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1.
Cancer Diagn Progn ; 4(2): 105-110, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38434924

RESUMO

Background/Aim: There is limited evidence about the significance of head and neck surgical observation at the time of diagnosis and follow-up of oral cancer after treatment. The aim of this study was to elucidate the prognosis and prognostic factors of oral squamous cell carcinoma (OSCC), analyze cases of double cancers, and highlight the importance of examinations during both diagnosis and post-treatment for OSCC. Patients and Methods: We performed a retrospective analysis of 272 OSCC cases treated for the first time during a 10-year period from April 2013 to March 2023 at Kyushu University Hospital. Information obtained in the clinical setting, such as age, stage, prognosis, and presence of double cancers, was used in the analysis. Results: The mean age of 272 patients was 69 years; 203 patients were males and 69 were females. The most common oral cancer sites were the tongue (54.4%). The 5-year overall survival rate was 63.8%. Double cancer was found in 93 patients (34.2%). Synchronous double cancers were found in 38 patients (14.0%), 50% of whose cancer types were head and neck cancers. Conclusion: We analyzed 272 OSCC patients treated at the Kyushu University Hospital, and the results were comparable to those reported by other institutions. Tumor site, age, and stage were identified as prognostic factors. Half of the patients with synchronous double cancers had head and neck cancer, and 3-10% of patients with double cancers after treatment for OSCC also had head and neck cancer, suggesting the importance of otorhinolaryngological observation at the time of the diagnosis and after treatment.

2.
J Immunother ; 47(3): 89-97, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38297883

RESUMO

In the tumor microenvironment, wherein cytotoxic lymphocytes interact with cancer cells, lymphocyte exhaustion, an immune checkpoint inhibitor target, is promoted. However, the efficacy of these inhibitors is limited, and improving response rates remains challenging. We previously reported that protein tyrosine phosphatase nonreceptor type (PTPN) 3 is a potential immune checkpoint molecule for activated lymphocytes and that PTPN3 inhibition should be a focus area for cancer immunotherapy development. Therefore, in this study, we focused on PTPN3-suppressive therapy in terms of lymphocyte exhaustion under hypoxic conditions, which are a cancer microenvironment, and investigated measures for improving the response to anti-programmed death receptor (PD)-1 antibody drugs. We found that PTPN3 expression was upregulated in activated lymphocytes under hypoxic conditions, similar to the findings for other immune checkpoint molecules, such as PD-1, T cell immunoglobulin mucin-3, and lymphocyte-activation gene-3; furthermore, it functioned as a lymphocyte exhaustion marker. In addition, PTPN3-suppressed activated lymphocytes promoted the mammalian target of rapamycin (mTOR)-Akt signaling pathway activation and enhanced proliferation, migration, and cytotoxic activities under hypoxic conditions. Furthermore, PTPN3 suppression in activated lymphocytes increased PD-1 expression and enhanced the antitumor effects of anti-PD-1 antibody drugs against head and neck cancer in vitro and in vivo. These results suggest that the suppression of PTPN3 expression in activated lymphocytes enhances the therapeutic effect of anti-PD-1 antibody drugs in head and neck cancer, especially under hypoxic conditions that cause lymphocyte exhaustion.


Assuntos
Antineoplásicos , Neoplasias de Cabeça e Pescoço , Humanos , Receptor de Morte Celular Programada 1 , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Linfócitos/metabolismo , Imunoterapia , Microambiente Tumoral , Proteína Tirosina Fosfatase não Receptora Tipo 3/metabolismo
3.
Sci Rep ; 13(1): 19636, 2023 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-37949965

