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1.
Front Oncol ; 14: 1379013, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846982

RESUMO

Background: Olfactory neuroblastoma (ONB) is a rare malignant tumor of the head and neck. Due to its rarity, standard systemic therapy for this condition has yet to be established. In particular, the use of immune checkpoint inhibitors (ICIs) for the recurrent or metastatic (R/M) ONB population remains unclear. Methods: We retrospectively evaluated 11 patients with R/M ONB who received any systemic chemotherapy at two Japanese institutions (National Cancer Center Hospital East and Kyushu Medical Center) between January 2002 and March 2022 and analyzed outcomes by use of anti-PD-1 antibody (nivolumab or pembrolizumab) monotherapy. Results: Of the 11 patients, 6 received ICI (ICI-containing treatment group) and the remaining 5 were treated with systemic therapy but not including ICI (ICI-non-containing treatment group). Overall survival (OS) was significantly longer in the ICI-containing group (median OS: not reached vs. 6.4 months, log-rank p-value: 0.035). The fraction of ICI systemic therapy in the entire treatment period of this group reached 85.9%. Four patients (66.7%) in the ICI-containing treatment group experienced immune-related adverse events (irAE), with grades of 1/2. No irAE of grade 3 or more was seen, and no patient required interruption or discontinuation of treatment due to toxicity. Conclusion: ICI monotherapy appears to be effective and to contribute to prolonged survival in R/M ONB.

2.
Front Oncol ; 13: 1221352, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074688

RESUMO

Background: Immune checkpoint inhibitors (ICIs) are essential in treating recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, the overall response rate (ORR) is limited to 10-20%, and subsequent chemotherapy is critical to maximizing the subjects' prognosis. Methods: We retrospectively reviewed 59 patients with R/M SCCHN treated with paclitaxel+cetuximab (PE)-based chemotherapy (PCE, paclitaxel+carboplatin+cetuximab; or PTX+Cmab, paclitaxel+cetuximab) following disease progression after either pembrolizumab or nivolumab monotherapy. Results: Of 59 patients, 15 were treated with pembrolizumab, with an ORR of 13.3%, and the remaining 44 with nivolumab, with an ORR of 11.4%. All patients in the pembrolizumab cohort had platinum-sensitive disease. Following ICI treatment, 19 patients were treated with PCE and the remaining 40 with PTX+Cmab. PE-based chemotherapy induced favorable and prompt tumor shrinkage even in cases where ICI was not effective, with a median change in the summed dimensions of target lesions of -43.4%, resulting in an ORR of 62.7%. Median time to response was 1.8 months. The patients in the pembrolizumab cohort appeared to have a numerically higher response rate than those receiving nivolumab (80.0% vs. 56.8%). For the 59 patients, progression-free survival and overall survival, calculated from the initiation of PE-based chemotherapy, were 4.6 months and 17.1 months, respectively. Grade ≥3 adverse events occurred in 40.7%, and no treatment-related death was observed. Conclusion: PE-based chemotherapy following ICI is encouraging for its robust antitumor efficacy in R/M SCCHN.

3.
Oral Oncol ; 147: 106615, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37931493

RESUMO

OBJECTIVES: Cetuximab-based chemotherapy is a standard 1st-line treatment for recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, few studies have reported survival data for a treatment sequence consisting of a PCE regimen (paclitaxel + carboplatin + cetuximab) followed by an immune checkpoint inhibitor. MATERIALS AND METHODS: We retrospectively assessed 37 patients with R/M SCCHN from the oral cavity, oropharynx, hypopharynx, and larynx who received PCE as 1st-line treatment followed by nivolumab as 2nd-line at the National Cancer Center Hospital East between December 2016 and July 2021. For comparison, we also analyzed 14 patients who did not receive nivolumab after PCE. RESULTS: Of the 37 patients who received nivolumab, overall response rate (ORR) by PCE was 48.6%, and median time to response and median progression-free survival (PFS) were 2.1 months (range: 0.8-4.8) and 4.4 months, respectively. In the nivolumab phase, ORR was 10.8%. 23 patients received 3rd-line therapy. Median PFS2, PFS3, and overall survival (OS) were 6.8, 11.6, and 19.5 months, respectively. Subgroup analysis by PD-L1 expression showed no significant difference in OS. Analysis of the comparison group revealed a trend toward improved OS in those who received nivolumab compared to those who did not (HR 0.47, 95%CI [0.19-1.13], p = 0.084). CONCLUSION: PCE followed by nivolumab shows a favorable survival outcome, representing the potential for rapid tumor response with PCE and extension of OS by the addition of nivolumab regardless of combined positive score.


