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When conducting clinical trials in intensive care and emergency medicine, physicians, ethics committees, and legal experts have differing views regarding the inclusion of patients who are incapable of giving consent. These different views on the participation of patients who are not capable of giving consent also complicate how clinical trials are prepared and conducted. Based on the results of a literature search, a consensus model (Cologne Model) was developed by physicians performing clinical research, ethics committees, and lawyers in order to provide patients, those scientifically responsible for the study, ethics committees, and probate (guardianship) judges with a maximum of patient safety and legal certainty, while simultaneously enabling scientific research.
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BACKGROUND: Histopathologic regression following neoadjuvant treatment (NT) of oesophageal cancer is a prognostic factor of survival, but the nodal status is not considered. Here, a score combining both to improve prediction of survival after neoadjuvant therapy is developed. METHODS: Seven hundred and fifteen patients with oesophageal squamous cell (SCC) or adenocarcinoma (AC) undergoing NT and esophagectomy were analysed. Histopathologic response was classified according to percentage of vital residual tumour cells (VRTC): complete response (CR) without VRTC, major response with <10% VRTC, minor response with >10% VRTC. Nodal stage was classified as ypN0 and ypN+. Kaplan-Meier and Cox regression were used for survival analysis. RESULTS: Survival analysis identified three groups with significantly different mortality risks: (1) low-risk group for CR (ypT0N0) with 72% 5-year overall survival (5y-OS), (2) intermediate-risk group for minor/major responders and ypN0 with 59% 5y-OS, and (3) high-risk group for minor/major responders and ypN+ with 20% 5y-OS (p < 0.001). Median survival in AC and SCC cohorts were comparable (3.8 (CI 95%: 3.1, 5.3) vs. 4.6 years (CI 95%: 3.3, not reached), p = 0.3). CONCLUSIONS: Histopathologic regression and nodal status should be combined for estimating AC and SCC prognosis. Poor survival in the high-risk group highlights need for adjuvant therapy.
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Adenocarcinoma , Neoplasias Esofágicas , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Esofágicas/patologia , Prognóstico , Terapia Combinada , Adenocarcinoma/patologia , Esofagectomia , Resultado do Tratamento , Estudos RetrospectivosRESUMO
INTRODUCTION: The inflammatory microenvironment has emerged as one of the focuses of cancer research. Little is known about the immune environment in esophageal adenocarcinoma (EAC) and possible tumor-escape mechanisms to avoid immune cell attack. PATIENTS AND METHODS: We measured T cell inflammation (CD3, CD8) in the microenvironment using a standardized software-based evaluation algorithm considering different predefined tumor areas as well as expression of MHC class 1 and PD-L1 on 75 analyzable primarily resected and locally advanced (≥ pT2) EACs. We correlated these findings statistically with clinical data. RESULTS: Patients with high amounts of T cell infiltration in their tumor center showed a significant survival benefit of 41.4 months compared to 16.3 months in T cell poor tumors (p = 0.025), although CD3 fails to serve as an independent prognostic marker in multivariate analysis. For the invasion zone, a correlation between number of T-cells and overall survival was not detectable. Loss of MHC1 protein expression on tumor cells was seen in 32% and PD-L1 expression using the combined positive score (CPS) in 21.2%. Most likely due to small numbers of cases, both markers are not prognostically relevant, even though PD-L1 expression correlates with advanced tumor stages. DISCUSSION: Our analyses reveal an outstanding, though not statistically independent, prognostic relevance of T-cell-rich inflammation in our group of EACs, in particular driven by the tumor center. For the first time, we describe that the inner part of the invasion zone in EACs shows significantly fewer T-cells than other tumor segments and is prognostically irrelevant. We also demonstrate that the loss of antigen presenting ability via MHC1 downregulation by the carcinoma cells is a common escape mechanism in EACs. Future work will need to show whether tumors with MHC class 1 loss respond less well to immunotherapy.
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Adenocarcinoma/imunologia , Neoplasias Esofágicas/imunologia , Linfócitos do Interstício Tumoral/citologia , Evasão Tumoral/imunologia , Microambiente Tumoral/imunologia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Antígeno B7-H1/análise , Antígeno B7-H1/metabolismo , Regulação para Baixo , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Antígenos HLA-A/análise , Antígenos HLA-A/metabolismo , Antígenos HLA-B/análise , Antígenos HLA-B/metabolismo , Humanos , Imunidade Celular , Inflamação/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/imunologia , Prognóstico , Fatores de TempoRESUMO
Hodgkin lymphoma (HL) in older patients appears to be a different disease compared with younger patients with historically lower survival rates. This is related to a variety of factors, including increased treatment-related toxicity, the presence of comorbidities, and biologic differences. In order to better assess the clinical characteristics, treatment strategies, and outcome of this particular population, we conducted a population-based, retrospective analysis including 269 patients with HL older than 60 years (median age 71 years, range 60-94), treated between 2000 and 2017 in 15 referral centers across Switzerland. Primary endpoints were overall survival (OS), progression-free survival (PFS), and cause-specific survival (CSS). The vast majority of patients were treated with curative intent, either with a combined modality approach (chemotherapy followed by radiation therapy) or with systemic therapy. At a median follow-up of 6.6 years (95% confidence interval [CI], 6.0-7.6), 5-year PFS was 52.2% (95% CI, 46.0-59.2), 5-year OS was 62.5% (95% CI, 56.4-69.2), and 5-year CSS was 85.1.8% (95% CI, 80.3-90.1) for the entire cohort. A significant difference in terms of CSS was observed for patients older than 71 years in comparison to patients aged 60-70 years (hazard ratio 2.6, 1.3-5.0, p = 0.005). Bleomycin-induced lung toxicity (BLT) was documented in 26 patients (17.7%) out of the 147 patients exposed to this compound and was more frequent in patients older than 71 years (15/60, 25%). Outcome of HL pts older than 71 years appeared to decrease substantially in comparison to the younger counterpart. Treatment-related toxicities appeared to be relevant, in particular, BLT. New, potentially less toxic strategies need to be investigated in prospective clinical trials in this particular frail population.
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Doença de Hodgkin/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SuíçaRESUMO
BACKGROUND: In esophageal carcinoma, the numbers of metastatic and total removed lymph nodes (LN) are well-established variables of long-term prognosis. The overall rate of retrieved LN depends on neoadjuvant treatment, the extent of surgical lymphadenectomy, and the modality of the pathological workup. The question in this study is whether technically extended histopathological preparation can increase the number of detected (metastatic) LN with an impact on nodal UICC staging. PATIENTS AND METHODS: A cohort of 77 patients with esophageal adenocarcinoma was treated with Ivor Lewis esophagectomy including standardized two-field lymphadenectomy. The specimens were grossed, and all manually detectable LN were retrieved. The remaining tissue was completely embedded by the advanced "acetone compression" retrieval technique. The primary outcome parameter was the total number of detected lymph nodes before and after acetone workup. RESULTS: A mean number of 23,1 LN was diagnosed after standard manual LN preparation. With complete embedding of the fatty tissue using acetone compression, the number increased to 40.5 lymph nodes (p < 0.0001). The mean number of metastatic LN increased from 3.2 to 4.2 nodal metastases following acetone compression (p < 0.0001). Additional LN metastases which caused a change in the primary (y)pN stage were found in ten patients (13.0%). CONCLUSIONS: Advanced lymph node retrieval by acetone compression allows a reliable statement on the real number of removed LN. Results demonstrate an impact on the nodal UICC stage. A future multicenter study will examine the prognostic impact of improved lymph node retrieval on long-term oncologic outcome.
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Adenocarcinoma , Neoplasias Esofágicas , Adenocarcinoma/cirurgia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Estadiamento de Neoplasias , PrognósticoRESUMO
OBJECTIVE: This study examined the indications for prehospital needle thoracostomy (pNT), the need for tube thoracostomy (TT) following pNT, and the outcomes of patients who underwent pNT. METHODS: This study is a retrospective chart review of patients who underwent pNT prior to trauma center arrival. Patients were identified from the trauma registry and a quality improvement (QI) database from 9/2014-9/2018. RESULTS: 59 patients underwent 63 pNTs during the time period. The indication for pNT was "hypotension" in only 5 patients (7.9%). A CT chest was obtained on 51 NT attempts with the catheter in place. In 48 (94.1%) NT attempts, the catheter was not in the pleural space. 44 (69.4%) TTs were placed on admission date. CONCLUSION: In patients undergoing pNT, hypotension was rarely the indication. Additionally, CT identified the catheter within the pleural space in only 3 (5.8%) NT attempts. TT placement was performed in 79.3% of NT attempts.
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Tubos Torácicos , Tratamento de Emergência , Agulhas , Pneumotórax/cirurgia , Toracostomia/instrumentação , Adulto , Feminino , Humanos , Masculino , Estudos Retrospectivos , Centros de Traumatologia , Falha de TratamentoRESUMO
Background: We analyzed whether co-occurring mutations influence the outcome of systemic therapy in ALK-rearranged non-small-cell lung cancer (NSCLC). Patients and methods: ALK-rearranged stage IIIB/IV NSCLC patients were analyzed with next-generation sequencing and fluorescence in situ hybridization analyses on a centralized diagnostic platform. Median progression-free survival (PFS) and overall survival (OS) were determined in the total cohort and in treatment-related sub-cohorts. Cox regression analyses were carried out to exclude confounders. Results: Among 216 patients with ALK-rearranged NSCLC, the frequency of pathogenic TP53 mutations was 23.8%, while other co-occurring mutations were rare events. In ALK/TP53 co-mutated patients, median PFS and OS were significantly lower compared with TP53 wildtype patients [PFS 3.9 months (95% CI: 2.4-5.6) versus 10.3 months (95% CI: 8.6-12.0), P < 0.001; OS 15.0 months (95% CI: 5.0-24.9) versus 50.0 months (95% CI: 22.9-77.1), P = 0.002]. This difference was confirmed in all treatment-related subgroups including chemotherapy only [PFS first-line chemotherapy 2.6 months (95% CI: 1.3-4.1) versus 6.2 months (95% CI: 1.8-10.5), P = 0.021; OS 2.0 months (95% CI: 0.0-4.6) versus 9.0 months (95% CI: 6.1-11.9), P = 0.035], crizotinib plus chemotherapy [PFS crizotinib 5.0 months (95% CI: 2.9-7.2) versus 14.0 months (95% CI: 8.0-20.1), P < 0.001; OS 17.0 months (95% CI: 6.7-27.3) versus not reached, P = 0.049] and crizotinib followed by next-generation ALK-inhibitor [PFS next-generation inhibitor 5.4 months (95% CI: 0.1-10.7) versus 9.9 months (95% CI: 6.4-13.5), P = 0.039; OS 7.0 months versus 50.0 months (95% CI: not reached), P = 0.001). Conclusions: In ALK-rearranged NSCLC co-occurring TP53 mutations predict an unfavorable outcome of systemic therapy. Our observations encourage future research to understand the underlying molecular mechanisms and to improve treatment outcome of the ALK/TP53 co-mutated subgroup.
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Quinase do Linfoma Anaplásico/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Rearranjo Gênico , Neoplasias Pulmonares/mortalidade , Mutação , Proteína Supressora de Tumor p53/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoescamoso/tratamento farmacológico , Carcinoma Adenoescamoso/genética , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Adenocarcinomas or combined adeno-neuroendocrine carcinomas (MANEC) of small bowel usually have a dismal prognosis with limited systemic therapy options. This is the first description of a patient showing a germline-related BRCA1 mutated MANEC of his ileum. The tumor presented a susceptibility to a combined chemotherapy and the PARP1-inhibitor olaparib. CASE PRESENTATION: A 74-year old male patient presented with a metastasized MANEC of his ileum. Due to clinical symptoms his ileum-tumor and the single brain metastasis were removed. We verified the same pathogenic (class 5) BRCA1 mutation in different tumor locations. There was no known personal history of a previous malignant tumor. Nevertheless we identified his BRCA1 mutation as germline-related. A systemic treatment was started including Gemcitabine followed by selective internal radiotherapy (SIRT) to treat liver metastases and in the further course Capecitabine but this treatment finally failed after 9 months and all liver metastases showed progression. The treatment failure was the reason to induce an individualized therapeutic approach using combined chemotherapy of carboplatin, paclitaxel and the Poly (ADP-ribose) polymerase- (PARP)-inhibitor olaparib analogous to the treatment protocol of Oza et al. All liver metastases demonstrated with significant tumor regression after 3 months and could be removed. In his most current follow up from December 2017 (25 months after his primary diagnosis) the patient is in a very good general condition without evidence for further metastases. CONCLUSION: We present first evidence of a therapy susceptible germline-related BRCA1 mutation in small bowel adeno-neuroendocrine carcinoma (MANEC). Our findings offer a personalized treatment option. The germline background was unexpected in a 74-year old man with no previously known tumor burden. We should be aware of the familiar background in tumors of older patients as well.
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Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteína BRCA1/genética , Carcinoma Neuroendócrino/tratamento farmacológico , Mutação em Linhagem Germinativa , Neoplasias do Íleo/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/secundário , Idoso , Neoplasias Encefálicas/secundário , Carboplatina/uso terapêutico , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/secundário , Humanos , Neoplasias do Íleo/genética , Neoplasias do Íleo/patologia , Neoplasias Hepáticas/secundário , Masculino , Paclitaxel/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêuticoRESUMO
Due to increasing medical costs and yet limited financial resources, medical treatment and economic analyses can no longer be separated; therefore, direct costing and cost unit accounting become more and more relevant as controlling tools in hospital management. Transthoracic esophagectomy is an integral part of the current treatment concept in patients with esophageal carcinoma. The question of the present study was whether the present diagnosis-related groups (DRG) system is a cost-effective tool to represent transthoracic esophagectomy. In this retrospective study at a high-volume center, 161 consecutive patients with esophageal carcinoma were included. All patients were surgically treated according to the current S3 guidelines by a transthoracic esophagectomy. Detailed and standardized documentation of the postoperative complications was made according to the classification of Clavien-Dindo and the guidelines of the Esophagectomy Complications Consensus Group (ECCG). For each individual patient, the respective actual costs were analyzed according to the Institute for the Remuneration System in Hospitals (InEK) cost accounting approach comparing DRG payments (DRG G03A) on a case level including all extra fees per DRG catalogue. The mean costs per case of all included 161 patients were 24,338⯠(median: 19,210â¯, range: 12,149-127,376â¯), while mean payments per case of 22,591⯠were recorded. For the entire study population, the profit margin was -281,330⯠(mean: -1747â¯). Only patients with an uncomplicated course (Clavien-Dindo 0) yielded a slightly positive profit margin of 2514â¯. With increasing complication score the profit margin became increasingly negative (Clavien-Dindo I: -2878â¯, Clavien-Dindo IVb: -58,543â¯). Within the analysis of the InEK target cost matrix, main cost drivers can be identified as medical services (22.3%) and non-medical infrastructure (18.7%). Surgical treatment according to the existing guidelines of patients with esophageal carcinoma is not cost-covering in high-volume centers and cannot be solely financed by existing DRG revenues.
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Neoplasias Esofágicas , Esofagectomia , Custos de Cuidados de Saúde , Complicações Pós-Operatórias , Grupos Diagnósticos Relacionados , Esofagectomia/efeitos adversos , Esofagectomia/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Complicações Pós-Operatórias/economia , Estudos RetrospectivosRESUMO
OBJECTIVES: The recent success of individualized lung cancer therapy has triggered fundamental changes in clinical research strategies. To date there is a strong focus on early proof of concept trials in genetically preselected small patient subgroups. This analysis focuses on the economic burden caused by such trials for advanced lung cancer patients in a German Comprehensive Cancer Center (CCC). METHODS: The profit margins between recruiting groups with ≤3 and >3 patients were compared. Clinical and economic data from clinical trials for advanced lung cancer (LC), pharma-sponsored trials (PhST) as well as investigator initiated trials (IIT), conducted between 2011 and 2015 at the Center for Integrated Oncology (CIO) Cologne, were analyzed using a profit-center calculation model. RESULTS: 161 patients were enrolled in 27 clinical trials. The key economic parameter determining costs and payments was the 'trial visits'. In comparison of the two groups (A≤3; B>3 patients enrolled) we found negative profit margins for the low recruiting group ( -1444). Concerning the number of visits significant differences were found between PhST and IIT (p=0.009). Additionally, sub-analysis show structural differences in cost composition by conducting PhST and IIT. CONCLUSION: Trials with low patient numbers and IIT, do not cover the cost. To ensure adequate, cost-covering compensation by pharmaceutical companies CCCs have to thoroughly calculate the cost of early proof of concept trials. The findings of this study also underline the need for novel structures in public funding for investigator-initiated clinical trials in precision medicine.
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Custos e Análise de Custo , Neoplasias Pulmonares/epidemiologia , Idoso , Institutos de Câncer , Ensaios Clínicos como Assunto , Feminino , Alemanha/epidemiologia , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Padrão de CuidadoAssuntos
Adjuvantes Imunológicos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Talidomida/análogos & derivados , Adjuvantes Imunológicos/efeitos adversos , Adjuvantes Imunológicos/economia , Adjuvantes Imunológicos/farmacocinética , Dexametasona/administração & dosagem , Esquema de Medicação , Custos de Medicamentos , Humanos , Análise de Sobrevida , Talidomida/efeitos adversos , Talidomida/economia , Talidomida/farmacocinética , Talidomida/uso terapêuticoRESUMO
A newly developed high-pressure rheometer for in situ X-ray scattering experiments is described. A commercial rheometer was modified in such a way that X-ray scattering experiments can be performed under different pressures and shear. First experiments were carried out on hyaluronan, a ubiquitous biopolymer that is important for different functions in the body such as articular joint lubrication. The data hint at a decreased electrostatic interaction at higher pressure, presumably due to the increase of the dielectric constant of water by 3% and the decrease of the free volume at 300â bar.
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The development of a dedicated small-angle X-ray scattering setup for the investigation of complex fluids at different controlled shear conditions is reported. The setup utilizes a microfluidics chip with a narrowing channel. As a consequence, a shear gradient is generated within the channel and the effect of shear rate on structure and interactions is mapped spatially. In a first experiment small-angle X-ray scattering is utilized to investigate highly concentrated protein solutions up to a shear rate of 300000â s(-1). These data demonstrate that equilibrium clusters of lysozyme are destabilized at high shear rates.
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Microfluídica , Espalhamento de RadiaçãoRESUMO
Lung cancer is a frequently occurring disease, particularly in the elderly; however, within the last 10 years the pharmaceutical treatment of lung cancer has been significantly improved. Due to a better understanding of the pathophysiological events and the identification of molecular subgroups of lung tumors, new therapeutic drugs have been developed that significantly prolong survival of patients with the respective molecular pattern. In particular immunotherapeutic agents, such as programmed death-ligand 1 (PD-L1) and programmed death 1 (PD1) antibodies have shown promising clinical results in a subgroup of lung cancer patients. Due to the high incidence of both lung cancer and rheumatic diseases they often occur together, which necessitates an interdisciplinary management. The success of improved therapy of lung cancer has led to a greater focus on the treatment of comorbidities; however, interventions into the immune system by immune checkpoint inhibitors can lead to new challenges when an autoimmune disease is simultaneously present. The possibility of an effective screening for lung cancer in the future also presents the prospect of an improvement in mortality, which raises the question of the optimal monitoring of patients with rheumatoid arthritis (RA) under immunosuppressive therapy. The aim of this review is to discuss the interaction between lung cancer and RA with respect to the currently available data.
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Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/prevenção & controle , Algoritmos , Comorbidade , Relação Dose-Resposta a Droga , Esquema de Medicação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Medicina Baseada em Evidências , Humanos , Equipe de Assistência ao Paciente , Prevalência , Medição de Risco , Fatores de Risco , Resultado do TratamentoAssuntos
Carcinoma de Células Escamosas/genética , Genes myc/genética , Neoplasias Orofaríngeas/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Alphapapillomavirus/isolamento & purificação , Feminino , Amplificação de Genes , Humanos , Hibridização In Situ/métodos , Neoplasias Pulmonares/genética , MasculinoRESUMO
The occurrence of varicella zoster virus (VZV) reactivation is increased after allogeneic transplantation, whereas limited data are available for herpes zoster (HZ) after autologous SCT (ASCT). We determined the incidence and the prognostic significance of HZ and its correlation with VZV serology in 191 consecutive myeloma patients undergoing high-dose melphalan chemotherapy with ASCT. We found that VZV reactivation occurred in 57 (30%) patients, in 8.5% during induction and in 21.5% after ASCT peaking at 8 months after ASCT. Disease burden due to HZ was assessed as high or rather high in 70% of the patients. By immune fluorescence and Serion Elisa VZV IgG assessment, 90.8% of all patients had specific anti-VZV antibodies at ASCT. Lower specific antibody titers at transplantation were observed in patients with HZ after ASCT than in those without reactivation (P=0.009). Finally, OS was better in myeloma patients with HZ after ASCT compared with patients without HZ (P=0.007). Our data indicate that VZV reactivation after ASCT is a frequent event carrying a significant disease burden and it is associated with improved survival. Low levels of specific VZV antibodies at ASCT suggest increased vulnerability for VZV reactivation.
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Anticorpos Antivirais/sangue , Herpes Zoster , Herpesvirus Humano 3/fisiologia , Mieloma Múltiplo , Transplante de Células-Tronco , Ativação Viral , Adulto , Idoso , Autoenxertos , Intervalo Livre de Doença , Feminino , Herpes Zoster/sangue , Herpes Zoster/etiologia , Herpes Zoster/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Mieloma Múltiplo/virologia , Taxa de SobrevidaRESUMO
Pulmonary metastasectomy is an established procedure in oncological therapeutic concepts. A systematic literature search and an analysis of all studies published since 01.01.2000 should evaluate the advantage of pulmonary metastasectomy for patients with primary head and neck cancer. Lung metastases develop in 1.9-13% of head and neck cancer patients. Following metastasectomy, patients reach a median survival of 9.5-78 months and 5-year survival rates of up to 58% are achieved. Intrathoracic recurrence occurs in 18.4-81.8% of patients, selected instances of which can be successfully treated by remetastasectomy. Patients with squamous cell carcinoma have the worst prognosis, but could also become long-term survivors (≥ 60 months). Pulmonary metastasectomy is frequently the only potentially curative therapeutic approach and offers a better long-term survival than nonsurgical therapies. Lung metastasectomy is thus the treatment of choice in selected patients with pulmonary metastases from primary head and neck cancer.
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Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Pneumonectomia/mortalidade , Medicina Baseada em Evidências , Humanos , Incidência , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Medição de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
New immune-modulating treatments like the anti-CTLA-4-antibodies-based therapies are increasingly used in medical oncology. The action of Ipilimumab, a monoclonal anti-CTLA-4-antibody used for the treatment of metastasized melanoma and other solid tumors, is well documented. Blocking the CTLA-4-receptors on lymphocytes leads to T-cell activation and hence reduction of the tumor-mediated immunotolerance. This mechanism constitutes the basis of the antiproliferative effects but is also responsible for a spectrum of specific adverse events (immune-related adverse events, IRAE). IRAE of the endocrine system comprise hypophysitis, thyroiditis and adrenalitis. Especially adrenal insufficiency can be fatal when not diagnosed and treated. Symptoms often are unspecific and early diagnosis and targeted treatment are crucial. We present a case report and summarize - based upon the current literature - the diagnosis and treatment of endocrinologic IRAEs.
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Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Antígeno CTLA-4/antagonistas & inibidores , Hipopituitarismo/induzido quimicamente , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Melanoma/tratamento farmacológico , Melanoma/secundário , Neoplasias Cutâneas/tratamento farmacológico , Doenças das Glândulas Suprarrenais/induzido quimicamente , Doenças das Glândulas Suprarrenais/diagnóstico , Antígeno CTLA-4/imunologia , Colite/induzido quimicamente , Colite/diagnóstico , Seguimentos , Humanos , Hipertireoidismo/induzido quimicamente , Hipertireoidismo/diagnóstico , Hipopituitarismo/diagnóstico , Ipilimumab , Masculino , Pessoa de Meia-Idade , Tireoidite/induzido quimicamente , Tireoidite/diagnósticoRESUMO
Finite element (FE) model studies have made important contributions to our understanding of functional biomechanics of the lumbar spine. However, if a model is used to answer clinical and biomechanical questions over a certain population, their inherently large inter-subject variability has to be considered. Current FE model studies, however, generally account only for a single distinct spinal geometry with one set of material properties. This raises questions concerning their predictive power, their range of results and on their agreement with in vitro and in vivo values. Eight well-established FE models of the lumbar spine (L1-5) of different research centers around the globe were subjected to pure and combined loading modes and compared to in vitro and in vivo measurements for intervertebral rotations, disc pressures and facet joint forces. Under pure moment loading, the predicted L1-5 rotations of almost all models fell within the reported in vitro ranges, and their median values differed on average by only 2° for flexion-extension, 1° for lateral bending and 5° for axial rotation. Predicted median facet joint forces and disc pressures were also in good agreement with published median in vitro values. However, the ranges of predictions were larger and exceeded those reported in vitro, especially for the facet joint forces. For all combined loading modes, except for flexion, predicted median segmental intervertebral rotations and disc pressures were in good agreement with measured in vivo values. In light of high inter-subject variability, the generalization of results of a single model to a population remains a concern. This study demonstrated that the pooled median of individual model results, similar to a probabilistic approach, can be used as an improved predictive tool in order to estimate the response of the lumbar spine.