RESUMO

Squamous cell carcinoma of the external auditory canal (EACSCC) is an extraordinarily rare and aggressive malignant disease. Establishment of EACSCC cell line with robust molecular characteristics is essential for the basic and translational research of EACSCC. Here, we show the newly established EACSCC cell line SCEACono2, derived from a patient with well-to-moderately differentiated EACSCC. We analyzed histologic and genetic features of SCEACono2 hiring multiple experiments, including next-generation sequencing (NGS). Immunocytochemical staining of SCEACono2 showed positivity of p53 and SCC1/2. Furthermore, SCEACono2 exhibited a unique characteristic that cytokeratin, vimentin as well as cancer stem cell markers (CD44, CD133, ALP and Oct3/4) were positive. SCEACono2 had an ability to form tumors at the temporal lesion xenograft nude mice model. NGS revealed that SCEACono2 harbored the somatic mutations of TP53 (p.G245S) and NOTCH1 (p.A465T). RNA-seq and downstream bioinformatics analysis revealed significant enrichment of genes involved in inflammation and cell adhesion in SCEACono2 compared to SCC-9 and HSC-4. STR profiling indicated no evidence of cross-contamination. In conclusion, SCEACono2 could serves as a promising and robust research resource of EACSCC in vitro and in vivo.


Assuntos
Carcinoma de Células Escamosas , Meato Acústico Externo , Camundongos , Animais , Humanos , Meato Acústico Externo/patologia , Camundongos Nus , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Células-Tronco Neoplásicas/patologia
4.
In Vivo ; 37(5): 2188-2196, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37652513

RESUMO

BACKGROUND/AIM: Pembrolizumab monotherapy and pembrolizumab with chemotherapy (combination therapy) are standard treatments for recurrent and metastatic head and neck squamous cell carcinoma (R/M-HNSCC). This study aimed to explore which of the two, pembrolizumab monotherapy or combination therapy is superior for long-term use. PATIENTS AND METHODS: Participants of the study were 139 patients with histologically confirmed squamous cell carcinoma who had been treated with pembrolizumab monotherapy or combination therapy at the Kyushu University and related facilities. We analysed differences regarding long-term survival rate and adverse events (AEs) between the pembrolizumab monotherapy and combination therapy groups. RESULTS: The overall 2-year progression-free survival and 2-year overall survival were 28.6% and 41.8%, respectively; these results were not significantly different between the two groups. Patients in the monotherapy group with AEs had a significantly better prognosis than those without AEs (in both the monotherapy and combination therapy groups). In the combination therapy group, there was no difference in prognosis between those with AEs and those without AEs (p=0.636). CONCLUSION: Considering the treatment of R/M-HNSCC from a long-term perspective, we identified that it is better to use pembrolizumab as monotherapy than to use it in combination with chemotherapy. Combination therapy did not improve prognosis; moreover, it can also cause additional adverse effects.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
5.
In Vivo ; 37(5): 2147-2154, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37652518

RESUMO

BACKGROUND/AIM: In recent years, individual patient cancer genomic profiling (CGP) has become more accessible, allowing determination of therapeutic strategies using driver gene mutations in cancer therapy. However, this precision oncology approach, tailored to specific patients, remains experimental. In this study, we verified the feasibility and benefit of using CGP to guide treatment of malignant head and neck tumors. We aimed to evaluate the profiling and clinical courses of patients with head and neck malignancies who underwent CGP and determine the extent to which CGP for head and neck malignancies has resulted in beneficial drug administration. PATIENTS AND METHODS: We analyzed CGP results, prognosis, and drug administration status in 27 patients. These patients had completed (or were expected to complete) standard therapy or had rare cancers without standard therapy. RESULTS: At least one somatic actionable gene alteration was seen in 25 (92.6%) patients, with a median number of actionable alterations per patient of 4 (range=0-11). Drugs in clinical trials were recommended to 22 (81.5%) patients, but none could participate. However, 3 patients (11.1%) could use approved drugs off-label based on CGP results. The most common genetic abnormality was TP53 (66.7%), with TP53 mutations leading to poor prognosis. CONCLUSION: CGP is clinically useful and serves as a bridge to increase the number of therapeutic options. However, candidate drugs confirmed using CGP may be ineffective when administered. Therefore, oncologists should not blindly accept CGP therapeutic recommendations but should make recommendations that lead to optimal therapies after proper verification.