Assuntos
Neoplasias de Cabeça e Pescoço , Nivolumabe , Humanos , Cetuximab/uso terapêutico , Nivolumabe/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/etiologia , Carboplatina/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/etiologia , Paclitaxel , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/patologia
5.
Front Oncol ; 13: 1185198, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37397398

RESUMO

Background: Despite advances in precision medicine, most patients with recurrent or metastatic salivary gland carcinoma still need conventional chemotherapies, such as the combination of taxane and platinum. However, evidence for these standardized regimens is limited. Methods: We retrospectively reviewed patients with salivary gland carcinoma treated with a taxane and platinum, which contained docetaxel at a dose of 60 mg/m2 plus cisplatin at a dose of 70 mg/m2 on day 1, or paclitaxel at a dose of 100 mg/m2 plus carboplatin at a dose of area under the plasma concentration-time curve = 2.5 on days 1 and 8 (both on 21-day cycles), between January 2000 and September 2021. Result: Forty patients with ten adenoid cystic carcinomas and thirty other pathologies were identified. Of these, 29 patients were treated with docetaxel plus cisplatin and 11 with paclitaxel plus carboplatin. For the total population, the objective response rate (ORR) and median progression-free survival (mPFS) were 37.5% and 5.4 months (95% confidence interval: 3.6-7.4 months), respectively. On subgroup analysis, docetaxel plus cisplatin provided favorable efficacy compared with paclitaxel plus carboplatin (ORR: 46.5% vs. 20.0%, mPFS: 7.2 vs. 2.8 months), and the findings were well retained in patients with adenoid cystic carcinoma (ORR: 60.0% vs. 0%, mPFS: 17.7 vs. 2.8 months). Grade 3/4 neutropenia was relatively frequent in the docetaxel plus cisplatin (59% vs.27%), although febrile neutropenia was uncommon (3%) in the cohort. No treatment-related death was seen in any case. Conclusion: The combination of taxane and platinum is generally effective and well-tolerated for recurrent or metastatic salivary gland carcinoma. In contrast, paclitaxel plus carboplatin appears unfavorable in terms of efficacy in certain patients, such as those with adenoid cystic carcinoma.

6.
Int J Clin Oncol ; 28(8): 1023-1032, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37344738

RESUMO

BACKGROUND: In recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), local therapy (LT) such as surgery or radiotherapy can be treatment options for improved survival or quality of life. To date, however, few reports have addressed the efficacy of LT for sites of disease progression after immune checkpoint inhibitors, including other cancers. METHODS: We conducted a retrospective analysis of patients with R/M SCCHN originating from the oral cavity, oropharynx, hypopharynx, and larynx and treated with nivolumab. We extracted patients undergoing salvage LT or palliative radiotherapy (RT) to the selected progressive lesion at any time after initiation of nivolumab. RESULTS: Twenty-four patients received LT. Salvage LT was performed in 9 (37.5%) patients, including surgery and definitive RT in 5 and 4 patients, respectively. Palliative RT was performed in 15 (62.5%) patients. LT was provided in 10 (41.7%) patients for oligoprogressive disease. Twelve (50.0%) patients received subsequent systemic therapy immediately after LT. Classification based on patient treatment divided the population into four subgroups with different prognoses (salvage LT followed by subsequent systemic therapy [n = 3], salvage LT alone [n = 6], palliative RT followed by subsequent systemic therapy [n = 9], and palliative RT alone [n = 6]). Median OS in this order was 24.5, 9.0, 7.3, and 2.4 months (p = 0.001). All patients in the salvage LT followed by subsequent systemic therapy group continued nivolumab. CONCLUSION: In R/M SCCHN patients who have received nivolumab, salvage LT for the selected progressive lesion with continuation of nivolumab potentially provides an excellent survival prognosis.


Assuntos
Neoplasias de Cabeça e Pescoço , Nivolumabe , Humanos , Nivolumabe/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Estudos Retrospectivos , Qualidade de Vida , Recidiva Local de Neoplasia/patologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico
8.
Eur J Cancer ; 184: 30-38, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36898232

RESUMO

BACKGROUND: Several reports have shown that the use of proton pump inhibitors (PPIs) and antibiotics (Abx) can reduce the efficacy of immune checkpoint inhibitors in various cancers. To date, however, the association of immune checkpoint inhibitors with PPI and/or Abx in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M SCCHN) has not been reported. METHODS: We retrospectively reviewed patients with platinum-refractory R/M SCCHN treated with nivolumab from May 2017 and March 2020 in our institute. Primary sites included the oral cavity, oropharynx, hypopharynx and larynx. The relationship between prognostic parameters, such as overall survival (OS), progression-free survival (PFS), PFS2 and PFS3, and clinical factors, including PPI or Abx use, was examined, and the creation of prognostic classification was also attempted. RESULTS: Of 110 patients identified, 56 patients received PPI and 24 patients received Abx within 30 days before or after the initiation of nivolumab. With a median follow-up of 17.2 months (range: 13.8-25.0), median PFS, PFS2, PFS3 and OS were 3.2, 8.1, 14.0 and 17.2 months, respectively. In univariate analysis, the use of PPI and of Abx was significantly associated with poor prognosis in all parameters (PFS, PFS2, PFS3 and OS). Median OS (hazard ratio; 95%confidence interval, p-value) by these covariates were 13.6 versus 23.8 months (1.70; 1.01-2.87, p = 0.046) for PPI and 10.0 versus 20.1 months (1.85; 1.00-3.41, p = 0.048) for Abx, respectively. Furthermore, these factors showed mutually independent adverse associations on multivariate analysis. CONCLUSION: The use of PPI and Abx attenuated the efficacy of nivolumab in R/M SCCHN. Further prospective evaluation is warranted.


Assuntos
Antibacterianos , Antineoplásicos Imunológicos , Neoplasias de Cabeça e Pescoço , Inibidores de Checkpoint Imunológico , Nivolumabe , Inibidores da Bomba de Prótons , Carcinoma de Células Escamosas de Cabeça e Pescoço , Inibidores da Bomba de Prótons/efeitos adversos , Antibacterianos/efeitos adversos , Nivolumabe/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Recidiva , Estudos Retrospectivos , Metástase Neoplásica , Intervalo Livre de Progressão
10.
Front Oncol ; 12: 951387, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36033502

RESUMO

Background: The addition of induction chemotherapy (IC) before chemoradiotherapy (CRT) has improved survival over CRT alone in locoregionally advanced nasopharyngeal cancer (LA-NPC). Nevertheless, this population would benefit from further development of a novel IC regimen with satisfactory efficacy and a more favorable safety profile. Methods: We retrospectively assessed 29 LA-NPC patients who received the combination of paclitaxel (PTX), carboplatin (CBDCA), and cetuximab (Cmab) (PCE) as IC (IC-PCE) at the National Cancer Center Hospital East between March 2017 and April 2021. IC-PCE consisted of CBDCA area under the plasma concentration-time curve (AUC) = 1.5, PTX 80 mg/m2, and Cmab with an initial dose of 400 mg/m2 followed by 250 mg/m2 administered weekly for a maximum of eight weeks. Results: Patient characteristics were as follows: median age, 59 years (range 24-75); 0, 1 performance status (PS), 25, 4 patients; and clinical stage III/IVA/IVB, 6/10/13. The median number of PCE cycles was 8(1-8). After IC-PCE, 26 patients received concurrent cisplatin and radiotherapy (CDDP-RT), one received concurrent carboplatin/5-fluorouracil and radiotherapy (CBDCA/5-FU-RT), and two received RT alone. The % completion of CDDP-RT was 88.5%. The response rate was 75.9% by IC and 100% at completion of CRT. The 3-year recurrence-free survival, locoregional failure-free survival, distant recurrence-free survival, and overall survival were 75.9%, 79.3%, 84.3%, and 96.3%, respectively. The incidence of adverse events of grade 3/4 was 34.5% during IC and 44.8% during CRT. Conclusion: IC-PCE is feasible and effective for LA-NPC and may be a treatment option for this disease.

11.
Int J Clin Oncol ; 27(11): 1669-1674, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35943644

RESUMO

BACKGROUND: Cetuximab (Cmab) plays an important role in the treatment for recurrent or metastatic head and neck cancer (R/M HNC). To date, however, no safety data on biweekly administration of cetuximab at a dose of 500 mg/m2 (biweekly Cmab) for Japanese HNC patients have been available. METHODS: We retrospectively reviewed the clinical records of five R/M HNC patients who received biweekly Cmab in our institute between January 2016 and September 2021 and compared the safety profile between two phases of weekly 250 mg/m2 and biweekly 500 mg/m2 Cmab in the identical patients. RESULTS: All patients initially received Cmab in combination with chemotherapy. Chemotherapy consisted of paclitaxel plus carboplatin in two patients, cisplatin + 5-FU in one patient, and paclitaxel in two patients. Three patients switched treatment schedule from weekly Cmab to biweekly Cmab, while two patients received biweekly Cmab after completion of chemotherapy. The main reason for switching to biweekly Cmab was an unacceptably long commuting time to the hospital. The median duration of Cmab was 217 days (49-321) during weekly Cmab with or without chemotherapy and 42 days (28-175) during biweekly Cmab. Median dose of biweekly Cmab was 4 (3-12). During biweekly Cmab, worsened (Grade ≥ 2) toxicities were observed in two patients: one with grade 2 dry skin and the second with grade 2 skin infection. None developed grade ≥ 3 adverse events or discontinued treatment due to Cmab-related adverse events. CONCLUSION: Biweekly Cmab was well tolerated and did not demonstrate severe toxicities related to Cmab for R/M HNC.


Assuntos
Cisplatino , Neoplasias de Cabeça e Pescoço , Humanos , Cetuximab , Carboplatina , Estudos Retrospectivos , Japão , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Recidiva Local de Neoplasia/patologia , Esquema de Medicação , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Paclitaxel , Fluoruracila
12.
Oral Oncol ; 130: 105932, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35636078

RESUMO

OBJECTIVES: In CheckMate 141, nivolumab significantly improved overall survival (OS) in patients with platinum-refractory recurrent or metastatic squamous cell carcinomas (R/M SCC) of the head and neck. However, reports on nivolumab for patients with non-SCC and/or a primary subsite excluded from CheckMate 141 are limited. MATERIALS AND METHODS: We conducted a retrospective analysis of R/M head and neck cancer patients who received nivolumab. The study subject excluded patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx. RESULTS: A total of 59 patients were included, consisting of 40 males and 19 females with a median age of 61 years. Half of the patients had non-SCC histology. The main primary site included the sinonasal cavity (n = 18), salivary gland (n = 15), and nasopharynx (n = 13). Three (6.0%) patients achieved a complete response and 5 (10.0%) a partial response, giving an overall response rate (ORR) of 16.6%. Median time-to-treatment failure (TTF) and OS were 3.7 and 16.2 months, respectively. Salivary gland and nasopharyngeal cancer achieved relatively higher ORR (25.0 and 36.4%, respectively). On analysis by primary site, nasopharyngeal cancer showed a significantly better TTF and OS than the other primary sites. On analysis by histological findings, no significant difference in TTF and OS was observed between non-SCC and SCC. CONCLUSION: Nivolumab for cancers involving the salivary gland/nasopharynx and non-SCC histology showed comparable efficacy to that in CheckMate 141. This result indicates that nivolumab may be effective even for patients not included in CheckMate 141.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Nasofaríngeas , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Nivolumabe/uso terapêutico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico
14.
Hum Pathol ; 109: 37-44, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33301751

