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INTRODUCTION: Endonasal dacryocystorhinostomy (EDCR) has good results. AIM: To perform a prospective histological investigation of the removed lacrimal sacs' walls. METHOD: Between 2016 and 2017, we carried out 21 operations in two groups: inflammatory (11 patients) and non-inflammatory (10 patients) lacrimation groups. The mean age was 60.5 years. Histological samples were investigated after staining them with hematoxylin-eosin. RESULTS: In the non-inflammatory group, histology revealed the incipient metaplasia of the ciliated goblet cells. In the lacrimal sac's wall, there is a chronic inflammation with mucinous metaplasia of the serous glands. In the inflammatory group, the metaplasia of the ciliated goblet cells is more pronounced. Chronic fibrotic inflammation destroys the lacrimal sac's wall, which is dilated, ruptured. The mucinous metaplasia of the serous glands is pronounced. CONCLUSIONS: The results of histological investigations of the lacrimal sacs removed in the course of EDCR are much alike in the inflammatory and non- inflammatory groups. Orv Hetil. 2018; 159(52): 2207-2211.
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Dacriocistorinostomia/métodos , Obstrução dos Ductos Lacrimais/patologia , Obstrução dos Ductos Lacrimais/terapia , Tecido Linfoide/patologia , Ducto Nasolacrimal/patologia , Ducto Nasolacrimal/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The organization of functional brain networks changes across human lifespan. The present study analyzed functional brain networks in healthy full-term infants (N = 139) within 1-6 days from birth by measuring neural synchrony in EEG recordings during quiet sleep. Large-scale phase synchronization was measured in six frequency bands with the Phase Lag Index. Macroscopic network organization characteristics were quantified by constructing unweighted minimum spanning tree graphs. The cortical networks in early infancy were found to be significantly more hierarchical and had a more cost-efficient organization compared with MST of random control networks, more so in the theta and alpha than in other frequency bands. Frontal and parietal sites acted as the main hubs of these networks, the topological characteristics of which were associated with gestation age (GA). This suggests that individual differences in network topology are related to cortical maturation during the prenatal period, when functional networks shift from strictly centralized toward segregated configurations. Hum Brain Mapp 38:4019-4033, 2017. © 2017 Wiley Periodicals, Inc.
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Encéfalo/fisiologia , Eletroencefalografia , Sono/fisiologia , Feminino , Humanos , Recém-Nascido , Modelos Lineares , Masculino , Vias Neurais/fisiologia , Processamento de Sinais Assistido por ComputadorRESUMO
INTRODUCTION: Forty percent of patients with gastric cancer have an unnecessarily extended lymph node dissection with a higher rate of morbidity and mortality. While the Maruyama computer program (MCP) can estimate the lymph node involvement before the surgery, the Maruyama Index (MI) could be a good predictor of overall and disease free survival. METHODS: To measure the probability calculations by MCP, we had to define different "cut-off" levels, with using the calculation of the receiver-operating characteristics analysis. The long term oncological results, as the overall survival (OS) and disease free survival (DFS) were calculated in correlation with the extension of lymphadenectomy (D1 versus D2) and Maruyama Index (MI < 5 versus MI ≥ 5). RESULTS: 74 patients were investigated by the Maruyama computer program preoperatively for the short-term results, and the data of 101 patients were eligible for evaluation of the long-term oncological outcomes. The MCP had a 90.2% of sensitivity, 63.3% of specificity and 78.4% of accuracy. The positive predictive value was 75.5% and the negative predictive value was 84%. In D1 group the DFS was 93.6 months and 68.7 months in D2 group (p = 0.41; HR = 1.34), and the OS was 74.6 and 72.2 months respectively (p = 0.66; HR = 0.87). In patients with MI < 5 the DFS was 92 months and 62.5 months in patients with MI ≥ 5 (p = 0.31; HR = 1.4), while the OS was 86 months and 60.4 months (p = 0.17; HR = 1.52). CONCLUSIONS: Our results proved, that the computerized prediction of LN metastases is efficient and the long term results suggest, that the MI < 5 has a better impact on survival, than the D-level guided surgery.
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Diagnóstico por Computador/métodos , Gastrectomia/métodos , Excisão de Linfonodo/métodos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasia Residual/patologia , Sensibilidade e Especificidade , Software , Neoplasias Gástricas/mortalidade , Taxa de SobrevidaRESUMO
OBJECTIVE: The Union for International Cancer Control (UICC) Node (N) classification is the most common used staging method for the prognosis of gastric cancer. It demands adequate, at least 16 lymph nodes (LNs) to be dissected; therefore different staging systems were invented. METHODS: Between March 2005 and March 2010, 164 patients were evaluated at the Department of General Surgery in the Kenézy Gyula Hospital and at the Department of General, Thoracic and Vascular Surgery in the Kaposi Mór Hospital. The 6th, 7th and 8th UICC N-staging systems, the number of examined LNs, the number of harvested negative LNs, the metastatic lymph node ratio (MLR) and the log odds of positive LNs (LODDS) were determined to measure their 5-year survival rates and to compare them to each other. RESULTS: The overall 5-year survival rate for all patients was 55.5% with a median overall survival time of 102 months. The tumor stage, gender, UICC N-stages, MLR and the LODDS were significant prognostic factors for the 5-year survival with univariate analysis. The 6th UICC N-stage did not follow the adequate risk in comparing N2 vs. N0 and N3 vs. N0 with multivariate investigation. Comparison of performances of the residual N classifications proved that the LODDS system was first in the prediction of prognosis during the evaluation of all patients and in cases with less than 16 harvested LNs. The MLR gave the best prognostic prediction when adequate (more than or equal to 16) lymphadenectomy was performed. CONCLUSIONS: We suggest the application of LODDS system routinely in western patients and the usage of MLR classification in cases with extended lymphadenectomy.
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In this paper, we investigated the isoform-specific roles of certain protein kinase C (PKC) isoforms in the regulation of skeletal muscle growth. Here, we provide the first intriguing functional evidence that nPKCδ (originally described as an inhibitor of proliferation in various cells types) is a key player in promoting both in vitro and in vivo skeletal muscle growth. Recombinant overexpression of a constitutively active nPKCδ in C2C12 myoblast increased proliferation and inhibited differentiation. Conversely, overexpression of kinase-negative mutant of nPKCδ (DN-nPKCδ) markedly inhibited cell growth. Moreover, overexpression of nPKCδ also stimulated in vivo tumour growth and induced malignant transformation in immunodeficient (SCID) mice whereas that of DN-nPKCδ suppressed tumour formation. The role of nPKCδ in the formation of rhabdomyosarcoma was also investigated where recombinant overexpression of nPKCδ in human rhabdomyosarcoma RD cells also increased cell proliferation and enhanced tumour formation in mouse xenografts. The other isoforms investigated (PKCα, ß, ε) exerted only minor (mostly growth-inhibitory) effects in skeletal muscle cells. Collectively, our data introduce nPKCδ as a novel growth-promoting molecule in skeletal muscles and invite further trials to exploit its therapeutic potential in the treatment of skeletal muscle malignancies.
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Proliferação de Células/fisiologia , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Músculo Esquelético/metabolismo , Proteína Quinase C-delta/metabolismo , Animais , Linhagem Celular Tumoral , Células Cultivadas , Humanos , CamundongosRESUMO
Separating concurrent sounds is fundamental for a veridical perception of one's auditory surroundings. Sound components that are harmonically related and start at the same time are usually grouped into a common perceptual object, whereas components that are not in harmonic relation or have different onset times are more likely to be perceived in terms of separate objects. Here we tested whether neonates are able to pick up the cues supporting this sound organization principle. We presented newborn infants with a series of complex tones with their harmonics in tune (creating the percept of a unitary sound object) and with manipulated variants, which gave the impression of two concurrently active sound sources. The manipulated variant had either one mistuned partial (single-cue condition) or the onset of this mistuned partial was also delayed (double-cue condition). Tuned and manipulated sounds were presented in random order with equal probabilities. Recording the neonates' electroencephalographic responses allowed us to evaluate their processing of the sounds. Results show that, in both conditions, mistuned sounds elicited a negative displacement of the event-related potential (ERP) relative to tuned sounds from 360 to 400 ms after sound onset. The mistuning-related ERP component resembles the object-related negativity (ORN) component in adults, which is associated with concurrent sound segregation. Delayed onset additionally led to a negative displacement from 160 to 200 ms, which was probably more related to the physical parameters of the sounds than to their perceptual segregation. The elicitation of an ORN-like response in newborn infants suggests that neonates possess the basic capabilities of segregating concurrent sounds by detecting inharmonic relations between the co-occurring sounds.
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Percepção Auditiva/fisiologia , Desenvolvimento Infantil/fisiologia , Potenciais Evocados/fisiologia , Eletroencefalografia , Feminino , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
OBJECTIVES: By measuring event-related brain potentials (ERPs), the authors tested the sensitivity of the newborn auditory cortex to sound lateralization and to the most common cues of horizontal sound localization. DESIGN: Sixty-eight healthy full-term newborn infants were presented with auditory oddball sequences composed of frequent and rare noise segments in four experimental conditions. The authors tested in them the detection of deviations in the primary cues of sound lateralization (interaural time and level difference) and in actual sound source location (free-field and monaural sound presentation). ERP correlates of deviance detection were measured in two time windows. RESULTS: Deviations in both primary sound localization cues and the ear of stimulation elicited a significant ERP difference in the early (90 to 140 msec) time window. Deviance in actual sound source location (the free-field condition) elicited a significant response in the late (290 to 340 msec) time window. CONCLUSIONS: The early differential response may indicate the detection of a change in the respective auditory features. The authors suggest that the late differential response, which was only elicited by actual sound source location deviation, reflects the detection of location deviance integrating the various cues of sound source location. Although the results suggest that all of the tested binaural cues are processed by the neonatal auditory cortex, utilizing the cues for locating sound sources of these cues may require maturation and learning.
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Sinais (Psicologia) , Potenciais Evocados Auditivos/fisiologia , Localização de Som/fisiologia , Percepção Auditiva/fisiologia , Eletroencefalografia , Potenciais Evocados/fisiologia , Humanos , Recém-NascidoRESUMO
INTRODUCTION: Ras guanine nucleotide exchange factors (RasGEFs) mediate the activation of the Ras signaling pathway that is over activated in many human cancers. The RasGRP3, an activator of H-Ras and R-Ras protein exerts oncogenic effects and the overexpression of the protein is observed in numerous malignant cancer types. Here, we investigated the putative alteration of expression and potential function of RasGRP3 in the formation and progression of human breast cancer. METHODS: The RasGRP3 and phosphoRasGRP3 expressions were examined in human invasive ductal adenocarcinoma derived samples and cell lines (BT-474, JIMT-1, MCF7, SK-BR-3, MDA-MB-453, T-47D) both in mRNA (Q-PCR) and protein (Western blot; immunohistochemistry) levels. To explore the biological function of the protein, RasGRP3 knockdown cultures were established. To assess the role of RasGRP3 in the viability of cells, annexin-V/PI staining and MitoProbe™ DilC1 (5) assay were performed. To clarify the function of the protein in cell proliferation and in the development of chemotherapeutic resistance, CyQuant assay was performed. To observe the RasGRP3 function in tumor formation, the Severe combined immunodeficiency (SCID) mouse model was used. To investigate the role of the protein in Ras-related signaling Q-PCR and Western blot experiments were performed. RESULTS: RasGRP3 expression was elevated in human breast tumor tissue samples as well as in multiple human breast cancer cell lines. Down-regulation of RasGRP3 expression in breast cancer cells decreased cell proliferation, induced apoptosis in MCF7 cells, and sensitized T-47D cells to the action of drugs Tamoxifen and trastuzumab (Herceptin). Gene silencing of RasGRP3 reduced tumor formation in mouse xenografts as well. Inhibition of RasGRP3 expression also reduced Akt, ERK1/2 and estrogen receptor alpha phosphorylation downstream from IGF-I insulin like growth factor-I (IGF-I) or epidermal growth factor (EGF) stimulation confirming the functional role of RasGRP3 in the altered behavior of these cells. CONCLUSIONS: Taken together, our results suggest that the Ras activator RasGRP3 may have a role in the pathological behavior of breast cancer cells and may constitute a therapeutic target for human breast cancer.
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Adenocarcinoma/genética , Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , Fatores de Troca do Nucleotídeo Guanina/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Animais , Anticorpos Monoclonais Humanizados/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fator de Crescimento Epidérmico/farmacologia , Feminino , Fatores de Troca do Nucleotídeo Guanina/antagonistas & inibidores , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/farmacologia , Camundongos , Camundongos SCID , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Invasividade Neoplásica , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Tamoxifeno/farmacologia , Trastuzumab , Ensaios Antitumorais Modelo de Xenoenxerto , Fatores ras de Troca de Nucleotídeo GuaninaRESUMO
A 15-year-old young girl was found dead at home. There were no indications of any intervention or the application of force. On the previous day, she was admitted to hospital because of palpitations, fatigue, a headache, and a swollen neck. During a physical examination, a swollen thyroid gland and tachycardia were found. In the family history, her mother had thyroid disease. According to the laboratory values, she had elevated thyroid hormone levels. After administration of beta-blockers, the patient was discharged and died at home during the night. The parents denounced the hospital for medical malpractice; therefore, a Forensic Autopsy was performed. Based on the available clinical data, the autopsy, histological and toxicological results, the cause of death was stated as multiorgan failure due to disseminated intravascular coagulation (DIC) caused by the autoimmune Graves disease. The forensic assessment of the case does not reveal medical malpractice. Post-mortem diagnoses of thyroid disorders in cases of sudden death can be challenging. However, as the reported case illustrates, the diagnosis could be established after a detailed evaluation of antemortem clinical data, autopsy results, histology, and a toxicological examination.
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BACKGROUND: Stage-adapted surgery guarantees the best outcome for patients with gastric cancer. Successful identification of lymph node involvement may help to reduce the number of extended lymphadenectomies. Preoperative diagnostic tools have low sensitivity and specificity for determining lymph node involvement. Evaluation of sentinel lymph nodes (SLNs) intraoperatively has good results, while the accuracy of the Maruyama computer program (MCP) is controversial. METHODS: We investigated 40 patients by the Maruyama computer model and labeled lymph nodes with blue dye for SLN mapping. To compare the probability calculations by MCP and the results of SLN mapping, we had to define a cutoff level; we did this using receiver-operating characteristics analysis. Sentinel lymph nodes were examined in frozen sections intraoperatively and by standard hematoxylin and eosin staining postoperatively. RESULTS: A total of 795 lymph nodes were removed and examined. The Maruyama computer model had a sensitivity of 91.3 %, specificity of 64 %, and accuracy of 80 % by the best cutoff point. The false-negative rate was 8.7 %. The sensitivity of SLN mapping was 95.7 %, the false-negative rate was 4.3 %, and the specificity was 100 %. The accuracy of SLN mapping was 97.4 %. Only the sensitivity of MCP and SLN biopsy was proven equivalent. CONCLUSIONS: Our results suggest that intraoperative SLN examination is superior to preoperative estimation with the MCP. Correct definition of lymph node involvement helps in planning the best stage-adapted surgery in gastric cancer.
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Diagnóstico por Computador/métodos , Metástase Linfática/diagnóstico , Biópsia de Linfonodo Sentinela/métodos , Software , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Amarelo de Eosina-(YS) , Reações Falso-Negativas , Feminino , Secções Congeladas , Hematoxilina , Humanos , Período Intraoperatório , Linfonodos/patologia , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Curva ROC , Sensibilidade e EspecificidadeRESUMO
Introduction: Gastric cancer ranks as the fifth most common cancer globally. The presence of lymph node metastasis is a significant prognostic factor influencing survival. Postoperative morbidity and nodal staging accuracy are heavily affected by the extent of lymph node dissection. Our study aimed to explore the potential integration of two contemporary methods, sentinel node navigation surgery (SNNS) and the Maruyama Computer Program (MCP), to improve the accuracy of nodal staging. Materials and methods: We conducted a prospective data collection involving patients with gastric adenocarcinoma from 2008 to 2018 at the Department of Surgery, University of Debrecen, Hungary. Data from 100 consecutive patients were collected. The primary and secondary endpoints included evaluating the rate of node-negative patients and the diagnostic accuracy of our combined approach. Results: Sentinel node mapping was successful in 97 out of 100 patients. We found that using the threshold value of the Maruyama Index (MI) ≥ 28, all metastatic stations of sentinel-node-negative patients could be identified. Our method achieved 100% sensitivity and negative predictive value, with a specificity of 60.42% (95% CI = 46.31%-72.98%). Discussion: The combined application of SNNS and MCP has proven to be an effective diagnostic technique in the synergistic approach for identifying metastasis-positive lymph node stations. Despite its limitations, this combination may assist clinicians in customizing lymphadenectomy for gastric cancer patients.
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Linfonodo Sentinela , Neoplasias Gástricas , Humanos , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Excisão de Linfonodo/métodos , Linfonodo Sentinela/patologia , Metástase Linfática/patologia , Estadiamento de Neoplasias , Linfonodos/patologiaRESUMO
BACKGROUND: Hypoxia and necrosis are common features of invasive cancer. The dynamic upregulation of carbonic anhydrase IX (CAIX), triggered by hypoxia-inducible factor 1 (HIF-1) is 1 of the mechanisms supporting cellular adaptation to hypoxia in solid tumors, including breast carcinoma. CAIX activity results in extracellular acidosis and in a profound reorganization of the tumor micro-environment, influencing biological behavior and prognosis. The main focus of our study was to evaluate the mass and distribution of the immune infiltrate, more specifically of CD8+ effector T-cells, in relation with tumoral CAIX expression. MATERIALS AND METHODS: Formalin-fixed and paraffin-embedded breast carcinoma sections were analyzed following double immunohistochemical staining for CAIX and CD8. Scanned digital slides were evaluated for both labelings, and CD8-related signal was determined within and outside CAIX-positive tumor areas using the HistoQuant (3DHistech) image analysis software. Statistical analysis was performed using GraphPad Prism software. RESULTS: Of the 34 breast carcinomas, 18 tested partially positive for CAIX. The remaining 16 cases were used as the CAIX-negative control group. Necrotic foci were generally associated with CAIX overexpression, and tumors exhibiting signs of necrosis had a significantly higher rate of relative CAIX expression compared with samples without necrosis (11.47±5.505 vs. without necrosis 3.765±3.5 P-value=0.0216). On the other hand, no statistically significant difference was found when comparing relative CD8+ lymphocyte counts in cases with necrosis as opposed to those where necrosis was absent (134.7±55.7 vs. 97.70±57.25; P value=0.1579). No difference in gross CD8+ T-lymphocyte infiltrate could be measured between CAIX positive and negative samples (98.48±37.32 vs. 95.99±50 P value=0.5928). However, in CAIX-expressing tumors a statistical correlation between the CD8+ T-lymphocyte infiltrate and the extent of CAIX-positive areas was observed. Within the same tumor, CD8+ T-lymphocyte counts showed a significant difference betweeen CAIX+ and CAIX- areas (13.06±9.4 vs. 135.6±62.2 P value <0.0001). CONCLUSION: Our measurements demonstrate for the first time that tumor areas with CAIX expression potentially hamper CD8+ T-lymphocyte infiltration in breast carcinoma. The hypoxia-driven adaptive micro-environment likely interferes with the specific response to biological and immune therapies requiring intact effector T-cell response.
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Neoplasias da Mama , Projetos de Pesquisa , Humanos , Feminino , Anidrase Carbônica IX , Hipóxia , Necrose , Microambiente TumoralRESUMO
BACKGROUND: Forty percent of patients with gastric cancer undergo unnecessary extended lymph node dissection which may result in higher rate of morbidity and mortality. Successful sentinel lymph node (SLN) mapping may help to reduce the number of extended lymphadenectomy. Various marking methods are in use to detect the sentinel lymph node in gastric cancer. METHODS: Forty consecutive patients underwent open gastric resection with blue dye mapping and modified D2 lymph node dissection. Sixteen patients (group A) were marked submucosally with endoscopy and 24 patients (group B) were labelled by the surgeon subserosally. The staining method and the lymphadenectomy were supervised by the same surgeon. RESULTS: A total of 795 lymph nodes were removed and examined. The mean number of blue nodes was 4.1 per patient in group A and 4.8 in group B. The false negative rate was 0% in group A and 7.7% in group B. The sensitivity and specificity of SLN mapping was 100% in the submucosal group. The specificity of subserosal marking method was 100%, while the seínsitivity was 92.3%. Submucosal and subserosal marking methods were proven to be equivalent in detection rate, sensitivity and specificity based on 90% confidence interval of the ratio of indicators. CONCLUSIONS: Our results suggest that sentinel lymph node mapping with blue dye alone represents a safety procedure and seems to be adaptable with high sensitivity and specificity, especially in cases of T1 and T2 tumors.
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Corantes , Gastrectomia , Linfonodos/patologia , Linfonodos/cirurgia , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Reações Falso-Negativas , Feminino , Gastrectomia/métodos , Mucosa Gástrica , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Membrana SerosaRESUMO
BACKGROUND: Forty percent of patients with gastric cancer have unnecessarily extended lymph node dissections with higher rates of morbidity and mortality than those in non-extended procedures. Successful sentinel lymph node (SLN) mapping may help to reduce the number of extended lymphadenectomies. METHODS: SLN mapping was investigated by a blue dye-only method in patients with gastric cancer. The first cohort of patients (n = 16) were marked submucosally by an endoscopist and in the second cohort of patients (n = 23) a subserosal injection was performed by the surgeon. RESULTS: Thirty-nine patients, all Caucasians, underwent gastric resection or total gastrectomy with SLN biopsy using patent blue-dye mapping and modified D2 lymphadenectomy. The mapping procedure and the lymphadenectomy were supervised by the same surgeon. A total of 770 lymph nodes were removed and examined. The mean number of blue nodes was 4.3 per patient. In 22/23 cases at least one SLN showed tumor involvement. The sensitivity of SLN mapping was 95.7%, the false-negative rate was 4.3%, and the specificity was 100%. The negative predictive value was 93.8% and the positive predictive value was 100%. In cases of T1 and T2 tumors the sensitivity was 100%. We found the two marking methods (submucosal vs. subserosal) to be equivalent and there was no side-effect of the blue-dye mapping. CONCLUSIONS: Our results suggest that SLN mapping with blue dye alone represents a safe procedure that seems to be adaptable for non-obese patients undergoing open surgery for gastric cancer in the Eastern European region. The procedure has high sensitivity and specificity, especially in cases of T1 and T2 tumors.
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Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Corantes , Metástase Linfática/patologia , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Gástricas/patologia , Idoso , Idoso de 80 Anos ou mais , Reações Falso-Negativas , Feminino , Gastrectomia , Humanos , Hungria , Excisão de Linfonodo/métodos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Neoplasias Gástricas/cirurgiaRESUMO
OBJECTIVE: To review the clinical experience in the treatment of patients with low-risk gestational trophoblastic neoplasia (GTN) over the past 30 years in a national trophoblastic disease center. STUDY DESIGN: Between January 1, 1977, and December 31, 2007, 302 patients with low-risk GTN were treated. The patients were directed to our institution from all parts of Hungary. The patients were 14 to 53 years of age with an average age of 28.3 years. Methotrexate (MTX)/folinic acid or actinomycin-D (Act-D) primary chemotherapy was selected based upon the patient's stage and prognostic score of GTN. RESULTS: Among 218 low-risk patients, 210 (96.3%) achieved remission as a result of MTX therapy. In 8 patients (3.7%), MTX-Act-D-cyclophosphamide (MAC) combination chemotherapy was needed to achieve complete remission, in some cases assisted by operation. Among 84 patients, 81 (96.4%) achieved remission as a result of Act-D therapy. In 3 cases (3.6%) complete remission was achieved by MAC combination chemotherapy. We detected metastases in 22.8% (69/302) of our low-risk patients. Chemotherapy, surgical intervention or other supplementary treatments resulted in 100% remission in cases of low-risk nonmetastatic and metastatic disease. CONCLUSION: Our data indicate that MTX/folinic acid or Act-D should be the primary treatment in patients with nonmetastatic or metastatic low-risk GTN. Importantly, patients with resistance to single-agent chemotherapy regularly achieve complete remission with MAC combination chemotherapy. Results show that patient care under the direction of experienced clinicians serves to optimize the opportunity for cure and minimize morbidity.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença Trofoblástica Gestacional/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico , Adolescente , Adulto , Ciclofosfamida/uso terapêutico , Dactinomicina/uso terapêutico , Feminino , Doença Trofoblástica Gestacional/patologia , Doença Trofoblástica Gestacional/cirurgia , Humanos , Hungria , Histerectomia , Leucovorina/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Gravidez , Indução de Remissão , Estudos Retrospectivos , Neoplasias Uterinas/patologia , Neoplasias Uterinas/cirurgia , Adulto JovemRESUMO
The purpose of this article is to describe a new, phonocardiography-based fetal telemonitoring system, which, due to its passive nature, allows long-term measurements even at the home of the pregnant woman. The input element of the system was the home monitor with two sensors for recording the trans-abdominal fetal heart signal and the uterine contractions. The recorded signal was transmitted by mobile network and Internet to an Evaluation Center, where it was analyzed in detail to obtain information about possible dysfunction of the fetal heart. The investigations on this system made clear that by advanced processing of the recorded signal the system captured many additional cardiac features compared with the traditional ultrasound-based cardiotocographic procedure.
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Cardiotocografia/instrumentação , Coração Fetal , Fonocardiografia/instrumentação , Cuidado Pré-Natal/métodos , Consulta Remota/instrumentação , Cardiotocografia/métodos , Feminino , Serviços de Assistência Domiciliar , Humanos , Hungria , Internet , Itália , Fonocardiografia/métodos , Gravidez , Consulta Remota/métodosRESUMO
Infant directed speech (IDS) may serve important functions in language acquisition and in adult-infant communication. The processing of IDS evolves during the first years of life. In order to serve as an effective tool of language acquisition, already very young infants should be able to distinguish IDS from adult directed speech (ADS). We tested whether the ability to discriminate these two speech registers is functional in neonates, by recording EEG from 98 newborn infants in response to Hungarian words naturally spoken in the IDS and the ADS register. Words presented in the ADS register elicited a centro-parietal slow positivity in the 200-600â¯ms time window whereas words in IDS register elicited a small frontal negativity in the 700-900â¯ms time window. We conclude that newborn infants differentiate natural speech sounds based on speech register.
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Córtex Cerebral/fisiologia , Relações Interpessoais , Desenvolvimento da Linguagem , Fonética , Percepção da Fala/fisiologia , Eletroencefalografia , Feminino , Humanos , Recém-Nascido , MasculinoRESUMO
Oncobiotic transformation of the gut microbiome may contribute to the risk of breast cancer. Recent studies have provided evidence that the microbiome secretes cytostatic metabolites that inhibit the proliferation, movement, and metastasis formation of cancer cells. In this study, we show that indolepropionic acid (IPA), a bacterial tryptophan metabolite, has cytostatic properties. IPA selectively targeted breast cancer cells, but it had no effects on non-transformed, primary fibroblasts. In cell-based and animal experiments, we showed that IPA supplementation reduced the proportions of cancer stem cells and the proliferation, movement, and metastasis formation of cancer cells. These were achieved through inhibiting epithelial-to-mesenchymal transition, inducing oxidative and nitrosative stress, and boosting antitumor immune response. Increased oxidative/nitrosative stress was due to the IPA-mediated downregulation of nuclear factor erythroid 2-related factor 2 (NRF2), upregulation of inducible nitric oxide synthase (iNOS), and enhanced mitochondrial reactive species production. Increased oxidative/nitrosative stress led to cytostasis and reductions in cancer cell stem-ness. IPA exerted its effects through aryl hydrocarbon receptor (AHR) and pregnane X receptor (PXR) receptors. A higher expression of PXR and AHR supported better survival in human breast cancer patients, highlighting the importance of IPA-elicited pathways in cytostasis in breast cancer. Furthermore, AHR activation and PXR expression related inversely to cancer cell proliferation level and to the stage and grade of the tumor. The fecal microbiome's capacity for IPA biosynthesis was suppressed in women newly diagnosed with breast cancer, especially with stage 0. Bacterial indole biosynthesis showed correlation with lymphocyte infiltration to tumors in humans. Taken together, we found that IPA is a cytostatic bacterial metabolite, the production of which is suppressed in human breast cancer. Bacterial metabolites, among them, IPA, have a pivotal role in regulating the progression but not the initiation of the disease.
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Immunglobulin E (IgE)-based, irregularly recurring, severe anaphylactic reactions occurred in a 50-year-old European white male patient suffering also from Crohn's disease. On the base of immunologic laboratory tests concerning the mechanism of the phenomenon, the idea arose whether molecules derived for certain microbial derivatives could enter the blood circulation via the damaged bowel walls in the patient with Crohn's disease and they might act as allergens. The microbial analysis diagnosed atypical Staphylococcus in the stool. The serum level of IgE was very high. The concomitant use of targeted antibiotics and anti-allergy and immunosuppressive agents resulted in a complete remission during a couple of months. Not only Crohn's disease has improved, but also the total serum IgE level has decreased significantly, and the unpredictable anaphylactic attacks have been completely eliminated. In Crohn's disease, the anaphylactic complications induced by atypical microbial allergens (e.g., derivatives of Staphylococcus) can be effectively treated after the recognition of this pathological mechanism. This is the first description of such a pathologic state. Orv Hetil. 2019; 160(38): 1514-1518.
Assuntos
Anafilaxia/tratamento farmacológico , Antialérgicos/uso terapêutico , Antibacterianos/uso terapêutico , Doença de Crohn/complicações , Imunoglobulina E/sangue , Imunossupressores/uso terapêutico , Staphylococcus , Anafilaxia/diagnóstico , Anafilaxia/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Resultado do TratamentoRESUMO
Introduction: Breast conserving surgery for breast cancer requires the analysis of surgical margins. If the tumor is not removed completely, additional treatments (reoperation, boost irradiation) are generally recommended. Aim: To analyze the information content of histopathology reports on surgical margins in consecutive cases of breast conservation for invasive female breast cancer, to evaluate the frequency of incompletely removed tumors and to estimate the rate of further treatments after incomplete removal. Method: Analysis of margin related data of consecutive histopathology reports from 8 Hungarian pathology units with locoregional treatment related data in case of unsafe margins. Results: 386 reports were analyzed after exclusions. 200 and 32 cases were identified as having unsafe margins according to the previous (<5 mm) and the new (0 mm) definition of unclear margin, respectively. Unsafe margins were more common with lobular carcinomas. Specimens with clear margins weighed more. Reoperations for unsafe margins were performed in 43/180 and 12/22 cases according to the previous and the new definitions, respectively. Only 75/137 patients without reoperation received boost irradiation of the tumor bed; information on boost radiotherapy was often missing. Residual cancer was identified in 15/43 reoperated patients, of whom 9 had >0 mm margin distance. Conclusions: Some pathology reports lack information on surgical margins. Unsafe margin rates decreased with the new definition. Residual cancer may be left behind in case of clear margins with no ink on tumor. Neither reoperation, nor boost radiotherapy is given to some patients with unclear surgical margins. Orv Hetil. 2019; 160(26): 1036-1044.