Assuntos
Neoplasias de Cabeça e Pescoço , Medicina de Precisão , Humanos , Medicina de Precisão/métodos , Oncologia , Mutação , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Genômica/métodos
6.
Anticancer Res ; 43(1): 183-190, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36585178

RESUMO

BACKGROUND/AIM: Differentiated thyroid cancer (DTC) has a good prognosis, except in the case of patients with radioiodine therapy (RIT)-refractory cancer. However, since DTC is essentially a slowly progressing cancer, it is usually judged to be a DTC with a poor prognosis after multiple RITs and yearly follow-up with echo, computed tomography (CT), and serum thyroglobulin values. This study investigated whether fluorodeoxyglucose-positron emission tomography/CT (FDG PET/CT) combined with initial RIT could identify early-stage patients with poor prognosis. PATIENTS AND METHODS: We evaluated 100 patients with high-risk DTC who underwent total thyroidectomy and received RIT at our institution. We analyzed the clinical outcomes of patients and 18F-FDG accumulation using univariate and multivariate Cox proportional hazards regression models. RESULTS: The 10-year overall survival (OS) was 87.9%, with no significant difference in OS between 18F-FDG accumulation at pre-total or near-total thyroidectomy (NTT) (p=0.180) and 131I accumulation at initial RIT (p=0.577). However, 18F-FDG positive patients had a significantly worse prognosis than negative patients (p=0.005) at initial RIT. CONCLUSION: 18F-FDG PET/CT plays an important role in both the diagnosis and prognostic prediction of RIT refractory disease in DTC patients. 18F-FDG PET/CT can be a useful tool particularly at the time of initial RIT since the 18F-FDG accumulation enables the screening of high-risk DTC with poor prognosis at a very early time stage.


Assuntos
Adenocarcinoma , Neoplasias da Glândula Tireoide , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Radioisótopos do Iodo/uso terapêutico , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/radioterapia , Tomografia por Emissão de Pósitrons , Adenocarcinoma/tratamento farmacológico
7.
Clin Case Rep ; 10(9): e6157, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36177082

RESUMO

Cervical esophageal perforation is rare, but it is associated with high mortality. We describe two patients with cervical esophageal perforation that required surgical treatment. In both cases, good outcomes were evenly achieved, despite the presence of risk factors. A prompt diagnosis and treatment with collaboration between a surgeon and a gastroenterologist are important.

8.
J Neurol Surg B Skull Base ; 83(Suppl 2): e40-e48, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35832936

RESUMO

Objective En bloc and margin-negative surgical resection seems to offer the best prognosis for patients with temporal bone squamous cell carcinoma (TB-SCC). In this study, we summarize the outcomes of surgical cases of advanced TB-SCC (T3-T4) that were managed in two institutions, with an accompanying description of the surgical procedure that was utilized: modified subtotal temporal bone resection (STBR), which involves the en bloc removal of the temporal bone including or transecting the otic capsule. Design This is a case series study with chart review. Setting The study was conducted at two academic tertiary care medical centers. Participants Chart information was collected for all patients who underwent surgical resection of advanced TB-SCC between July 1998 and February 2019. The resulting dataset contained 43 patients with advanced TB-SCC who underwent en bloc resection during the review period. Tumor staging followed the modified Pittsburgh classification. Disease-specific survival (DSS) rates were calculated according to the Kaplan-Meier method. Main Outcome Measure This study shows disease-specific 5-year DSS rate. Results The 5-year DSS rate of the cases who underwent en bloc resection was 79.7%. En bloc lateral temporal bone resection was employed in a total of 25 cases (DSS: 79.0%). En bloc modified STBR was utilized in 18 cases (DSS: 81.7%). Conclusion En bloc margin-negative resection is a reliable treatment strategy for advanced TB-SCC. Modified STBR can be a treatment option for TB-SCC without marked posterior extension.

