tazi, Y; Floquet, A; Selle, F; Berton-Rigaud, D; Lesoin, A; Kalbacher, E; Lortholary, A; Favier, L; Treilleux, I; Ray-Coquard, I

    2017-01-01

    Backround:Patients with metastatic endometrial carcinoma have a poor prognosis and PIK3CA mutations and amplifications are common in these cancers. This study evaluated the efficacy and safety of the pure PI3K inhibitor BKM120 in advanced or recurrent endometrial carcinoma.

  9. Development of hepatocellular carcinoma in chronic hepatitis B patients with advanced fibrosis is independent of viral genotype.

    PubMed

    Kumar, Rajneesh; Testoni, Barbara; Fresquet, Judith; Lim, Tony Kiat Hon; Hao, Ying; Tan, Hui Hui; Chow, Wan Cheng; Zoulim, Fabien

    2017-05-01

    Hepatitis B is leading cause of liver related morbidity in Asia with predominant genotypes B and C in East-Asia. Data on Serum, intrahepatic viral-markers, and long-term follow-up of prevalent genotypes (GT) B and C in patients with biopsy proven advanced fibrosis are sparse. To compare serum, intrahepatic viral-markers and development of hepatocellular carcinoma (HCC) in GT-B and C in patients with advanced fibrosis (Ishak ≥ 4). Sixty-three treatment-naïve patients identified with advanced fibrosis on liver-biopsy performed between 1998 and 2000 at Singapore General Hospital. FFPE tissue was available for 59 patients and serum for 42 patients. HBV-DNA was quantified in serum and liver while qHBsAg quantified in serum. Patients were followed-up till December 2015. The median age was 47 ± 16 years, with 77.7% males. About 19 were GT-B, 43 patients were GT-C, and 1 had both GT-B and C. Mean follow-up was 13.5 years. The median serum HBV-DNA was 6.25 ± 2.17 and 6.58 ± 1.85 log IU/ml, serum HBsAg was 3.29 ± 0.80 and 3.45 ± 1.85 log IU/ml, and intrahepatic HBV-DNA was 0.52 ± 3.73 copies/cell and 0.4 ± 1.37 copies/cell in the GT-B and C, respectively (P > 0.1 in all). Complete cirrhosis (Ishak-6) was present in 47.6%, Ishak-5 fibrosis in 33.3%, and Ishak-4 fibrosis in 19% at recruitment. On follow-up HCC developed in 8/43 in GT-C and in 3/19 GT-B (P = 0.86). Advanced age and cirrhosis were significant factors for development of HCC. No difference in serum HBV-DNA, qHBsAg or intrahepatic HBV-DNA was seen in the two genotypes. HCC development seen over long-term follow-up was independent of genotypes in patients with advanced fibrosis. J. Med. Virol. 89:845-848, 2017. © 2016 Wiley Periodicals, Inc.

  10. Frequency of Elevated Hepatocellular Carcinoma (HCC) Biomarkers in Patients with Advanced Hepatitis C

    PubMed Central

    Sterling, Richard K.; Wright, Elizabeth C.; Morgan, Timothy R.; Seeff, Leonard B.; Hoefs, John C.; Di Bisceglie, Adrian M.; Dienstag, Jules L.; Lok, Anna S.

    2013-01-01

    Background Prospective studies of serum HCC biomarkers in patients with advanced hepatitis C are lacking. Aims To determine frequencies and performance of elevated alpha-fetoprotein (AFP), AFP-L3, and des-gamma-carboxy prothrombin (DCP) levels as HCC biomarkers in advanced hepatitis C. Methods Patients in the HALT-C Trial were tested every 3 months for 42 months. Screening ultrasound was performed every 12 months. Levels of biomarkers were compared in patients in whom HCC did or did not develop. Results 855 patients were evaluated; HCC developed in 46. Among patients without HCC, 73.2% had AFP consistently <20, 24.5% had at least one AFP between 20-199, while 2.3% had at least one AFP value ≥200 ng/mL; 73.7% had DCP consistently <90, 11.6% had at least one DCP between 90-149, and 14.7% had at least one DCP value ≥150 mAU/mL. AFP-L3 ≥10% was present at least once in 9.0% and in 17.1% of those with AFP >20 ng/mL. Among all patients with elevated biomarkers, a diagnosis of HCC was made in 0-31.6% (depending on the biomarker and cutoff) during the subsequent 24 months. AFP ≥200 ng/mL had the highest specificity (99%), but sensitivity was ≤20%. DCP ≥40 mAU/mL had the highest sensitivity (76%), but specificity was ≤58%. Independent predictors of elevated AFP were gender (female), race (Black), more advanced disease, and HCC. Elevated DCP was associated with more advanced disease and HCC. Conclusions Mild-moderate elevations in total AFP and DCP but not AFP-L3 occur frequently in patients with chronic hepatitis C and advanced fibrosis, are related to factors other than HCC, and are poor predictors of HCC. PMID:21931376

  11. Usefulness of human epididymis protein 4 in predicting cytoreductive surgical outcomes for advanced ovarian tubal and peritoneal carcinoma

    PubMed Central

    Tang, Zhijian; Chang, Xiaohong; Ye, Xue; Li, Yi; Cheng, Hongyan

    2015-01-01

    Objective Human epididymis protein 4 (HE4) is a promising biomarker of epithelial ovarian cancer (EOC). But its role in assessing the primary optimal debulking (OD) of EOC remains unknown. The purpose of this study is to elucidate the ability of preoperative HE4 in predicting the primary cytoreductive outcomes in advanced EOC, tubal or peritoneal carcinoma. Methods We reviewed the records of 90 patients with advanced ovarian, tubal or peritoneal carcinoma who underwent primary cytoreduction at the Department of Obstetrics and Gynecology of Peking University People’s Hospital between November 2005 and October 2010. Preoperative serum HE4 and CA125 levels were detected with EIA kit. A receiver operating characteristic (ROC) curve was used to determine the most useful HE4 cut-off value. Logistic regression analysis was performed to identify significant preoperative clinical characteristics to predict optimal primary cytoreduction. Results OD was achieved in 47.7% (43/48) of patients. The median preoperative HE4 level for patients with OD vs. suboptimal debulking was 423 and 820 pmol/L, respectively (P<0.001). The areas under the ROC curve for HE4 and CA125 were 0.716 and 0.599, respectively (P=0.080). The most useful HE4 cut-off value was 473 pmol/L. Suboptimal cytoreduction was obtained in 66.7% (38/57) of cases with HE4 ≥473 pmol/L compared with only 27.3% (9/33) of cases with HE4 <473 pmol/L. At this threshold, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for diagnosing suboptimal debulking were 81%, 56%, 67%, and 73%, respectively. Logistic regression analysis showed that the patients with HE4 ≥473 pmol/L were less likely to achieve OD (odds ratio =5.044, P=0.002). Conclusions Preoperative serum HE4 may be helpful to predict whether optimal cytoreductive surgery could be obtained or whether extended cytoreduction would be needed by an interdisciplinary team. PMID:26157328

  12. Reducing the Risk of Xerostomia and Mandibular Osteoradionecrosis: The Potential Benefits of Intensity Modulated Radiotherapy in Advanced Oral Cavity Carcinoma

    SciTech Connect

    Ahmed, Merina; Hansen, Vibeke N.; Harrington, Kevin J.; Nutting, Christopher M.

    2009-10-01

    Radiation therapy for squamous cell carcinoma of the oral cavity may be curative, but carries a risk of permanent damage to bone, salivary glands, and other soft tissues. We studied the potential of intensity modulated radiotherapy (IMRT) to improve target volume coverage, and normal tissue sparing for advanced oral cavity carcinoma (OCC). Six patients with advanced OCC requiring bilateral irradiation to the oral cavity and neck were studied. Standard 3D conformal radiotherapy (3DCRT) and inverse-planned IMRT dose distributions were compared by using dose-volume histograms. Doses to organs at risk, including spinal cord, parotid glands, and mandible, were assessed as surrogates of radiation toxicity. PTV1 mean dose was 60.8 {+-} 0.8 Gy for 3DCRT and 59.8 {+-} 0.1 Gy for IMRT (p = 0.04). PTV1 dose range was 24.7 {+-} 6 Gy for 3DCRT and 15.3 {+-} 4 Gy for IMRT (p = 0.001). PTV2 mean dose was 54.5 {+-} 0.8 Gy for 3DCRT and for IMRT was 54.2 {+-} 0.2 Gy (p = 0.34). PTV2 dose range was improved by IMRT (7.8 {+-} 3.2 Gy vs. 30.7 {+-} 12.8 Gy, p = 0.006). Homogeneity index (HI) values for PTV2 were closer to unity using IMRT (p = 0.0003). Mean parotid doses were 25.6 {+-} 2.7 Gy for IMRT and 42.0 {+-} 8.8 Gy with 3DCRT (p = 0.002). The parotid V30 in all IMRT plans was <45%. The mandible V50, V55, and V60 were significantly lower for the IMRT plans. Maximum spinal cord and brain stem doses were similar for the 2 techniques. IMRT provided superior target volume dose homogeneity and sparing of organs at risk. The magnitude of reductions in dose to the salivary glands and mandible are likely to translate into reduced incidence of xerostomia and osteoradionecrosis for patients with OCC.

  13. Reducing the risk of xerostomia and mandibular osteoradionecrosis: the potential benefits of intensity modulated radiotherapy in advanced oral cavity carcinoma.

    PubMed

    Ahmed, Merina; Hansen, Vibeke N; Harrington, Kevin J; Nutting, Christopher M

    2009-01-01

    Radiation therapy for squamous cell carcinoma of the oral cavity may be curative, but carries a risk of permanent damage to bone, salivary glands, and other soft tissues. We studied the potential of intensity modulated radiotherapy (IMRT) to improve target volume coverage, and normal tissue sparing for advanced oral cavity carcinoma (OCC). Six patients with advanced OCC requiring bilateral irradiation to the oral cavity and neck were studied. Standard 3D conformal radiotherapy (3DCRT) and inverse-planned IMRT dose distributions were compared by using dose-volume histograms. Doses to organs at risk, including spinal cord, parotid glands, and mandible, were assessed as surrogates of radiation toxicity. PTV1 mean dose was 60.8 +/- 0.8 Gy for 3DCRT and 59.8 +/- 0.1 Gy for IMRT (p = 0.04). PTV1 dose range was 24.7 +/- 6 Gy for 3DCRT and 15.3 +/- 4 Gy for IMRT (p = 0.001). PTV2 mean dose was 54.5 +/- 0.8 Gy for 3DCRT and for IMRT was 54.2 +/- 0.2 Gy (p = 0.34). PTV2 dose range was improved by IMRT (7.8 +/- 3.2 Gy vs. 30.7 +/- 12.8 Gy, p = 0.006). Homogeneity index (HI) values for PTV2 were closer to unity using IMRT (p = 0.0003). Mean parotid doses were 25.6 +/- 2.7 Gy for IMRT and 42.0 +/- 8.8 Gy with 3DCRT (p = 0.002). The parotid V30 in all IMRT plans was <45%. The mandible V50, V55, and V60 were significantly lower for the IMRT plans. Maximum spinal cord and brain stem doses were similar for the 2 techniques. IMRT provided superior target volume dose homogeneity and sparing of organs at risk. The magnitude of reductions in dose to the salivary glands and mandible are likely to translate into reduced incidence of xerostomia and osteoradionecrosis for patients with OCC.

  14. IMRT With Simultaneous Integrated Boost and Concurrent Chemotherapy for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Montejo, Michael E.; Shrieve, Dennis C.; Bentz, Brandon G.; Hunt, Jason P.; Buchman, Luke O.; Agarwal, Neeraj; Hitchcock, Ying J.

    2011-12-01

    Purpose: To evaluate the efficacy and toxicity of accelerated radiotherapy with concurrent chemotherapy in advanced head-and-neck squamous cell carcinoma. Methods and Materials: Between April 2003 and May 2008, 43 consecutive patients with advanced head-and-neck squamous cell carcinoma received accelerated chemoradiation with concurrent cisplatin or cetuximab. The doses for intensity-modulated radiotherapy with simultaneous integrated boost were 67.5, 60.0, and 54 Gy in 30 daily fractions of 2.25, 2.0, and 1.8 Gy to the planning target volumes for gross disease, high-risk nodes, and low-risk nodes, respectively. Results: Of the patients, 90.7% completed chemoradiotherapy as prescribed. The median treatment duration was 43 days (range, 38-55 days). The complete response rate was 74.4%. With median follow-up of 36.7 months (range, 16.8-78.1 months) in living patients, the estimated 1-, 2-, and 5-year locoregional control, overall survival, and disease-free survival rates were 82%, 82%, and 82%; 73%, 65%, and 61%; and 73%, 73%, and 70%, respectively. One treatment-related death occurred from renal failure. Grade 3 mucositis and dermatitis occurred in 13 patients (30.2%) and 3 patients (6.9%), respectively. Grade 2 xerostomia occurred in 12 patients (27.9%). In patients with adequate follow-up, 82% were feeding tube free by 6 months after therapy; 13% remained feeding tube dependent at 1 year. Grade 3 soft-tissue fibrosis, esophageal stricture, osteoradionecrosis, and trismus occurred in 3 patients (6.9%), 5 patients (11.6%), 1 patient (2.3%), and 3 patients (6.9%), respectively. Conclusions: Our results show that intensity-modulated radiotherapy with simultaneous integrated boost with concurrent chemotherapy improved local and regional control. Acute and late toxicities were tolerable and acceptable. A prospective trial of this fractionation regimen is necessary for further assessment of its efficacy and toxicity compared with other approaches.