RESUMO

Salivary secretory carcinoma (SASC) is frequently associated with ETV6-neurotrophic tyrosine receptor kinase (NTRK) 3 fusion and more rarely with RET, MET, or ALK rearrangement. We aimed to elucidate the potential diagnostic utility of pan-tropomyosin receptor kinase (Trk) immunohistochemistry and its relationship with the fusion gene subtype in SASC. We examined 33 cases of SASC for immunoexpression of pan-Trk, ALK and ROS1, and gene rearrangement of the ETV6, NTRK3, and RET genes using fluorescence in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR). Thirty (90.9%) of 33 SASCs harbored ETV6-NTRK3 fusion gene transcripts by RT-PCR and/or both ETV6 and NTRK3 gene rearrangements by FISH, and 3 cases (9.1%) had RET gene rearrangement. Most NTRK3-rearranged SASCs (27/33 cases; 81.8%) had conventional ETV6 exon 5-NTRK3 exon 15 fusion, whereas 2 cases (6.1%) had both the conventional fusion and a novel ETV6 exon 4-NTRK3 exon 15 fusion variant. In the remaining one case (3%), only FISH revealed both ETV6 and NTRK3 rearrangements, suggesting an ETV6-NTRK3 fusion with an as yet undetermined break point. All 30 SASCs with ETV6-NTRK3 fusion and/or NTRK3 rearrangement showed nuclear and cytoplasmic immunoreactivity for pan-Trk. In contrast, 3 SASCs with RET rearrangement showed negative or only weak cytoplasmic staining for pan-Trk. There was no case harboring ALK and ROS1 rearrangements. All 17 non-SASC tumors were negative for pan-Trk. The results suggest that nuclear and cytoplasmic immunoreactivity for pan-TRK may be helpful to identify ETV6-NTRK3-fused SASCs and to distinguish them from RET-rearranged SASCs and morphological mimics.


Assuntos
Neoplasias da Mama/imunologia , Carcinoma/imunologia , Proteínas de Fusão Oncogênica/imunologia , Proteínas Proto-Oncogênicas c-ret/imunologia , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/análise , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Carcinoma/genética , Carcinoma/metabolismo , Criança , Feminino , Rearranjo Gênico/genética , Humanos , Imuno-Histoquímica/métodos , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Proto-Oncogênicas c-ret/metabolismo , Receptores Proteína Tirosina Quinases/genética , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/imunologia , Neoplasias das Glândulas Salivares/patologia , Tropomiosina/genética , Adulto Jovem
15.
Hum Pathol ; 106: 82-92, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32980422

RESUMO

NTRK1/3, ALK, and ROS1 translocations have been reported in a minor subset of papillary thyroid carcinomas (PTCs). We aimed to elucidate the prevalence and clinicopathological characteristics of these gene rearrangements and the utility of immunohistochemistry (IHC) in PTC and anaplastic thyroid carcinoma (ATC). We screened nonradiation-exposed cases of 307 PTCs and 16 ATCs by IHC for pan-Trk, ALK, and ROS1, followed by fluorescence in situ hybridization (FISH). In the PTC group, IHC for pan-Trk, ALK, and ROS1 was positive in 18 cases (5.9%), 1 case (0.3%), and 12 cases (3.9%), respectively. Among the pan-Trk IHC-positive cases (n = 18), 2 cases (11.1%; 0.7% of all PTCs) had NTRK1 or NTRK3 gene rearrangement with conventional PTC histology. The ALK IHC-positive case (n = 1) was the follicular variant of PTC with consistent ALK gene rearrangement. ROS1 gene rearrangement was not detectable in the ROS1 IHC-positive PTCs (0/12) by FISH. Most (approximately 70%) of the pan-Trk or ROS1 IHC-positive/FISH-negative cases had BRAF gene mutation with conventional PTC morphology. In the ATC group, neither ALK nor ROS1 IHC was positive, whereas pan-Trk IHC was positive in 1 case (6.3%) in which NTRK1 gene rearrangement was confirmed by FISH. These results suggest that NTRK, ALK, and ROS1 rearrangements are rare molecular events in nonradiation-exposed Japanese patients with PTC and ATC. Although IHC is not an entirely specific surrogate for these abnormalities and does not serve as a stand-alone companion diagnosis, the combined use of IHC and molecular testing may be helpful for determining promising therapeutic strategies with tyrosine kinase inhibitors.


Assuntos
Biomarcadores Tumorais/genética , Rearranjo Gênico , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Câncer Papilífero da Tireoide/genética , Carcinoma Anaplásico da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Receptor trkA/genética , Receptor trkC/genética , Reprodutibilidade dos Testes , Câncer Papilífero da Tireoide/patologia , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto Jovem
16.
Kyobu Geka ; 73(5): 344-347, 2020 May.
Artigo em Japonês | MEDLINE | ID: mdl-32398390

RESUMO

We present a 76-year-old male patient on chronic dialysis for over 10 years with contained rupture of a mycotic abdominal aortic aneurysm, which was successfully treated by thoracic endovascular aortic repair(TEVAR) and computed tomography(CT) guided percutaneous drainage. Endovascular repair of mycotic aortic aneurysm is nowadays feasible and can be a suitable alternative especially in frail patients.


Assuntos
Aneurisma Infectado , Aneurisma da Aorta Abdominal , Ruptura Aórtica , Procedimentos Endovasculares , Idoso , Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular , Humanos , Masculino , Resultado do Tratamento
17.
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
18.
Pathol Res Pract ; 214(4): 586-592, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29496310

RESUMO

Differential diagnosis among basal cell adenoma (BCA), basal cell adenocarcinoma (BCAC), adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA) of the salivary gland can be challenging due to their similar histological appearance. Although frequent nuclear ß-catenin expression and CTNNB1 mutations have been reported in BCA, further details of the Wnt/ß-catenin signal alterations are unclear. The aim of this study was to assess the diagnostic utility of Wnt/ß-catenin signal alteration in BCA and morphological mimics. We performed immunohistochemical staining for ß-catenin and mutation analysis for Wnt/ß-catenin-related genes (CTNNB1, APC, AXIN1 and AXIN2) in BCA (n = 34), BCAC (n = 3), ACC (n = 67) and PA (n = 31). We also analyzed ACC-specific MYB and MYBL1 gene rearrangements by fluorescence in situ hybridization (FISH). Nuclear ß-catenin expression (≥3%) was present in 32/34 cases (94.1%) of BCA, and the nuclear ß-catenin labeling index was significantly higher than in other tumor types (p = < 0.0001). In BCA, we found mutations in CTNNB1, APC and AXIN1 genes (41.1%, 2.9% and 8.8%, respectively). In BCAC, nuclear ß-catenin expression with CTNNB1 mutation was present in 1/3 cases (33.3%). As for ACC, nuclear ß-catenin expression was observed in 3/67 cases (4.4%), but all 3 cases harbored either MYB or MYBL1 gene rearrangement. The results suggest that nuclear ß-catenin immunoreactivity with appropriate criteria may be helpful to distinguish BCA from histologically similar tumors. However, a minor subset of ACCs with nuclear ß-catenin expression require careful diagnosis. In addition, Wnt/ß-catenin signal alteration may play a role in the pathogenesis of BCA and BCAC.


Assuntos
Adenocarcinoma/diagnóstico , Adenoma Pleomorfo/diagnóstico , Adenoma/diagnóstico , Carcinoma Adenoide Cístico/diagnóstico , Neoplasias das Glândulas Salivares/diagnóstico , Via de Sinalização Wnt , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenoma/genética , Adenoma/metabolismo , Adenoma/patologia , Adenoma Pleomorfo/genética , Adenoma Pleomorfo/metabolismo , Adenoma Pleomorfo/patologia , Proteína da Polipose Adenomatosa do Colo/genética , Proteína da Polipose Adenomatosa do Colo/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína Axina/genética , Proteína Axina/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/metabolismo , Glândulas Salivares/patologia , Adulto Jovem , beta Catenina/genética , beta Catenina/metabolismo
19.
Drug Metab Dispos ; 46(5): 740-748, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29475833

RESUMO

Bosentan is a substrate of hepatic uptake transporter organic anion-transporting polypeptides (OATPs), and undergoes extensive hepatic metabolism by cytochrome P450 (P450), namely, CYP3A4 and CYP2C9. Several clinical investigations have reported a nonlinear relationship between bosentan doses and its systemic exposure, which likely involves the saturation of OATP-mediated uptake, P450-mediated metabolism, or both in the liver. Yet, the underlying causes for the nonlinear bosentan pharmacokinetics are not fully delineated. To address this, we performed physiologically based pharmacokinetic (PBPK) modeling analyses for bosentan after its intravenous administration at different doses. As a bottom-up approach, PBPK modeling analyses were performed using in vitro kinetic parameters, other relevant parameters, and scaling factors. As top-down approaches, three different types of PBPK models that incorporate the saturation of hepatic uptake, metabolism, or both were compared. The prediction from the bottom-up approach (models 1 and 2) yielded blood bosentan concentration-time profiles and their systemic clearance values that were not in good agreement with the clinically observed data. From top-down approaches (models 3, 4, 5-1, and 5-2), the prediction accuracy was best only with the incorporation of the saturable hepatic uptake for bosentan. Taken together, the PBPK models for bosentan were successfully established, and the comparison of different PBPK models identified the saturation of the hepatic uptake process as a major contributing factor for the nonlinear pharmacokinetics of bosentan.


Assuntos
Fígado/metabolismo , Sulfonamidas/metabolismo , Transporte Biológico/fisiologia , Bosentana , Citocromo P-450 CYP2C9/metabolismo , Citocromo P-450 CYP3A/metabolismo , Hepatócitos/metabolismo , Humanos , Modelos Biológicos , Transportadores de Ânions Orgânicos/metabolismo , Distribuição Tecidual/fisiologia
20.
Interact Cardiovasc Thorac Surg ; 26(4): 696-699, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29253220

RESUMO

Six patients with acute Type A aortic dissection were medically treated due to advanced age, patient refusal and comorbidity despite surgical indication. Computed tomography after onset revealed a thrombosed false lumen in 3 patients and a patent false lumen with flap in 3 patients. All patients were stable during admission except 1 patient who presented with shock. After admission, treatment including strict control of systolic blood pressure was started according to a predetermined treatment strategy. All patients had no significant complications during hospitalization. All patients survived and returned to their usual activities. Medical treatment for stable elderly patients is a possible therapeutic option for acute Type A aortic dissection.


Assuntos
Anti-Hipertensivos/uso terapêutico , Aneurisma da Aorta Torácica/terapia , Dissecção Aórtica/terapia , Hidratação/métodos , Respiração Artificial/métodos , Procedimentos Cirúrgicos Vasculares/métodos , Doença Aguda , Idoso de 80 Anos ou mais , Dissecção Aórtica/diagnóstico , Aneurisma da Aorta Torácica/diagnóstico , Feminino , Humanos , Masculino , Tomografia Computadorizada por Raios X
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