9.
Cancer Med ; 11(21): 3960-3968, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35352507

RESUMO

There is no useful biomarker to evaluate treatment response and early relapse in head and neck squamous cell carcinoma (HNSCC). Circulating tumor DNA (ctDNA) is a promising biomarker for detecting minimal residual diseases and monitoring treatment effect. We investigated whether individualized ctDNA analysis could help monitor treatment response and relapse in HNSCC. Mutation analysis of tumor and peripheral blood mononuclear cell (PBMC) DNAs of 26 patients with HNSCC was performed using a custom squamous cell carcinoma (SCC) panel. The identified individualized mutated genes were defined as ctDNA candidates. We investigated whether frequent ctDNA monitoring via digital PCR (dPCR) is clinically valid for HNSCC patients. TP53 was the most frequently mutated gene and was detected in 14 of 24 cases (58.2%), wherein two cases were excluded owing to the absence of tumor-specific mutations in the SCC panel. Six cases were excluded because of undesignable and unusable primer-probes for dPCR. Longitudinal ctDNA was monitored in a total of 18 cases. In seven cases, ctDNA tested positive again or did not test negative, and all seven cases relapsed after initial curative treatment. In 11 cases, after initial curative treatment, ctDNA remained negative and patients were alive without recurrence. Patients who remained negative for ctDNA during follow-up after initial curative treatment (n = 11) had a significantly better prognosis than those who reverted to ctDNA positivity (n = 7; p < 0.0001; log-rank test). Individualized ctDNA monitoring using SCC panel and dPCR might be a novel and promising biomarker for HNSCC.


Assuntos
Carcinoma de Células Escamosas , DNA Tumoral Circulante , Neoplasias de Cabeça e Pescoço , Humanos , DNA Tumoral Circulante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Leucócitos Mononucleares , DNA de Neoplasias/genética , Biomarcadores Tumorais/genética , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Mutação , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/genética
10.
Audiol Res ; 11(2): 263-274, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207894

RESUMO

BACKGROUND: There is no guideline for hearing compensation after temporal bone resection. This study aimed to retrospectively analyze surgical cases with reconstruction for hearing preservation after temporal bone malignancy resection and propose a new alternative to compensate for hearing loss. METHODS: We retrospectively reviewed the medical records of 30 patients who underwent lateral temporal bone surgery for temporal bone malignancy at our institution and examined their hearing abilities after surgery. RESULT: The hearing outcomes of patients with an external auditory meatus reconstruction varied widely. The mean postoperative air-bone gap at 0.5, 1, 2, and 4 kHz ranged from 22.5 dB to 71.25 dB. On the other hand, the average difference between the aided sound field thresholds with cartilage conduction hearing aid and bone conduction thresholds at 0.5, 1, 2, and 4 kHz ranged from -3.75 to 41.25. More closely located auricular cartilage and temporal bone resulted in smaller differences between the aided sound field and bone conduction thresholds. CONCLUSIONS: There is still room for improvement of surgical techniques for reconstruction of the auditory meatus to preserve hearing after temporal bone resection. The cartilage conduction hearing aid may provide non-invasive postoperative hearing compensation after lateral temporal bone resection.

11.
Laryngoscope ; 131(12): 2674-2683, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34143491

RESUMO

OBJECTIVES/HYPOTHESIS: The tumor immune microenvironment in temporal bone squamous cell carcinoma (TBSCC), including the programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs), has not been established. STUDY DESIGN: Retrospective cohort study. METHODS: We performed immunohistochemistry analyses to retrospectively analyze 123 TBSCC cases for PD-L1 expression and TILs and their prognostic significance. We also evaluated the prognostic correlations between these immunomarkers and the therapeutic responses to chemoradiotherapy (CRT). RESULTS: PD-L1 expression (≥1%) was detected in 62 (50.4%) TBSCC cases and was significantly associated with worse prognosis: progression-free survival (PFS), P < .0001; overall survival (OS), P = .0009. A high density of CD8+ TILs was significantly associated with better prognosis (PFS, P = .0012; OS, P = .0120). In contrast, a high density of Foxp3+ TILs tended to be associated with an unfavorable prognosis (PFS, P = .0148; OS, P = .0850). With regard to the tumor microenvironment subtypes defined by CD8+ TILs and PD-L1 expression, the CD8low /PD-L1+ group showed significantly worse prognosis. Among the 36 neoadjuvant CRT-treated cases, PD-L1 expression was significantly associated with worse OS (P = .0132). Among the 32 CRT-treated cases without surgery, a high density of CD8+ TILs tended to be more highly associated with complete response to CRT compared to a low density of CD8+ TILs (P = .0702). CONCLUSIONS: These results indicate that the evaluation of the tumor immune microenvironment may contribute to the prediction of prognoses and the selection of an individualized therapeutic strategy for patients with TBSCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2674-2683, 2021.