  15. Pim1 kinase synergizes with c-MYC to induce advanced prostate carcinoma

    PubMed Central

    Wang, Jie; Kim, Jongchan; Roh, Meejeon; Franco, Omar E.; Hayward, Simon W.; Wills, Marcia L.; Abdulkadir, Sarki A.

    2010-01-01

    The oncogenic PIM1 kinase has been implicated as a cofactor for c-MYC in prostate carcinogenesis. Here we show that in human prostate tumors, coexpression of c-MYC and PIM1 is associated with higher Gleason grades. Using a tissue recombination model coupled with lentiviral-mediated gene transfer we find that Pim1 is weakly oncogenic in naïve adult mouse prostatic epithelium. However, it cooperates dramatically with c-MYC to induce prostate cancer within 6-weeks. Importantly, c-MYC/Pim1 synergy is critically dependent on Pim1 kinase activity. c-MYC/Pim1 tumors showed increased levels of the active serine-62 (S62) phosphorylated form of c-MYC. Grafts expressing a phosphomimetic c-MYCS62D mutant had higher rates of proliferation than grafts expressing wild type c-MYC but did not form tumors like c-MYC/Pim1 grafts, indicating that Pim1 cooperativity with c-MYC in vivo involves additional mechanisms other than enhancement of c-MYC activity by S62 phosphorylation. c-MYC/Pim1-induced prostate carcinomas demonstrate evidence of neuroendocrine (NE) differentiation. Additional studies, including the identification of tumor cells coexpressing androgen receptor and NE cell markers synaptophysin and Ascl1 suggested that NE tumors arose from adenocarcinoma cells through transdifferentiation. These results directly demonstrate functional cooperativity between c-MYC and PIM1 in prostate tumorigenesis in vivo and support efforts for targeting PIM1 in prostate cancer. PMID:20140016

  16. Advances of multidetector computed tomography in the characterization and staging of renal cell carcinoma

    PubMed Central

    Tsili, Athina C; Argyropoulou, Maria I

    2015-01-01

    Renal cell carcinoma (RCC) accounts for approximately 90%-95% of kidney tumors. With the widespread use of cross-sectional imaging modalities, more than half of RCCs are detected incidentally, often diagnosed at an early stage. This may allow the planning of more conservative treatment strategies. Computed tomography (CT) is considered the examination of choice for the detection and staging of RCC. Multidetector CT (MDCT) with the improvement of spatial resolution and the ability to obtain multiphase imaging, multiplanar and three-dimensional reconstructions in any desired plane brought about further improvement in the evaluation of RCC. Differentiation of RCC from benign renal tumors based on MDCT features is improved. Tumor enhancement characteristics on MDCT have been found closely to correlate with the histologic subtype of RCC, the nuclear grade and the cytogenetic characteristics of clear cell RCC. Important information, including tumor size, localization, and organ involvement, presence and extent of venous thrombus, possible invasion of adjacent organs or lymph nodes, and presence of distant metastases are provided by MDCT examination. The preoperative evaluation of patients with RCC was improved by depicting the presence or absence of renal pseudocapsule and by assessing the possible neoplastic infiltration of the perirenal fat tissue and/or renal sinus fat compartment. PMID:26120380

  17. Nivolumab in the treatment of advanced renal cell carcinoma: clinical trial evidence and experience

    PubMed Central

    Mennitto, Alessia; Grassi, Paolo; Ratta, Raffaele; Verzoni, Elena; Prisciandaro, Michele; Procopio, Giuseppe

    2016-01-01

    Renal cell carcinoma (RCC) is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Cytokine-based immunotherapies, including interferon-α and interleukin-2, have been used for the treatment of metastatic RCC (mRCC). Long-term responses and complete remissions were observed, but durable clinical benefit efficacy in the overall population was limited and associated with significant toxicity. As a consequence, new generation agents targeting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways replaced interferon alpha (IFN-α). Strategies of tumor immune evasion include T-cell suppression by negative signals deriving from the interaction between programmed death-1 (PD-1) on the T cell and its ligand (PDL-1) on the tumor cells. Nivolumab, a programmed death 1 checkpoint inhibitor, blocks this pathway, thus reversing T-cell suppression and activating antitumor responses. The aim of this review is to summarize the safety and efficacy data of nivolumab in mRCC. Objective responses and safety profile of single-agent nivolumab are favorable in both previously treated and treatment-naïve mRCC patients. Despite toxic effects, combination therapies with nivolumab have shown promising results, indicating a potential role in the treatment of mRCC. Tailoring immunotherapy on a patient-to-patient basis represents a major challenge for the future. PMID:27695530

  18. An Extremely Rare Case of Advanced Metastatic Small Cell Neuroendocrine Carcinoma of Sinonasal Tract.

    PubMed

    Thar, Yu Yu; Patel, Poras; Huang, Tiangui; Guevara, Elizabeth

    2016-01-01

    Small cell neuroendocrine carcinoma (SNEC) is a rare form of malignancy. It mainly presents as bronchogenic neoplasm, and the extrapulmonary form accounts for only 0.1% to 0.4% of all cancers. These extrapulmonary tumors have been described most frequently in the urinary bladder, prostate, esophagus, stomach, colon and rectum, gall bladder, head and neck, cervix, and skin. Primary SNEC of the sinonasal tract is extremely rare with only less than 100 cases reported in the literature. Because of extreme rarity and aggressiveness of the tumor, the management for this entity varies considerably mandating multimodality approach. In this paper, we report a patient presented with left-sided facial swelling, and the histopathologic examination confirmed primary SNEC of left sinonasal tract. The tumor involved multiple paranasal sinuses with invasion into the left orbit and left infratemporal fossa and metastasized to cervical lymph nodes and bone. The patient encountered devastating outcome in spite of optimal medical management and treatment with palliative chemotherapy highlighting the necessity for further research of primary SNEC of head and neck.

  19. An Extremely Rare Case of Advanced Metastatic Small Cell Neuroendocrine Carcinoma of Sinonasal Tract

    PubMed Central

    Guevara, Elizabeth

    2016-01-01

    Small cell neuroendocrine carcinoma (SNEC) is a rare form of malignancy. It mainly presents as bronchogenic neoplasm, and the extrapulmonary form accounts for only 0.1% to 0.4% of all cancers. These extrapulmonary tumors have been described most frequently in the urinary bladder, prostate, esophagus, stomach, colon and rectum, gall bladder, head and neck, cervix, and skin. Primary SNEC of the sinonasal tract is extremely rare with only less than 100 cases reported in the literature. Because of extreme rarity and aggressiveness of the tumor, the management for this entity varies considerably mandating multimodality approach. In this paper, we report a patient presented with left-sided facial swelling, and the histopathologic examination confirmed primary SNEC of left sinonasal tract. The tumor involved multiple paranasal sinuses with invasion into the left orbit and left infratemporal fossa and metastasized to cervical lymph nodes and bone. The patient encountered devastating outcome in spite of optimal medical management and treatment with palliative chemotherapy highlighting the necessity for further research of primary SNEC of head and neck. PMID:27529044

  20. Advances of Salivary Proteomics in Oral Squamous Cell Carcinoma (OSCC) Detection: An Update

    PubMed Central

    Sannam Khan, Rabia; Khurshid, Zohaib; Akhbar, Shazia; Faraz Moin, Syed

    2016-01-01

    Oral cancer refers to malignancies that have higher morbidity and mortality rates due to the late stage diagnosis and no early detection of a reliable diagnostic marker, while oral squamous cell carcinoma (OSCC) is amongst the world’s top ten most common cancers. Diagnosis of cancer requires highly sensitive and specific diagnostic tools which can support untraceable hidden sites of OSCC, yet to be unleashed, for which plenty of biomarkers are identified; the most recommended biomarker detection medium for OSCC includes biological fluids, such as blood and saliva. Saliva holds a promising future in the search for new clinical biomarkers that are easily accessible, less complex, accurate, and cost effective as well as being a non-invasive technique to follow, by analysing the malignant cells’ molecular pathology obtained from saliva through proteomic, genomic and transcriptomic approaches. However, protein biomarkers provide an immense potential for developing novel marker-based assays for oral cancer, hence this current review offers an overall focus on the discovery of a panel of candidates as salivary protein biomarkers, as well as the proteomic tools used for their identification and their significance in early oral cancer detection. PMID:28248250

  1. Intraoperative photodynamic therapy for larynx carcinomas

    NASA Astrophysics Data System (ADS)

    Loukatch, Erwin V.; Latyshevska, Galina; Fekeshgazi, Ishtvan V.

    1995-05-01

    We made an experimental and clinical researches to examine Intraoperative Photodynamic Therapy (IPT) as a method to prevent the recidives of tumors. In experimental researches on models with radio-inducated fibrosarcomas and Erlich carcinomas of mice the best method of IPT was worked out. The therapeutic effect was studied also on patients with laryngeal cancer. In researches on C3H mice the antirecidive effect of IPT established with local administration of methylene blue and Ar-laser. We found that IPT (He-Ne laser combined with methylene blue administration) was endured by patients with laryngeal cancers without problems. We got good results of treatment 42 patients with laryngeal cancers with middle localization during three years with using IPT method. This can show the perspectives of using this method in treatment of other ENT-oncological diseases.

  2. Functional NBS1 polymorphism is associated with occurrence and advanced disease status of nasopharyngeal carcinoma.

    PubMed

    Zheng, Jian; Zhang, Chun; Jiang, Lan; You, Yonghe; Liu, Yuehui; Lu, Jiachun; Zhou, Yifeng

    2011-09-01

    As a component of the MRN (MRE11/RAD50/NBS1) complex, NBS1 plays an important role in cellular response to DNA damage and the maintenance of chromosomal integrity. The NBS1 E185Q polymorphism (8360G>C, rs1805794) has been frequently studied in some cancers with discordant results, but its association with nasopharyngeal carcinoma (NPC) in Chinese population has not been investigated. Moreover, there is no report about the association between NBS1 3'UTR variant rs2735383 and the risk of NPC. A multiple center case-control analysis was performed to assess the association between NBS1 polymorphisms and NPC risk in Eastern and Southern Chinese population. The genotypes and haplotypes were determined in 1052 cases and 1168 controls and the associations with risk of NPC were estimated by logistic regression. Cell migration assays were performed in 24-well transwell chambers to detect the effects of NBS1 E185Q SNP on cell migration. We observed significant difference in genotype frequencies at the rs1805794 C/G site between cases and controls (P(trend) < 0.0001). The C allele increases the risk for invasive disease or metastatic disease, compared with G allele. More over, CNE-2 cells (NPC cell line) transfected with pcDNA-NBS1-185Q (8360CC) had significantly higher migration levels than those transfected with pcDNA-NBS1-185E (8360GG) (P = 0.024). These findings suggest that E185Q polymorphism in NBS1 may be a genetic modifier for the occurrence and aggression of NPC.

  3. Associations of ATM Polymorphisms With Survival in Advanced Esophageal Squamous Cell Carcinoma Patients Receiving Radiation Therapy

    SciTech Connect

    Du, Zhongli; Zhang, Wencheng; Zhou, Yuling; Yu, Dianke; Chen, Xiabin; Chang, Jiang; Qiao, Yan; Zhang, Meng; Huang, Ying; Wu, Chen; Xiao, Zefen; Tan, Wen; and others

    2015-09-01

    Purpose: To investigate whether single nucleotide polymorphisms (SNPs) in the ataxia telangiectasia mutated (ATM) gene are associated with survival in patients with esophageal squamous cell carcinoma (ESCC) receiving radiation therapy or chemoradiation therapy or surgery only. Methods and Materials: Four tagSNPs of ATM were genotyped in 412 individuals with clinical stage III or IV ESCC receiving radiation therapy or chemoradiation therapy, and in 388 individuals with stage I, II, or III ESCC treated with surgery only. Overall survival time of ESCC among different genotypes was estimated by Kaplan-Meier plot, and the significance was examined by log-rank test. The hazard ratios (HRs) and 95% confidence intervals (CIs) for death from ESCC among different genotypes were computed by a Cox proportional regression model. Results: We found 2 SNPs, rs664143 and rs664677, associated with survival time of ESCC patients receiving radiation therapy. Individuals with the rs664143A allele had poorer median survival time compared with the rs664143G allele (14.0 vs 20.0 months), with the HR for death being 1.45 (95% CI 1.12-1.89). Individuals with the rs664677C allele also had worse median survival time than those with the rs664677T allele (14.0 vs 23.5 months), with the HR of 1.57 (95% CI 1.18-2.08). Stratified analysis showed that these associations were present in both stage III and IV cancer and different radiation therapy techniques. Significant associations were also found between the SNPs and locosregional progression or progression-free survival. No association between these SNPs and survival time was detected in ESCC patients treated with surgery only. Conclusion: These results suggest that the ATM polymorphisms might serve as independent biomarkers for predicting prognosis in ESCC patients receiving radiation therapy.

  4. Clinicopathological evaluation of pre-operative chemoradiotherapy with S-1 as a treatment for locally advanced oral squamous cell carcinoma

    PubMed Central

    KAWANO, SHINTARO; ZHENG, YANQUN; OOBU, KAZUNARI; MATSUBARA, RYOTA; GOTO, YUICHI; CHIKUI, TORU; YOSHITAKE, TADAMASA; KIYOSHIMA, TAMOTSU; JINNO, TEPPEI; MARUSE, YASUYUKI; MITATE, EIJI; KITAMURA, RYOJI; TANAKA, HIDEAKI; TOYOSHIMA, TAKESHI; SUGIURA, TSUYOSHI; NAKAMURA, SEIJI

    2016-01-01

    The administration of pre-operative chemotherapy with S-1 and concurrent radiotherapy at a total dose of 30 Gy was clinicopathologically evaluated as a treatment for locally advanced oral squamous cell carcinoma (OSCC) in the present study. The participants comprised 81 patients with OSCC, consisting of 29 patients with stage II disease, 12 patients with stage III disease and 40 patients with stage IV disease. All patients received a total radiation dose of 30 Gy in daily fractions of 2 Gy, 5 times a week, for 3 weeks, and the patients were concurrently administered S-1 at a dose of 80–120 mg, twice daily, over 4 consecutive weeks. Radical surgery was performed in all cases at 2–6 weeks subsequent to the end of pre-operative chemoradiotherapy. The most common adverse event was oropharyngeal mucositis, but this was transient in all patients. No severe hematological or non-hematological toxicities were observed. The clinical and histopathological response rates were 70.4 and 75.3%, respectively. Post-operatively, local failure developed in 6 patients (7.4%) and neck failure developed in 2 patients (2.5%). Distant metastases were found in 7 patients (8.6%). The overall survival rate, disease-specific survival rate and locoregional control rate at 5 years were 87.7, 89.9 and 90.6%, respectively. Locoregional recurrence occurred more frequently in patients that demonstrated a poor histopathological response compared with patients that demonstrated a good response (P<0.01). These results indicate that pre-operative S-1 chemotherapy with radiotherapy at a total dose of 30 Gy is feasible and effective for patients with locally advanced OSCC, and that little or no histopathological response may be a risk factor for locoregional recurrence in this treatment. PMID:27123119

  5. Relationship between level of lymph node metastasis and survival in locally advanced head and neck squamous cell carcinoma

    PubMed Central

    Xing, Yan; Zhang, Jianjun; Lin, Heather; Gold, Kathryn A.; Sturgis, Erich M.; Garden, Adam S.; Lee, J. Jack; William, William N.

    2015-01-01

    Background The current head and neck squamous cell carcinoma (HNSCC) staging system may not capture the full prognostic implications of regional lymph node involvement. We sought to investigate the impact of level of lymph node metastasis (LNM) on survival Methods The Surveillance, Epidemiology, and End Results (SEER) registry was queried for oral cavity (OC), oropharynx (OP), larynx (LAR), and hypopharynx (HP) HNSCC. Multivariate Cox proportional hazards model was used to evaluate whether level of LNM is an independent prognostic factor. Site-specific recursive-partitioning analysis (RPA) was performed to classify patients into different risk groups. Results Totally, 14,499 patients including OC (N=2,463), OP (N=8,567), LAR (N=2,332) and HP (N=1,137) were analyzed. Both AJCC N classification and level of LNM showed significant effects on overall survival (OS) in patients with OC, OP or LAR, but not in HP. In patients with N2 disease, AJCC subclassification (N2a, N2b, N2c) was significantly associated with OS of patients with OP and LAR, but not OC or HP, while level of LNM (primary, secondary, and tertiary) was significantly associated with OS in patients with OC, OP and LAR, but not HP. Using RPA, we designed a simple, primary site-specific prognostic tool integrating AJCC T classification, N classification, and level of LNM that can be easily utilized by health care providers in clinic. Conclusions Level of LNM is an independent prognostic factor for patients with locally advanced HNSCC and could add to the prognostic value of AJCC T and N classification in patients with locally advanced HNSCC. PMID:26554754

  6. Effectiveness of combined (131)I-chTNT and radiofrequency ablation therapy in treating advanced hepatocellular carcinoma.

    PubMed

    Tu, Jianfei; Ji, Jiansong; Wu, Fazong; Wang, Yonghui; Zhang, Dengke; Zhao, Zhongwei; Ying, Xihui

    2015-03-01

    To investigate the effectiveness of monoclonal antibody ((131)I-chTNT) and radiofrequency ablation (RFA) combination therapy in treating middle-advanced stage hepatocellular carcinoma (HCC). Thirty-four patients diagnosed with HCC patients, divided into two groups comprised of 22 and 12 cases were included in this retrospective study. The two groups received RFA with or without ((131)I-chTNT) therapy, respectively. The patients in these groups were followed up for a median of 31 and 35 months, respectively. Patient survival was evaluated using Kaplan-Meier method and safety profiles were determined by analyzing liver, thyroid, and bone marrow toxicities. This retrospective study showed that survival time of the patients who received combination therapy was significantly longer than that of the RFA group (P = 0.052). The median progress-free survival of patients in the two groups was 23 and 7 months, respectively, and the difference was significant (P = 0.04). Tumor recurred in 3.5-8.7 months in four of the combination group patients, among which three had newly developed lesions. The red blood cells and platelets counts were not altered on day 7 and 1 month of the treatment, however, number of white blood cells was significantly increased on day 7 which was reversed back to the normal range in 2 weeks. The ALT and AST were also not significantly altered on day 7 and 1 month of therapy. In middle-advanced stage HCC patients, the combination of (131)I-chTNT and RFA therapy was found to be significantly more effective than the RFA treatment alone as assessed in short-term follow-up. However, the dose we used was insufficient to completely block the local recurrence of the lesions with a diameter of 5 cm or larger.

  7. Targeted Therapy in Locally Advanced and Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (LA-R/M HNSCC)

    PubMed Central

    Echarri, María José; Lopez-Martin, Ana; Hitt, Ricardo

    2016-01-01

    Surgery and radiotherapy are the standard treatment options for patients with squamous cell carcinoma of the head and neck (SCCHN). Chemoradiotherapy is an alternative for patients with locally advanced disease. In recurrent/metastatic disease and after progression to platin-based regimens, no standard treatments other than best supportive care are currently available. Most SCCHN tumours overexpress the epidermal growth factor receptor (EGFR). This receptor is a tyrosine-kinase membrane receptor that has been implicated in angiogenesis, tumour progression and resistance to different cancer treatments. In this review, we analysed the different drugs and pathways under development to treat SCCHN, especially recurrent/metastatic disease. Until now, the EGFR signalling pathway has been considered the most important target with respect to new drugs; however, new drugs, such as immunotherapies, are currently under study. As new treatments for SCCHN are developed, the influence of therapies with respect to overall survival, progression free survival and quality of life in patients with this disease is changing. PMID:26927178

  8. Circulating Tumour Cells as an Independent Prognostic Factor in Patients with Advanced Oesophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy

    PubMed Central

    Su, Po-Jung; Wu, Min-Hsien; Wang, Hung-Ming; Lee, Chia-Lin; Huang, Wen-Kuan; Wu, Chiao-En; Chang, Hsien-Kun; Chao, Yin-Kai; Tseng, Chen-Kan; Chiu, Tzu-Keng; Lin, Nina Ming-Jung; Ye, Siou-Ru; Lee, Jane Ying-Chieh; Hsieh, Chia-Hsun

    2016-01-01

    The role of circulating tumour cells (CTCs) in advanced oesophageal cancer (EC) patients undergoing concurrent chemoradiotherapy (CCRT) remains uncertain. A negative selection protocol plus flow cytometry was validated to efficiently identify CTCs. The CTC number was calculated and analysed for survival impact. The protocol’s efficacy in CTC identification was validated with a recovery rate of 44.6 ± 9.1% and a coefficient of variation of 20.4%. Fifty-seven patients and 20 healthy donors were enrolled. Initial staging, first response to CRT, and surgery after CRT were prognostic for overall survival, with P values of <0.0001, <0.0001, and <0.0001, respectively. The CTC number of EC patients is significantly higher (P = 0.04) than that of healthy donors. Multivariate analysis for disease-specific progression-free survival showed that surgery after response to CCRT, initial stage, and CTC number (≥21.0 cells/mL) played independent prognostic roles. For overall survival, surgery after CCRT, performance status, initial stage, and CTC number were significant independent prognostic factors. In conclusion, a negative selection plus flow cytometry protocol efficiently detected CTCs. The CTC number before CCRT was an independent prognostic factor in patients with unresectable oesophageal squamous cell carcinoma. Further large-scale prospective studies for validation are warranted. PMID:27530152

  9. Significant survival benefit of adjuvant chemotherapy after concurrent chemoradiotherapy in locally advanced high-risk nasopharyngeal carcinoma

    PubMed Central

    Liang, Zhong-Guo; Chen, Xiao-Qian; Lin, Guo-Xiang; Yu, Bin-Bin; Chen, Kai-Hua; Zhong, Qiu-Lu; Nong, Si-Kai; Li, Ling; Qu, Song; Su, Fang; Zhao, Wei; Li, Ye; Zhu, Xiao-Dong

    2017-01-01

    The present study aimed to define high-risk patients who may benefit from additional adjuvant chemotherapy (AC) after concurrent chemotherapy in combination with intensity-modulated radiotherapy among patients with loco-regionally advanced nasopharyngeal carcinoma (NPC). A cohort of 511 NPC patients who received concomitant chemoradiotherapy (CCRT) with or without AC between January 2007 and December 2012 were retrospectively analysed. One hundred seventy-seven patients received CCRT alone, whereas 334 received CCRT + AC. The survival analysis showed that ages >45 years old, T3-T4 stages, N2-N3 disease and serum albumin levels ≤42 g/L were significant independent prognostic factors for overall survival (OS). Using these four risk factors, a prognostic model for OS was created as follows: (1) low-risk group: 0–1 risk factors; and (2) high-risk group: 2–4 risk factors. In the CCRT alone and CCRT + AC groups, significant differences in survival were found between the high- and low-risk groups. Patients in the high-risk group exhibited improved OS due to the addition of AC to CCRT, but no survival benefits were found in the low-risk group. In conclusion, high-risk patients may benefit from the addition of AC to CCRT regarding OS. PMID:28150694

  10. Contribution of the toxic advanced glycation end-products-receptor axis in nonalcoholic steatohepatitis-related hepatocellular carcinoma

    PubMed Central

    Takino, Jun-ichi; Nagamine, Kentaro; Hori, Takamitsu; Sakasai-Sakai, Akiko; Takeuchi, Masayoshi

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The main etiologies of HCC are hepatitis B virus and hepatitis C virus (HCV), and non-hepatitis B/non-hepatitis C HCC (NBNC-HCC) has also been identified as an etiological factor. Although the incidence of HCV-related HCC in Japan has decreased slightly in recent years, that of NBNC-HCC has increased. The onset mechanism of NBNC-HCC, which has various etiologies, remains unclear; however, nonalcoholic steatohepatitis (NASH), a severe form of nonalcoholic fatty liver disease, is known to be an important risk factor for NBNC-HCC. Among the different advanced glycation end-products (AGEs) formed by the Maillard reaction, glyceraldehyde-derived AGEs, the predominant components of toxic AGEs (TAGE), have been associated with NASH and NBNC-HCC, including NASH-related HCC. Furthermore, the expression of the receptor for AGEs (RAGE) has been correlated with the malignant progression of HCC. Therefore, TAGE induce oxidative stress by binding with RAGE may, in turn, lead to adverse effects, such as fibrosis and malignant transformation, in hepatic stellate cells and tumor cells during NASH or NASH-related HCC progression. The aim of this review was to examine the contribution of the TAGE-RAGE axis in NASH-related HCC. PMID:26483867

  11. Subcutaneous administration of interleukin 2 and interferon-alpha-2b in advanced renal cell carcinoma: a confirmatory study.

    PubMed Central

    Facendola, G.; Locatelli, M. C.; Pizzocaro, G.; Piva, L.; Pegoraro, C.; Pallavicini, E. B.; Signaroldi, A.; Meregalli, M.; Lombardi, F.; Beretta, G. D.

    1995-01-01

    Recent clinical studies have suggested that the combination of subcutaneous recombinant human interleukin 2 (rIL-2) and interferon alpha (rIFN-alpha) is especially promising in advanced renal cell carcinoma. We assessed the safety, activity and toxicity of home therapy with these two agents in 50 patients. Each treatment cycle consisted of a 2 day pulse phase, with 9 x 10(6) IU m-2 of rIL-2 being given subcutaneously every 12 h, followed by a 6 week maintenance phase during which rIL-2 1.8 x 10(6) IU m-2 was administered subcutaneously every 12 h on days 1-5 and rIFN-alpha 2b 5 x 10(6) IU m-2 once a day on days 1, 3 and 5. Objective responses (CR+PR) occurred in 9/50 (18%) patients, six of whom (12%) achieved a complete response. Disease stabilisation was observed in 17 cases (34%) and 18 patients progressed during therapy. In the other six cases, treatment was interrupted early for toxicity or patient refusal. One patient died of myocardial infarction during the second cycle. The overall median survival was 12 months. Home therapy with subcutaneous rIL-2 + rIFN-alpha 2b proved to be active, feasible and moderately toxic, but serious adverse events can sometimes occur. PMID:8519672

  12. Positron Emission Tomography for Neck Evaluation Following Definitive Treatment with Chemoradiotherapy for Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Bar-Ad, Voichita; Mishra, Mark; Ohri, Nitin; Intenzo, Charles

    2013-01-01

    Objectives The objective of the current review was to assess published data on the role of Positron Emission Tomography (PET) for evaluation of nodal residual disease after definitive chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC). Methods Studies were identified by searching PubMed electronic databases. Only studies using a post-chemoradiotherapy PET for nodal residual disease evaluation were included in the present review. Both prospective and retrospective studies were included. Information regarding sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET for detecting nodal residual disease after definitive chemoradiotherapy for HNSCC was extracted and analyzed. Results Twenty published studies were included in the present review. Existing data suggest that a negative post-chemoradiotherapy PET scan is associated with a negative predictive value up to 100%. The sensitivity of PET in detecting nodal residual disease is greater for scans performed ≥ 10 weeks after definitive treatment with chemoradiotherapy for HNSCC. Conclusions Further studies are needed to quantify the reliability of PET in detecting nodal residual disease after chemoradiotherapy for locoregionally advanced HNSCC. The optimal timing of PET imaging after chemoradiotherapy remains to be defined. PMID:21864252

  13. Phase I study of TAC-101, an oral synthetic retinoid, in Japanese patients with advanced hepatocellular carcinoma.

    PubMed

    Okusaka, Takuji; Ueno, Hideki; Ikeda, Masafumi; Takezako, Yoriko; Morizane, Chigusa

    2012-08-01

    Preclinical models have shown that TAC-101 (4-[3,5-bis(trimethylsilyl) benzamide] benzoic acid), an oral synthetic retinoid, has antitumor activity in hepatocellular carcinoma (HCC). We conducted a phase I study in Japanese patients with advanced HCC to examine the pharmacokinetics, recommended dose, safety, and efficacy of TAC-101. The administered dose of TAC-101 was 10 mg/day in four patients (level 1), 20 mg/day in six (level 2), and 30 mg/day in three (level 3). There was no dose-limiting toxicity at level 1. Only one patient each had dose-limiting toxicity at level 2 (grade 2 fatigue, recovery requiring eight or more consecutive days of rest) and at level 3 (grade 3 splenic vein thrombosis). Level 3 (30 mg/day) was considered the maximum tolerated dose and 20 mg/day the recommended dose by a panel of medical experts, placing maximum emphasis on safety. The most frequent adverse events were fatigue, headache, and dermal symptoms such as rash. Pharmacokinetic parameters in Japanese patients with HCC were similar to those in patients in the United States, most of whom were Caucasian. Although no patient had a complete or partial response, the disease control rate was 38.5%. In conclusion, the recommended dose of TAC-101 for patients with HCC is 20 mg/day. TAC-101 had an acceptable toxicity profile, warranting further evaluation in clinical trials.

  14. Toxicity of abdominopelvic radiation in advanced ovarian carcinoma patients after cisplatin/cyclophosphamide therapy and second-look laparotomy

    SciTech Connect

    Shelley, W.E.; Starreveld, A.A.; Carmichael, J.A.; O'Connell, G.; Roy, M.; Swenerton, K.

    1988-03-01

    Twenty-seven advanced ovarian carcinoma patients who had received six courses of cyclophosphamide/cisplatin and had either microscopic disease (15 patients) or no pathologically detectable disease (12 patients) after second-look laparotomy were treated with abdominopelvic radiation (2250 cGy to the abdomen and pelvis and a 2250-cGy pelvic boost). Acute myelosuppression or gastrointestinal toxicity prevented completion of treatment in only three patients. However, bowel obstruction occurred in 13 (48%), ten of whom required surgery. Five of these ten had recurrent tumor, but the other five did not. Subsequently two of the latter five did develop a recurrence, one in the lung and one in the liver. A third patient died as an indirect result of radiation damage to the bowel. Median follow-up duration is 17 months from completion of radiation. So far, 13 (48%) have developed progressive disease: four (33%) of the 12 who had a negative second-look laparotomy and nine (60%) of the 15 who had microscopic disease before radiation. While acute toxicity is tolerable, the incidence of serious chronic bowel toxicity is high. Efforts should be made to alter this therapy in order to decrease the frequency of long-term morbidity.

  15. Transcript Profiling Identifies Iqgap2−/− Mouse as a Model for Advanced Human Hepatocellular Carcinoma

    PubMed Central

    Gnatenko, Dmitri V.; Xu, Xiao; Zhu, Wei; Schmidt, Valentina A.

    2013-01-01

    It is broadly accepted that genetically engineered animal models do not always recapitulate human pathobiology. Therefore identifying best-fit mouse models of human cancers that truly reflect the corresponding human disease is of vital importance in elucidating molecular mechanisms of tumorigenesis and developing preventive and therapeutic approaches. A new hepatocellular carcinoma (HCC) mouse model lacking a novel putative tumor suppressor IQGAP2 has been generated by our laboratory. The aim of this study was to obtain the molecular signature of Iqgap2−/− HCC tumors and establish the relevance of this model to human disease. Here we report a comprehensive transcriptome analysis of Iqgap2−/− livers and a cross-species comparison of human and Iqgap2−/− HCC tumors using Significance Analysis of Microarray (SAM) and unsupervised hierarchical clustering analysis. We identified the Wnt/β-catenin signaling pathway as the top canonical pathway dysregulated in Iqgap2−/− livers. We also demonstrated that Iqgap2−/− hepatic tumors shared genetic signatures with HCC tumors from patients with advanced disease as evidenced by a 78% mouse-to-human microarray data set concordance rate with 117 out of 151 identified ortholog genes having similar expression profiles across the two species. Collectively, these results indicate that the Iqgap2 knockout mouse model closely recapitulates human HCC at the molecular level and supports its further application for the study of this disease. PMID:23951254

  16. The Prognostic Value of Baseline Lymphocyte, Neutrophil, and Monocyte Counts in Locally Advanced Cervical Carcinoma Treated with Radiation

    PubMed Central

    Himler, Justin; Nagel, Christa I.; Resnick, Kimberly

    2017-01-01

    Background. To determine the prognostic significance of pretreatment levels of circulating lymphocyte (CLC), neutrophil (CNC), and monocyte (CMC) counts in patients with locally advanced cervical carcinoma (CC) treated with definitive radiation. Methods. A retrospective, dual-institution review of patients with Stage IB2-IVA CC from 2005 to 2015. Progression-free (PFS) and Overall Survival (OS) were determined for high and low CLC, CNC, and CMC groups. Multivariate analysis was used to confirm prognostic value of baseline leukocyte counts. Results. 181 patients were included. Median follow-up time was 26 (3–89) months. CNC had no effect on PFS or OS. PFS was similar between CMC groups; however, OS was significantly improved for patients with low CMC (62.5 versus 45.3 months, p = 0.016). High CLC was associated with improved PFS (48.5 versus 27.8 months, p = 0.048) and OS (58.4 versus 34.9 months, p = 0.048). On multivariate analysis, high CNC was associated with increased relapse risk (HR 1.12, p = 0.006) and low CLC was associated with increased mortality risk (HR 0.67, p = 0.027). Conclusion. This study demonstrates that leukocyte values can provide prognostic information in CC. These hypothesis-generating findings warrant further prospective investigations. PMID:28239396

  17. Phase II trial of biweekly docetaxel, cisplatin, and 5-fluorouracil chemotherapy for advanced esophageal squamous cell carcinoma.

    PubMed

    Tanaka, Yoshihiro; Yoshida, Kazuhiro; Yamada, Atsuko; Tanahashi, Toshiyuki; Okumura, Naoki; Matsuhashi, Nobuhisa; Yamaguchi, Kazuya; Miyazaki, Tatsuhiko

    2016-06-01

    The prognosis of esophageal cancer patients is still unsatisfactory. Although a docetaxel, cisplatin, and 5-Fu (DCF) regimen has been reported, it is often difficult to accomplish because of severe toxicity. Therefore, we developed a new biweekly DCF (Bi-DCF) regimen and previously reported the recommended dose in a phase I dose-escalation study. We then performed a phase II study of Bi-DCF for advanced esophageal squamous cell carcinoma (SCC). Patients with clinical stage II/III were eligible. Patients received 2 courses of chemotherapy: docetaxel 35 mg/m(2) with cisplatin 40 mg/m(2) on days 1 and 15 and 400 mg/m(2) 5-fluorouracil on days 1-5 and 15-19 every 4 weeks. After completion of the chemotherapy, patients received esophagectomy. The primary endpoint was the completion rate of protocol treatment. Thirty-two patients were enrolled. The completion rate of protocol treatment (completion of two courses of preoperative chemotherapy and R0 surgery) was 100 %. During chemotherapy, the most common grade 3 or 4 toxicities were neutropenia (31.3 %). No treatment-related death was observed, and the incidence of operative morbidity was tolerable. The overall response rate after the chemotherapy was 90.3 %. This Bi-DCF regimen was well tolerated and highly active. This trial was registered with the University Hospital Medical Information Network (No. UMIN 000014625).

  18. Current Advancement in Multidisciplinary Treatment for Resectable cStage II/III Esophageal Squamous Cell Carcinoma in Japan

    PubMed Central

    Matsuda, Satoru; Kawakubo, Hirofumi; Ando, Nobutoshi; Kitagawa, Yuko

    2016-01-01

    Multidisciplinary treatment comprising surgery, chemotherapy, and radiotherapy for resectable esophageal squamous cell carcinoma (ESCC) is widely used with improved prognosis. Transthoracic esophagectomy (TTE) with extended lymph node (LN) dissection, known as three field LN dissection, has been recommended for ESCC using open thoracotomy or the thoracoscopic approach. The Japan Clinical Oncology Group (JCOG) trial (JCOG1409) is investigating the patients’ long term survival using the thoracoscopic approach that has been shown to reduce the incidence of postoperative respiratory complication. For perioperative treatment, neoadjuvant chemotherapy using cisplatin plus 5-fluorouracil (5-FU), has been accepted as the standard of care in Japan based on the JCOG9907 trial. In Western countries, neoadjuvant chemoradiotherapy was shown to prolong overall survival for esophageal cancer, including ESCC. Although surgery has been recognized as an initial curative treatment for esophageal cancer, definitive chemoradiotherapy is an alternative treatment for patients who are unable to undergo thoracotomy or who decline to undergo surgery. This article reviews multidisciplinary treatment advances for ESCC. However, current standard treatments are country dependent and the ongoing trial may help standardize ESCC treatment across various societies. PMID:27384595

  19. [Presurgical treatment of axitinib reduced operation risk by downsizing the vena cava tumor thrombus in advanced renal cell carcinomas: two case reports].

    PubMed

    Hamada, Akihiro; Yamasaki, Toshinari; Negoro, Hiromitsu; Kobayashi, Takashi; Terada, Naoki; Sugino, Yoshio; Matsui, Yoshiyuki; Inoue, Takahiro; Kamba, Tomomi; Yoshimura, Koji; Ogawa, Osamu

    2014-12-01

    In cases of advanced renal cell carcinoma with inferior vena cava (IVC) thrombus, surgical resection of both tumor and thrombus contributes to the improvement of patient's prognosis, but the risk of perioperative complication is still high. We experienced two cases of advanced renal tumors with IVC tumor thrombus down-sized by presurgical treatment of axitinib. Axitinib treatment showed a marked tumor reduction effect without any severe adverse event. We could remove both tumor and thrombus without perioperative complications. In these two cases, downsizing of IVC thrombus enabled us to reduce the extent of the surgery.

  20. VX-970, Cisplatin, and Radiation Therapy in Treating Patients With Locally Advanced HPV-Negative Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2017-02-14

    Head and Neck Squamous Cell Carcinoma; Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma

  1. Could preoperative short-course radiotherapy be the treatment of choice for localized advanced rectal carcinoma?

    PubMed Central

    Ciria, Juan Pablo; Eguiguren, Mikel; Cafiero, Sergio; Uranga, Intza; Diaz de Cerio, Ivan; Querejeta, Arrate; Urraca, Jose Maria; Minguez, Julian; Guimon, Elena; Puertolas, Jose Ramón

    2014-01-01

    Short-course preoperative radiotherapy (RT) is widely used in northern Europe for locally advanced resectable rectal cancer, but its role in the era of advanced imaging techniques is uncertain. Here, we reviewed articles and abstracts on SCRT published from 1974 through 2013 with the goal of identifying patients who might be best suited for short-course RT. We included relevant articles comparing surgery with or without preoperative radiation published before and after the advent of total mesorectal excision. We also analyzed two randomized trials directly comparing short-course RT with conventionally fractionated chemoradiation (the Polish Colorectal Study Group and the Trans-Tasman Radiation Oncology Group) that compared short-course RT with conventional chemoradiotherapy. We conclude from our review that short-course RT can be generally applied for operable rectal cancer and produces high rates of pelvic control with acceptable toxicity; it reduces local recurrence rates but does not increase overall survival. SCRT seems to be best used for tumors considered “low risk,” i.e., those that are >5 cm from the anal margin, without circumferential margin involvement, and involvement of fewer than 4 lymph nodes. Whether sequential chemotherapy can further improve outcomes remains to be seen, as does the best time for surgery (immediately or 6–8 weeks after RT). We further recommend that selection of patients for short-course RT should be based on findings from magnetic resonance imaging or transrectal ultrasonography. PMID:25535578

  2. Phase 2 Study of Combined Sorafenib and Radiation Therapy in Patients With Advanced Hepatocellular Carcinoma

    SciTech Connect

    Chen, Shang-Wen; Lin, Li-Ching; Kuo, Yu-Cheng; Liang, Ji-An; Kuo, Chia-Chun; Chiou, Jeng-Fong

    2014-04-01

    Purpose: This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC). Methods and Materials: Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter. Results: Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions ≥ grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade ≥2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progression-free survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score ≥2 was associated with an inferior outcome in overall survival. Six patients (15%) developed treatment-related hepatic toxicity grade ≥3 during the sequential phase, and 3 of them were fatal. Conclusions: When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score ≥2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation.

  3. A Phase II Study of Sorafenib in Advanced Uterine Carcinoma / Carcinosarcoma: A Trial of the Chicago, PMH, and California Phase II Consortia

    PubMed Central

    Nimeiri, Halla S.; Oza, Amit M.; Morgan, Robert J.; Huo, Dezheng; Elit, Laurie; Knost, James A.; Wade, James L.; Agamah, Edem; Vokes, Everett E.; Fleming, Gini F.

    2010-01-01

    Objectives To determine the efficacy and safety of single agent sorafenib, an oral multi-targeted tyrosine kinase inhibitor, in patients with advanced uterine carcinoma and carcinosarcoma. Methods This multi-institutional non-randomized phase II trial enrolled two cohorts: patients with uterine carcinoma (cohort A) and uterine carcinosarcoma (cohort B). Eligibility criteria included measurable disease, 0–1 prior chemotherapy regimens, and ECOG performance status ≤ 2. Sorafenib at a dose of 400 mg was administered orally twice daily. A cycle was defined as 28 days. Objective tumor response was the primary endpoint and was assessed following every two cycles. Results Fifty–six patients (40 with carcinoma, 16 with carcinosarcoma) were enrolled between March 2005 and August 2007. Two (5%) patients with uterine carcinoma had a partial response (PR) and 17 (42.5%) achieved stable disease (SD). Five had SD lasting at least 4 months. The 6-month progression free survival rate for patients with carcinoma was 29%, and the median overall survival was 11.4 months. No patients with carcinosarcoma had an objective response. Four (25%) had SD, and one had SD lasting 18 months. The 6-month progression free survival rate was 13%, and the median overall survival was 5.0 months. Grade 3/4 drug related toxicities included: hypertension (13%), hand-foot syndrome (13%), hypophosphatemia (7%), anemia (5%), rash (5%), diarrhea (5%), thrombosis (5%), fatigue (5%) and bleeding (5%). Conclusion Sorafenib had minimal activity in patients with uterine carcinoma. Predictive factors for potential benefit are needed. PMID:20117828

  4. Mycobacterium conceptionense Bloodstream Infection in a Patient with Advanced Gastric Carcinoma.

    PubMed

    Yaita, Kenichiro; Matsunaga, Mototsugu; Tashiro, Naotaka; Sakai, Yoshiro; Masunaga, Kenji; Miyoshi, Hiroaki; Oshima, Koichi; Chikamatsu, Kinuyo; Takaki, Akiko; Mitarai, Satoshi; Watanabe, Hiroshi

    2017-01-24

    A 65-year-old Japanese male farmer with advanced gastric adenocarcinoma and multiple hepatic metastases was admitted to our hospital. Blood culture results were positive on day 5, and Gram-positive rods were detected. According to the results of Ziehl-Neelsen staining and a cultured colony of this bacterium, we suspected a mycobacterial infection. Suspecting a rapidly growing mycobacterium (RGM), we started multidrug therapy with levofloxacin, clarithromycin, and ethambutol, and the patient recovered from the bloodstream infection. Further gene examination (16S rRNA, hsp65, and sodA) revealed an isolate of Mycobacterium conceptionense. M. conceptionense was first identified as an RGM in 2006. Among previous case reports of M. conceptionense infections, bone and soft tissue infections in hosts with a disorder of the normal structure (e.g., surgical sites) were dominant. We report the characteristics of M. conceptionense infection in this first Japanese case report and a review of the literature.

  5. Molecularly targeted therapies for advanced or metastatic non-small-cell lung carcinoma

    PubMed Central

    Bayraktar, Soley; Rocha-Lima, Caio M

    2013-01-01

    Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related death in both men and women in the United States. Platinum-based doublet chemotherapy has been a standard for patients with advanced stage disease. Improvements in overall survival and quality of life have been modest. Improved knowledge of the aberrant molecular signaling pathways found in NSCLC has led to the development of biomarkers with associated targeted therapeutics, thus changing the treatment paradigm for many NSCLC patients. In this review, we present a summary of many of the currently investigated biologic targets in NSCLC, discuss their current clinical trial status, and also discuss the potential for development of other targeted agents. PMID:23696960

  6. Dose escalation study of carbon ion radiotherapy for locally advanced carcinoma of the uterine cervix

    SciTech Connect

    Kato, Shingo . E-mail: s.kato@nirs.go.jp; Ohno, Tatsuya; Tsujii, Hirohiko; Nakano, Takashi; Mizoe, Jun-etsu; Kamada, Tadashi; Miyamoto, Tadaaki; Tsuji, Hiroshi; Kato, Hirotoshi; Yamada, Shigeru; Kandatsu, Susumu; Yoshikawa, Kyosan; Ezawa, Hidefumi; Suzuki, Michiya

    2006-06-01

    Purpose: To evaluate the toxicity and efficacy of carbon ion radiotherapy (CIRT) for locally advanced cervical cancer by two phase I/II clinical trials. Methods and Materials: Between June 1995 and January 2000, 44 patients were treated with CIRT. Thirty patients had Stage IIIB disease, and 14 patients had Stage IVA disease. Median tumor size was 6.5 cm (range, 4.2-11.0 cm). The treatment consisted of 16 fractions of whole pelvic irradiation and 8 fractions of local boost. In the first study, the total dose ranged from 52.8 to 72.0 gray equivalents (GyE) (2.2-3.0 GyE per fraction). In the second study, the whole pelvic dose was fixed at 44.8 GyE, and an additional 24.0 or 28.0 GyE was given to the cervical tumor (total dose, 68.8 or 72.8 GyE). Results: No patient developed severe acute toxicity. In contrast, 8 patients developed major late gastrointestinal complications. The doses resulting in major complications were {>=}60 GyE. All patients with major complications were surgically salvaged. The 5-year local control rate for patients in the first and second studies was 45% and 79%, respectively. When treated with {>=}62.4 GyE, the local control was favorable even for the patients with stage IVA disease (69%) or for those with tumors {>=}6.0 cm (64%). Conclusions: In CIRT for advanced cervical cancer, the dose to the intestines should be limited to <60 GyE to avoid major complications. Although the number of patients in this study was small, the results support continued investigation to confirm therapeutic efficacy.

  7. Thymostimulin versus placebo for palliative treatment of locally advanced or metastasised hepatocellular carcinoma: a phase III clinical trial

    PubMed Central

    2010-01-01

    Background Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma (HCC) in vitro and palliative efficacy in advanced HCC in two independent phase II trials. The aim of this study was to assess the efficacy of thymostimulin in a phase III trial. Methods The study was designed as a prospective randomised, placebo-controlled, double-blind, multicenter clinical phase III trial. Between 10/2002 and 03/2005, 135 patients with locally advanced or metastasised HCC (Karnofsky ≥60%/Child-Pugh ≤ 12) were randomised to receive thymostimulin 75 mg s.c. 5×/week or placebo stratified according to liver function. Primary endpoint was twelve-month survival, secondary endpoints overall survival (OS), time to progression (TTP), tumor response, safety and quality of life. A subgroup analysis according to liver function, KPS and tumor stage (Okuda, CLIP and BCLC) formed part of the protocol. Results Twelve-month survival was 28% [95%CI 17-41; treatment] and 32% [95%CI 19-44; control] with no significant differences in median OS (5.0 [95% CI 3.7-6.3] vs. 5.2 [95% CI 3.5-6.9] months; p = 0.87, HR = 1.04 [95% CI 0.7-1.6]) or TTP (5.3 [95%CI 2.0-8.6] vs. 2.9 [95%CI 2.6-3.1] months; p = 0.60, HR = 1.13 [95% CI 0.7-1.8]). Adjustment for liver function, Karnofsky status or tumor stage did not affect results. While quality of life was similar in both groups, fewer patients on thymostimulin suffered from accumulating ascites and renal failure. Conclusions In our phase III trial, we found no evidence of any benefit to thymostimulin in the treatment of advanced HCC and there is therefore no justification for its use as single-agent treatment. The effect of thymostimulin on hepato-renal function requires further confirmation. Trial Registration Current Controlled Trials ISRCTN64487365. PMID:20735834

  8. Budget impact analysis of first-line treatment with pazopanib for advanced renal cell carcinoma in Spain

    PubMed Central

    2013-01-01

    Background Due to economic constraints, cancer therapies are under close scrutiny by clinicians, pharmacists and payers alike. There is no published pharmacoeconomic evidence guiding the choice of first-line therapy for advanced renal cell carcinoma (RCC) in the Spanish setting. We aimed to develop a model describing the natural history of RCC that can be used in healthcare decision-making. We particularly analyzed the budget impact associated with the introduction of pazopanib compared to sunitinib under the Spanish National Healthcare System (NHS) perspective. Methods We developed a Markov model to estimate the future number of cases of advanced RCC (patients with favorable or intermediate risk) resulting either from initial diagnosis or disease progression after surgery. The model parameters were obtained from the literature. We assumed that patients would receive either pazopanib or sunitinib as first-line therapy until disease progression. Pharmacological costs and costs associated with the management of adverse events (AE) were considered. A univariate sensitivity analysis was undertaken in order to test the robustness of the results. Results The model predicted an adult RCC prevalence of 7.5/100,000 (1-year), 20.7/100,000 (3-year) and 32.5/100,000 (5-year). These figures are very close to GLOBOCAN reported RCC prevalence estimates of 7.6/100,000, 20.2/100,000 and 31.1/100,000, respectively. The model predicts 1,591 advanced RCC patients with favorable or intermediate risk in Spain in 2013. Annual per patient pharmacological costs were €32,365 and €39,232 with pazopanib and sunitinib, respectively. Annual costs associated with the management of AE were €662 and €974, respectively. Overall annual per patient costs were €7,179 (18%) lower with pazopanib compared to sunitinib. For every point increase in the percentage of patients treated with pazopanib, the NHS would save €67,236. If all the 1,591 patients predicted were treated with pazopanib, the

  9. Direct and indirect autofluorescence laryngoscopy in the diagnosis of laryngeal cancer and its precursor lesions.

    PubMed

    Arens, C; Dreyer, T; Malzahn, K; Glanz, H

    2004-01-01

    Autofluorescence endoscopy has proven to facilitate the detection and delineation of precancerous lesions, carcinoma in situ and microinvasive cancer during bronchoscopy. The aim of the present study is to evaluate the diagnostic potential and limitations of this imaging technique applied during direct and indirect laryngoscopy. In a prospective study, 109 patients with suspected precancerous or cancerous lesions were investigated preoperatively by indirect autofluorescence laryngoscopy as well as during microlaryngoscopy. Autofluorescence was induced by filtered blue light (375-440 nm) of a xenon short arc lamp and processed by a CCD camera system (D-light-AF System, Storz, Tuttlingen, Germany). Autofluorescence images were immediately assessed for diagnosis, compared to the direct autofluorescence picture obtained during microlaryngoscopy and compared with pathohistological findings. Comparable to direct autofluorescence images, normal laryngeal mucosa showed a typical green fluorescence signal. Moderate and high epithelial dysplasia, carcinoma in situ, and microinvasive cancer displayed a diminished green fluorescence. False negative results were related to extreme hyperkeratosis. False positive cases showed mild dysplasia with inflammatory reactions or scarring. In 98 cases (90%) we found concordant results. According to our results, the presented technique seems to be a promising diagnostic tool for the early detection of laryngeal cancer and its precursor lesions during direct and indirect laryngoscopy. Scarring, marked hyperkeratosis, and inflammation can limit the predictive value of the method.

  10. Indirect autofluorescence laryngoscopy in the diagnosis of laryngeal cancer and its precursor lesions.

    PubMed

    Arens, C; Dreyer, T; Glanz, H; Malzahn, K

    2004-02-01

    Direct autofluorescence endoscopy of the larynx has proven to facilitate the detection and delineation of precancerous lesions, carcinoma in situ and cancer. The aim of the present study was to evaluate the diagnostic potential and limitations of this imaging technique applied during indirect laryngoscopy. In a prospective study, 116 patients with suspected precancerous or cancerous lesions were investigated preoperatively by indirect autofluorescence laryngoscopy. Autofluorescence was induced by filtered blue light (375-440 nm) of a xenon short-arc lamp and processed by a CCD camera system (D-light-AF System, Storz, Tuttlingen, Germany). Autofluorescence images were immediately assessed for diagnosis, compared to the direct autofluorescence picture obtained during microlaryngoscopy and compared to pathohistological findings. Comparable to direct autofluorescence images, normal laryngeal mucosa showed a typical green fluorescence signal. Moderate and high epithelial dysplasia, carcinoma in situ and cancer displayed a diminished green fluorescence. False negative results were related to extreme hyperkeratosis. False positive cases showed mild dysplasia with inflammatory reactions or scarring. In 103 cases (89%), we found concordant results. According to our results, the presented technique seems to be a promising diagnostic tool for the early detection of laryngeal cancer and its precursor lesions during indirect laryngoscopy. Scarring, marked hyperkeratosis and inflammation can limit the predictive value of the method.

  11. Sunitinib, Cetuximab, and Radiation Therapy in Treating Patients With Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2013-07-01

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  12. [A successful case of systemic chemotherapy followed by liver resection for advanced hepatocellular carcinoma with highly vascular invasion and multiple pulmonary metastases].

    PubMed

    Mizukami, Tatsuzo; Kamiyama, Toshiya; Nakanishi, Kazuaki; Taniguchi, Masahiko; Yokoo, Hideki; Tahara, Munenori; Kakisaka, Tatsuhiko; Kamachi, Hirofumi; Matsushita, Michiaki; Todo, Satoru

    2011-05-01

    The prognosis for hepatocellular carcinoma with extrahepatic metastasis or vascular invasion is very poor. We treated a case successfully by combining chemotherapy and liver resection for hepatocellular carcinoma with multiple pulmonary metastases and vascular invasion. A 56-year-old man who complained of abdominal pain in his right side was transported to the hospital by ambulance. Because CT scan revealed the rupture of hepatocellular carcinoma, he underwent emergency transcatheter arterial embolization (TAE). A close examination revealed tumor thrombus in the inferior vena cava and posterior segment of the portal vein branch, with multiple pulmonary metastases. We conducted right hepatic lobectomy and removal of the inferior vena cava tumor thrombus. After the operation, pulmonary metastatic lesions gradually grew larger, so the oral administration of S-1 at 120 mg per day was started. At the end of the first course, the CT scan revealed that multiple pulmonary metastases were significantly reduced, and treatment was maintained until the end of 4 courses. A prolongation of survival could be expected by combining systemic chemotherapy and liver resection for advanced hepatocellular carcinoma such as the present case.

  13. Accelerated fractionation radiation therapy for advanced squamous cell carcinoma of the head and neck

    SciTech Connect

    Giri, P.G.; Gemer, L.S. )

    1991-09-01

    The authors treated 14 patients who had advanced head and neck cancer with an accelerated fractionation schedule of irradiation consisting of two fractions given 6 hours apart. In the morning a volume of 1.7 Gy was given to an area that encompassed the entire tumor, enlarged lymph nodes, and all areas at risk for microscopic disease. Six hours later, 1.1 Gy was given to an area that included only the tumor and any enlarged lymph nodes, with a 2-cm margin. The treatment was well tolerated; of the 13 patients who completed therapy, six did not require a break in therapy, and seven patients did. The median rest period was 2 days. There was no grade 4 toxicity. Grade 3 toxicity included skin changes (one case), mucositis (two), dysphagia (two), weight loss (three), and a decrease in the hemoglobin level (one case). The response rate in the 13 who completed therapy was 13/13 (100%); 11 of the 13 (83%) had a complete response. Only one of the 11 who achieved a complete response had failure at the primary site. At a median follow-up of 24 months, the absolute survival was 7/13 (54%) and the corrected survival was 7/10 (70%). This technique permits radiation therapy to be given on an accelerated schedule without a planned break in treatment. The overall response rate and survival at 2 years was excellent.

  14. Irreversible electroporation in the treatment of locally advanced pancreas and liver metastases of colorectal carcinoma

    PubMed Central

    Wichtowski, Mateusz; Nowaczyk, Piotr; Kocur, Jacek

    2016-01-01

    Aim of the study Irreversible electroporation is a new, non-thermal ablation technique in the treatment of parenchymal organ tumors which uses short high voltage pulses of electricity in order to induce apoptosis of targeted cells. In this paper the application of this method of treatment in locally advanced pancreatic cancer (LAPC) and liver cancer is analyzed. Material and methods Between 04.2014 and 09.2014 two patients with LAPC and one with colorectal liver metastasis (CRLM) were qualified for treatment with irreversible electroporation. Both patients remained under constant observation and control. PubMed/Medline, Embase and Google Scholar databases were searched and eight original reports on irreversible electroporation of pancreatic and liver tumors based on the biggest groups of patients were found. Results Two patients with LAPC and one with CRLM were qualified for ablation with irreversible electroporation. In all three patients a successful irreversible electroporation (IRE) procedure of the whole tumor was conducted. In the minimum seven-month follow-up 100% local control was achieved – without progression. In the literature review the local response to treatment ranged from 41% to 100%. The event-free survival rate in six-month observation was 94%. Conclusions Ablation with irreversible electroporation is a new non-thermal ablation technique which has been demonstrated, both in the previously published studies and in the cases described in this paper, as a safe and efficient therapeutic method for patients with LAPC and CRLM. PMID:27095938

  15. Cine MRI of swallowing in patients with advanced oral or oropharyngeal carcinoma: a feasibility study.

    PubMed

    Kreeft, Anne Marijn; Rasch, Coen R N; Muller, Sara H; Pameijer, Frank A; Hallo, Eeke; Balm, Alfons J M

    2012-06-01

    Treatment of oral and oropharyngeal cancer may cause dysphagia. Purpose is to examine whether cine magnetic resonance imaging (MRI) yields additional information compared to standard examination in the evaluation of posttreatment dysphagia and mobility of oral and oropharyngeal structures. Thirty-four cine MRIs were made in 23 patients with advanced oral and oropharyngeal cancer, consisting of an MR image every 800 ms during swallowing which is compared to videofluoroscopy and quality of life questionnaires. A scoring system was applied to assess mobility on cine MR and videofluoroscopy leading to a score ranging from 9 to 17. Cine MRI of the swallowing in a midsagittal plane visualized the tumor (if located in the same plane), important anatomic structures and surgical reconstructions. Posttreatment mobility on cine MRI and videofluoroscopy was significantly diminished compared to pretreatment, mean pretreatment cine MRI score was 10.8 and posttreatment 12.4 (p = 0.017). Impaired mobility on cine MRI was significantly correlated to more swallowing problems (Spearman's correlation coefficient 0.73, p = 0.04), on videofluoroscopy not. Cine MRI is a promising new technique as an adjunct to standard examinations for evaluation of swallowing in patients with oral and oropharyngeal cancer. Cine MRI directly visualizes the dynamics of swallowing and allows evaluation of pre- and posttreatment differences. Abnormal findings are significantly correlated with subjective swallowing complaints of patients.

  16. Gene and microRNA expression reveals sensitivity to paclitaxel in laryngeal cancer cell line

    PubMed Central

    Xu, Cheng-Zhi; Xie, Jin; Jin, Bin; Chen, Xin-Wei; Sun, Zhen-Feng; Wang, Bao-Xing; Dong, Pin

    2013-01-01

    Paclitaxel is a widely used chemotherapy drug for advanced laryngeal cancer patients. However, the fact that there are 20-40% of advanced laryngeal cancer patients do not response to paclitaxel makes it necessary to figure out potential biomarkers for paclitaxel sensitivity prediction. In this work, Hep2, a laryngeal cancer cell line, untreated or treated with lower dose of paclitaxel for 24 h, was applied to DNA microarray chips for gene and miR expression profile analysis. Expression of eight genes altered significantly following paclitaxel treatment, which was further validated by quantitative real-time PCR. Four up-regulated genes were ID2, BMP4, CCL4 and ACTG2, in which ID2 and BMP4 were implicated to be involved in several drugs sensitivity. While the down-regulated four genes, MAPK4, FASN, INSIG1 and SCD, were mainly linked to the endoplasmic reticulum and fatty acid biosynthesis, these two cell processes that are associated with drug sensitivity by increasing evidences. After paclitaxel treatment, expression of 49 miRs was significantly altered. Within these miRs, the most markedly expression-changed were miR-31-star, miR-1264, miR-3150b-5p and miR-210. While the miRs putatively modulated the mRNA expression of the most significantly expression-altered genes were miR-1264, miR-130a, miR-27b, miR-195, miR-1291, miR-214, miR-1277 and miR-1265, which were obtained by miR target prediction and miRNA target correlation. Collectively, our study might provide potential biomarkers for paclitaxel sensitivity prediction and drug resistance targets in laryngeal cancer patients. PMID:23826416

  17. [Electrostimulation of laryngeal muscles with fluctuating currents in the treatment of patients with unilateral laryngeal paralysis].

    PubMed

    Romanenko, S G; Tokarev, O P; Vasilenko, Iu S

    2001-01-01

    Intralaryngeal electrostimulation of the laryngeal muscles with fluctuating currents with simultaneous mobilization of the arytenoid cartilage and paralysed vocal cord were used in 42 patients with unilateral laryngeal paralysis. The treatment was combined with phonopedic lessons. The control group consisted of 32 patients receiving standard electrostimulation with diadynamic currents. The effect was evaluated by changes in vocal acoustic parameters and stroboscopic parameters. In patients with paramedian fixation of the vocal cords voice improvement was obtained irrespective of electrostimulation type. For patients with intermedian and lateral fixation of the vocal cords more effective was intralaryngeal electrostimulation with fluctuating currents. A good therapeutic effect was achieved in patients with dislocation of the arytenoid cartilage.

  18. Up-regulation of miR-187 modulates the advances of oral carcinoma by targeting BARX2 tumor suppressor

    PubMed Central

    Lin, Shu-Chun; Kao, Shou-Yen; Chang, Jennifer Chen-Yu; Liu, Ying-Chieh; Yu, En-Hao; Tseng, Ssu-Hsueh; Liu, Chung-Ji; Chang, Kuo-Wei

    2016-01-01

    Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide. Aberrations in miRNA regulation are known to play important roles in OSCC pathogenesis. miR-187 was shown to be up-regulated in head and neck malignancies in our previous screening. This study further investigated the oncogenic potential, clinical implications, and targets of miR-187 in OSCC. We observed that miR-187 increased oncogenicity, particularly migration, of OSCC cells. miR-187 expression increased the xenografic tumorigenicity and metastasis in mice. In addition, metastatic human OSCC had higher miR-187 expression than did non-metastatic tumors. Through vigorous screening, we confirmed BarH-like Homeobox 2 (BARX2) gene as an miR-187 target. BARX2 expression suppressed the migration, invasion, anchorage-independent colony formation, and orthotopic tumorigenesis of OSCC cells. The migratory phenotype and neck metastasis induced by miR-187 was rescued by BARX2 expression. BARX2 expression was down-regulated in the vast majority of OSCC, and this down-regulation was particularly conspicuous in tumors with advanced nodal metastasis. In addition, plasma miR-187 was significantly higher in OSCC patients than in normal individuals. This study highlights the roles of miR-187-BARX2 in driving the carcinogenesis of OSCC. The results suggest that miR-187 is a potential serological marker for OSCC and that targeting of miR-187 might prove effective in attenuating nodal metastasis. PMID:27542258

  19. Preoperative Intensity Modulated Radiation Therapy and Chemotherapy for Locally Advanced Vulvar Carcinoma: Analysis of Pattern of Relapse

    SciTech Connect

    Beriwal, Sushil; Shukla, Gaurav; Shinde, Ashwin; Heron, Dwight E.; Kelley, Joseph L.; Edwards, Robert P.; Sukumvanich, Paniti; Richards, Scott; Olawaiye, Alexander B.; Krivak, Thomas C.

    2013-04-01

    Purpose: To examine clinical outcomes and relapse patterns in locally advanced vulvar carcinoma treated using preoperative chemotherapy and intensity modulated radiation therapy (IMRT). Methods and Materials: Forty-two patients with stage I-IV{sub A} (stage I, n=3; stage II, n=13; stage III, n=23; stage IV{sub A}, n=3) vulvar cancer were treated with chemotherapy and IMRT via a modified Gynecological Oncology Group schema using 5-fluorouracil and cisplatin with twice-daily IMRT during the first and last weeks of treatment or weekly cisplatin with daily radiation therapy. Median dose of radiation was 46.4 Gy. Results: Thirty-three patients (78.6%) had surgery for resection of vulva; 13 of these patients also had inguinal lymph node dissection. Complete pathologic response was seen in 48.5% (n=16) of these patients. Of these, 15 had no recurrence at a median time of 26.5 months. Of the 17 patients with partial pathological response, 8 (47.1%) developed recurrence in the vulvar surgical site within a median of 8 (range, 5-34) months. No patient had grade ≥3 chronic gastrointestinal/genitourinary toxicity. Of those having surgery, 8 (24.2%) developed wound infections requiring debridement. Conclusions: Preoperative chemotherapy/IMRT was well tolerated, with good pathologic response and clinical outcome. The most common pattern of recurrence was local in patients with partial response, and strategies to increase pathologic response rate with increasing dose or adding different chemotherapy need to be explored to help further improve outcomes.

  20. Proteomic Analysis of Matched Formalin-Fixed, Paraffin-Embedded Specimens in Patients with Advanced Serous Ovarian Carcinoma

    PubMed Central

    Smith, Ashlee L.; Sun, Mai; Bhargava, Rohit; Stewart, Nicolas A.; Flint, Melanie S.; Bigbee, William L.; Krivak, Thomas C.; Strange, Mary A.; Cooper, Kristine L.; Zorn, Kristin K.

    2013-01-01

    Objective: The biology of high grade serous ovarian carcinoma (HGSOC) is poorly understood. Little has been reported on intratumoral homogeneity or heterogeneity of primary HGSOC tumors and their metastases. We evaluated the global protein expression profiles of paired primary and metastatic HGSOC from formalin-fixed, paraffin-embedded (FFPE) tissue samples. Methods: After IRB approval, six patients with advanced HGSOC were identified with tumor in both ovaries at initial surgery. Laser capture microdissection (LCM) was used to extract tumor for protein digestion. Peptides were extracted and analyzed by reversed-phase liquid chromatography coupled to a linear ion trap mass spectrometer. Tandem mass spectra were searched against the UniProt human protein database. Differences in protein abundance between samples were assessed and analyzed by Ingenuity Pathway Analysis software. Immunohistochemistry (IHC) for select proteins from the original and an additional validation set of five patients was performed. Results: Unsupervised clustering of the abundance profiles placed the paired specimens adjacent to each other. IHC H-score analysis of the validation set revealed a strong correlation between paired samples for all proteins. For the similarly expressed proteins, the estimated correlation coefficients in two of three experimental samples and all validation samples were statistically significant (p < 0.05). The estimated correlation coefficients in the experimental sample proteins classified as differentially expressed were not statistically significant. Conclusion: A global proteomic screen of primary HGSOC tumors and their metastatic lesions identifies tumoral homogeneity and heterogeneity and provides preliminary insight into these protein profiles and the cellular pathways they constitute.

  1. Survival analysis of patients with advanced-stage nasopharyngeal carcinoma according to the Epstein-Barr virus status

    PubMed Central

    Peng, Hao; Chen, Lei; Zhang, Yuan; Guo, Rui; Li, Wen-Fei; Mao, Yan-Ping; Tan, Ling-Long; Sun, Ying; Zhang, Fan; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Ma, Jun

    2016-01-01

    Purpose The main aim of this study is to analyze the prognostic differences in nasopharyngeal carcinoma (NPC) patients who are positive and negative for Epstein-Barr virus (EBV). Results Of the 1106 patients, 248 (22.4%) had undetectable pre-treatment plasma EBV DNA levels. The total distant metastasis rate for EBV-negative group vs. EBV-positive group were 3.6% (9/248) vs. 15.0% (128/858) (P < 0.001). The estimated 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) for EBV-negative group vs. EBV-positive group were 88.9% vs. 76.9% (P < 0.001), 93.6% vs. 85.9% (P = 0.001), 96.7% vs. 84.8% (P < 0.001) and 94.1% vs. 90.0% (P = 0.1), respectively. Multivariate analysis revealed that the EBV status was an independent prognostic factor for DFS (HR, 1.813; 95% CI, 1.219-2.695; P = 0.003), OS (HR, 1.828; 95% CI, 1.075-3.107; P = 0.026) and DMFS (HR, 3.678; 95% CI, 1.859-7.277; P <0.001), and overall stage still remained the most important prognostic factor in patients with stage III-IVB NPC. Methods and Materials Data on 1106 patients with non-metastatic, histologically proven advanced-stage (III-IVB) NPC who underwent intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. Patient survival between different EBV status groups were compared. Conclusions EBV status was an independent prognostic factor for patients with stage III–IVB NPC. Neoadjuvant chemotherapy (NCT) plus concurrent chemoradiotherapy (CCRT) should be better treatment regimen for EBV-positive patients since distant metastasis was the main failure pattern, and CCRT may be enough for EBV-negative patients. PMID:27008701

  2. Second-line ramucirumab therapy for advanced hepatocellular carcinoma (REACH): an East Asian and non-East Asian subgroup analysis

    PubMed Central

    Park, Joon Oh; Ryoo, Baek-Yeol; Yen, Chia-Jui; Kudo, Masatoshi; Yang, Ling; Abada, Paolo B.; Cheng, Rebecca; Orlando, Mauro; Zhu, Andrew X.; Okusaka, Takuji

    2016-01-01

    Purpose REACH investigated second-line ramucirumab therapy for advanced hepatocellular carcinoma. Results Median overall survival was 8.2 months for ramucirumab and 6.9 months for placebo (HR, 0.835; 95% CI, 0.634–1.100; p = 0.2046) for East Asians, and 10.1 months for ramucirumab and 8.0 months for placebo (HR, 0.895; 95% CI, 0.690–1.161; p = 0.4023) for non-East Asians. Median overall survival in patients with baseline alpha-fetoprotein ≥ 400 ng/mL was 7.8 months for ramucirumab and 4.2 months for placebo (HR, 0.749; 95% CI, 0.519–1.082; p = 0.1213) for East Asians (n = 139), and 8.2 months for ramucirumab and 4.5 months for placebo (HR, 0.579; 95% CI, 0.371–0.904; p = 0.0149) for non-East Asians (n = 111). The most common grade ≥ 3 treatment-emergent adverse events in East Asians and non-East Asians included hypertension and malignant neoplasm progression. Materials and methods A post-hoc analysis of East Asians (N = 252) and non-East Asians (N = 313) in the intent-to-treat population was performed. Conclusions In East Asians and non-East Asians, ramucirumab did not significantly prolong overall survival. In patients with baseline alpha-fetoprotein ≥ 400 ng/mL, a potentially larger survival benefit was observed in both subgroups. Safety for East Asians was similar to non-East Asians. PMID:27776351

  3. Prevalence of regional and distant metastasis in cats with advanced oral squamous cell carcinoma: 49 cases (2005-2011).

    PubMed

    Soltero-Rivera, Maria M; Krick, Erika L; Reiter, Alexander M; Brown, Dorothy C; Lewis, John R

    2014-02-01

    The objective of this study was to evaluate the prevalence of regional and distant metastasis in cats with advanced oral squamous cell carcinoma (SCC) in a retrospective case series. Forty-nine cats with cytologically- or histopathologically-confirmed oral SCC presented to the Matthew J Ryan Veterinary Hospital of the University of Pennsylvania. History, clinical and laboratory results, diagnostic imaging findings and survival times were obtained from the medical records of patients who received diagnostic evaluation for metastasis. The prevalence of metastasis was assessed by means of mandibular lymph node cytology and three-view thoracic radiography. The prevalence of mandibular lymph node metastasis was 31% (15/49). Evidence of possible thoracic metastasis was seen in 10% (5/49) of cases. Of the patients with mandibular lymph node metastasis, 53% (8/15) were maxillary, 27% mandibular (4/15), 13% sublingual (2/15) and 7% caudal pharyngeal (1/15). Pulmonary metastasis was seen in three mandibular, one maxillary and one sublingual mass. Forty-one patients died or were euthanased owing to progression of local disease, and seven patients were lost to follow-up. The prevalence of regional metastasis in this study was more common than most previously reported studies, while the rate of pulmonary metastasis was higher than has previously been published. Although significant conclusions cannot be drawn, control of the primary tumor, regardless of tumor size at diagnosis, appears to be an important factor in improving survival time, and therefore treatment of metastasis may be important in those cases where long-term control of the primary tumor is possible.

  4. Sorafenib Tosylate With or Without Doxorubicin Hydrochloride in Treating Patients With Locally Advanced or Metastatic Liver Cancer

    ClinicalTrials.gov

    2016-12-30

    Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma; BCLC Stage D Adult Hepatocellular Carcinoma; Localized Non-Resectable Adult Liver Carcinoma; Recurrent Adult Liver Carcinoma

  5. Concomitant endometrial and gallbladder metastasis in advanced multiple metastatic invasive lobular carcinoma of the breast: A rare case report

    PubMed Central

    Bezpalko, Kseniya; Mohamed, Mohamed A.; Mercer, Leo; McCann, Michael; Elghawy, Karim; Wilson, Kenneth

    2015-01-01

    Introduction At time of presentation, fewer than 10% of patients have metastatic breast cancer. The most common sites of metastasis in order of frequency are bone, lung, pleura, soft tissue, and liver. Breast cancer metastasis to the uterus or gallbladder is rare and has infrequently been reported in the English literature. Presentation of case A 47 year old female with a recent history of thrombocytopenia presented with abnormal vaginal bleeding. Pelvic ultrasound revealed multiple uterine fibroids and endometrial curettings revealed cells consistent with lobular carcinoma of the breast. Breast examination revealed edema and induration of the lower half of the right breast. Biopsy of the right breast revealed invasive lobular carcinoma. Bone marrow aspiration obtained at a previous outpatient visit revealed extensive involvement by metastatic breast carcinoma. Shortly after discharge, the patient presented with acute cholecystitis and underwent cholecystectomy. Microscopic examination of the gallbladder revealed metastatic infiltrating lobular carcinoma. The final diagnosis was invasive lobular carcinoma of the right breast with metastasis to the bone marrow, endometrium, gallbladder, regional lymph nodes, and peritoneum. Discussion The growth pattern of invasive lobular carcinoma of the breast is unique and poses a challenge in diagnosing the cancer at an early stage. Unlike other types of breast cancer, it tends to metastasize more to the peritoneum, ovary, and gastrointestinal tract. Metastasis to the endometrium or gallbladder is rare. Conclusion Metastatic spread should be considered in the differential diagnosis of patients with invasive lobular breast carcinoma presenting with abnormal vaginal bleeding or acute cholecystitis. PMID:26275738

  6. Feasibility of gemcitabine and oxaliplatin in patients with advanced biliary tract carcinoma and a performance status of 2.

    PubMed

    Mir, Olivier; Coriat, Romain; Dhooge, Marion; Perkins, Géraldine; Boudou-Rouquette, Pascaline; Brezault, Catherine; Ropert, Stanislas; Durand, Jean-Philippe; Chaussade, Stanislas; Goldwasser, François

    2012-08-01

    The use of gemcitabine and oxaliplatin is well documented in selected patients with advanced biliary tract carcinoma (BTC), but little is known on the feasibility of systemic treatments in patients with a performance status (PS) of 2. We retrospectively examined the medical records of consecutive BTC patients with a PS of 2 receiving gemcitabine 1000 mg/m(2) plus oxaliplatin 100 mg/m(2) every 2 weeks from January 2003 to December 2011 in our institution. Body composition was analysed by computed tomography scan to detect sarcopenia. The primary evaluation criterion was safety. The secondary evaluation criteria were the response rate, progression-free survival (PFS) and overall survival (OS). Twenty-eight patients (median age: 63 years, range 41-83) received a total of 175 cycles (median per patient: 6, range 2-12). Ten patients (35.7%) had sarcopenia on the pretreatment computed tomography scan. The most frequent toxicities were thrombocytopenia (grades 2-4: n=4, 14.3%), peripheral neuropathy (grades 2-3: n=9, 32.1%) and cholangitis (n=4, 14.3%). The best response was a partial response in 10.7% of patients [95% confidence interval (CI): 0-22.2] and stable disease in 42.9% of patients. The median PFS and OS were 4.6 (95% CI: 2.5-6.3) and 7.5 (95% CI: 5.2-9.5) months, respectively. The median PFS and OS were significantly longer in patients without sarcopenia: 7.0 months (95% CI: 4.4-8.0) vs. 2.2 months (95% CI: 2.0-2.5), P less than 0.01, and 10.4 months (95% CI: 7.5-11.6) vs. 4.9 months (95% CI: 3.7-5.2), P less than 0.01, respectively. In our experience, gemcitabine-oxaliplatin was feasible and induced effective palliation in PS2 patients with advanced BTC. Further studies are warranted to confirm these findings.

  7. Laryngeal Structure and Function in the Pediatric Larynx: Clinical Applications

    ERIC Educational Resources Information Center

    Sapienza, Christine M.; Ruddy, Bari Hoffman; Baker, Susan

    2004-01-01

    This article presents an overview of the normal anatomy and physiology of the pediatric larynx, followed by some examples of pediatric voice disorders that were chosen to exemplify the alterations to the laryngeal anatomy and the subsequent modifications to laryngeal function. Vocal fold nodules are primarily reviewed due to their high incidence…

  8. Laryngeal structure and function in dogs with cough.

    PubMed

    Johnson, Lynelle R

    2016-07-15

    OBJECTIVE To investigate the prevalence and type of laryngeal abnormalities in dogs examined because of cough that did not have signs of upper airway disease and to compare the prevalence of those abnormalities among dogs with various respiratory tract diseases. DESIGN Prospective study. ANIMALS 138 dogs with cough that did not have signs of upper airway disease. PROCEDURES The study was conducted between July 2001 and October 2014 and included dogs examined for cough that had laryngoscopic and bronchoscopic examinations performed by 1 examiner. Laryngeal hyperemia and swelling were recorded, and laryngeal function was assessed before and after doxapram stimulation when indicated. Results were compared among dogs on the basis of cough duration (acute [< 2 weeks], subacute [2 weeks to 2 months], and chronic [> 2 months]) and disease diagnosed (inflammatory airway disease, airway collapse, lower respiratory tract infection, and eosinophilic bronchopneumopathy). RESULTS Laryngeal hyperemia was detected in 73 of 134 (54%) dogs with cough of subacute or chronic duration, and its prevalence did not vary significantly among dogs with various diseases. Thirteen dogs had laryngeal paresis, and 13 dogs had laryngeal paralysis; dysphonia (n = 2) and stridor (1) were uncommon findings in those dogs. The prevalence of laryngeal dysfunction (paresis or paralysis) did not differ significantly among diseases. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that 26 of 138 (19%) dogs examined because of cough alone had laryngeal dysfunction, which suggested that a complete laryngoscopic examination should be included in the diagnostic evaluation of dogs with cough.

  9. Using Laryngeal Electromyography to Differentiate Presbylarynges from Paresis

    ERIC Educational Resources Information Center

    Stager, Sheila V.; Bielamowicz, Steven A.

    2010-01-01

    Purpose: Differential diagnosis of patients over 64 years of age reporting hoarseness is challenging. Laryngeal electromyography (LEMG) was used to determine the status of the recurrent and superior laryngeal nerves. The authors hypothesized that individuals with hoarseness but normal LEMG would have measures similar to those of patients from…

  10. 21 CFR 874.3730 - Laryngeal prosthesis (Taub design).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3730 Laryngeal prosthesis (Taub design). (a) Identification. A laryngeal prosthesis (Taub design) is a device intended to direct... device is interposed between openings in the trachea and the esophagus and may be removed and...

  11. 21 CFR 874.3730 - Laryngeal prosthesis (Taub design).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3730 Laryngeal prosthesis (Taub design). (a) Identification. A laryngeal prosthesis (Taub design) is a device intended to direct... device is interposed between openings in the trachea and the esophagus and may be removed and...

  12. Quantitative PCR Analysis of Laryngeal Muscle Fiber Types

    ERIC Educational Resources Information Center

    Van Daele, Douglas J.

    2010-01-01

    Voice and swallowing dysfunction as a result of recurrent laryngeal nerve paralysis can be improved with vocal fold injections or laryngeal framework surgery. However, denervation atrophy can cause late-term clinical failure. A major determinant of skeletal muscle physiology is myosin heavy chain (MyHC) expression, and previous protein analyses…

  13. 21 CFR 874.3730 - Laryngeal prosthesis (Taub design).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Laryngeal prosthesis (Taub design). 874.3730 Section 874.3730 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3730 Laryngeal...

  14. 21 CFR 874.3730 - Laryngeal prosthesis (Taub design).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Laryngeal prosthesis (Taub design). 874.3730 Section 874.3730 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3730 Laryngeal...

  15. 21 CFR 874.3730 - Laryngeal prosthesis (Taub design).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Laryngeal prosthesis (Taub design). 874.3730 Section 874.3730 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3730 Laryngeal...

  16. Denileukin Diftitox Used in Treating Patients With Advanced Refractory Ovarian Cancer, Primary Peritoneal Carcinoma, or Epithelial Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-05-02

    Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  17. Central nervous system control of the laryngeal muscles in humans

    PubMed Central

    Ludlow, Christy L.

    2005-01-01

    Laryngeal muscle control may vary for different functions such as: voice for speech communication, emotional expression during laughter and cry, breathing, swallowing, and cough. This review discusses the control of the human laryngeal muscles for some of these different functions. Sensori-motor aspects of laryngeal control have been studied by eliciting various laryngeal reflexes. The role of audition in learning and monitoring ongoing voice production for speech is well known; while the role of somatosensory feedback is less well understood. Reflexive control systems involving central pattern generators may contribute to swallowing, breathing and cough with greater cortical control during volitional tasks such as voice production for speech. Volitional control is much less well understood for each of these functions and likely involves the integration of cortical and subcortical circuits. The new frontier is the study of the central control of the laryngeal musculature for voice, swallowing and breathing and how volitional and reflexive control systems may interact in humans. PMID:15927543

  18. An unusual course of the left recurrent laryngeal nerve.

    PubMed

    Khaki, Amir A; Tubbs, R Shane; Shoja, Mohammadali M; Zarrintan, Sina

    2007-04-01

    Variation in the course of the left recurrent laryngeal nerve is seemingly very rare. During the routine dissection of an adult male cadaver, the entire left recurrent laryngeal nerve after branching from the left vagus nerve was noted to travel medial to the ligamentum arteriosum. We hypothesize that this rare variation may occur, if the left recurrent laryngeal nerve passes inferior to the fifth rather than the sixth aortic arch during embryological development. As our case report demonstrates, the relationship between the ligamentum arteriosum and the left recurrent laryngeal nerve is not absolute. Although seemingly rare, cardiothoracic surgeons must consider variations of the left recurrent laryngeal nerve during surgical procedures in the region of the ligamentum arteriosum in order to minimize potential postoperative complications.

  19. Laryngeal Elevation Velocity and Aspiration in Acute Ischemic Stroke Patients

    PubMed Central

    Zhang, Jing; Zhou, Yun; Wei, Na; Yang, Bo; Wang, Anxin; Zhou, Hai; Zhao, Xingquan; Wang, Yongjun; Liu, Liping; Ouyoung, Melody; Villegas, Brenda; Groher, Michael

    2016-01-01

    Objectives Aspiration after stroke has been associated with aspiration pneumonia, which contributes to increased mortality of stroke. Laryngeal elevation is a core mechanism for protection from aspiration. Few studies have explored the predictive value of laryngeal elevation velocity for aspiration after stroke. This study aimed to explore the ability of laryngeal elevation velocity to predict aspiration in patients with acute ischemic stroke. Methods This was a prospective cohort study that included consecutive acute ischemic stroke patients treated at a teaching hospital during a 10-month period. Patients underwent magnetic resonance imaging (MRI) to confirm the diagnosis of acute ischemic stroke. Patients who were at risk of aspiration and could swallow 5 ml of diluted barium (40%, w/v) for a videofluoroscopic swallowing (VFS) study were included. The association between abnormal indices in the oral and pharyngeal phase of the VFS study and aspiration was examined using univariate analyses. These indices included the lip closure, tongue movement and control, laryngeal elevation velocity and range, the latency of pharyngeal swallowing, pharyngeal transit time (PTT), abnormal epiglottis tilt, residual barium in the pharynx, and the duration of upper esophageal sphincter (UES) opening. The laryngeal elevation velocity (%/s) was calculated as the range of laryngeal elevation (%) from the resting position to the maximum superior position or to the position where the laryngeal vestibule is fully closed divided by the corresponding duration of laryngeal elevation. The range of laryngeal elevation (%) was the percentage calculated as the distance between the resting laryngeal position and the maximum superior excursion position or position where the laryngeal vestibule is fully closed divided by the distance between the resting laryngeal position and the lowest edge of the mandible. A logistic regression analysis was used to determine the predictive value for aspiration

  20. 9 CFR 310.15 - Disposition of thyroid glands and laryngeal muscle tissue.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... laryngeal muscle tissue. 310.15 Section 310.15 Animals and Animal Products FOOD SAFETY AND INSPECTION... of thyroid glands and laryngeal muscle tissue. (a) Livestock thyroid glands and laryngeal muscle tissue shall not be used for human food. (b) Livestock thyroid glands and laryngeal muscle tissue may...

  1. 9 CFR 310.15 - Disposition of thyroid glands and laryngeal muscle tissue.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... laryngeal muscle tissue. 310.15 Section 310.15 Animals and Animal Products FOOD SAFETY AND INSPECTION... of thyroid glands and laryngeal muscle tissue. (a) Livestock thyroid glands and laryngeal muscle tissue shall not be used for human food. (b) Livestock thyroid glands and laryngeal muscle tissue may...

  2. 9 CFR 310.15 - Disposition of thyroid glands and laryngeal muscle tissue.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... laryngeal muscle tissue. 310.15 Section 310.15 Animals and Animal Products FOOD SAFETY AND INSPECTION... of thyroid glands and laryngeal muscle tissue. (a) Livestock thyroid glands and laryngeal muscle tissue shall not be used for human food. (b) Livestock thyroid glands and laryngeal muscle tissue may...

  3. 9 CFR 310.15 - Disposition of thyroid glands and laryngeal muscle tissue.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... laryngeal muscle tissue. 310.15 Section 310.15 Animals and Animal Products FOOD SAFETY AND INSPECTION... of thyroid glands and laryngeal muscle tissue. (a) Livestock thyroid glands and laryngeal muscle tissue shall not be used for human food. (b) Livestock thyroid glands and laryngeal muscle tissue may...

  4. 9 CFR 310.15 - Disposition of thyroid glands and laryngeal muscle tissue.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... laryngeal muscle tissue. 310.15 Section 310.15 Animals and Animal Products FOOD SAFETY AND INSPECTION... of thyroid glands and laryngeal muscle tissue. (a) Livestock thyroid glands and laryngeal muscle tissue shall not be used for human food. (b) Livestock thyroid glands and laryngeal muscle tissue may...

  5. FADD Expression as a Prognosticator in Early-Stage Glottic Squamous Cell Carcinoma of the Larynx Treated Primarily With Radiotherapy

    SciTech Connect

    Schrijvers, Michiel L.; Pattje, Wouter J.; Slagter-Menkema, Lorian; Mastik, Mirjam F.; Gibcus, Johan H.; Langendijk, Johannes A.; Wal, Jacqueline E. van der; Laan, Bernard F.A.M. vn der

    2012-07-15

    Purpose: We recently reported on the identification of the Fas-associated death domain (FADD) as a possible driver of the chromosome 11q13 amplicon and the association between increased FADD expression and disease-specific survival in advanced-stage laryngeal carcinoma. The aim of this study was to examine whether expression of FADD and its Ser194-phosphorylated isoform (pFADD) predicts local control in patients with early-stage glottic carcinoma primarily treated with radiotherapy only. Methods and Materials: Immunohistochemical staining for FADD and pFADD was performed on pretreatment biopsy specimens of 92 patients with T1-T2 glottic squamous cell carcinoma primarily treated with radiotherapy between 1996 and 2005. Cox regression analysis was used to correlate expression levels with local control. Results: High levels of pFADD were associated with significantly better local control (hazard ratio, 2.40; 95% confidence interval, 1.04-5.55; p = 0.040). FADD overexpression showed a trend toward better local control (hazard ratio, 3.656; 95% confidence interval, 0.853-15.663; p = 0.081). Multivariate Cox regression analysis showed that high pFADD expression was the best predictor of local control after radiotherapy. Conclusions: This study showed that expression of phosphorylated FADD is a new prognostic biomarker for better local control after radiotherapy in patients with early-stage glottic carcinomas.

  6. Expression and clinical significance of the Kv3.4 potassium channel subunit in the development and progression of head and neck squamous cell carcinomas.

    PubMed

    Menéndez, Sofía Tirados; Rodrigo, Juan P; Allonca, Eva; García-Carracedo, Darío; Alvarez-Alija, Gustavo; Casado-Zapico, Sara; Fresno, Manuel F; Rodríguez, Carmen; Suárez, Carlos; García-Pedrero, Juana M

    2010-08-01

    The concept of ion channels as membrane therapeutic targets and diagnostic/prognostic biomarkers has attracted growing attention. We therefore investigated the expression pattern and clinical significance of the Kv3.4 potassium channel subunit during the development and progression of head and neck squamous cell carcinomas (HNSCCs). KCNC4 mRNA levels were determined by real-time RT-PCR in both HNSCC tissue specimens and derived cell lines. Kv3.4 protein expression was evaluated by immunohistochemistry in paraffin-embedded tissue specimens from 84 patients with laryngeal/pharyngeal squamous cell carcinomas and 67 patients with laryngeal dysplasias. Molecular alterations were correlated with clinicopathological parameters and patient outcome. Increased KCNC4 mRNA levels were found in 15 (54%) of 28 tumours, compared to the corresponding normal epithelia and varied mRNA levels were detected in 12 HNSCC-derived cell lines analysed. Increased Kv3.4 protein expression was observed in 34 (40%) of 84 carcinomas and also at early stages of HNSCC tumourigenesis. Thus, 35 (52%) of 67 laryngeal lesions displayed Kv3.4-positive staining in the dysplastic areas, whereas both stromal cells and normal adjacent epithelia exhibited negligible expression. No significant correlations were found between Kv3.4-positive expression in HNSCC and clinical data; however, Kv3.4 expression tended to diminish in advanced-stage tumours. Interestingly, patients carrying Kv3.4-positive dysplasias experienced a significantly higher laryngeal cancer incidence than did those with negative lesions (p = 0.0209). In addition, functional studies using HNSCC cells revealed that inhibition of Kv3.4 expression by siRNA leads to the inhibition of cell proliferation via selective cell cycle arrest at the G2/M phase without affecting apoptosis. Collectively, these data demonstrate for the first time that Kv3.4 expression is frequently increased during HNSCC tumourigenesis and correlated significantly with a

  7. Structural Organization of the Laryngeal Motor Cortical Network and Its Implication for Evolution of Speech Production

    PubMed Central

    Kumar, Veena; Croxson, Paula L.

    2016-01-01

    The laryngeal motor cortex (LMC) is essential for the production of learned vocal behaviors because bilateral damage to this area renders humans unable to speak but has no apparent effect on innate vocalizations such as human laughing and crying or monkey calls. Several hypotheses have been put forward attempting to explain the evolutionary changes from monkeys to humans that potentially led to enhanced LMC functionality for finer motor control of speech production. These views, however, remain limited to the position of the larynx area within the motor cortex, as well as its connections with the phonatory brainstem regions responsible for the direct control of laryngeal muscles. Using probabilistic diffusion tractography in healthy humans and rhesus monkeys, we show that, whereas the LMC structural network is largely comparable in both species, the LMC establishes nearly 7-fold stronger connectivity with the somatosensory and inferior parietal cortices in humans than in macaques. These findings suggest that important “hard-wired” components of the human LMC network controlling the laryngeal component of speech motor output evolved from an already existing, similar network in nonhuman primates. However, the evolution of enhanced LMC–parietal connections likely allowed for more complex synchrony of higher-order sensorimotor coordination, proprioceptive and tactile feedback, and modulation of learned voice for speech production. SIGNIFICANCE STATEMENT The role of the primary motor cortex in the formation of a comprehensive network controlling speech and language has been long underestimated and poorly studied. Here, we provide comparative and quantitative evidence for the significance of this region in the control of a highly learned and uniquely human behavior: speech production. From the viewpoint of structural network organization, we discuss potential evolutionary advances of enhanced temporoparietal cortical connections with the laryngeal motor cortex in