RESUMO
Apocrine carcinoma cases with sebaceous differentiation have not been reported and can be misdiagnosed as sebaceous carcinoma. We present two cases of apocrine carcinoma with marked sebocyte-like cytological features. Tumors were observed in the left axilla of a 68-year-old man (Case 1) and the right axilla of a 72-year-old man (Case 2). Both patients presented with multiple lymph node metastases. Histopathology revealed densely distributed solid nests of tumor cells containing foamy cytoplasm and enlarged round nuclei with prominent nucleoli. The tumor cells diffusely expressed adipophilin, PRAME (cytoplasmic pattern), androgen receptor, BerEP4, and GCDFP15 but did not express p63 in both cases. PIK3CA E726K and H1047R mutations were detected in Cases 1 and 2, respectively. Tumor location in the axilla, the presence of eosinophilic granular cytoplasm, prominent nucleoli, and PIK3CA mutations, immunoreactivity for BerEP4 and GCDFP15, and lack of p63 immunoexpression findings matched apocrine carcinoma characteristics, but not sebaceous carcinoma. Thus, apocrine carcinoma can demonstrate intracytoplasmic lipid accumulation and rarely exhibit sebocyte-like cytological features. Apocrine carcinoma should be distinguished from sebaceous carcinoma due to the former's higher metastatic potential and lack of association with Muir-Torre syndrome.
Assuntos
Adenocarcinoma Sebáceo , Carcinoma de Apêndice Cutâneo , Síndrome de Muir-Torre , Neoplasias das Glândulas Sebáceas , Neoplasias das Glândulas Sudoríparas , Masculino , Humanos , Idoso , Adenocarcinoma Sebáceo/patologia , Neoplasias das Glândulas Sudoríparas/patologia , Células Epiteliais/patologia , Neoplasias das Glândulas Sebáceas/diagnóstico , Neoplasias das Glândulas Sebáceas/patologia , Antígenos de NeoplasiasRESUMO
Japanese patients with very high-risk cutaneous squamous cell carcinomas (cSCCs), based on the National Comprehensive Cancer Network guidelines, have been reported to display a higher cumulative incidence of relapse and disease-specific death (DSD) than those with high-risk cSCC. Therefore, prognosis prediction is crucial for Japanese patients with very high-risk cSCCs. Herein, we aimed to evaluate the prognostic prediction ability of our novel Japanese Risk Factor Scoring Systems (JARF scoring) in a Japanese cohort of cSSC patients. Data of 424 Japanese patients with resectable very high-risk cSCCs were analysed. We compared the prognostic ability of the following three staging systems: Brigham and Women's Hospital (BWH) tumour staging, number of NCCN very high-risk factors, and JARF scoring, including recurrent tumour, high-risk histological features, deep tumour invasion and lymphatic or vascular involvement as risk factors. The prognostic ability of these staging systems was evaluated according to the cumulative incidence of local recurrence (LR), regional lymph node metastasis (RLNM), DSD, and overall survival (OS). When BWH staging was used, high T stage led to significantly poor outcomes only in the cumulative incidence of RLNM (p = 0.01). The presence of very high-risk NCCN factors led to significantly poor outcomes in terms of RLNM (p = 0.03) and OS (p = 0.02). Meanwhile, a high number of risk factors in the JARF scoring system clearly led to poor outcomes in terms of LR (p = 0.01), RLNM (p < 0.01), DSD (p = 0.03), and OS (p < 0.01). The JARF scoring system may accurately predict the risk of recurrence and death in very high-risk cSCC patients in Japan.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Humanos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Estudos Transversais , População do Leste Asiático , Japão , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgiaRESUMO
BACKGROUND AND OBJECTIVES: In cutaneous squamous cell carcinoma (cSCC), adherence to guideline-recommended fixed surgical margins is often difficult, and narrower margins are preferable. This study aimed to evaluate relapse and disease-specific death with narrower margins for high or very high-risk cSCC. PATIENTS/METHODS: We retrospectively investigated high or very high-risk cSCC patients who underwent tumor excision. Patients were divided into guideline-recommended standard margin group (SMG) and narrower-margin group (NMG). Co-primary outcomes were local relapse, SCC relapse, and SCC death. Cumulative incidence function (CIF) was used to describe SCC death probability and competing risk mortality. Gray's test was used to compare differences in CIF between the groups. RESULTS: In total, 1,000 patients with cSCC (high-risk, 570; very high-risk, 430) were included. In the high-risk cohort, there were no significant differences in incomplete excision rate (IER) between SMG and NMG (2.6 % vs. 3.0 %, P > 0.99). However, in the very high-risk cohort, IER in SMG was significantly lower than in NMG (8.9 % vs. 16.2 %, P = 0.03). No significant differences were observed between SMG and NMG for local relapse (high-risk, P = 0.56; very high-risk, P = 0.70), SCC relapse (high-risk, P = 0.30; very high-risk, P = 0.47), and SCC death (high-risk, P = 0.23; very high-risk, P = 0.83). CONCLUSIONS: Surgical margin size has limited impact on margin control, relapse, and disease-specific death in high-risk cSCC.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Humanos , Margens de Excisão , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgiaRESUMO
HINTERGRUND UND ZIELE: Bei kutanen Plattenepithelkarzinomen (PEK) ist die Einhaltung der in Leitlinien empfohlenen festen Resektionsränder oft schwierig und knappere Ränder sind wünschenswert. Ziel dieser Studie war die Bewertung des Auftretens von Rezidiven und krankheitsspezifischen Todesfällen bei knapperen Resektionsrändern für PEK mit hohem oder sehr hohem Risiko. PATIENTEN/METHODEN: PEK-Patienten mit hohem oder sehr hohem Risiko, bei denen eine Tumorexzision durchgeführt wurde, wurden retrospektiv untersucht. Die Patienten wurden in eine Gruppe mit Standardrand gemäß Leitlinienempfehlung (standard margin group, SMG) und eine Gruppe mit knapperen Rändern (narrower-margin group, NMG) eingeteilt. Gemeinsame primäre Endpunkte waren lokales Rezidiv, PEK-Rezidiv und PEK-bedingter Tod. Die Wahrscheinlichkeit eines PEK-bedingten Tods und konkurrierender Mortalitätsrisiken wurde mittels kumulativer Inzidenzfunktion (CIF) beschrieben. Unterschiede bei der CIF zwischen den Gruppen wurden mit dem Test nach Gray verglichen. ERGEBNISSE: Insgesamt wurden 1.000 Patienten mit PEK (hohes Risiko, 570; sehr hohes Risiko, 430) eingeschlossen. In der Kohorte mit hohem Risiko gab es keine signifikanten Unterschiede bei der unvollständigen Exzisionsrate (IER) zwischen SMG und NMG (2,6 % vs. 3,0 %, P > 0,99). In der Kohorte mit sehr hohem Risiko war die IER in der SMG jedoch signifikant geringer als in der NMG (8.9 % vs. 16.2 %, P = 0,03). Keine signifikanten Unterschiede zwischen SMG und NMG wurden für Lokalrezidiv (hohes Risiko, P = 0.56; sehr hohes Risiko, P = 0,70), PEK-Rezidiv (hohes Risiko, P = 0,30; sehr hohes Risiko, P = 0,47) und PEK-bedingtem Tod (hohes Risiko, P = 0,23; sehr hohes Risiko, P = 0,83) beobachtet. SCHLUSSFOLGERUNGEN: Die Größe des Resektionsrands hat einen begrenzten Einfluss auf Randkontrolle, Rezidive und krankheitsspezifischen Tod bei PEK mit hohem Risiko.
RESUMO
Polyherbal medicines are composed of multiple herbs and have traditionally been used in East Asian countries for the remedy of physiological symptoms. Although the effects of polyherbal formulations have been investigated at the molecular and behavioral levels, less is known about whether and how medicinal herbs affect the central nervous system in terms of neurophysiology. We introduced a novel blended herbal formulation that consisted of 35% linden, 21% mulberry, 20% lavandin, 20% butterfly pea, and 4% tulsi. After intraperitoneal administration of this formulation or saline, we simultaneously recorded epidural electrocorticograms (ECoGs) from the olfactory bulb (OB), primary somatosensory cortex (S1), and primary motor cortex (M1), along with electromyograms (EMGs) and electrocardiograms (ECGs), of rats exploring an open field arena. Using the EMGs and OB ECoGs, we segmented the behavioral states of rats into active awake, quiet awake, and sleeping states. Compared to saline, herbal medicine significantly shortened the total sleep time. Moreover, we converted the ECoG signal into a frequency domain using a fast Fourier transform (FFT) and calculated the powers at various ECoG oscillation frequencies. In the sleeping state, a slow component (0.5-3 Hz) of S1 ECoGs was significantly enhanced following the administration of the formulation, which suggests a region- and frequency-specific modulation of extracellular field oscillations by the polyherbal medicine.
Assuntos
Ondas Encefálicas/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Sono/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Ondas Encefálicas/fisiologia , Eletrocorticografia/instrumentação , Eletrocorticografia/métodos , Eletrodos Implantados , Eletromiografia , Injeções Intraperitoneais , Masculino , Modelos Animais , Morus/química , Córtex Motor/efeitos dos fármacos , Córtex Motor/fisiologia , Bulbo Olfatório/efeitos dos fármacos , Bulbo Olfatório/fisiologia , Ratos , Sono/fisiologia , Córtex Somatossensorial/efeitos dos fármacos , Córtex Somatossensorial/fisiologia , Técnicas Estereotáxicas , Tilia/química , Fatores de Tempo , Vigília/fisiologia , WisteriaRESUMO
BACKGROUND: Amputation is the standard of care even for early-stage subungual melanomas (SUMs), known as nail apparatus melanoma, because the nail bed and nail matrix are close to the distal phalanx. However, a recent study demonstrated that not all patients with SUMs had histologic invasion of the underlying distal phalanx. As most SUMs occur in the thumb or big toe, amputation of either the thumb or big toe substantially interferes with activities of daily living, including poor cosmesis, loss of function, and phantom pain. Non-amputative digit preservation surgery can thus be applied in such cases without compromising patient prognosis. METHODS: We are conducting a multi-institutional single-arm trial to confirm the safety and efficacy of non-amputative digit preservation surgery. We will compare our results with those reported in the Japanese Melanoma Study, in which patients underwent amputation for SUMs as a traditional standard of care. Patients aged between 20 and 80 years with stage I, II, or III without evidence of tumor invasion to the underlying distal phalanx on preoperative radiograph are included in the study. The primary endpoint is major relapse-free survival (major RFS), which does not include local recurrence as an event; secondary endpoints include overall survival, digit-preservation survival, relapse-free survival, local relapse-free survival, partial relapse-free survival, and incidence of adverse events. A total of 85 patients from 21 Japanese institutions will be recruited within 5.5 years, and the follow-up period will last at least 5 years. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in August 2017, and patient enrollment began in November 2017. Ethical approval was obtained from each institution's Institutional Review Board prior to patient enrollment. DISCUSSION: This is the first prospective trial to confirm the safety and efficacy of non-amputative digit preservation surgery for SUM without distant metastasis or bony invasion. The results of this trial could provide evidence to support this less-invasive surgery as a new standard of care to preserve adequately functioning digits. TRIAL REGISTRATION: Registry number: UMIN000029997 . Date of Registration: 16/Nov/2017. Date of First Participant Enrollment: 12/Dec/2017.
Assuntos
Melanoma/epidemiologia , Melanoma/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Doenças da Unha/epidemiologia , Doenças da Unha/cirurgia , Atividades Cotidianas , Adulto , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica/efeitos adversos , Amputação Cirúrgica/métodos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Masculino , Oncologia/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Estudos Prospectivos , Polegar/patologia , Polegar/cirurgia , Dedos do Pé/patologia , Dedos do Pé/cirurgia , Adulto JovemAssuntos
Glândulas Apócrinas , Classe I de Fosfatidilinositol 3-Quinases , Hiperplasia , Neoplasias das Glândulas Sudoríparas , Humanos , Glândulas Apócrinas/patologia , Hiperplasia/patologia , Hiperplasia/genética , Feminino , Masculino , Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias das Glândulas Sudoríparas/genética , Neoplasias das Glândulas Sudoríparas/patologia , Pessoa de Meia-Idade , Mutação , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Idoso , Adulto , Nevo/patologia , Nevo/genéticaRESUMO
STUDY DESIGN: This was a retrospective multicenter study. OBJECTIVE: To develop a novel progression risk stratification scoring system for early-onset scoliosis. SUMMARY OF BACKGROUND DATA: There is a lack of investigations into variables affecting the risk of curve progression in early-onset scoliosis, which prevents stratification. A novel risk score system is needed to help in progression risk estimation. METHODS: A retrospective analysis was done at three centers, from 1995 to 2020. Scoliosis cases before the age of 10 years, were included. Medical identifier, date of birth, sex, primary diagnosis, curve type, date/modality of treatment, date of follow-up appointments, and Cobb angles, were collected. Five ranks were selected for stratification. Categories with the same ranks were discarded. Point scores started at 0, for the lowest risk, and ended at 4, for highest risk. Iterations of variable combinations were conducted and clinical relevance was determined by evaluating sensitivity, specificity, positive predictive value, and negative predictive value based on score ranges for low and high risk of progression. RESULTS: A total of 476 (230 males, 246 females) early-onset scoliosis patients were collected. The average age at diagnosis was 4.8 years (SD±2.8 yr). The average follow-up duration was 9.3 years (SD±6.9 yr, range: 5 mo-38 yr). Appointments totaled 2911, giving 2182 observations for the analysis. Patient observations numbered: 800 (36.7%) ending in progression, 1265 (58.0%) for nonprogression, 117 (5.4%) for inadequate follow-up, and 368 (16.9%) for rapid progression. The risk scoring system contained four categories: etiology, age, curve magnitude, and curve type. Categorized point combinations totaled 755, giving 1975 iterations. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated to be 85.8%, 96.5%, 89.7%, and 95.1%, respectively. CONCLUSION: A novel progression risk score for early-onset scoliosis was derived. The system can reliably differentiate between low and high-risk cases in clinical settings. Further validation in other regions may be important for verifying clinical relevance. LEVEL OF EVIDENCE: Level 3.
Assuntos
Escoliose , Masculino , Feminino , Humanos , Pré-Escolar , Criança , Estudos Retrospectivos , Escoliose/diagnóstico , Escoliose/epidemiologia , Escoliose/terapia , Valor Preditivo dos Testes , Fatores de Risco , Progressão da DoençaRESUMO
PURPOSE: To determine the frequencies of various diseases associated with all types of early-onset scoliosis, both idiopathic and nonidiopathic. METHODS: Retrospective collection of patients within a 21-year interval. Children under 10 years old presenting with scoliosis were included. Medical records were used to collect: identifier, date of birth, sex, diagnosis, follow-up, curve pattern, comorbidities, initial and final cobb angle. Different patient variables were tabulated with associated comorbidities for comparison. RESULTS: The cohort contained 469 patients, with 227(48.4%) males and 242(51.6%) females. Total comorbidities equaled 1051, where 190 were unique. Only 124(26.4%) patients had an isolated diagnosis of early-onset scoliosis, 79(16.8%) had a single comorbidity, and 266(56.7%) had multiple comorbidities. "Global developmental delay" was most commonly observed, 198(42.2%) times. The central nervous system was involved more often than other organ systems, seen in 394(54.4%) instances. Males had more comorbidities than females. Idiopathic patients had the least number of comorbidities, while neuromuscular patients had the most. Idiopathic types had more musculoskeletal conditions, while congenital types had more cardiovascular diseases. Curve sides did not affect distributions. Cases which progressed had more comorbidities, especially in the respiratory, digestive, and cardiovascular systems. Diseases that could affect either extremity or side, were more likely to be bilateral. CONCLUSIONS: Early-onset scoliosis patients may present with complex comorbidities in multiple organ systems. The most commonly observed disease entities were: global developmental delay, developmental dysplasia of the hip, and epilepsy. Clinicians should be aware of the common associations, in order to screen for and begin appropriate investigations, referrals, and treatments in affected cases. LEVEL OF EVIDENCE: Level III.
Assuntos
Escoliose , Criança , Masculino , Feminino , Humanos , Escoliose/epidemiologia , Escoliose/terapia , Estudos Retrospectivos , Comorbidade , Extremidades , Moldes CirúrgicosRESUMO
Understanding how antimicrobial peptides (AMPs) interact with human cells is important to the development of antimicrobial agents as well as anticancer drugs. However, little is known about the mechanisms by which AMPs bind to cells and exert cytotoxicity. Negatively charged gangliosides on the cell surface are a potential target for cell binding. In this study, we investigated the interaction of F5W-magainin 2 (MG) with gangliosides in detail. MG was colocalized with gangliosides on HeLa cells, indicating that gangliosides act as a receptor for MG. MG also bound to gangliosides in model membranes. The affinity increased with the number of negatively charged sialic acid residues. Physicochemical studies revealed that MG interacts with the monosialoganglioside GM1 differently from the typical bacterial anionic phospholipid phosphatidylglycerol. MG bound to GM1 more strongly than to phosphatidylglycerol, and the binding isotherm for GM1 could be analyzed by the Langmuir equation assuming charge neutralization. This is in contrast to the binding of AMPs to phosphatidylglycerol-containing bilayers, which has been described by the electrostatic attraction-surface partitioning model. Fluorescence resonance energy transfer experiments supported the clustering of GM1, but not phosphatidylglycerol, by MG. Quenching data suggested that MG is bound to the sugar region of GM1. The bound peptide assumed a helical structure and induced the leakage of calcein and the coupled flip-flop of lipids, indicating the peptide also forms a toroidal pore in GM1-containing vesicles. However, the membrane permeabilizing activity was weaker against GM1-containing membranes than phosphatidylglycerol-doped liposomes in accordance with the trapping of the peptide in the sugar region. These results shed light on AMP-human cell interaction.
Assuntos
Gangliosídeo G(M1)/metabolismo , Magaininas/metabolismo , Peptídeos Catiônicos Antimicrobianos/farmacologia , Transferência Ressonante de Energia de Fluorescência , Gangliosídeos/metabolismo , Células HeLa , Humanos , Fosfatidilcolinas/metabolismo , Fosfatidilgliceróis/metabolismo , Lipossomas Unilamelares/metabolismoRESUMO
BACKGROUND CONTEXT: Despite the many advances in understanding and treating early-onset scoliosis, the incidence and prevalence of this disease in the population remains unknown. Such knowledge is important for guiding clinical practice, directing research and raising awareness. PURPOSE: To identify the incidence and prevalence of early-onset scoliosis, including all categories, within the population. STUDY DESIGN: A regional multicenter retrospective cohort study PATIENT SAMPLE: All patients diagnosed with early-onset scoliosis in the region, who were followed-up between January 2000 and December 2020. OUTCOME MEASURES: Frequency distributions for early-onset scoliosis subtypes, demographics, curve patterns and progression statuses. METHODS: Relevant population data, for children under 10 years old, was extracted from the official government census for the years 2000 to 2020. Identification of cases was carried out by pediatricians at mandatory government funded regular child wellness check-up visits. Outpatient records were reviewed for all included patients, with extraction of the following: Medical identifier, date of birth, date of initial visit, sex, primary diagnosis, length of follow-up, curve pattern, initial cobb angle, and final cobb angle. Incidence and prevalence values were calculated using population figures and case numbers. Kaplan-Meier survival analysis and Log-rank testing was performed on curve progression data. RESULTS: The regional population of children, under the age of 10 years, included a total of 2,295,929 children, 1,170,149 (51.0%) males and 1,125,780 (49.0%) females, between the years 2000 and 2020. Early-onset scoliosis cases followed within the same timeframe, totaled 469 patients, 227 (48.4%) males and 242 (51.6%) females. The annual incidence of early-onset scoliosis was found to be 0.019% (95% CI: 0.015%-0.023%), and the prevalence was 0.077% (95% CI: 0.059%-0.096%). The most common age at first presentation was 6 years old. More females (51.6%) than males (48.4%) were observed, and more left-sided curves (54.2%) than right-sided curves (45.8%) were encountered, with the majority being single thoracic curves (38.2%). Scoliosis curves did not progress in 44.3% of cases, while they progressed in 38% of them. Follow-up was inadequate to determine progression status in 17.7% of cases. Neuromuscular etiologies were the most common, at 40.1%, of which 83.5% had cerebral palsy. CONCLUSIONS: Based on the regional population included in this study, the annual incidence of early-onset scoliosis in children under 10 years old was calculated to be 0.019%, while the prevalence of early-onset scoliosis in children under 10 years old was found to be 0.077%.
Assuntos
Escoliose , Criança , Feminino , Humanos , Incidência , Masculino , Prevalência , Estudos Retrospectivos , Escoliose/epidemiologia , Escoliose/terapiaRESUMO
Basal cell carcinoma is the most common type of skin cancer, and surgical excision with clear margins is the standard of care. Surgical margins are determined based on risk factors (high or low risk) for recurrence according to the National Comprehensive Cancer Network and Japanese basal cell carcinoma guidelines. The clarity of the clinical tumor border (well-defined or poorly defined) is considered a risk factor, and significant discrepancies in the judgment of clinical tumor borders among dermato-oncologists may occur. Therefore, we analyzed the dermato-oncologists' concordance in judging the clinical tumor border of basal cell carcinoma. Forty-seven dermato-oncologists (experts: 37; young trainees: 10) participated in this study. The datasets of clinical and dermoscopic photographs of 79 Japanese cases of head and neck basal cell carcinoma were used to determine the concordance in the judgment of clinical tumor border. The probability of the border that was selected more often was used to calculate the rater agreement rate for each dataset. Correct judgment was defined as a more frequently selected border, and the concordance rate of clarity of clinical tumor border for each dermato-oncologist was calculated based on the definition of the correct judgment. A median concordance rate of 85% or higher for all dermato-oncologists was predefined as an acceptable rate for clinical use. Of the 79 datasets, rater agreement rates were 80-100%, 60-79%, and 51-59% for 55, 19, and five datasets, respectively. The median concordance rate for all dermato-oncologists was 86% (interquartile range: 82-89%). There was no significant difference in the concordance rate between the experts and the trainees (median, 87% vs. 85.5%; p = 0.58). The concordance rates of dermato-oncologists for all datasets were relatively high and acceptable for clinical use.
Assuntos
Carcinoma Basocelular , Neoplasias de Cabeça e Pescoço , Neoplasias Cutâneas , Carcinoma Basocelular/patologia , Carcinoma Basocelular/cirurgia , Humanos , Japão , Julgamento , Margens de Excisão , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgiaRESUMO
BACKGROUND: Basal cell carcinoma (BCC) is the most common skin cancer. While Mohs micrographic surgery is commonly accepted for BCC treatment, surgical excision with free margins is widely considered the best treatment modality for BCCs in Japan. However, little is known about the predictors of the invasion levels of BCCs. OBJECTIVE: To investigate the optimization of deep surgical margins by identifying factors significantly influencing the invasion levels of facial BCCs. METHODS: The tumor invasion level was defined as the deepest part of a tumor. Tumor thickness was measured from the top of the granular layer to the deepest extension of the tumor or from the ulcer base overlying the deepest point of invasion in ulcerated lesions. Factors independently associated with tumor thickness and invasion level were identified by multivariate analysis. Six variables were tested: age, sex, anatomical region (nose, orbit, others), histologic pattern (aggressive, non-aggressive), presence of pigmentation, and diameter. RESULTS: We included 718 cases of facial BCCs involving 705 Japanese patients. The most frequent anatomical region and histologic pattern were the nose and nodular pattern, respectively. Only tumor diameter showed a correlation with tumor thickness (ß = 0.377, P < 0.001). Tumor diameter (AOR = 71.189, 95 % CI: 11.420-430.931, P = 0.01) and the following anatomical regions showed correlations with the invasion level: nose/others: AOR=2.769, 95 % CI: 1.235-6.493, P = 0.01; orbit/others: AOR=6.369, 95 % CI: 2.728-15.429, P < 0.001; orbit/nose: AOR=2.300, 95 % CI: 1.056-4.984, P = 0.04. CONCLUSIONS: This study serves as a guide for optimizing deep surgical margins and planning surgery for facial BCCs considering independently associated factors.
Assuntos
Carcinoma Basocelular/cirurgia , Procedimentos Cirúrgicos Dermatológicos/métodos , Neoplasias Faciais/cirurgia , Margens de Excisão , Neoplasias Cutâneas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/patologia , Procedimentos Cirúrgicos Dermatológicos/estatística & dados numéricos , Face , Neoplasias Faciais/diagnóstico , Neoplasias Faciais/patologia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Planejamento de Assistência ao Paciente , Prognóstico , Estudos Retrospectivos , Pele/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Carga Tumoral , Adulto JovemRESUMO
Vitiligo is an autoimmune disorder resulting from the destruction of melanocytes. Several reports indicate the association between vitiligo and treatment response in advanced melanoma during immunotherapy. It has not been investigated, however, if an increase of vitiligo while on treatment with anti-programmed death 1 (PD-1) antibodies is associated with more durable responses. The aim of this study is to evaluate the correlation between the vitiligo dynamics and clinical efficacy of anti-PD-1 antibodies. This study included advanced melanoma patients who were treated with nivolumab or pembrolizumab and developed vitiligo thereafter. Correlation between vitiligo expansion (defined as an increase of lesion size at two separate time points at least 4 weeks apart) as well as vitiligo extent (body surface area [BSA] affected) and clinical efficacy based on response rate, progression-free survival and overall survival was assessed. We retrospectively reviewed 29 patients. The median time from the initiation of anti-PD-1 antibody to vitiligo onset was 4.3 months in patients who showed a response and 5.5 months in patients who showed no response (P = 0.31). Twelve patients showed vitiligo expansion, and in nine of these patients, vitiligo increased to grade 2 (covering ≥ 10% BSA). Vitiligo expansion and grade 2 vitiligo showed no improvement in treatment response (P = 0.59 and 0.25) but were associated with prolonged progression-free survival (P = 0.019 and 0.04). Grade 2 vitiligo also showed a trend for prolonged overall survival (P = 0.07). Trend of expansion and larger vitiligo extent may be predictive factors of prolonged survival during anti-PD-1 antibody in melanoma patients.
Assuntos
Inibidores de Checkpoint Imunológico/efeitos adversos , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Vitiligo/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Masculino , Melanoma/diagnóstico , Melanoma/imunologia , Melanoma/mortalidade , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Intervalo Livre de Progressão , Estudos Retrospectivos , Índice de Gravidade de Doença , Pele/imunologia , Pele/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/mortalidade , Vitiligo/induzido quimicamente , Vitiligo/imunologiaAssuntos
Melanoma , Neoplasias Cutâneas , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Mutação , Linhagem Celular Tumoral , Proteínas de Membrana/genética , GTP Fosfo-Hidrolases/genética , Melanoma Maligno CutâneoRESUMO
Antibodies against programmed cell death protein 1, such as nivolumab and pembrolizumab, are widely used for treating various cancers, including advanced melanoma. Nivolumab significantly prolongs survival in patients with metastatic melanoma, and sequential administration with lipilimumab may improve outcomes when switched at the appropriate time. Biomarkers are therefore needed to evaluate nivolumab efficacy soon after first administration. This study analyzed serum levels of soluble cluster of differentiation 163 (sCD163) in 59 cases of advanced cutaneous melanoma and 16 cases of advanced mucosal melanoma treated using nivolumab. Serum levels of sCD163 were significantly increased after 6 weeks in responders compared to non-responders after initial administration of nivolumab for cutaneous melanoma. In contrast, no significant difference between responders and non-responders was seen among patients with non-cutaneous melanoma. These results suggest that sCD163 may be useful as a biomarker for selecting patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy.