Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 63
Filtrar
1.
Clin Implant Dent Relat Res ; 25(1): 152-165, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36369670

RESUMO

INTRODUCTION: Excessive surgical trauma is believed to be among the most important causes for early implant losses. As thermal injury to the bone is not only dependent on the amount of generated heat but also on the tissue exposure time, and the greatest temperature increase was found within the withdrawing period, the entire osteotomy procedure with the parameters contributing to thermal damage is of particular clinical relevance. The aim of this study was to investigate the thermal performance of metal-based and ceramic implant drills regarding the temperature exposure time during the whole osteotomy process. MATERIALS AND METHODS: This investigation consisted of 240 individual preparations in total, comprising two different drilling depths (10 and 16 mm), two irrigation methods (external and without irrigation), two implant drill materials (stainless steel and zirconia), and three consecutive drill diameters per material (2.0/2.2, 2.8, and 3.5 mm) with 10 identical repetitions. Real-time multichannel temperature measurement was conducted during automated drilling procedures in standardized bovine bone specimens. RESULTS: The maximum temperature changes were highly associated with the time period of passive drill withdrawing (p ≤ 0.05), irrespective of drill material, drilling depth, or drill diameter. Statistically significant differences in temperature generation between stainless steel and ceramic drills were observed in irrigated testing sites at both drilling depths with smaller drill diameters (2.0/2.2 and 2.8 mm, p ≤ 0.05). CONCLUSION: Results of this in vitro study could demonstrate a strong association between the highest temperature increase and the passive withdrawing time period in both investigated drill materials. Considering these findings and the resulting thermal bone damage due to the whole surgical procedure, high overall temperatures in combination with a prolonged heat exposure time may impact the future osseointegration process.


Assuntos
Implantes Dentários , Aço Inoxidável , Animais , Bovinos , Temperatura , Temperatura Alta , Implantação Dentária Endóssea/efeitos adversos , Implantação Dentária Endóssea/métodos , Cerâmica
2.
Stat Methods Med Res ; 31(1): 76-86, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34812663

RESUMO

Generalised pseudo-values have been suggested to evaluate the impact of allogeneic stem cell transplantation on childhood leukaemia. The approach compares long-term survival of two cohorts defined by the availability or non-availability of suitable donors for stem cell transplantation. A patient's cohort membership becomes known only after completed donor search with or without an identified donor. If a patient suffers an event during donor search, stem cell transplantation will no longer be indicated. In such a case, donor search will be ceased and cohort membership will remain unknown. The generalised pseudo-values approach considers donor identification as binary time-dependent covariate and uses inverse-probability-of-censoring weighting to adjust for non-identified donors. The approach leads to time-consuming computations due to multiple redefinitions of the risk set for pseudo-value calculation and an explicit adjustment for waiting-time bias. Here, the problem is looked at from a different angle. By considering the probability that a donor would have been identified after ceasing of donor search, weights for common pseudo-values are defined. This leads to a faster alternative approach as only a single risk set is necessary. Extensive computer simulations show that both, the generalised and the new weighted pseudo-values approach, provide approximately unbiased estimates. Confidence interval coverage is satisfactory for typical clinical scenarios. In situations, where donor identification takes considerably longer than usual, the weighted pseudo-values approach is preferable. Both approaches complement each other as they have different potential in addressing further aspects of the underlying medical question.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia , Criança , Processos Grupais , Humanos , Probabilidade , Transplante de Células-Tronco
3.
Clin Oral Implants Res ; 32(2): 154-166, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33220104

RESUMO

OBJECTIVES: The aim of this study was to evaluate thermal effects of ceramic and metal implant drills during implant site preparation using a standardised bovine model. MATERIAL AND METHODS: A total of 320 automated intermittent osteotomies of 10- and 16-mm drilling depths were performed using zirconium dioxide-based and stainless steel drills. Various drill diameters (2.0/ 2.2, 2.8, 3.5, 4.2 mm ∅) and different cooling methods (without/ with external saline irrigation) were investigated at room temperature (21 ± 1°C). Temperature changes were recorded in real time using two custom-built multichannel thermoprobes in 1- and 2-mm distance to the osteotomy site. For comparisons, a linear mixed model was estimated. RESULTS: Comparing thermal effects, significantly lower temperatures could be detected with steel-based drills in various drill diameters, regardless of drilling depth or irrigation method. Recorded temperatures for metal drills of all diameters and drilling depths using external irrigation were below the defined critical temperature threshold of 47°C, whereas ceramic drills of smaller diameters reached or exceeded the harmful temperature threshold at 16-mm drilling depths, regardless of whether irrigation was applied or not. The results of this study suggest that the highest temperature changes were not found at the deepest point of the osteotomy site but were observed at subcortical and deeper layers of bone, depending on drill material, drill diameter, drilling depth and irrigation method. CONCLUSIONS: This standardised investigation revealed drill material and geometry to have a substantial impact on heat generation, as well as external irrigation, drilling depth and drill diameter.


Assuntos
Osteotomia , Aço Inoxidável , Animais , Osso e Ossos , Bovinos , Cerâmica , Implantação Dentária Endóssea , Temperatura Alta , Temperatura
4.
Z Gastroenterol ; 58(12): 1191-1200, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33291175

RESUMO

BACKGROUND: Iron deficiency and anemia are common findings in IBD. Treatment of anemia improves quality of life. Neurological symptoms like depression or anxiety are also common in IBD; however, their relationship with ID has not been studied in detail. METHODS: Prospective, single center, non-interventional trial in an IBD cohort (n = 98), which is generally at risk for ID. Quality of sleep (using the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Insomnia Severity Index) and the presence of fatigue (Piper fatigue scale), depression (Self-rating Depression Scale [SDS]) or anxiety (Self-rating Anxiety Scale [SAS]) were related to ID (ferritin, transferrin saturation), anemia (hemoglobin), and inflammatory disease activity (CRP). RESULTS: ID was present in 35 %, anemia in 16 %, and inflammation in 30 %. The overall quality of sleep in this cohort was similar to that reported for the general population. ID, anemia, or inflammation had no influence on the PSQI (median 4.0 [CI 3.0-5.0]), the ESS 5.5 (5.0-7.0), and the ISI 4.00 (2.5-5.5). Fatigue (PFS; present in 30 %), anxiety (SAS; present in 24 %), and depression (SDS; present in 33 %) were more common than in the general population. Iron deficient and anemic patients were more likely to be depressed (p = 0.02 and p < 0.01) and showed a trend towards presence of fatigue (p = 0.06 and 0.07). Systemic inflammation as measured by CRP had no effect on any of these conditions. CONCLUSION: In this IBD cohort, ID and anemia affect depression and possibly fatigue independent of the presence of inflammation.


Assuntos
Anemia Ferropriva/etiologia , Depressão/etiologia , Fadiga/etiologia , Doenças Inflamatórias Intestinais/complicações , Qualidade de Vida , Anemia Ferropriva/epidemiologia , Anemia Ferropriva/psicologia , Depressão/epidemiologia , Depressão/psicologia , Fadiga/epidemiologia , Fadiga/psicologia , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/psicologia , Estudos Prospectivos
5.
Virchows Arch ; 477(4): 545-555, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32383007

RESUMO

Reliable determination of Ki67 labeling index (Ki67-LI) on core needle biopsy (CNB) is essential for determining breast cancer molecular subtype for therapy planning. However, studies on agreement between molecular subtype and Ki67-LI between CNB and surgical resection (SR) specimens are conflicting. The present study analyzed the influence of clinicopathological and sampling-associated factors on agreement. Molecular subtype was determined visually by Ki67-LI in 484 pairs of CNB and SR specimens of invasive estrogen receptor (ER)-positive, human epidermal growth factor (HER2)-negative breast cancer. Luminal B disease was defined by Ki67-LI > 20% in SR. Correlation of molecular subtype agreement with age, menopausal status, CNB method, Breast Imaging Reporting and Data System imaging category, time between biopsies, type of surgery, and pathological tumor parameters was analyzed. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. CNB had a sensitivity of 77.95% and a specificity of 80.97% for identifying luminal B tumors in CNB, compared with the final molecular subtype determination after surgery. The correlation of Ki67-LI between CNB and SR was moderate (ROC-AUC 0.8333). Specificity and sensitivity for CNB to correctly define molecular subtype of tumors according to SR were significantly associated with tumor grade, immunohistochemical progesterone receptor (PR) and p53 expression (p < 0.05). Agreement of molecular subtype did not significantly impact RFS and OS (p = 0.22 for both). The identified factors likely mirror intratumoral heterogeneity that might compromise obtaining a representative CNB. Our results challenge the robustness of a single CNB-driven measurement of Ki67-LI to identify luminal B breast cancer of low (G1) or intermediate (G2) grade.