Assuntos
Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas/imunologia , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Cranianas/imunologia , Osso Temporal/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/análise , Biópsia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias Cranianas/mortalidade , Neoplasias Cranianas/patologia , Neoplasias Cranianas/cirurgia , Osso Temporal/imunologia , Osso Temporal/cirurgia , Microambiente Tumoral/imunologia
12.
Laryngoscope ; 131(8): 1782-1789, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33538330

RESUMO

OBJECTIVE/HYPOTHESIS: Squamous cell carcinoma (SCC) of the temporal bone is an extremely rare condition. This rarity has led to a delay in the establishment of a standard treatment protocol and adequate staging system. Identification of prognostic markers of this disease from a variety of fields is desirable in the establishment of treatment guidelines for temporal bone SCC. The aim of this study is to assess the prognostic role of inflammation-based prognostic scores in cases of temporal bone SCC. STUDY DESIGN: Case reries with chart review. METHODS: A total of 71 cases of primary malignancy eligible for curative treatment at a single tertiary medical institute were retrospectively analyzed. Univariate and multivariate regression analyzes were used to investigate the association between the inflammation-based scores and 5-year overall survival. RESULTS: Univariate Cox regression analyzes showed that a high neutrophil-to-lymphocyte ratio, high platelet-to-lymphocyte ratio, low lymphocyte-to-monocyte ratio, a Glasgow prognostic score of 2, and the systemic inflammation score of 2 were significantly associated with a poor prognosis, as well as a classification of T4 stage, presence of cervical lymph node metastasis, high white blood cell counts, and high C-reactive protein levels. The multivariate analysis showed that a clinical stage of T4 and a systemic inflammation score of 2 were independent prognostic markers. CONCLUSIONS: Inflammation-based prognostic markers are associated with the survival of patients with temporal bone SCC, as well as other head and neck SCCs. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1782-1789, 2021.


Assuntos
Plaquetas/metabolismo , Carcinoma de Células Escamosas/sangue , Linfócitos/metabolismo , Neutrófilos/metabolismo , Neoplasias Cranianas/sangue , Osso Temporal , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Contagem de Células Sanguíneas , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida
13.
Laryngoscope ; 131(2): E583-E589, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32267551

RESUMO

OBJECTIVES/HYPOTHESIS: The extreme rarity of temporal bone squamous cell carcinoma (TB-SCC) has delayed the accumulation of high-quality clinical evidence. For the purposes of retrospective meta-analysis in the future, a large dataset with information from various institutions would be ideal. Our objective here was to retrospectively review cases of TB-SCC encountered at a single tertiary referral center and explore survival outcomes and prognostic factors. STUDY DESIGN: Retrospective chart review. METHODS: The medical records of all TB-SCC cases were retrospectively reviewed. The resulting dataset contained 71 cases of primary cancer eligible for initial definitive (curative) treatment. RESULTS: T4 status was associated with lower disease-specific 5-year survival than T1 to T3 staging (T1: 100%, T2: 92%, T3: 86%, T4: 51%). Survival was significantly higher in operable than in inoperable cases, even when restricted to advanced (T3/T4) cancers. The tumor extension to the middle ear cavity was observed in 13/17 of T3 cases, but it was not associated with poor survival. In addition, among operable cases, negative surgical margins were associated with significantly higher survival than positive margins. CONCLUSIONS: Definitive treatments can offer disease-specific 5-year survival of over 85% in T1 to T3 cases of TB-SCC. The tumor extension to the middle ear cavity is not associated with poor survival. T4 status, inoperability, nodal invasion, and positive surgical margin are identified as a predictor of poor prognosis. Still, the matter of how to deal with unresectable tumors remains an outstanding issue in the treatment of TB-SCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E583-E589, 2021.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Neoplasias Cranianas/diagnóstico , Osso Temporal , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Cranianas/mortalidade , Neoplasias Cranianas/cirurgia , Neoplasias Cranianas/terapia , Análise de Sobrevida , Osso Temporal/cirurgia
14.
Front Oncol ; 10: 1229, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850367

RESUMO

Objective: The extreme rarity of temporal bone squamous cell carcinoma (TB-SCC) has delayed the accumulation of high-quality clinical evidence. Our objective here was to explore anatomical factors associated with the prognosis of T4 TB-SCC cases. Study Design: Case series with chart review. Setting: Two academic tertiary care medical centers. Subjects and Methods: The medical records of all TB-SCC cases were retrospectively reviewed in two institutions. The resulting data set contained 30 cases of primary T4 cancer eligible for initial definitive (curative) treatment. Disease-specific survival was calculated according to the Kaplan-Meier method. Cox proportional hazards model was used to identify anatomical prognosis factors. Results: The disease-specific 5-years survival rate of 30 cases of T4 TB-SCC was 53.9%. The tumor invasion to the pterygoid muscle, posterior fossa dura, and sigmoid sinus and destruction of the ossicles were associated with poor prognosis in univariate analysis. The multivariate analysis reveals that the invasion of the ossicles, posterior fossa dura, and sigmoid sinus is an independent prognostic factor [hazard ratio (HR): 4.528 (95% CI: 1.161-17.658), p = 0.030; HR: 5.135 (95% CI: 1.616-16.315), p = 0.006; HR: 4.292 (95% CI: 1.385-13.303), p = 0.012]. The invasion of the carotid canal, petrous apex, middle fossa dura, otic capsule, pterygoid muscle, and middle ear had a high HR (HR > 2). The more invaded anatomical factors present in patients resulted in a poorer patient disease-specific prognosis, with a statistically significant difference. Conclusions: Assessing which anatomical structures are susceptible to invasion by tumors may be important for predicting TB-SCC patient prognosis and selecting appropriate treatment planning, especially surgical intervention. In addition to previously reported factors, the destruction of the ossicles in the middle ear cavity can be an anatomical prognosis factor.

15.
Cancer Sci ; 111(8): 3010-3019, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32500594

RESUMO

External auditory canal squamous cell carcinoma (EACSCC) is an extremely rare and aggressive malignancy. Due to its rarity, the molecular and genetic characteristics of EACSCC have not yet been elucidated. To reveal the genetic alterations of EACSCC, we performed whole exome sequencing (WES) on 11 primary tumors, 1 relapsed tumor and 10 noncancerous tissues from 10 patients with EACSCC, including 1 with a rare case of synchronous bilateral EACSCC of both ears. WES of the primary tumor samples showed that the most frequently mutated gene is TP53 (63.6%). In addition, recurrent mutations in CDKN2A, NOTCH1, NOTCH2, FAT1 and FAT3 were detected in multiple samples. The mutational signature analysis of primary tumors indicated that the mutational processes associated with the activation of apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) deaminases are the most common in EACSCC, suggesting its similarity to SCC from other primary sites. Analysis of arm-level copy number alterations detected notable amplification of chromosomes 3q, 5p and 8q as well as deletion of 3p across multiple samples. Focal chromosomal aberrations included amplifications of 5p15.33 (ZDHHC11B) and 7p14.1 (TARP) as well as deletion of 9p21.3 (CDKN2A/B). The protein expression levels of ZDHHC11B and TARP in EACSCC tissues were validated by immunohistochemistry. Moreover, WES of the primary and relapsed tumors from a case of synchronous bilateral EACSCC showed the intrapatient genetic heterogeneity of EACSCC. In summary, this study provides the first evidence for genetic alterations of EACSCC. Our findings suggest that EACSCC mostly resembles other SCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Meato Acústico Externo/patologia , Neoplasias da Orelha/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Variações do Número de Cópias de DNA , Análise Mutacional de DNA , Neoplasias da Orelha/patologia , Feminino , Amplificação de Genes , Heterogeneidade Genética , Humanos , Masculino , Pessoa de Meia-Idade , Sequenciamento do Exoma
16.
Ann Otol Rhinol Laryngol ; 128(11): 1006-1012, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31161776

RESUMO

OBJECTIVES: Small cell carcinomas in extrapulmonary sites (ESmCCs) are very rare. ESmCCs originating in the head and neck account for approximately 10% of all ESmCCs, and there are few reports about this disease. ESmCCs have an aggressive natural history characterized by widespread metastasis. The aim of this study was to investigate the characteristics and outcomes of patients with ESmCCs of the head and neck. METHODS: The outcomes of 21 patients with ESmCCs of the head and neck treated between January 2001 and December 2015 at the authors' hospital and associated facilities were reviewed. RESULTS: There were 18 men and 3 women, and the median age was 74 years (range, 53-91 years). The tumor site was the larynx in 6 patients; the paranasal sinus in 5; the hypopharynx in 3; the oropharynx in 2; the nasopharynx in 2; and the oral cavity, salivary gland, and primary unknown in 1 patient each. The extent of the disease was staged as follows: stage I or II, 3 cases; stage III, 4 cases; stage IVA, 9 cases; stage IVB, 1 case; and stage IVC, 4 cases. The median observation time was 17 months (range, 1-103 months). Four patients (19%) had distant metastasis at initial treatment, and 13 patients (62%) developed distant metastasis within 3 years. Treatments were administered, including radical surgery (9 patients), radiation therapy (5 patients), chemoradiotherapy (7 patients), and chemotherapy (6 patients). The 1- and 3-year overall survival rates of patients were 56% and 37%, respectively. More than half of the patients died of distant metastasis. CONCLUSIONS: ESmCCs of the head and neck have a poor prognosis, similar to those of carcinomas in many other sites. Control of distant metastasis would contribute to improving the prognosis of ESmCCs of the head and neck. Further studies are required for better understanding these disease entities and their response to treatment modalities.


Assuntos
Carcinoma de Células Pequenas/diagnóstico , Neoplasias de Cabeça e Pescoço/patologia , Estadiamento de Neoplasias , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Pequenas/secundário , Carcinoma de Células Pequenas/terapia , Quimiorradioterapia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Japão/epidemiologia , Metástase Linfática , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Tomografia Computadorizada por Raios X
17.
Auris Nasus Larynx ; 46(1): 135-140, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30078551

RESUMO

OBJECTIVE: The usefulness of pretreatment measurement of SCC antigen in patients with head and neck SCC is still controversial. Our aim of this study was to evaluate the clinical usefulness of serum SCC antigen, SCCA1 and SCCA2 in the management of patients with head and neck SCC. METHODS: Serum samples for the analysis of SCCA1, SCCA2 and SCC antigen were taken from head and neck SCC patients before treatment. Serum SCC antigen was assayed with a solid phase immunoradiometric assay. The SCCA1 and SCCA2 protein level was determined by a sandwich ELISA. RESULTS: Fifty-two of 96 cases (54%) showed evaluated serum SCC antigen levels above the upper limit. The serum SCCA2 level was significantly higher in the head and neck SCC patients than in control group, whereas there were no significant differences in the serum SCCA1 level between head and neck SCC patients and control group. 72% of head and neck SCC patients demonstrated SCCA2 levels higher than 0.15, whereas 68% of the control subjects had SCCA2 levels less than 0.15. CONCLUSION: The serum SCCA2 levels were increased during the progression of cancer and might be a useful tool for the management of head and neck SCC.


Assuntos
Antígenos de Neoplasias/sangue , Neoplasias de Cabeça e Pescoço/sangue , Serpinas/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Neoplasias Hipofaríngeas/sangue , Neoplasias Laríngeas/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/sangue , Neoplasias Nasais/sangue , Neoplasias Orofaríngeas/sangue , Neoplasias dos Seios Paranasais/sangue , Adulto Jovem
18.
Head Neck ; 40(12): 2583-2589, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30376194

RESUMO

BACKGROUND: Differentiating inverted papilloma from squamous cell carcinoma (SCC) is sometimes difficult. We evaluated the clinical usefulness of serum SCCA1 and SCCA2 in the management of patients with inverted papilloma or SCC. METHODS: Serum and tissue samples for the analysis of SCCA1, SCCA2, and SCC antigen were taken from 18 patients with sinonasal inverted papilloma and 23 cases with sinonasal SCC. The SCCA1, SCCA2, and SCC antigen levels were determined. RESULTS: The serum SCCA1 concentration was significantly higher in the inverted papilloma group than in the SCC group, whereas the serum SCCA2 level was significantly higher in the SCC group than in the inverted papilloma group. CONCLUSION: Patients with sinonasal inverted papilloma predominantly express SCCA1 protein, whereas those with SCC predominantly express SCCA2. This suggests that combined measurements of both serum SCCA1 and SCCA2 concentrations can be very useful for distinguishing sinonasal inverted papilloma from SCC.


Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Nasais/diagnóstico , Papiloma Invertido/diagnóstico , Serpinas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/sangue , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasais/sangue , Papiloma Invertido/sangue , Curva ROC , Estatísticas não Paramétricas
19.
Auris Nasus Larynx ; 45(3): 553-557, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28739190

RESUMO

OBJECTIVES: Primary squamous cell carcinoma (SCC) of the thyroid is a rare disease. It usually presents with locally advanced disease and has an overall poor prognosis. In this study, we investigated the characteristics and outcomes of patients with SCC of the thyroid, and reported our experience with chemotherapy with lenvatinib in the treatment of SCC of the thyroid. METHODS: The management outcome of 10 patients who had SCC of the thyroid between January 2000 and 2015 at Kyushu University Hospital or associated facilities was reviewed. RESULTS: There were 3 males and 7 females, ranging in age from 53 to 77 years. Extent of disease was staged as follows: stage IVA, 3 cases; stage IVB, 3 cases; stage IVC, 4 cases. Only tracheostomy was applied for 2 cases, surgical resection, such as total thyroidectomy and neck dissection, for the other 8 cases. Radiotherapy following surgical treatment was applied for 9 cases. Four patients started on oral lenvatinib due to recurrent or progressive SCC of the thyroid. The one year actuarial survival rate of patients was 22.7%. There was no 2-year survivor of all patients. CONCLUSIONS: Treatment should primarily be targeted at surgical resection with negative margins in patients with resectable disease. Lenvatinib may show promise to potentially extend survival.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Esvaziamento Cervical/métodos , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia/métodos , Idoso , Carcinoma de Células Escamosas/patologia , Quimioterapia Adjuvante , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia Adjuvante/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/patologia , Traqueostomia , Resultado do Tratamento
20.
Int J Clin Oncol ; 22(3): 442-447, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28062933

RESUMO

BACKGROUND: The role of induction chemotherapy (IC) in the treatment of resectable advanced head and neck squamous cell carcinoma has not been elucidated, and the most effective IC regimen for chemoselection is still unknown. At our institute we have not used the triple combination of docetaxel, cisplatin, fluorouracil (TPF) for chemoselection, but rather the double combination of docetaxel + cisplatin (TP). The aim of this study is to report the outcome of patients with advanced hypopharyngeal cancer treated by single cycle of IC with TP followed by chemoradiation (CRT) or surgery. METHODS: A total of 29 patients with resectable advanced hypopharyngeal cancer who were treated with a single cycle of IC were entered into the study. Responders were treated by CRT while nonresponders underwent surgery. Outcomes were analyzed using the Kaplan-Meier method. RESULTS: A single cycle of IC with TP achieved response in 21 of the 29 patients. The major side effect was neutropenia which could be managed without delaying the sequential treatment. The 2-year overall survival and disease-specific survival were both 74.0% (stage III 100%, stage IVA 69.1%). The cumulative 2-year laryngeal preservation rate was 100% for stage III and 53.6% for stage IVA. CONCLUSION: A single cycle of IC with the combination of docetaxel + cisplatin may be sufficient to select advanced hypopharyngeal cancer patients with radio-sensitivity. IC intended for organ preservation strategies should be low toxic. Our strategy may be a useful for providing the benefits of IC and the opportunity for curative surgery without delay.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hipofaríngeas/tratamento farmacológico , Quimioterapia de Indução/métodos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia , Cisplatino/administração & dosagem , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Humanos , Neoplasias Hipofaríngeas/mortalidade , Neoplasias Hipofaríngeas/patologia , Neoplasias Hipofaríngeas/terapia , Quimioterapia de Indução/efeitos adversos , Laringectomia/métodos , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão , Estudos Retrospectivos , Análise de Sobrevida , Taxoides/administração & dosagem , Resultado do Tratamento
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