RESUMO
BACKGROUND: This study aimed to create a prognostic model to predict disease recurrence among patients with lymph node involvement but no prostate-specific antigen (PSA) persistence and to explore its clinical utility. METHODS: The study analyzed patients with lymph node involvement after pelvic lymph node dissection with radical prostatectomy in whom no PSA persistence was observed between 2006 and 2019 at 33 institutions. Prognostic factors for recurrence-free survival (RFS) were analyzed by the Cox proportional hazards model. RESULTS: Among 231 patients, 127 experienced disease recurrence. The factors prognostic for RFS were PSA level at diagnosis (≥ 20 vs. < 20 ng/mL: hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.09-2.52; P = 0.017), International Society of Urological Pathology grade group at radical prostatectomy (RP) specimen (group ≥ 4 vs. ≤ 3: HR, 1.63; 95% CI 1.12-2.37; P = 0.010), pathologic T-stage (pT3b/4 vs. pT2/3a: HR, 1.70; 95% CI 1.20-2.42; P = 0.0031), and surgical margin status (positive vs. negative: HR, 1.60; 95% CI 1.13-2.28; P = 0.0086). The prognostic model using four parameters were associated with RFS and metastasis-free survival. CONCLUSION: The prognostic model in combination with postoperative PSA value and number of lymph nodes is clinically useful for discussing treatment choice with patients.
Assuntos
Linfonodos , Metástase Linfática , Recidiva Local de Neoplasia , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/sangue , Prostatectomia/métodos , Antígeno Prostático Específico/sangue , Pessoa de Meia-Idade , Taxa de Sobrevida , Seguimentos , Prognóstico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/sangue , Idoso , Linfonodos/patologia , Linfonodos/cirurgia , Excisão de Linfonodo , Estudos Retrospectivos , Estadiamento de Neoplasias , Gradação de Tumores , Margens de ExcisãoRESUMO
To behave adaptively, animals must learn to predict future reward, or value. To do this, animals are thought to learn reward predictions using reinforcement learning. However, in contrast to classical models, animals must learn to estimate value using only incomplete state information. Previous work suggests that animals estimate value in partially observable tasks by first forming "beliefs"-optimal Bayesian estimates of the hidden states in the task. Although this is one way to solve the problem of partial observability, it is not the only way, nor is it the most computationally scalable solution in complex, real-world environments. Here we show that a recurrent neural network (RNN) can learn to estimate value directly from observations, generating reward prediction errors that resemble those observed experimentally, without any explicit objective of estimating beliefs. We integrate statistical, functional, and dynamical systems perspectives on beliefs to show that the RNN's learned representation encodes belief information, but only when the RNN's capacity is sufficiently large. These results illustrate how animals can estimate value in tasks without explicitly estimating beliefs, yielding a representation useful for systems with limited capacity.
Assuntos
Aprendizagem , Reforço Psicológico , Animais , Teorema de Bayes , Recompensa , Redes Neurais de ComputaçãoRESUMO
BACKGROUND: The therapeutic role of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) for prostate cancer is not established. In clinical practice, PLND is primarily performed in cases of high-risk prostate cancer. The detection of lymph node metastasis plays a crucial role in determining the need for subsequent treatments. This study aims to evaluate the prognosis of prostate cancer patients with lymph node involvement (LNI) by stratifying them based on postoperative prostate-specific antigen (PSA) levels to identify biomarkers that can guide postoperative treatment strategies. METHODS: Analysis was conducted on 383 patients, selected from 572 initially eligible, who underwent RP with LNI across 33 Japanese Urological Oncology Group institutions from 2006 to 2019. Patients were grouped according to postoperative PSA levels and salvage treatments received. Follow-up focused on castration resistance-free survival (CRFS), metastasis-free survival (MFS), and overall survival (OS). RESULTS: In the persistent PSA group (PSA ≥ 0.1 ng/mL), CRFS and MFS were significantly shorter compared to the non-persistent PSA group (PSA < 0.1 ng/mL), and there was a tendency for shorter OS. In the persistent PSA group, patients with postoperative PSA values above the median (PSA ≥ 0.52 ng/mL) showed shorter CRFS and MFS. Furthermore, in the PSA ≥ 0.52 group, androgen deprivation therapy (ADT) plus radiotherapy (RT) combination had prolonged CRFS and MFS compared with ADT alone. CONCLUSIONS: This study provides valuable insights into stratifying patients based on postoperative PSA levels to tailor postoperative treatment strategies, potentially improving the prognosis of prostate cancer patients with LNI.