Assuntos
Neoplasias da Mama/química , Antígeno Ki-67/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia com Agulha de Grande Calibre , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Intervalo Livre de Progressão , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Proteína Supressora de Tumor p53/análise
6.
Gut Liver ; 14(2): 218-224, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30428508

RESUMO

Background/Aims: von Willebrand factor antigen (vWF-Ag) is a noninvasive predictor of portal hypertension that serves as a negative prognostic marker in various malignancies. Increased portal hypertension is associated with higher postoperative morbidity and decreased survival after hepatectomy. The purpose of this study was to determine the correlation between vWF-Ag, postoperative morbidity and oncological outcome. Methods: This analysis includes 55 patients who underwent liver resection for hepatocellular carcinoma (HCC) between 2008 and 2015 with available preoperative vWF-Ag levels. The primary endpoints were postoperative complications and long-term outcome, including overall and disease-free survival. Results: The median plasma level of vWF-Ag was 191% (range, 162.5% to 277%). There was a significant correlation between vWF-Ag levels and tumor size in the resected specimens (p=0.010, r=0.350). Patients who developed any grade of postoperative complication had significantly higher preoperative vWF-Ag levels (216% [range, 178% to 283.25%] vs 176% [range, 148% to 246%], p=0.041). Median overall survival was 39.8 months in patients with high vWF-Ag levels (≥191%) compared with 73.4 months in patients with low levels (<191%, p=0.007). Of note, there was a remarkable disparity in the number of patients who died of HCC with low versus high vWF-Ag levels (14.8% vs 28.6%, p=0.011). Conclusions: vWF-Ag may serve as a prognostic marker for the outcome of patients undergoing liver resection for HCC that is closely connected to tumor size, postoperative complication rate and long-term outcome.


Assuntos
Carcinoma Hepatocelular/sangue , Hepatectomia/mortalidade , Neoplasias Hepáticas/sangue , Complicações Pós-Operatórias/mortalidade , Fator de von Willebrand/análise , Idoso , Biomarcadores/sangue , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
7.
Sci Rep ; 9(1): 8421, 2019 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182746

RESUMO

Postoperative liver dysfunction remains a major concern following hepatic resection. In order to identify patients who are at risk of developing liver dysfunction, indocyanine green (ICG) clearance has been proposed to predict postoperative liver function. All patients who underwent liver resection at the Medical University Vienna, Austria between 2006 and 2015 with preoperative ICG clearance testing (PDR, R15) were analyzed in this study. Postoperative liver dysfunction was analyzed as defined by the International Study Group of Liver Surgery. Overall, 698 patients (male: 394 (56.4%); female: 304 (43.6%)) with a mean age of 61.3 years (SD: 12.9) were included in this study, including 313 minor liver resections (44.8%) and 385 major liver resections (55.2%). One hundred and seven patients developed postoperative liver dysfunction after liver resection (15.3%). Factors associated with liver dysfunction were: male sex (p = 0.043), major liver resection (p < 0.0001), and preoperative ICG clearance (PDR (p = 0.002) and R15 (p < 0.0001)). Notably ICG clearance was significantly associated with liver dysfunction in minor and major liver resections respectively and remained a predictor upon multivariable analysis. An optimal cut-off for preoperative ICG clearance to accurately predict liver dysfunction was PDR < 19.5%/min and R15 > 5.6%. To the best of our knowledge, this is the largest study analyzing the predictive value of preoperative ICG clearance assessment in patients undergoing liver resection. ICG clearance is useful to identify patients at risk of postoperative liver dysfunction.


Assuntos
Hepatectomia , Verde de Indocianina/metabolismo , Fígado/fisiopatologia , Fígado/cirurgia , Feminino , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório
8.
JAMA Dermatol ; 155(11): 1291-1299, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31215969

RESUMO

IMPORTANCE: The recent advances in the field of machine learning have raised expectations that computer-aided diagnosis will become the standard for the diagnosis of melanoma. OBJECTIVE: To critically review the current literature and compare the diagnostic accuracy of computer-aided diagnosis with that of human experts. DATA SOURCES: The MEDLINE, arXiv, and PubMed Central databases were searched to identify eligible studies published between January 1, 2002, and December 31, 2018. STUDY SELECTION: Studies that reported on the accuracy of automated systems for melanoma were selected. Search terms included melanoma, diagnosis, detection, computer aided, and artificial intelligence. DATA EXTRACTION AND SYNTHESIS: Evaluation of the risk of bias was performed using the QUADAS-2 tool, and quality assessment was based on predefined criteria. Data were analyzed from February 1 to March 10, 2019. MAIN OUTCOMES AND MEASURES: Summary estimates of sensitivity and specificity and summary receiver operating characteristic curves were the primary outcomes. RESULTS: The literature search yielded 1694 potentially eligible studies, of which 132 were included and 70 offered sufficient information for a quantitative analysis. Most studies came from the field of computer science. Prospective clinical studies were rare. Combining the results for automated systems gave a melanoma sensitivity of 0.74 (95% CI, 0.66-0.80) and a specificity of 0.84 (95% CI, 0.79-0.88). Sensitivity was lower in studies that used independent test sets than in those that did not (0.51; 95% CI, 0.34-0.69 vs 0.82; 95% CI, 0.77-0.86; P < .001); however, the specificity was similar (0.83; 95% CI, 0.71-0.91 vs 0.85; 95% CI, 0.80-0.88; P = .67). In comparison with dermatologists' diagnosis, computer-aided diagnosis showed similar sensitivities and a 10 percentage points lower specificity, but the difference was not statistically significant. Studies were heterogeneous and substantial risk of bias was found in all but 4 of the 70 studies included in the quantitative analysis. CONCLUSIONS AND RELEVANCE: Although the accuracy of computer-aided diagnosis for melanoma detection is comparable to that of experts, the real-world applicability of these systems is unknown and potentially limited owing to overfitting and the risk of bias of the studies at hand.

9.
Transpl Int ; 32(1): 59-65, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30099769

RESUMO

We assessed whether standardized application of an absorbable polysaccharide hemostatic powder (HaemoCer™) has an effect on lymphocele rate after kidney transplantation. For this nonrandomized prospective trial, we first aimed to know our center-specific lymphocele rate diagnosed by ultrasound imaging. We retrospectively assessed all patient records of the elapsed year resulting in a center-specific rate of 20%, this was consistent with literature. The power analysis showed that 108 patients were required to detect a 50% reduction in lymphocele rate. During the prospective study period, 155 patients undergoing kidney transplantation were recruited to receive HaemoCer™ intraoperatively. In two patients, the product accidentally was not used. Six patients were excluded from analysis because of failure to complete follow-up (one early death and five early graft failures). Of the remaining 147 patients, 15 developed lymphoceles, which represents a rate of 10.2%; (95% CI: 6.3-16.2%). Compared to the expected occurrence, this was significantly lower (P = 0.003). Lymphoceles appeared to be associated with preoperative donor-specific antibody, retransplantation and immunoadsorption in HLA or ABO incompatible donors. At our institution, the frequency of lymphoceles after kidney transplantation appeared to be significantly reduced when HaemoCer™ was applied routinely. The magnitude of the effect warrants randomized evaluation.


Assuntos
Hemostáticos/uso terapêutico , Transplante de Rim/métodos , Linfocele/prevenção & controle , Polissacarídeos/uso terapêutico , Adsorção , Adulto , Idoso , Coagulação Sanguínea , Feminino , Hemostasia , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Peritônio/patologia , Complicações Pós-Operatórias/prevenção & controle , Pós , Estudos Prospectivos , Reoperação , Estudos Retrospectivos
10.
Eur J Surg Oncol ; 45(4): 538-543, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30366878

RESUMO

INTRODUCTION: Axillary ultrasound staging (AUS) is an important tool to guide clinical decisions in breast cancer therapy, especially regarding axillary surgery but also radiation therapy. It is unknown whether biological subtypes influence axillary staging using ultrasound (AUS). METHOD: This is a retrospective single center analysis. All patients with breast cancer, a preoperative axillary ultrasound and a complete surgical axillary staging were included between 1999 and 2014, except patients with neoadjuvant chemotherapy (NACT). The results of the AUS were compared with final pathological results. Biological subtypes were identified by immunohistochemistry. RESULTS: 583 women were included in the study. Sensitivity, Specificity, positive and negative predictive value for AUS were 39%, 96%, 91% and 83%. While sensitivity was significantly lower in Luminal A and B patients (25.0%; 39.8%) as compared to non Luminal breast cancer patients (TN 68.8%; Her2+ 71.4%; p = 0.0032), there were no significant differences between the groups with respect to specificity, PPV and NPV. CONCLUSION: Solely regarding sensitivity of AUS, our study could show significant differences between biological subtypes of breast cancer with lower sensitivity in Luminal patients. While PPV was excellent, standing for a low overtreatment rate using AUS for clinical decision making, sensitivity was poor overall, comparable to the results of other studies.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Ultrassonografia , Adulto , Idoso , Axila , Feminino , Humanos , Antígeno Ki-67/metabolismo , Linfonodos/cirurgia , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Adulto Jovem
11.
Invest New Drugs ; 37(1): 127-138, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29998365

RESUMO

Background Purpose of this phase Ib trial was to establish the maximum tolerable dose (MTD) of capecitabine and to escalate the dosages of erlotinib and bevacizumab to determine the recommended phase II dose (RP2D) in patients with advanced/metastatic pancreatic adenocarcinoma not pretreated for metastatic disease. Methods Starting doses were capecitabine 500 mg/m2 bid orally continuously, erlotinib 100 mg orally daily, and bevacizumab 5 mg/kg intravenously q 2 weeks. Dose escalation was performed according to a 3 + 3 design for capecitabine until MTD, for erlotinib and bevacizumab until the maximum doses registered by applying a substance-related, toxicity-based scheme accompanied by pharmacokinetic analysis. Circulating tumor cells (CTCs) were determined pretherapeutically by immunohistochemical identification after enrichment with immunomagnetic separation. Results Thirty patients were evaluable at six dose levels. 900 mg/m2 bid were determined as MTD for capecitabine based on dose-limiting toxicities: cutaneous in two patients and vascular in another. The most severe (Grade (G)3/4) drug-related treatment-emergent adverse events (toxicities) belonged to the categories gastrointestinal, vascular, cutaneous, cardiovascular, metabolic/nutritional or hematological. G3 toxicities occurred in 14 (47%), G3 + G4 in a single (3%) patient. 2 out of 28 patients (7%) exerted partial response, 17 (61%) stable disease. Pharmacokinetic evaluation revealed lack of drug-drug interaction between capecitabine and erlotinib and their metabolites. Presence of CTCs was associated with shorter progression-free survival (p = 0.009). Conclusions The study met the primary objective. RP2D was capecitabine 800 mg/m2 bid continuously, erlotinib 150 mg daily, and bevacizumab 10 mg/kg q 2 weeks. The regimen could be applied safely, but demonstrated limited efficacy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Bevacizumab/administração & dosagem , Capecitabina/administração & dosagem , Estudos de Coortes , Cloridrato de Erlotinib/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Taxa de Sobrevida , Distribuição Tecidual , Resultado do Tratamento
12.
Eur Surg ; 50(4): 160-166, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30559831

RESUMO

BACKGROUND: In operable esophageal cancer patients, neoadjuvant therapy benefits only those who respond to the treatment. The • Pancho trial represents the first prospective randomized trial evaluating the relevance of the mark53 status for predicting the effect of two different neoadjuvant chemotherapies. METHOD: Biomarker analysis was conducted using the mark53 analysis. Calculation of patient number needed was based on a 60% rate of marker positivity, deduced from the results of a phase II pilot study. RESULTS: From 2007-2012, the • Pancho trial recruited 235 patients with operable esophageal cancer in Austria. A total of 181 patients were eligible and could be subjected to mark53 analysis and randomization. After randomizing 74 patients, the overall TP53 mutation rate was 79%. However, due to the high prevalence of marker positivity, the number of projected patients was increased to 181 patients in order to ensure a sufficient number of marker-negative patients. After completion of the trial, the overall TP53 mutation rate was 77.9%. CONCLUSION: Due to high medical need, the recruitment for the academic trial was excellent. Mark53 analysis clearly detected more mutations in the TP53 gene as compared to the cancer-specific p53 literature. Final analysis examining the interaction between the mark53 status and the effect of chemotherapies applied in the • Pancho trial is now awaited.

13.
Ann N Y Acad Sci ; 1434(1): 46-53, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30112858

RESUMO

Technological progress within the last 15-20 years has significantly increased our knowledge about the molecular basis of cancer development, tumor progression, and treatment response. As a consequence, a vast number of biomarkers have been proposed, but only a small fraction of them have found their way into clinical use. The aim of this paper is to describe the specific demands a clinically relevant biomarker should meet and how biomarkers can be tested stepwise. We name this procedure the "triple-R principle": robustness, reproducibility, and relevance. The usefulness of this principle is illustrated with the marker TP53. Since it is mutated in a broad spectrum of cancer entities, TP53 can be considered a very promising marker. Thus, TP53 has been studied in detail but there is still no explicit consensus about its clinical value. By considering our own experience and reviewing the literature, we demonstrate that a major problem of current biomarker research is disregard of whether the biomarker is prognostic or predictive. As an example, it is demonstrated that TP53 is not a prognostic marker, but rather a purely predictive marker, and that disregard of this fact has made this otherwise strong biomarker appear as not being clinically useful so far.


Assuntos
Biomarcadores Tumorais , Neoplasias , Proteína Supressora de Tumor p53 , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/metabolismo , Prognóstico , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
14.
Ann Surg ; 268(5): 894-902, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30080722

RESUMO

BACKGROUND: Neoadjuvant chemotherapy (neoCTx) followed by hepatic resection is the treatment of choice for patients with colorectal cancer liver metastasis (CLM). Treatment response is generally assessed using radiologic imaging after several cycles of chemotherapy. However, earlier assessment of response would be desirable since nonresponders could be switched early to an alternative chemotherapy regimen. Recent evidence suggests that circulating free methylated tumor DNA is a highly sensitive biomarker and may more accurately reflect tumor burden and treatment response than conventional markers for CRC. PATIENTS AND METHODS: Thirty-four patients with CLM who received neoCTx prior to intended hepatic resection were included in this prospective nonrandomized study. Peripheral blood plasma was collected at baseline and before each cycle of neoCTx and was then analyzed for aberrant methylation of 48 CRC-associated genes. Methylation marker levels were correlated with baseline tumor volume and treatment response and compared with the standard tumor markers CEA and CA 19-9. RESULTS: The methylation markers SEPT9, DCC, BOLL, and SFRP2 were present in all patients at baseline and displayed a stronger correlation with tumor volume than CEA and CA 19-9. Serial measurement of these methylation markers allowed for discrimination between operated and nonoperated patients already after 1 cycle of neoCTx with high sensitivity and specificity. The early dynamic changes of SEPT9 and DCC also seemed to correlate with pathohistological response. CONCLUSION: Our data suggest that serial measurements of CRC-associated methylation markers could be a particularly valuable tool for early response assessment in patients receiving neoCTx for CLM.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/patologia , Metilação de DNA , DNA de Neoplasias/sangue , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Prospectivos , Sensibilidade e Especificidade , Carga Tumoral
15.
Wien Klin Wochenschr ; 130(11-12): 398-403, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29435759

RESUMO

BACKGROUND: The Neutrophil-to-lymphocyte-ratio has recently gained increased attention as a prognostic marker for malignant disease and short term outcomes. There is little data available in patients with Crohn's disease, thus the present study was conducted to correlate preoperative Neutrophil-to-lymphocyte-ratio values with disease phenotype and postoperative course. METHODS: We comprised 373 patients, who underwent intestinal resection for symptomatic Crohn's disease at an academic tertiary referral centre between 2000 and 2014. Preoperative Neutrophil-to-lymphocyte-ratio values were calculated and analyzed in regard to disease phenotype and 30-day morbidity rate. All relevant data were obtained from the institutional database and individual chart review. RESULTS: Male patients had significantly higher preoperative Neutrophil-to-lymphocyte-ratio values compared to female patients (5 vs. 4; p = 0.0075). A higher Neutrophil-to-lymphocyte-ratio was also found in patients with an acute indication for surgery (6.15 vs. 4.3; p = 0.0374), presenting with abscesses (5.36 vs. 4.28; p = 0.0254), inflammatory masses (5.23 vs. 4.08; p = 0.0294) or malignancy in the resected specimen (9.06 vs. 4.35, p = 0.0231). Surprisingly, patients developing postsurgical complications showed significantly lower Neutrophil-to-lymphocyte-ratio values (3.77 vs. 4.67; p = 0.0461). CONCLUSIONS: Elevated preoperative Neutrophil-to-lymphocyte-ratio in symptomatic Crohn's disease is not predictive for complications. However, Neutrophil-to-lymphocyte-ratio showed a significant correlation with specific disease phenotypes. Most strikingly, Neutrophil-to-lymphocyte-ratio was highly elevated in patients with a colorectal cancer in the resected specimen, which needs to be addressed in future studies.


Assuntos
Biomarcadores/sangue , Doença de Crohn , Linfócitos , Neutrófilos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Crohn/sangue , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fator de Necrose Tumoral alfa , Adulto Jovem
16.
BMC Med Res Methodol ; 18(1): 14, 2018 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-29351735

RESUMO

BACKGROUND: Investigating the impact of a time-dependent intervention on the probability of long-term survival is statistically challenging. A typical example is stem-cell transplantation performed after successful donor identification from registered donors. Here, a suggested simple analysis based on the exogenous donor availability status according to registered donors would allow the estimation and comparison of survival probabilities. As donor search is usually ceased after a patient's event, donor availability status is incompletely observed, so that this simple comparison is not possible and the waiting time to donor identification needs to be addressed in the analysis to avoid bias. It is methodologically unclear, how to directly address cumulative long-term treatment effects without relying on proportional hazards while avoiding waiting time bias. METHODS: The pseudo-value regression technique is able to handle the first two issues; a novel generalisation of this technique also avoids waiting time bias. Inverse-probability-of-censoring weighting is used to account for the partly unobserved exogenous covariate donor availability. RESULTS: Simulation studies demonstrate unbiasedness and satisfying coverage probabilities of the new method. A real data example demonstrates that study results based on generalised pseudo-values have a clear medical interpretation which supports the clinical decision making process. CONCLUSIONS: The proposed generalisation of the pseudo-value regression technique enables to compare survival probabilities between two independent groups where group membership becomes known over time and remains partly unknown. Hence, cumulative long-term treatment effects are directly addressed without relying on proportional hazards while avoiding waiting time bias.


Assuntos
Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Modelos de Riscos Proporcionais , Análise de Regressão , Algoritmos , Humanos , Estimativa de Kaplan-Meier , Leucemia/terapia , Modelos Estatísticos , Probabilidade , Reprodutibilidade dos Testes , Transplante de Células-Tronco/métodos , Análise de Sobrevida , Fatores de Tempo , Doadores de Tecidos
17.
Eur Surg ; 50(4): 177-182, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31497036

RESUMO

BACKGROUND: The modified Glasgow prognostic score (mGPS) has recently gained increased attention as a prognostic marker for malignant disease survival and postoperative short-term complications. Due to lacking data, the present study was conducted to correlate the mGPS with the postoperative course in patients following surgery for Crohn's disease. METHODS: We enrolled 341 patients who underwent intestinal resection for symptomatic Crohn's disease at a tertiary referral centre between 2000 and 2014. All relevant data were obtained from the institutional database and individual chart review. Thirty-day morbidity was defined according to the Clavien-Dindo classification. RESULTS: A total of 79 (23.17%) postoperative complications were identified (grade I and II: n = 54, 15.84%; grade III and IV: n = 23, 6.74%; grade V: n = 2, 0.59%). The mGPS did not show any correlation with an eventful postoperative course following surgery (no complication: median mGPS: 1, range 0-2; complications: median mGPS: 1, range 0-2; p = 0.8521). In addition, the occurrence of an anastomotic leakage was not associated with a higher mGPS (p = 0.8592). Patients with an acute indication for surgery (n = 29, 11.44%) had higher median mGPS (median: 2, range 0-2) in contrast to patients who were operated on electively (median: 1, range 0-2; p = 0.0003). No other correlation between surgical characteristics and mGPS was detected. CONCLUSIONS: In the present study, we could clearly demonstrate that an acute indication for surgery in symptomatic Crohn's disease is associated with higher mGPS scores. However, the mGPS did not correlate with postoperative complications. Further studies are required to define the prognostic value of mGPS in Crohn's disease patients.

18.
J Craniomaxillofac Surg ; 45(8): 1143-1149, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28554537

RESUMO

BACKGROUND: Autotransplantation of teeth (TX) is a predictable treatment option, although this type of therapy is often overlooked compared to other types of restorations. PURPOSE: As current literature contains few long-term studies concerning the outcome of autotransplanted immature molars, the aim was to evaluate results after a follow-up period of 5 years. MATERIAL AND METHODS: This retrospective study enrolled all patients treated with immature autotransplanted molars after a follow-up period of 5 years. In order to ensure comparable results, survival rate was investigated as well as clinical and radiological parameters. Contralateral teeth (TC) were used as controls for further assessments and for ensuring comparable future results. RESULTS: 52 patients with 66 TX were examined. Mean age at the time of surgery was 19.64 years. Tooth survival rate after 5 years was 89.39%. The results for parameters such as PPD, BOP, mobility, dental caries, periapical pathologies and endodontic treatments showed no differences. In contrast, dental restorations (p < 0.001), occlusal contacts (p = 0.003) and sensitivity (p < 0.001) differed significantly between TX and TC. CONCLUSIONS: The current findings clearly confirm that TX is an effective alternative treatment option to fixed prosthodontic restorations and dental implants, and provides for results equivalent to those with the patients' natural teeth.


Assuntos
Sobrevivência de Enxerto , Dente/transplante , Adolescente , Autoenxertos , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
19.
Ann Surg Oncol ; 24(1): 236-243, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27730370

RESUMO

BACKGROUND: Several clinical risk scores for patients with colorectal liver metastases (CLM) were established in cohorts of patients undergoing liver resection (LR) without neoadjuvant chemotherapy (NAC). The purpose of the study was to evaluate the predictive values of four common risk scores in the setting of NAC and the impact of score changes during NAC. METHODS: Risk scores (Fong, Nordlinger, Nagashima, and Konopke) were retrospectively calculated for 336 patients undergoing LR for CLM, including 109 patients without and 227 patients with NAC. In patients with NAC, the scores were calculated before and after NAC. RESULTS: In patients without NAC (n = 109), all risk scores except the Konopke score showed a significant correlation with disease-free survival (DFS). Only the Nagashima score also was predictive for overall survival (OS). In patients with NAC (n = 227), all scores except the Konopke score were predictive for DFS and OS before and after NAC. Score changes in the Fong and the Nagashima score showed a significant correlation with DFS and OS. CONCLUSIONS: Nagashima score was the most universally applicable score and predicted prognosis in all tested scenarios.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Quimioterapia Adjuvante , Feminino , Hepatectomia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Taxa de Sobrevida
20.
Int J Surg ; 33 Pt A: 182-6, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27535116

RESUMO

PURPOSE: Due to a lack of data, the present study was designed to assess the impact of advanced age on surgical characteristics and short-term outcome of patients operated on for symptomatic Crohn's disease. METHODS: We enrolled 454 consecutive Crohn's disease patients, who underwent intestinal resection at an academic tertiary referral center between 1997 and 2012. Patients were divided into 3 groups according to their age (group I: <30 years, group II: 30-50 years, group III: >50 years) and analyzed retrospectively. RESULTS: Altogether, 152 (33.5%) patients were included in group I, 234 (51.5%) in group II and 68 (15.0%) in group III. Abscess formation and penetrating disease were significantly more common in younger patients (p = 0.0014 and p = 0.0182). The number of intestinal resections was higher in older patients (p < 0.0001), whereas the laparoscopic approach was more frequently observed in younger adults (p = 0.0006). Group II (n = 58 (24.8%)) and group III (n = 15 (22.1%)) showed significantly more complications compared to group I (n = 20 (13.2%)) (p = 0.0346). Notably, major complications and anastomotic leaks were significantly higher in older patients (p = 0.0004). CONCLUSION: Crohn's disease patients of advanced age show different surgical characteristics compared to younger patients and are at an increased risk of developing postoperative complications.


Assuntos
Doença de Crohn/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA