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Information about extramammary Paget's (EMPD) treatment is limited because of the rarity of the disease. The prognosis differs between in situ EMPD and invasive EMPD; therefore, therapy should be planned according to the disease stage. We collected data on 643 EMPD cases treated between 2015 and 2019 in Japan and assessed recent trends in EMPD treatment and prognosis based on the EMPD-oriented TNM staging. Among the 643 patients, 317 had stage 0 (49.3%), 185 had stage I (28.8%), 51 had stage II (7.9%), 18 had stage IIIA (2.8%), 48 had stage IIIB (7.5%) and 24 had stage IV (3.7%) disease. Each stage showed a distinct survival curve, with the exception of stages II and IIIA. Curative surgery was most common in patients with stage 0-III disease. Chemotherapy was the first-line therapy, mainly in patients with stage IIIB and IV disease, most commonly with docetaxel (DTX), followed by DTX + tegafur gimeracil oteracil potassium (TS-1) and TS-1. Patients with local disease exhibited a 4.4% recurrence rate. Univariate analysis revealed no prognostic differences according to age, sex or primary tumour site. SLNB was not related to disease-specific survival. In multivariate analysis, female sex significantly predicted local relapse in stage 0-I (HR 3.09; 95% CI, 1.13-8.43), and initial treatment with curative surgery was significantly protective in terms of disease-specific survival in stage II-IIIA (HR, 0.17; 95% CI, 0.04-0.71) and stage IIIB-IV (HR 0.16; 95% CI, 0.05-0.51). Further clinical studies are needed to improve the prognosis of patients with stage II-IV EMPD.
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Enfermedad de Paget Extramamaria , Silicatos , Titanio , Humanos , Femenino , Enfermedad de Paget Extramamaria/tratamiento farmacológico , Enfermedad de Paget Extramamaria/patología , Recurrencia Local de Neoplasia/patología , Pronóstico , Estadificación de NeoplasiasRESUMEN
Talimogene laherparepvec (T-VEC) is approved for the treatment of unresectable melanoma in the USA, Europe, and Australia. This phase I, multicenter, open-label, dose de-escalation study evaluated the safety and efficacy of T-VEC in Japanese patients with unresectable stage IIIB-IV melanoma. Eligible adult patients had histologically confirmed stage IIIB-IVM1c cutaneous melanoma, may have received prior systemic anticancer therapy, must have had ≥1 injectable lesion, serum lactate dehydrogenase ≤1.5x upper limit of normal, ECOG performance status of 0 or 1, and adequate hematologic, hepatic, and renal function. T-VEC was injected intralesionally (first dose, ≤4.0 ml of 106 PFU/ml; after 3 weeks and then every 2 weeks thereafter, ≤4.0 ml of 108 PFU/ml). Primary endpoints were dose-limiting toxicities (DLTs) and durable response rate (DRR). Of 18 enrolled patients (72.2% female), 16 had received ≥1 prior line of therapy. Ten patients discontinued T-VEC due to disease progression. Median (range) follow-up was 20.0 (4-37) months. No DLTs were observed; 17 (94.4%) patients had treatment-emergent adverse events (AEs). Fourteen (77.8%) patients had treatment-related AEs; the most frequent were pyrexia (44.4%), malaise (16.7%), chills, decreased appetite, pruritus, and skin ulcer (11.1% each). The primary efficacy endpoint was met: 2 (11.1%) patients had a durable partial response ≥6 months. The DRR was consistent with that observed in a phase III trial of T-VEC in non-Asian patients. The safety profile was consistent with the patients' underlying disease and the known safety profile of T-VEC.
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Productos Biológicos , Melanoma , Viroterapia Oncolítica , Neoplasias Cutáneas , Adulto , Productos Biológicos/efectos adversos , Femenino , Herpesvirus Humano 1 , Humanos , Japón , Masculino , Melanoma/tratamiento farmacológico , Melanoma/patología , Viroterapia Oncolítica/efectos adversos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: Although pre-emptive therapy with oral tetracycline, moisturizer, sunscreen, and topical corticosteroid is useful for preventing acneiform eruption (AfE) due to epidermal growth factor receptor (EGFR) inhibitors, no studies have examined the efficacy of topical corticosteroids themselves, or investigated the optimal potency of corticosteroid for treating facial AfE (FAfE). PATIENTS AND METHODS: Screened patients with RAS wild-type colorectal cancer started pre-emptive therapy with oral minocycline and moisturizer on initiation of cetuximab or panitumumab therapy. Patients who developed grade 1 or 2 FAfE were randomly allocated to two groups: a ranking-down (RD) group that started with a very strong corticosteroid and serially ranked down every 2 weeks unless FAfE exacerbated; and a ranking-up (RU) group that started with a weak corticosteroid and serially ranked up at exacerbation. FAfE grade, patient quality of life, and adverse events (AEs) with topical corticosteroid were evaluated every 2 weeks. The primary endpoint was the total number of times grade 2 or higher FAfE was identified in the central review of the 8-week treatment period. RESULTS: No significant differences in total numbers of grade 2 or higher FAfE or in AEs caused by topical corticosteroids were observed between groups during the 8 weeks. Incidence of grade 2 or higher FAfE tended to be lower in the RD group during the first 2 weeks. CONCLUSION: Considering the long-term care of FAfE, the RU regimen appears suitable and should be considered the standard treatment for FAfE due to EGFR inhibitor therapy. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN000024113).
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Erupciones Acneiformes , Neoplasias del Colon , Neoplasias Colorrectales , Erupciones Acneiformes/inducido químicamente , Erupciones Acneiformes/tratamiento farmacológico , Erupciones Acneiformes/prevención & control , Cetuximab/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Receptores ErbB , Glucocorticoides/uso terapéutico , Humanos , Calidad de VidaRESUMEN
BACKGROUND: Nivolumab, the anti-programmed cell death protein 1 antibody, has been approved for advanced melanoma, mainly based on evidence from Western countries. The profile of melanoma differs between Caucasian and Asian patients. This study was performed to obtain post-marketing data of nivolumab in Japanese patients with advanced melanoma. METHODS: This prospective, observational study involved patients with unresectable or metastatic melanoma treated with nivolumab at dosages of 2 mg/kg every 3 weeks or 3 mg/kg every 2 weeks. The primary endpoints were objective response rate and overall survival. The secondary endpoints were progression-free survival and the objective response rate according to immune-related Response Evaluation Criteria in Solid Tumours. RESULT: Among 124 patients analysed, mucosal melanoma was the most common subtype, followed by acral lentiginous, nodular, superficial spreading and lentigo maligna melanoma. Response Evaluation Criteria in Solid Tumours evaluation showed an objective response rate of 17.7%. The median survival time was 15.93 months, and the 1-year overall survival rate was 66%. Outcomes were not significantly different among melanoma subtypes. Better overall survival and/or progression-free survival but not objective response rate were associated with performance status 0, lower levels of lactate dehydrogenase, C-reactive protein and neutrophil-to-lymphocyte ratio. Patients with immune-related adverse events showed a better objective response rate, 3-month landmark overall survival and progression-free survival than patients without immune-related adverse events. CONCLUSION: The objective response rate and median survival time in Japanese patients treated with nivolumab were lower in daily practice than the >30% and >30 months, respectively, seen in global phase III trials. The occurrence of immune-related adverse events may be a predictor for survival and response to treatment with nivolumab.
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Melanoma , Nivolumab , Neoplasias Cutáneas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/uso terapéutico , Femenino , Humanos , Japón/epidemiología , Masculino , Melanoma/tratamiento farmacológico , Persona de Mediana Edad , Nivolumab/uso terapéutico , Estudios Prospectivos , Neoplasias Cutáneas/tratamiento farmacológico , Adulto JovenRESUMEN
BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is one of the most common skin cancers. Prognosis is favorable following surgical resection of early-stage disease, but the management of the metastatic disease is challenging. Several prognostic risk factors have been described in the American Joint Committee on Cancer/the Union for International Cancer Control (UICC) 8th edition staging and the Brigham and Women's Hospital T classification system. However, their clinical validity in Asian populations is unclear because of racial differences in the clinical characteristics of CSCC. This study aimed to identify factors that could predict lymph node metastasis in Asian patients. METHODS: This retrospective single-center study evaluated 540 patients with primary CSCC between 1989 and 2013. Five factors were evaluated for their ability to predict lymph node metastasis: maximum tumor diameter, tumor thickness, depth of invasion, degree of differentiation, and infiltrative growth pattern (INF). RESULTS: Tumor diameter > 2 cm (p < 0.0001), tumor thickness > 6 mm (p < 0.0001), invasion beyond the subcutaneous fat (p < 0.0001), poor differentiation (p = 0.042), and INFc infiltration (p < 0.0001) were associated with lymph node metastasis in the univariate analyses. In the multivariate analysis, lymph node metastasis was independently associated with tumor size > 2 cm [hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.4-6.2; p = 0.006], tumor thickness > 6.0 mm (HR 2.9, 95% CI 1.3-6.4; p = 0.007), and invasion beyond the subcutaneous fat (HR 2.3, 95% CI 1.0-5.1; p = 0.045). CONCLUSION: Larger tumor diameter, greater tumor thickness, and deeper invasion included in the UICC T classification system are associated with increased risks of lymph node metastasis from CSCC in Japanese patients.
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Carcinoma de Células Escamosas , Neoplasias Cutáneas , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Japón , Ganglios Linfáticos/patología , Metástasis Linfática , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Cutáneas/patologíaRESUMEN
The immune checkpoint inhibitor nivolumab inhibits the programmed death 1 receptor and suppresses the immune resistance of cancer cells. This is a long-term follow up of a single-arm, open-label, multicenter, phase II study of nivolumab in untreated Japanese patients with stage III/IV or recurrent melanoma. In addition, a post-hoc subgroup analysis stratified by melanoma types was performed. Nivolumab was administered intravenously at a dose of 3 mg/kg every 2 weeks. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), best overall response, the disease control rate and change in tumor diameter. Safety was assessed by recording treatment-related adverse events (TRAE), including select immune-related adverse events. Of the 24 patients initially included in the primary phase II study, 10 survived for over 3 years (41.7%). The ORR was 34.8% (90% confidence interval [CI]: 20.8, 51.9) for all patients. When analyzing by melanoma type, the ORR was 66.7% (90% CI: 34.7, 88.3) for superficial spreading, 33.3% (90% CI: 11.7, 65.3) for mucosal, and 28.6% (90% CI: 10.0, 59.1) for acral lentiginous tumors. The median OS was 32.9 months, the 3-year OS rate was 43.5%, and the 3-year PFS rate was 17.2%. A long-term response was observed in all the tumor types. The most common TRAE included skin toxicity (45.8%) and endocrine disorders (29.2%). This study demonstrated the long-term efficacy and tolerability of nivolumab in patients with advanced or recurrent melanoma, irrespective of melanoma type.
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Melanoma/tratamiento farmacológico , Nivolumab/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Administración Intravenosa , Anciano , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/uso terapéutico , Pueblo Asiatico , Estudios de Seguimiento , Humanos , Japón , Estimación de Kaplan-Meier , Masculino , Melanoma/etnología , Melanoma/patología , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Nivolumab/administración & dosificación , Nivolumab/efectos adversos , Prurito/inducido químicamente , Neoplasias Cutáneas/etnología , Neoplasias Cutáneas/patología , Vitíligo/inducido químicamente , Melanoma Cutáneo MalignoRESUMEN
Onco-cardiology, a new academic field, aims to improve the quality of life and prognosis of cancer patients and survivors with cardiovascular diseases (CVD). With the aging of the population, an epidemic of cancer with CVD is emerging in developed countries. Cancer and CVD share risk factors, pathophysiology, treatments, and preventive and rehabilitative measures. A multidisciplinary team-based approach is needed to support cancer treatment to maximize its effectiveness and minimize its cardiotoxic potential. Basic and clinical onco-cardiology are already being practiced harmoniously. However, systematization in academia and clinical practice and accumulation of evidence have just started. In this review, we present the epidemiology, common risk factors between cancer and CVD, future epidemic of CVD in patients with cancer, and the necessity for an onco-cardiological approach to managing the burden of CVD in cancer patients and survivors.
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Antineoplásicos/efectos adversos , Enfermedades Cardiovasculares/epidemiología , Epidemias , Neoplasias/terapia , Traumatismos por Radiación/epidemiología , Sobrevivientes , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/terapia , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico , Neoplasias/epidemiología , Prevalencia , Pronóstico , Traumatismos por Radiación/diagnóstico , Traumatismos por Radiación/terapia , Radioterapia/efectos adversos , Medición de Riesgo , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Cardiovascular disease (CVD) and cancer are major causes of death in Japan. As most CVDs are chronic and often aggravate, long-term follow-up is necessary. Although some cancer patients and survivors have CVD, its prognostic significance and prevalence are unknown. Therefore, we conducted a retrospective study at our center to determine the prevalence of cancer patients with CVD. METHODS: In 2015, our 10-year (2005-2014) cancer registry was summarized. Comorbidities including left ventricular dysfunction, atrial fibrillation (AF), ischemic heart disease, aortic stenosis, venous thromboembolism (VTE), and elevation of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were examined. RESULTS: In total, 26,235 de novo cancer patients were registered and 16,130 survived until January 1, 2015. The 5-year survival rate was 64.0% for all cancer patients and 44.2% for cancer patients with CVD. Cox proportional hazards analysis adjusting for age, cancer stage, and body mass index revealed that AF [hazard ratio (HR) 1.219, male; P = 0.038], VTE (HR 1.517, male; P = 0.003 and HR 2.089, female; P < 0.001), and NT-proBNP elevation (HR 1.861, female; P = 0.002) were significantly associated with death. The CVD prevalence among cancer survivors in 2015 was 8.7% vs 3.5% for males vs females. AF was the most common CVD (prevalence: male, 4.0%; female, 1.0%). The prevalence of most CVD in adults increased progressively with age, with male predominance (12.1% for male and 7.5% for female patients in the 80 s age group). CONCLUSIONS: One in 10 elderly cancer survivors has serious CVD. AF, VTE, and heart failure were critical comorbidities. Cardiologists and cancer-care providers should recognize CVD presence and monitor patients closely, providing medications or interventions concurrently with cancer therapy.
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Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Neoplasias/complicaciones , Sobrevivientes/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/etiología , Niño , Preescolar , Comorbilidad , Femenino , Humanos , Lactante , Recién Nacido , Japón/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
n the original publication, in a title of Table 2.
RESUMEN
BACKGROUND: The number of cancer patients in Japan is estimated to rise to 3.5 million by 2025. The disease burden may be further complicated by comorbidities caused by cardiovascular disease (CVD). Predicting the number of cancer patients with CVD can help anticipate future resource needs. METHODS: We used statistics derived from the Niigata Cancer Center CVD Study (2015) as well as population estimates from the National Cancer Center's Cancer Registry and Statistics survey of 2017 for convenience. We simply multiplied the projected number of cancer patients through the year 2039 by the CVD prevalence in 2015, with patients classified by sex, age, and cancer type to estimate the number of cancer patients with CVD. RESULTS: The total number of Japanese cancer patients with CVD was 253,000 in 2015 and is predicted to increase rapidly by 30,000 in 2020 and peak at 313,000 in 2030-2034. Men will dominate the CVD population at 2.5-fold the number of women. The growth rate of the population with both cancer and CVD will be greater than that of the cancer-only population (1.23 vs 1.18, P < 0.001), and will comprise notably high proportions of patients with prostatic, breast, and uterine cancers (1.80, 1.57, and 1.66, P < 0.001, respectively). CONCLUSION: Future cancer patients will be older and more likely to have CVD. Although men will continue to dominate this population, the increase in the number of women will be pronounced. Cancer care providers should be trained to recognize CVD and provide any necessary interventions concurrently with cancer therapy.
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Enfermedades Cardiovasculares/epidemiología , Neoplasias/complicaciones , Adolescente , Adulto , Anciano , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Japón/epidemiología , Masculino , Persona de Mediana Edad , Proyectos Piloto , Prevalencia , Pronóstico , Sistema de Registros , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenAsunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Pueblos del Este de Asia , Ipilimumab/uso terapéutico , Melanoma/tratamiento farmacológico , Melanoma/etiología , Nivolumab/uso terapéutico , Estudios Retrospectivos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/etiologíaRESUMEN
Treating advanced or recurrent melanoma remains a challenge. Cancer cells can evade the immune system by blocking T-cell activation through overexpression of the inhibitory receptor programmed death 1 (PD-1) ligands. The PD-1 inhibitor nivolumab blocks the inhibitory signal in T cells, thus overcoming the immune resistance of cancer cells. Nivolumab has shown promising anticancer activity in various cancers. We carried out a single-arm, open-label, multicenter, phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma. Twenty-four patients with stage III/IV or recurrent melanoma were enrolled and received i.v. nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was overall response rate evaluated by an independent radiology review committee. The independent radiology review committee-assessed overall response rate was 34.8% (90% confidence interval, 20.8-51.9), and the overall survival rate at 18 months was 56.5% (90% confidence interval, 38.0-71.4). Treatment-related adverse events (AEs) of grade 3 or 4 only occurred in three patients (12.5%). Two patients discontinued nivolumab because of AEs, but all AEs were considered manageable by early diagnosis and appropriate treatment. Subgroup analyses showed that nivolumab was clinically beneficial and tolerable regardless of BRAF genotype, and that patients with treatment-related select AEs and with vitiligo showed tendency for better survival. In conclusion, nivolumab showed favorable efficacy and safety profiles in Japanese patients with advanced or recurrent melanoma, with or without BRAF mutations. (Trial registration no. JapicCTI-142533.).
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Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Melanoma/tratamiento farmacológico , Anciano , Pueblo Asiatico , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Melanoma/metabolismo , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/metabolismo , Nivolumab , Proteínas Proto-Oncogénicas B-raf/metabolismo , Tasa de SupervivenciaRESUMEN
Promising antitumor activities of nivolumab, a fully humanized IgG4 inhibitor antibody against the programmed death-1 protein, were suggested in previous phase 1 studies. The present phase 2, single-arm study (JAPIC-CTI #111681) evaluated the antitumor activities of nivolumab and explored its predictive correlates in advanced melanoma patients at 11 sites in Japan. Intravenous nivolumab 2 mg/kg was given repeatedly at 3-week intervals to 35 of 37 patients enrolled from December 2011 to May 2012 until they experienced unacceptable toxicity, disease progression, or complete response. Primary endpoint was objective response rate. Serum levels of immune modulators were assessed at multiple time points. As of 21 October 2014, median response duration, median progression-free survival, and median overall survival were 463 days, 169 days, and 18.0 months, respectively. The overall response rate and 1- and 2-year survival rates were 28.6%, 54.3%, and 42.9%, respectively. Thirteen patients remained alive at the end of the observation period and no deaths were drug related. Grade 3-4 drug-related adverse events were observed in 31.4% of patients. Pretreatment serum interferon-γ, and interleukin-6 and -10 levels were significantly higher in the patients with objective tumor responses than in those with tumor progression. In conclusion, giving repeated i.v. nivolumab had potent and durable antitumor effects and a manageable safety profile in advanced melanoma patients, strongly suggesting the usefulness of nivolumab for advanced melanoma and the usefulness of pretreatment serum cytokine profiles as correlates for predicting treatment efficacy.
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Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Biomarcadores/metabolismo , Citocinas/metabolismo , Melanoma/tratamiento farmacológico , Melanoma/metabolismo , Anciano , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Masculino , Melanoma/patología , Nivolumab , Tasa de SupervivenciaAsunto(s)
Melanoma , Humanos , Melanoma/tratamiento farmacológico , Pronóstico , Estudios Retrospectivos , SíndromeRESUMEN
The Dermatologic Oncology Group of Japan Clinical Oncology Group has started a randomized phase III trial to confirm the superiority of adjuvant therapy with locoregional interferon beta in overall survival over surgery alone for patients with pathological stage II/III cutaneous melanoma (JCOG1309). Patients in the interferon beta arm receive intra- or subcutaneous injections of interferon beta directly into the surgical site at a flat dose of 3 million units once per day. Treatment is repeated for 10 consecutive days every 8 weeks for a total of 3 courses during the induction phase, then 1-day injection every 4 weeks for 2.5 years. A total of 240 patients will be accrued from 17 Japanese institutions within 6.5 years. Primary endpoint is overall survival. Secondary endpoints are relapse-free survival, distant metastasis-free survival, pattern of recurrence, and adverse events. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000017494 [http://www.umin.ac.jp/ctr/index.htm].
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Interferón beta/uso terapéutico , Oncología Médica , Melanoma/tratamiento farmacológico , Melanoma/cirugía , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/cirugía , Quimioterapia Adyuvante , Terapia Combinada , Supervivencia sin Enfermedad , Humanos , Japón , Selección de Paciente , Resultado del Tratamiento , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND: Axillary lymph node dissection (ALND) has been recommended to include levels I-III for melanoma patients who have evidence of metastasis in the axillary sentinel lymph node (SLN). The extent of the subsequent axillary dissection is in debate. The objective of this study was to determine the frequency of metastasis of level III nodes in addition to that of level II nodes in this setting. METHODS: A multi-institutional retrospective study was undertaken in 14 melanoma treatment centers in Japan. RESULTS: Between 2007 and 2012, 69 patients with involved axillary SLNs underwent a subsequent ALND and 55 underwent level I and II dissections. Level III metastatic nodes, which is our primary endpoint, were seen in only 1 patient (1.5 %). The level II metastatic rate was 4.4 %. CONCLUSIONS: Our study sample size was small, but melanoma patients with positive SLN rarely had level III disease, suggesting that level III dissection may be unnecessary. We also found that level II metastasis was not so frequent. More evidence is needed to standardize the extent of ALND and to identify the patients who would have the most benefit with undergoing level II dissection for positive axillary SLNs.
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Escisión del Ganglio Linfático , Melanoma/patología , Melanoma/cirugía , Biopsia del Ganglio Linfático Centinela , Ganglio Linfático Centinela/patología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Axila , Femenino , Humanos , Incidencia , Japón/epidemiología , Metástasis Linfática/diagnóstico , Masculino , Melanoma/epidemiología , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias Cutáneas/epidemiología , Resultado del TratamientoRESUMEN
Deep dermatophytosis is an invasive and sometimes life-threatening fungal infection mainly reported in immunocompromised patients. However, a caspase recruitment domain-containing protein 9 (CARD9) deficiency has recently been reported to cause deep dermatophytosis. Herein, we report the first Japanese case of deep dermatophytosis associated with CARD9 deficiency. An 80-year-old Japanese man with tinea corporis presented with subcutaneous nodules on his left sole. Histopathological findings revealed marked epithelioid cell granulomas with filamentous fungal structures in the deep dermis and subcutis, and the patient was diagnosed with deep dermatophytosis. Despite antifungal therapy, the subcutaneous nodule on his left sole gradually enlarged, his left calcaneal bone was invaded, and the patient finally underwent amputation of his left leg. Genetic analysis revealed a homozygous CARD9 c.586 A > G (p. Lys196Glu) variant, suggesting a CARD9 deficiency. Here, we discuss the clinical features of CARD9 deficiency-associated deep dermatophytosis with a case report and review of the literature.
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Arthrodermataceae , Candidiasis Mucocutánea Crónica , Tiña , Masculino , Humanos , Anciano , Anciano de 80 o más Años , Candidiasis Mucocutánea Crónica/genética , Candidiasis Mucocutánea Crónica/patología , Candidiasis Mucocutánea Crónica/terapia , Tiña/microbiología , Trichophyton/genética , Proteínas Adaptadoras de Señalización CARDRESUMEN
Pembrolizumab demonstrated an acceptable safety profile and promising antitumor activity in Japanese patients with advanced melanoma in the phase 1b KEYNOTE-041 (Study of Pembrolizumab [MK-3475] in Participants With Advanced Melanoma) trial. To evaluate the long-term efficacy and safety of pembrolizumab in Japanese patients with advanced melanoma in KEYNOTE-041. The current analysis reports results of additional follow-up of approximately 12 months since the initial analysis. Eligible patients had locally advanced (unresectable stage III) or metastatic (stage IV) melanoma not amenable to local therapy and had received two or fewer prior systemic therapies. Pembrolizumab 2 mg/kg was given every 3 weeks for up to 2 years or until confirmed progression or unacceptable toxicity. Primary end points included safety, tolerability, and overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 by independent central review. The data cutoff for this analysis was August 30, 2017. Forty-two patients were followed up for a median of 22.3 months (range, 2.63-30.82 months). The ORR was 24.3% (nine of 37 evaluable patients [95% confidence interval (CI), 11.8%-41.2%]). Two patients with partial response at the time of the initial analysis achieved complete response. The median overall survival (OS) was 25.1 months (95% CI, 13.1-not reached] and the 30-month OS rate was 46.3% (95% CI, 29.8%-61.3%). The median duration of response was not reached. Treatment-related adverse events (TRAEs) were reported in 78.6% of patients; the incidence of grade 3 to 5 TRAEs was 23.8%. No additional treatment-related deaths occurred since the initial analysis. Pembrolizumab provided durable antitumor activity and an acceptable safety profile in Japanese patients with advanced melanoma.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Antineoplásicos Inmunológicos , Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/tratamiento farmacológico , Melanoma/mortalidad , Melanoma/patología , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/mortalidad , Estudios de Seguimiento , Adulto , Japón , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/administración & dosificación , Estadificación de Neoplasias , Anciano de 80 o más Años , Resultado del Tratamiento , Pueblos del Este de AsiaRESUMEN
Although the efficacy of dermoscopic diagnosis of basal cell carcinoma (BCC) has already been established, most studies have been conducted in Western countries. However, there are racial differences in the clinicopathological characteristics of BCC, highlighting the need for a survey among Asians. Herein, we aimed to investigate the diagnostic accuracy of dermoscopy in 934 Japanese patients with BCC and statistically analyze the clinicopathological factors affecting diagnostic accuracy. We analyzed 5093 skin lesions, including 934 BCCs that were diagnosed consecutively from 1998 to 2018. The sensitivity and specificity of dermoscopic diagnosis for BCC were calculated. The sensitivity and specificity of dermoscopic diagnosis were 92.2% and 96.0%, respectively. There were 73 false-negative cases of BCCs that were clinically diagnosed with other diseases. The most common incorrect clinical diagnosis was seborrheic keratosis (n = 18), followed by melanocytic nevus (n = 15). Multiple logistic regression analysis showed that sensitivity was significantly lower in BCCs located on the trunk and extremities, which showed low pigmentation (less than 10% of the lesion surface) and were diagnosed by a resident dermatologist. Experience of 3-6 months of 12 resident dermatologists revealed increased sensitivity. Dermoscopy is a reliable tool for the accurate diagnosis of BCC in Japanese individuals. Care should be taken when diagnosing BCCs of the trunk and extremities, and the less-pigmented subtype because of lower sensitivity. A certain amount of experience is required to improve the skills for dermoscopy.