Assuntos
Excisão de Linfonodo , Metástase Linfática , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata , Humanos , Masculino , Antígeno Prostático Específico/sangue , Idoso , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/terapia , Prognóstico , Linfonodos/patologia , Estudos Retrospectivos , Período Pós-Operatório , Terapia de Salvação , Antagonistas de Androgênios/uso terapêuticoRESUMO
OBJECTIVES: This study aimed to determine whether elective neck dissection can help improve outcomes in early-stage tongue and floor squamous cell carcinoma (SCC) by statistically analysing the relationship between information obtained from biopsy specimens and the incidence and prognosis of cervical lymph node metastasis (CLM). MATERIALS AND METHODS: Biopsy specimens of 103 patients diagnosed with early cT1-T2 cancer of the tongue and floor of the mouth were included. RESULTS: Multivariate analysis showed that the three parameters significantly correlated with CLM, and univariate analyses showed that budding score (BS) ≥ 5 and pathological depth of invasion (pDOI) ≥ 5 mm were independent risk factors for CLM. There were significant differences in the 5-year cumulative disease-specific survival between the BS < 5 and BS ≥ 5 groups, the pDOI < 5 mm and pDOI ≥ 5 mm groups, and the positive and negative budding and depth of invasion (BD) score groups. CONCLUSION: In early-stage tongue and floor of the mouth cancers with maximum tumour diameter ≤ 20 mm, it may be necessary to treat occult CLM during initial surgery based on the following preoperative criteria: pDOI ≥ 5 mm or BS ≥ 5 in biopsy specimens and DOI ≥ 8 mm on imaging. The BD model exhibited the highest specificity and proved helpful for CLM prediction. CLINICAL RELEVANCE: pDOI ≥ 5 mm and BS ≥ 5 were independent predictors of CLM and prognosis in early-stage tongue and floor of the mouth cancers with a maximum tumour diameter of 20 mm.
Assuntos
Carcinoma de Células Escamosas , Metástase Linfática , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias da Língua , Humanos , Masculino , Feminino , Metástase Linfática/patologia , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/secundário , Neoplasias da Língua/patologia , Neoplasias da Língua/cirurgia , Idoso , Adulto , Prognóstico , Esvaziamento Cervical , Soalho Bucal/patologia , Neoplasias Bucais/patologia , Neoplasias Bucais/cirurgia , Fatores de Risco , Biópsia , Idoso de 80 Anos ou mais , Estudos RetrospectivosRESUMO
In recent years, trade liberalisation has led to the spread of antibiotic-resistant bacteria (ARB) in food products. Because ARB has reportedly been found in imported foods, the spread of plasmid-mediated ARB through food products is a concern. Here, we report the complete genome sequences of ESBL-producing Vibrio vulnificus and V. alginolyticus strains harbouring a plasmid isolated from imported seafood. First, V. vulnificus and V. alginolyticus were isolated from purchased frozen and thawed Litopenaeus vannamei shrimp, and genome extraction and sequencing were performed. Hybrid genome assemblies were performed using Unicycler and annotated using DFAST. Then genome analysis was performed using BRIG. Plasmid comparisons showed that the plasmids carried by both Vibrios are remarkably similar and encode the same antibiotic-resistance genes. The 270-310 kb region specific to both Vibrios were isolated in this study and encodes the antibiotic-resistance genes blaCTX-M and qnr. Furthermore, the mobile genetic factors ISEc9, ISVch4, and ISVpa4 are located upstream and downstream of these genes. This is the first report of ESBL-producing V. vulnificus and V. alginolyticus harbouring a common plasmid encoding ISEc9 upstream of blaCTX-M-55 and qnrS2 isolated from imported seafood.
Assuntos
Vibrio vulnificus , Vibrio , Vibrio vulnificus/genética , Antibacterianos/farmacologia , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Plasmídeos/genética , Vibrio/genética , Alimentos Marinhos/microbiologia , beta-Lactamases/genéticaRESUMO
OBJECTIVES: To understand the real-world outcomes for patients with penile cancer in the Kyushu-Okinawa area before the introduction of practice guidelines in Japan. METHODS: We retrospectively collected medical information on patients with penile squamous cell carcinoma and penile intraepithelial neoplasia at 12 university hospitals and their affiliated hospitals in the Kyushu-Okinawa area from January 2009 to December 2020. Patients with unknown clinical stage were excluded. Patient background characteristics and survival, as well as pretreatment factors involved in survival, were investigated. RESULTS: A total of 196 patients were included. Patients with clinical stage 0, I, IIA, IIB, IIIA, IIIB and IV comprised 9.7, 26.0, 22.4, 2.6, 10.7, 14.3 and 14.3%, respectively. The median follow-up was 26 months, and the mean 5-year overall survival and cancer-specific survival rates were 74.3 and 79.8%, respectively. On univariate analysis, tumor diameter ≥ 30 mm, penile shaft tumor, Eastern Cooperative Oncology Group performance status ≥ 1, cT ≥ 3, cN ≥ 2 and cM1 were associated with significantly poorer cancer-specific survival. On multivariate analysis, pretreatment factors of cN ≥ 2 (hazard ratio, 32.5; 95% confidence interval, 5.08-208; P = 0.0002), Eastern Cooperative Oncology Group performance status ≥ 1 (4.42; 1.79-10.9; P = 0.0012) and cT ≥ 3 (3.34; 1.11-10.1; P = 0.0319) were identified as independent prognostic factors. CONCLUSIONS: The study revealed basic data for future penile cancer treatment and research, including survival rates according to clinical stages, and identified cN ≥ 2, Eastern Cooperative Oncology Group performance status ≥ 1 and cT ≥ 3 at initial diagnosis as independent prognostic factors. Evidence for penile cancer in Japan is particularly scarce, and future large-scale prospective studies are warranted.
Assuntos
Neoplasias Penianas , Masculino , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias Penianas/cirurgia , Neoplasias Penianas/patologia , Japão , Estadiamento de Neoplasias , Resultado do TratamentoRESUMO
PURPOSE: To evaluate the image quality qualitatively and quantitatively, as well as apparent diffusion coefficient (ADC) values of modified reduced field-of-view diffusion-weighted magnetic resonance imaging (MRI) using spatially tailored two-dimensional radiofrequency pulses with tilted excitation plane (tilted r-DWI) based on single-shot echo planar imaging (SS-EPI) compared with full-size field-of-view DWI (f-DWI) using readout segmented (RS)-EPI in patients with rectal cancer. MATERIALS AND METHODS: Twenty-two patients who underwent an MRI for further evaluation of rectal cancer were included in this retrospective study. All MR images were analyzed to compare image quality, lesion conspicuity, and artifacts between f-DWI with RS-EPI and tilted r-DWI with SS-EPI. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and ADC values were also compared. The Wilcoxon signed-rank test or paired t test was performed to compare the qualitative and quantitative assessments. RESULTS: All image quality scores, except aliasing artifacts, were significantly higher (p < 0.01 for all) in tilted r-DWI than f-DWI with RS-EPI. CNR in tilted r-DWI was significantly higher than in f-DWI with RS-EPI (p < 0.01), while SNR was not significantly different. Regarding the ADC values, no significant difference was observed between tilted r-DWI and f-DWI with RS-EPI (p = 0.27). CONCLUSION: Tilted r-DWI provides a better image quality with fewer artifacts and higher rectal lesion conspicuity than f-DWI with RS-EPI, indicating the feasibility of this MR sequence in evaluating rectal cancer in clinical practice.
Assuntos
Imagem Ecoplanar , Neoplasias Retais , Humanos , Imagem Ecoplanar/métodos , Estudos Retrospectivos , Razão Sinal-Ruído , Neoplasias Retais/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Reprodutibilidade dos TestesRESUMO
The treatment for lymph node involvement (LNI) after radical prostatectomy (RP) has not been established. This study aimed to reveal the outcomes of various management strategies among patients with LNI after RP. Retrospectively, 561 patients with LNI after pelvic lymph node dissection (PLND) with RP treated between 2006 and 2019 at 33 institutions participating in the Japanese Urological Oncology Group were investigated. Metastasis-free survival (MFS) was the primary outcome. Patients were stratified by prostate-specific antigen (PSA) persistence after RP. Cox regression models were used to analyze the relationships between clinicopathological characteristics and survival. Survival analyses were conducted using the Kaplan-Meier method and log-rank test with or without propensity score matching. Prognoses, including MFS and overall survival, were prominently inferior among patients with persistent PSA compared with those without persistent PSA. In multivariate analysis, androgen deprivation therapy (ADT) plus radiotherapy (RT) was associated with better MFS than ADT alone among patients with persistent PSA (hazard ratio = 0.37; 95% confidence interval = 0.15-0.93; p = 0.034). Similarly, MFS and overall survival were significantly better for ADT plus RT than for ADT alone among patients with persistent PSA after propensity score matching. This study indicated that PSA persistence in LNI prostate cancer increased the risk of poor prognoses, and intensive treatment featuring the addition of RT to ADT might improve survival.
Assuntos
Antagonistas de Androgênios , Neoplasias da Próstata , Antagonistas de Androgênios/uso terapêutico , Androgênios , Humanos , Linfonodos/patologia , Masculino , Antígeno Prostático Específico , Prostatectomia/métodos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Estudos RetrospectivosRESUMO
A common morphological feature of typical angiosperms is the patterning of lateral organs along primary axes of asymmetry-a proximodistal, a mediolateral, and an adaxial-abaxial axis. Angiosperm leaves usually have distinct adaxial-abaxial identity, which is required for the development of a flat shape. By contrast, many unifacial leaves, consisting of only the abaxial side, show a flattened morphology. This implicates a unique mechanism that allows leaf flattening independent of adaxial-abaxial identity. In this study, we report a role for auxin in outgrowth of unifacial leaves. In two closely related unifacial-leaved species of Juncaceae, Juncus prismatocarpus with flattened leaves, and Juncus wallichianus with transversally radialized leaves, the auxin-responsive gene GLYCOSIDE HYDROLASE3 displayed spatially different expression patterns within leaf primordia. Treatment of J. prismatocarpus seedlings with exogenous auxin or auxin transport inhibitors, which disturb endogenous auxin distribution, eliminated leaf flatness, resulting in a transversally radialized morphology. These treatments did not affect the radialized morphology of leaves of J. wallichianus. Moreover, elimination of leaf flatness by these treatments accompanied dysregulated expression of genetic factors needed to specify the leaf central-marginal polarity in J. prismatocarpus. The findings imply that lamina outgrowth of unifacial leaves relies on proper placement of auxin, which might induce initial leaf flattening and subsequently act to specify leaf polarity, promoting further flattening growth of leaves.
Assuntos
Ácidos Indolacéticos/metabolismo , Magnoliopsida/genética , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/metabolismo , Transporte Biológico , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/metabolismo , Magnoliopsida/enzimologia , Magnoliopsida/crescimento & desenvolvimento , Folhas de Planta/enzimologia , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Proteínas de Plantas/genética , Plântula/enzimologia , Plântula/genética , Plântula/crescimento & desenvolvimentoRESUMO
Although the spread of plasmid-mediated antibiotic-resistant bacteria is a public health concern, food contamination with plasmid-mediated antibiotic-resistant Escherichia coli in Vietnam has not been well investigated. This study aimed to describe the prevalence of colistin-resistant, carbapenem-resistant, and endemic blaCTX-M in extended-spectrum ß-lactamase (ESBL) producing E. coli isolates. Colistin and carbapenem-resistant ESBL-producing E. coli were isolated from chickens in Vietnam and Japan. Colistin-resistant and AmpC/ESBL-producing E. coli (52% and 93%, respectively) were detected in chickens from Vietnam, in comparison to 52.7%, AmpC/ESBL-producing E. coli found in chicken from Japan. Carbapenem-resistant E. coli has not been isolated in Vietnam and Japan. Genotyping revealed that colistin-resistant E. coli harboured mcr-1, and most of the AmpC/ESBL-related genes were blaCTX-M-55 and blaCTX-M-65 together with blaTEM in Vietnamese chickens and blaCMY-2 in Japanese chickens. Multi-drug resistance analysis showed that ESBL-producing E. coli isolates had greater resistance to quinolones, streptomycin, and chloramphenicol than colistin-resistant E. coli isolates from Vietnam, suggesting the selection of multiple antibiotic resistance genes in ESBL-producing E. coli. In conclusion, colistin-resistant E. coli was detected in approximately half of the chicken samples, the majority of which harboured mcr-1. The high prevalence of ESBL-producing E. coli has remained constant in the last 5 years. The predominant blaCTX-M in ESBL-producing E. coli was blaCTX-M-55 or blaCTX-M-65, with the coexistence of blaTEM in Vietnam. These results can be implemented in monitoring systems to overcome the development of antimicrobial resistance.
Assuntos
Infecções por Escherichia coli , Proteínas de Escherichia coli , Animais , Antibacterianos/farmacologia , Galinhas , Colistina/farmacologia , Escherichia coli/genética , Infecções por Escherichia coli/veterinária , Proteínas de Escherichia coli/genética , Carne , Plasmídeos/genética , Vietnã , beta-Lactamases/genéticaRESUMO
Penile cancer is a rare cancer for which no medical guidelines have been established before in Japan. These guidelines aim to standardize, as much as possible, the therapeutic modality for penile cancer, for which empirical evidence is limited on a global scale, thereby bolstering therapeutic outcomes for patients with penile cancer. The new guidelines conform to the Minds Guide for Developing Clinical Practice Guidelines (2017) as much as possible. However, virtually no randomized comparative studies and meta-analyses based on such randomized studies have been conducted. Therefore, only the findings available at present were listed after conducting an exhaustive literature review of items with extremely low evidence levels and for which bodies of evidence and grades of recommendation were not evaluated. Clinical questions were set for items with a relatively large number of studies, including retrospective studies. However, since it is virtually impracticable to summarize bodies of evidence by systematic reviews, recommendation grades and evidence levels were discussed and determined by the consensus panel of the Preparatory Committee. The following were outlined: epidemiological, pathological, diagnostic, therapeutic, follow-up, and quality of life-related findings. Additionally, seven clinical questions were established to determine recommendation grades and evidence levels. We hope that these guidelines will prove to be useful to medical professionals engaged in clinical practice related to penile cancer in Japan and anticipate that critical reviews of the guidelines will lead to further refinement of the next edition.
Assuntos
Neoplasias Penianas , Guias de Prática Clínica como Assunto , Humanos , Japão , Masculino , Neoplasias Penianas/diagnóstico , Neoplasias Penianas/terapia , Qualidade de Vida , Estudos RetrospectivosRESUMO
BACKGROUND: Fibrous sclerosing tumours and hypertrophic lesions in IgG4-related disease (IgG4-RD) are formed in various organs throughout the body, but disease in the oral region is not included among individual organ manifestations. We report a case of ossifying fibrous epulis that developed from the gingiva, as an instance of IgG4-RD. CASE PRESENTATION: A 60-year-old Japanese man visited the Department of Oral and Maxillofacial Surgery, Gunma University Hospital, with a chief complaint of swelling of the left mandibular gingiva. A 65 mm × 45 mm pedunculated tumour was observed. The bilateral submandibular lymph nodes were enlarged. The intraoperative pathological diagnosis of the enlarged cervical lymph nodes was inflammation. Based on this diagnosis, surgical excision was limited to the intraoral tumour, which was subsequently pathologically diagnosed as ossifying fibrous epulis. Histopathologically, the ossifying fibrous epulis exhibited increased levels of fibroblasts and collagen fibres, as well as infiltration by numerous plasma cells. The IgG4/IgG cell ratio was > 40%. Serologic analysis revealed hyper-IgG4-emia (> 135 mg/dL). The patient met the comprehensive clinical diagnosis criteria and the American College of Rheumatology and European League Against Rheumatism classification criteria for IgG4-RD. Based on these criteria, we diagnosed the ossifying fibrous epulis in our patient as an IgG4-related disease. A pathological diagnosis of IgG4-related lymphadenopathy was established for the cervical lymph nodes. Concomitant clinical findings were consistent with type II IgG4-related lymphadenopathy. CONCLUSIONS: A routine serological test may be needed in cases with marked fibrous changes (such as epulis) in the oral cavity and plasma cells, accompanied by tumour formation, to determine the possibility of individual-organ manifestations of IgG4-related disease.
Assuntos
Neoplasias Gengivais , Doença Relacionada a Imunoglobulina G4 , Linfadenopatia , Humanos , Imunoglobulina G , Doença Relacionada a Imunoglobulina G4/complicações , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/patologia , Masculino , Pessoa de Meia-Idade , Estados UnidosRESUMO
Testicular epidermoid cysts are relatively rare, accounting for about 1% of all testicular tumors, and are often treated by high orchiectomy. We describe here the case of a testicular epidermoid cyst treated by testicle-sparing surgery due to a preoperative diagnosis. A 23-year-old man complained of a painless mass in the right scrotum. Physical examination revealed a firm little fingertip-sized smooth-surfaced mass in the right testis. Ultrasonography showed a hypoechoic lesion with an echogenic rim in the right testis. A T2-weighted magnetic resonance image showed a well-demarcated mass with a low signal outline. On the basis of a preoperative diagnosis of epidermoid cyst, intraoperative testicular frozen section was performed, and the mass was resected surgically while preserving the testis.
Assuntos
Cisto Epidérmico , Doenças Testiculares , Adulto , Cisto Epidérmico/diagnóstico por imagem , Cisto Epidérmico/cirurgia , Humanos , Masculino , Orquiectomia , Doenças Testiculares/diagnóstico por imagem , Doenças Testiculares/cirurgia , Ultrassonografia , Adulto JovemRESUMO
Streptococcal toxic shock syndrome (STSS) is a severe invasive infection characterized by the sudden onset of shock, multi-organ failure, and puerperal sepsis and shows high mortality. Its primary cause is group A streptococcus (GAS, Streptococcus pyogenes). In this study, we genotyped the cell-surface M virulence protein gene (emm) from 621 GAS isolates obtained from patients with STSS in Japan in 2013-2018 and performed antimicrobial susceptibility testing using the broth microdilution method. The predominant emm type was found to be 1, followed by 89, 12, and 3, which were identified in more than 70 % of STSS isolates. The proportions of emm3 and emm89 increased from 2.4 % and 12.0 %, respectively, during 2010-2012 to 5.6 % and 23.3 % during 2013-2018. In contrast, the proportion of emm1 decreased from 60.6 % to 39.3 % during the same two periods. Some emm types showed increasing proportions and were not isolated from patients with STSS in 2010-2012. Among these, an emm76 type increased in prevalence and was not included in the 30-valent M protein-based vaccine. Continual investigation of changes in the epidemiology of GAS which causes STSS can provide useful monitoring information such as future vaccination strategies and the emergence status of antimicrobial-resistant bacteria.
Assuntos
Choque Séptico , Infecções Estreptocócicas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genética , Farmacorresistência Bacteriana , Humanos , Japão , Choque Séptico/tratamento farmacológico , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/epidemiologia , Streptococcus pyogenes/genéticaRESUMO
BACKGROUND: Standard treatments for small cell carcinoma of the cervix (SCCC) have not been established. In this study, we aimed to estimate the optimal treatment strategy for SCCC. METHODS: This was a multicenter retrospective study. Medical records of patients with pathologically proven SCCC treated between 2003 and 2016 were retrospectively analyzed. Overall survival (OS) was plotted using the Kaplan-Meier method. Log-rank tests and Cox regression analysis were used to assess the differences in survival according to stage, treatment strategy, and chemotherapy regimen. RESULTS: Data of 78 patients were collected, and after excluding patients without immunohistopathological staining, 65 patients were evaluated. The median age of the included patients was 47 (range: 24-83) years. The numbers of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stages I-IIA, IIB-IVA, IVB were 23 (35%), 34 (52%), and 8 (12%), respectively. Of 53 patients who had undergone chemotherapy, 35 and 18 received SCCC and non-SCCC regimens as their first-line chemotherapy regimen, respectively. The 5-year OS for all patients was 49%, while for patients with FIGO stages I-IIA, IIB-IVA, IVB, it was 60, 50, and 0%, respectively. The 5-year OS rates for patients who underwent treatment with SCCC versus non-SCCC regimens were 59 and 13% (p < 0.01), respectively. This trend was pronounced in locally advanced stages. Multivariate analysis showed that FIGO IVB at initial diagnosis was a significant prognostic factor in all patients. Among the 53 patients who received chemotherapy, the SCCC regimen was associated with significantly better 5-year OS in both the uni- and multivariate analyses. CONCLUSION: Our results suggest that the application of an SCCC regimen such as EP or IP as first-line chemotherapy for patients with locally advanced SCCC may play a key role in OS. These findings need to be validated in future nationwide, prospective clinical studies.
Assuntos
Carcinoma de Células Pequenas/terapia , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma de Células Pequenas/mortalidade , Carcinoma de Células Pequenas/patologia , Causas de Morte , Quimiorradioterapia , Feminino , Humanos , Japão , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Adulto JovemRESUMO
BACKGROUNDS: Epithelial mesenchymal transition (EMT) is a critical process involved in the invasion and metastasis of cancer, including lung cancer (LC). Transforming growth factor (TGF)-ß is one of factors capable of inducing EMT. Polyinosinic-polycytidylic acid (polyI:C), a synthetic agonist for toll-like receptor (TLR) 3, can enhance immune responses and has been used as an adjuvant for cancer vaccines; however, it remains unclear whether it influences other process, such as EMT. In the present study, we examined the effects of polyI:C on TGF-ß-treated A549 human LC cells. METHODS AND RESULTS: By in vitro cell proliferation assay, polyI:C showed no effect on the growth of A549 cells treated with TGF-ß1 at the concentration range up to 10 µg/ml; however, it markedly suppressed the motility in a cell scratch and a cell invasion assay. By Western blotting, polyI:C dramatically decreased TGF-ß1-induced Ak strain transforming (Akt) phosphorylation and increased phosphatase and tensin homologue (PTEN) expression without affecting the Son of mothers against decapentaplegic (Smad) 3 phosphorylation or the expression level of E-cadherin, N-cadherin or Snail, indicating that polyI:C suppressed cell motility independently of the 'cadherin switching'. The Akt inhibitor perifosine inhibited TGF-ß1-induced cell invasion, and the PTEN-specific inhibitor VO-OHpic appeared to reverse the inhibitory effect of polyI:C. CONCLUSION: PolyI:C has a novel function to suppress the motility of LC cells undergoing EMT by targeting the phosphatidylinositol 3-kinase/Akt pathway partly via PTEN and may prevent or reduce the metastasis of LC cells.
Assuntos
Adenocarcinoma Bronquioloalveolar/metabolismo , Movimento Celular/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Poli I-C/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/farmacologia , Células A549 , Adenocarcinoma Bronquioloalveolar/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/patologia , Compostos Organometálicos/farmacologia , PTEN Fosfo-Hidrolase/antagonistas & inibidores , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Fosforilação/efeitos dos fármacos , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Recombinantes/farmacologia , Receptor 3 Toll-Like/agonistasRESUMO
PURPOSE: Oral adverse events, such as dental inflammation with exacerbation, are stressful and lead to poor nutrition in patients undergoing cancer therapy. Thus, the prediction of risk factors for dental inflammation with exacerbation is important before cancer therapy is initiated. We hypothesized that, during cancer therapy (DIECT), fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging could be useful to predict dental inflammation with exacerbation. METHODS: We enrolled 124 patients who underwent FDG-PET/CT for diagnostic staging before cancer treatment. We then assessed DIECT outcomes after basic perioperative oral treatment. Moreover, we evaluated clinical parameters, therapeutic strategies, periodontal examination (probing depth (PD) and bleeding on probing (BOP)), dental imaging, and FDG-PET/CT imaging results of patients with and without DIECT. Furthermore, PET/CT images were assessed as per the FDG accumulation of the dental lesion (PAD) grading system. RESULTS: Univariate analysis demonstrated significant differences in age, periodontal examination (PD and BOP), and PAD grade between patients with and without DIECT. Furthermore, multivariate logistic regression analysis identified independent predictive factors for a positive periodontal examination (PD) (odds ratio (OR) 5.9, 95% confidence interval (CI) 1.8-19.7; P = 0.004) and PAD grade (OR 11.6, 95% CI 3.2-41.2; P = 0.0002). In patients with cancer, PAD grade using FDG-PET/CT imaging was an independent and informative risk factor for DIECT. CONCLUSION: Our results suggested that, for patients with DIECT, periodontal examination and PAD grade were independent predictive factors. Hence, regardless of the presence or absence of any lesion on dental imaging, PAD grade might be an additional tool, in addition to periodontal examination that potentially improves oral care management.
Assuntos
Fluordesoxiglucose F18/efeitos adversos , Inflamação/etiologia , Neoplasias/complicações , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/efeitos adversos , Idoso , Feminino , Fluordesoxiglucose F18/farmacologia , Humanos , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fatores de RiscoRESUMO
The prevalence of food-borne bacteria in developing countries is less well understood than in developed countries. The ISO11290-1 isolation method is commonly used to study Listeria contamination in chicken; however, all isolates are identified as untargeted Bacillus cereus. This study aimed to determine the classification, antibiotic susceptibility, and virulence genes of B. cereus isolated from retail chickens in Vietnam. Bacterial isolation using the ISO11290-1 method yielded 12 strains of B. cereus from seven out of 60 chickens. For determining bacterial diversity, panC and multilocus sequence typing (MLST) analyses were performed. PanC analysis showed that all seven strains belong to the phylogenetic group III, to which the highest risk of foodborne illnesses was associated. MLST analysis showed that most strains contained a ST205 complex; further, all strains were found to be resistant to ampicillin, ciprofloxacin, and tetracycline. Virulence genes were also investigated. ces, a cereulide-related gene, was detected in 50% of the isolated strains, followed by cytK, nheA, and hblA enterotoxins in 41.7%, 16.7%, and 25% of the strains, respectively. In conclusion, B. cereus may be erroneously detected when attempting to detect Listeria in food using the ISO11290-1 method. Further study of the prevalence of B. cereus in Vietnamese food is needed to improve food safety.
Assuntos
Bacillus cereus , Preparações Farmacêuticas , Animais , Bacillus cereus/genética , Galinhas , Enterotoxinas , Microbiologia de Alimentos , Tipagem de Sequências Multilocus , Filogenia , VietnãRESUMO
Targeting the programmed cell death-1 signaling pathway has been approved for the anti-cancer therapy in several cancers including urothelial cancer. To determine predictive factors of the responsiveness to pembrolizumab in urothelial cancer patients, a retrospective study that used clinical information and paraffin-embedded samples obtained from patients diagnosed with urothelial cancer between 2015 and 2020 were performed. Seventeen patients who underwent total cystectomy or nephroureterectomy of the primary lesion and were treated with pembrolizumab for chemo-resistant disease were enrolled, and immunohistochemical analysis was performed. A key difference in the characteristics between the non-responder group and the responder group was the age of the patients (74 vs. 63 years, p = 0.0194). Although there was no statistically significant difference, the histological subtype with sarcomatoid and micropapillary components was only seen in the non-responder group, and squamous differentiation and lymph node metastasis were only seen in cases with a complete response. In the results of immunohistochemistry, the density of CD8-positive T-cells and Tregs was significantly increased in the responder group than in the non-responder group. In conclusion, younger age and a high number of tumor-infiltrating lymphocytes were predictive factors of a good response to immune checkpoint inhibitors, although further studies with more enrolled patients are necessary.
Assuntos
Anticorpos Monoclonais Humanizados , Neoplasias da Bexiga Urinária , Fatores Etários , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Linfócitos T CD8-Positivos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Linfócitos T Reguladores , Neoplasias da Bexiga Urinária/tratamento farmacológicoRESUMO
An 18-year-old male was aware of painless left testicular enlargement. Contrast-enhanced computed tomography showed a retroperitoneal tumor, multiple liver tumors, and multiple lung tumors. A left testicular tumor was suspected, and left inguinal orchiectomy was performed. The pathological diagnosis was choriocarcinoma, yolk sac tumor, and embryonal carcinoma. Although bleomycin, etoposide and cisplatin therapy was performed as first-line chemotherapy and paclitaxel, iphosfamide and cisplatin therapy was performed as second-line chemotherapy, the tumor markers did not become negative. Retroperitoneal lymph node dissection and partial hepatectomy were performed as desperation surgery. However a new brain metastatic lesion appeared; then, radiation therapy (whole brain irradiation, stereotactic radiotherapy) and gemcitabine, oxaliplatin therapy were performed. The tumor marker became negative, and lung metastases were resected followed by right lower lung lobectomy. No recurrence has been observed for one year and six months after the lobectomy.