RESUMO
BACKGROUND: Da Vinci® Single Port (dvSP) was recently developed. Its application in colorectal surgery is under investigation. The aim of this study was to explore the safety and feasibility of dvSP for intersphincteric (dvSP-ISR), right colectomy (dvSP-RC), and transverse colectomy (dvSP-TC). Surgical indication and short-term results were analyzed. METHODS: All consecutive patients from a prospective database of patients who underwent dvSP-ISR, dvSP-RC, and dvSP-TC at Korea University Anam Hospital from November 2020 to December 2021, were analyzed. Perioperative, pathological, and oncological short-term outcomes were analyzed. RESULTS: A total of 7 dvSP-ISR, 5 dvSP-RC, and 1 dvSP-TC were performed. Median age was 56.0 (55.0-61.0) years for the dvSP-ISR and 54.0 (44.7-63.5) years for the dvSP-RC/TC. Median body mass index was 22.8 (17.1-24.8) kg/m2 for the dvSP-ISR and 23.6 (20.8-26.9) kg/m2 for the dvSP-RC/TC. All dvSP-ISR patients received neoadjuvant long-course chemoradiotherapy, including one patient with squamocellular carcinoma who was treated with 5-fluorouracil (5-FU)/mitomycin. All other patients, excluding one dvSP-RC patient with Crohn's disease, had an adenocarcinoma. Median operation time was 280 (240-370) minutes for the dvSP-ISR and 220 (201-270) minutes for the dvSP-RC/TC. Estimated blood loss was insignificant. No intraoperative complications or conversions to multiport/open surgery was reported. Median post-operative stay was 7.0 (6.0-10.0) days for the dvSP-ISR and 5.0 (4.0-6.7) days for the dvSP-RC/TC. Quality of mesorectum was complete for six patients, and nearly complete for one. Median number of retrieved lymph nodes were 21 (17-25) for the dvSP-ISR and 28 (24-49) for the dvSP-RC/TC. Proximal and distal resection margins were tumor free. Four patients experienced post-operative complications not related to the platform which were: ileus, voiding dysfunction, infected pelvic hematoma, and wound infection. Median follow-up was 9 (6-11) months and 11 (7-17) months for the dvSP-ISR and dvSP-RC/TC, respectively. Two patients had systemic recurrence; all others were tumor free. CONCLUSIONS: The dvSP platform is safe and feasible for intersphincteric resection with right lower quadrant access, and right/transverse colectomy with suprapubic access. Further studies are needed to evaluate benefit differences compared to multiport robotic platform.
Assuntos
Adenocarcinoma , Cirurgia Colorretal , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Adenocarcinoma/cirurgia , Colectomia/métodos , Humanos , Laparoscopia/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversosRESUMO
BACKGROUND: Recurrence of pancreatic cancer after primary pancreatectomy occurs in the vast majority of patients. The role of surgical treatment for recurrent pancreatic cancer is not well established. METHODS: Patients who underwent primary pancreatectomy with curative intent from 2000 to 2014 at a single large-volume centre were evaluated retrospectively. CT or PET was used to select patients with an isolated recurrence. The clinicopathological features and survival outcomes were compared according to treatment modalities. RESULTS: Of the 1610 patients with pancreatic cancer who underwent resection, 1346 (83·6 per cent) were diagnosed with recurrent pancreatic cancer. Recurrence was locoregional in 366 patients (27·2 per cent), distant multifocal in 251 (18·6 per cent), distant isolated in 188 (14·0 per cent), locoregional plus distant in 153 (11·4 per cent) and peritoneal seeding in 388 (28·8 per cent). Of the 1346 patients with recurrence, 197 (14·6 per cent) had isolated recurrence; of these, 48 (24·4 per cent of all isolated recurrences; 3·6 per cent of all recurrences) underwent resection. Median survival of the 197 patients after diagnosis of isolated recurrence was 14·7 months; it was longer in patients who underwent surgical resection than among those treated non-surgically (23·5 versus 12·0 months; P = 0·014). Multivariable analysis showed that chemotherapy and resection for recurrence were associated with better prognosis. Median survival after recurrence was longest in the 23 patients with isolated pulmonary recurrence (33·3 months). Survival after recurrence was better in patients who underwent resection of isolated recurrence in the remnant pancreas (median 28·0 versus 12·0 months, P = 0·010) and lung (median 36·5 versus 9·5 months; P = 0·010) than in those who did not undergo resection. CONCLUSION: Surgical resection may be considered an option for treatment of patients with isolated recurrent pancreatic cancer.
Assuntos
Adenocarcinoma/terapia , Recidiva Local de Neoplasia/terapia , Neoplasias Pancreáticas/terapia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/mortalidade , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/mortalidade , Tomografia por Emissão de Pósitrons , Reoperação , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Personal watercrafts (PWC) account for a disproportionate amount of water based injuries. Current literature suggests those with less PWC experience are more at risk for injury. Previous studies have not specifically evaluated the orthopedic implications of PWC usage or how various mechanisms of injury (MOI) contribute to different injury patterns. HYPOTHESIS: PWC injuries will frequently require orthopedic intervention. The presence of an orthopedic injury will result in increased injury severity score (ISS), hospital and intensive care unit (ICU) length of stay (LOS). Patients visiting our region will have less PWC experience and so are more prone to serious injuries. MATERIALS AND METHODS: Retrospective cohort study at a single Level 1 trauma center of admitted patients sustaining PWC injuries from 02/2004-03/2017. The following were studied: demographics, mechanism, season, ISS, hospital and ICU LOS, follow-up, fracture characteristics and management. RESULTS: Hundred and twenty-seven patients were admitted due to PWC injury, 66 (52.0%) sustained an orthopedic injury, totaling 103 fractures (48 [46.6%] lower extremity, 26 [25.2%] upper extremity, 14 [13.6%] vertebral, 11 [10.7%] pelvic ring and 4 [3.9%] acetabulum). The mean age of orthopedic patients was 29 years (range 8-62). Handle bar injuries were significantly associated with open fractures, (13 of 25 open fractures, 3 of which became infected). Injuries occurring during the winter were associated with a higher ISS, yet more injuries occurred in the summer. A patient being a "visitor" to the region did not influence ISS. The mean LOS was 12.6 days for orthopedic patients. Eighteen orthopedic patients (27.3%) required ICU admission and 36 (54.5%) patients required orthopedic surgery (mean 2.11 operations). DISCUSSION: A majority of PWC injuries resulted in extremity fractures with a moderate percentage requiring orthopedic surgery. Correlations between PWC experience and injury incidence can provide information for increased safety. LEVEL OF EVIDENCE: IV; retrospective.
Assuntos
Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Equipamentos Esportivos/efeitos adversos , Esportes Aquáticos/lesões , Adolescente , Adulto , Criança , Feminino , Florida/epidemiologia , Fraturas Ósseas/cirurgia , Fraturas Expostas/etiologia , Humanos , Incidência , Escala de Gravidade do Ferimento , Unidades de Terapia Intensiva , Tempo de Internação , Extremidade Inferior/lesões , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos/estatística & dados numéricos , Ossos Pélvicos/lesões , Estudos Retrospectivos , Estações do Ano , Navios , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Extremidade Superior/lesões , Adulto JovemRESUMO
STUDY DESIGN: Single-center retrospective study. OBJECTIVES: To evaluate the monitoring rate, sensitivity and specificity of intraoperative monitoring (IOM) during removal of intradural extramedullary (IDEM) or epidural metastatic spinal tumors. Also, to assess the efficacy of monitoring somatosensory-evoked potentials (SSEP) when motor-evoked potentials (MEP) are not measurable. SETTING: The Neuro-Oncology Clinic, National Cancer Center, Korea. METHODS: Patients (n=101) with IDEM or epidural metastatic spinal tumors at the cord level underwent surgeries monitored with SSEP and/or MEP. The monitoring rate was defined as negative when MEP or SSEP could not be measured after reversal of the neuromuscular block under general anesthesia. Positive IOM changes included more than a 50% change in the MEP or SSEP amplitude and more than a 10% delay in SSEP latency. RESULTS: MEP was measurable in 73% of patients. The MEP monitoring rate in patients with motor power grades of 3 or less was 39%, which was lower than that of SSEP (83%). The sensitivity, specificity and predictability of MEP for motor changes were 93, 90 and 91%, respectively. Conversely, the sensitivity, specificity and predictability of SSEP were 62, 97 and 89%, respectively. In patients in whom MEP was not measurable (n=24), SSEP was monitored with a predictability of 83%. CONCLUSION: In cases of extramedullary spinal tumors, MEP shows a higher sensitivity than SSEP does. However, the monitoring rate of MEP in non-ambulatory patients was lower than that of SSEP. In those cases, SSEP can be useful to monitor for postoperative neurological deficits.
Assuntos
Neoplasias Epidurais/fisiopatologia , Neoplasias Epidurais/cirurgia , Monitorização Neurofisiológica Intraoperatória , Neoplasias da Medula Espinal/fisiopatologia , Neoplasias da Medula Espinal/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Epidurais/secundário , Potencial Evocado Motor , Potenciais Somatossensoriais Evocados , Estudos de Viabilidade , Feminino , Humanos , Monitorização Neurofisiológica Intraoperatória/métodos , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/prevenção & controle , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias da Medula Espinal/secundário , Resultado do Tratamento , Adulto JovemRESUMO
This study aimed to analyze the use of the revised International Prognostic Scoring System (IPSS-R) assessed after hypomethylating treatment (HMT) for patients with myelodysplastic syndrome (MDS) undergoing an allogeneic stem cell transplantation (SCT). Among 115 patients who received pre-SCT HMT, comparison analysis of the prognostic values between the IPSS-R at the time of HMT (IPSS-R@HMT) and at the time of SCT after HMT (IPSS-R@SCT) showed a significantly higher predictive power for overall survival (OS) of the latter. Alteration in IPSS-R risk occurred in 60%, while the patients with 'down-staged' IPSS-R@SCT showed better OS compared with those with 'unchanged' or 'up-staged' risk. On multivariate analysis in all 201 patients, IPSS-R@SCT, monosomal karyotype, treatment failure to pre-SCT treatment, and high hematopoietic cell transplantation-comorbidity index were independently associated with OS. Constructed using these factors, the MDS Transplantation Prognostic Scoring System (MTPSS) identified four risk groups with 4-year OS of 76.4% in low, 61.4% in intermediate-1 and 21.9% in intermediate-2 risk groups, whereas all in the high risk group died within 2 years after SCT (P<0.001). Our study emphasizes the need for further studies aiming to evaluate a transplantation prognostic model such as the MTPSS to make appropriate decisions for transplantation in MDS.
Assuntos
Metilação de DNA/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes Mielodisplásicas/terapia , Adolescente , Adulto , Idoso , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Comorbidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Cariótipo , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/mortalidade , Prognóstico , Medição de Risco , Análise de Sobrevida , Adulto JovemRESUMO
Allogeneic stem cell transplantation from HLA-matched siblings (MSD-SCT) for elderly patients with severe aplastic anemia (SAA) is not a widely accepted first-line treatment. Recently, fludarabine, lower-dose cyclophosphamide and antithymocyte globulin conditioning (Flu/lower-dose Cy/ATG) with lower toxicities has been investigated. To determine whether this regimen can overcome the negative effects of age, we analyzed 117 adult patients with SAA who received MSD-SCT using Flu/lower-dose Cy/ATG, and compared outcomes between 63 younger age group (YAG; ⩽40 years) and 54 older age group (OAG; >40 years) patients. No primary graft failure was observed. Neutrophil engraftment was significantly faster in the YAG compared with the OAG (12 vs 13 days; P=0.04). The incidences of acute grade II-IV (9.5% vs 9.3% at day 100; P=0.42) and chronic GVHD (8.1% vs 9.5% at 5 years; P=0.80), secondary graft failure (20.8% vs 7.9% at 5 years; P=0.11) and transplant-related mortality (5.4% and 11.1% at 5 years; P=0.91) were not significantly different between the YAG and OAG. In addition, failure-free (73.7% vs 81.0% at 5 years; P=0.73) and overall survival rates (93.7% vs 88.9% at 5 years; P=0.20) were comparable. Our results suggest that MSD-SCT using Flu/lower-dose Cy/ATG may be a feasible first-line treatment even in older patients with SAA.
Assuntos
Anemia Aplástica/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Vidarabina/análogos & derivados , Adolescente , Adulto , Fatores Etários , Anemia Aplástica/complicações , Anemia Aplástica/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Irmãos , Análise de Sobrevida , Resultado do Tratamento , Vidarabina/uso terapêutico , Adulto JovemRESUMO
OBJECTIVE: This literature review analysed facial nerve management strategies in jugular paraganglioma surgery and discusses the tumour resection rate and the facial nerve outcome associated with each technique. METHODS: A retrospective review of PubMed and Medline articles on the surgical treatments for jugular paraganglioma was performed. Tumour resection rates and post-operative facial nerve function after non-rerouting, short anterior rerouting and long anterior rerouting approaches were evaluated for each article. RESULTS: A total of 15 studies involving a total of 688 patients were included. Post-operative facial nerve function was similar after non-rerouting and short anterior rerouting approaches (p = 0.169); however, both of these techniques had significantly better post-operative facial nerve outcomes compared with long anterior rerouting (p < 0.001 and p = 0.001, respectively). The total tumour removal rate was significantly higher for long anterior rerouting than with the non-rerouting approach (p = 0.016). There was no difference in total tumour removal rate between the long and short anterior rerouting approaches (p = 0.067) and between the short anterior rerouting and non-rerouting approaches (p = 0.867). CONCLUSION: No strict guidelines for facial nerve management in jugular paraganglioma resection are available. Although long anterior rerouting provides the best tumour exposure along with a low morbidity rate, case-by-case selection of the surgical approach is recommended.
Assuntos
Nervo Facial/cirurgia , Tumor do Glomo Jugular/cirurgia , Nervo Facial/fisiologia , Traumatismos do Nervo Facial/fisiopatologia , Traumatismos do Nervo Facial/prevenção & controle , Paralisia Facial/fisiopatologia , Paralisia Facial/prevenção & controle , Tumor do Glomo Jugular/fisiopatologia , Humanos , Tratamentos com Preservação do Órgão/métodos , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Reactive oxygen species (ROS) are chemically reactive molecules that perform essential functions in living organisms. Accumulating evidence suggests that many types of cancer cells exhibit elevated levels of ROS. Conversely, generation of ROS has become an effective method to kill cancer cells. (E)-3-hydroxy-3-(4-(4-nitrophenyl)-2-oxobut-3-en-1-yl) indolin-2-one, which is an NO2 group-containing compound designated herein as HOI-02, generated ROS and, in a dose-dependent manner, decreased esophageal cancer cell viability and inhibited anchorage-independent growth, followed by apoptosis and G2-M arrest. Moreover, results of an in vivo study using a patient-derived xenograft mouse model showed that HOI-02 treatment suppressed the growth of esophageal tumors, without affecting the body weight of mice. The expression of Ki-67 was significantly decreased with HOI-02 treatment. In addition, the phosphorylation of c-Jun, and expression of p21, cleaved caspase 3, and DCFH-DA were increased in the HOI-02-treated group compared with the untreated control group. In contrast, treatment of cells with (E)-3-(4-(4-aminophenyl)-2-oxobut-3-en-1-yl)-3-hydroxyindolin-2-one, which is an NH2 group-containing compound designated herein as HOI-11, had no effect. Overall, we identified HOI-02 as an effective NO2 group-containing compound that was an effective therapeutic or preventive agent against esophageal cancer cell growth.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Esofágicas/tratamento farmacológico , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Indóis/farmacologia , Nitrobenzenos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Neoplasias Esofágicas/patologia , Humanos , Masculino , Camundongos SCID , Pessoa de Meia-Idade , Transdução de Sinais , Fator de Transcrição AP-1/metabolismo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoAssuntos
Proteínas de Ligação a DNA/genética , Síndromes Mielodisplásicas , Proteínas Proto-Oncogênicas/genética , Transplante de Células-Tronco , Proteína Supressora de Tumor p53/genética , Adolescente , Adulto , Idoso , Aloenxertos , Dioxigenases , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Taxa de SobrevidaRESUMO
We investigated the prognostic relevance of IKZF1 deletions in 118 adult Ph-positive ALL patients who had minimal residual disease (MRD) data under a uniform treatment of allo-SCT following first-line imatinib-based chemotherapy. IKZF1 deletions were identified in 93 patients (78.8%). IKZF1-deleted patients had a lower proportion of early-stable molecular responders compared with wild-type patients (28.0 vs 56.0%, P=0.028). After a median follow-up of 72 months, IKZF1-deleted patients had a trend for higher cumulative incidence of relapse (CIR) (38.0 vs 13.3%, P=0.052), particularly in a subgroup of early-stable molecular responders (n=40; 21.4 vs 0%, P=0.088), but comparable disease-free survival to wild-type patients. Patients with biallelic-null deletions showed higher CIR (74.6 vs 13.3%, P=0.003) and lower disease-free survival (20.0 vs 67.5%, P=0.022) than wild-type patients. In multivariate analysis, MRD kinetics were closely related to outcomes, while neither IKZF1 deletions nor their functional subtypes retained an independent statistical power. Within the limitation of sample size, however, considering both the negative impact of IKZF1 deletions on MRD kinetics and a trend for relationship between IKZF1 deletions and relapse in early-stable molecular responders, IKZF1 deletions may have a potentially additive effect on unfavorable prognosis in a specific MRD-based subgroup of adult Ph-positive ALL transplants.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzamidas/uso terapêutico , Fator de Transcrição Ikaros/genética , Piperazinas/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Pirimidinas/uso terapêutico , Adolescente , Adulto , Antineoplásicos/administração & dosagem , Feminino , Humanos , Fator de Transcrição Ikaros/deficiência , Fator de Transcrição Ikaros/metabolismo , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Deleção de Sequência , Resultado do Tratamento , Adulto JovemRESUMO
Methionine sulfoxide reductase A (MSRA) protects proteins from oxidation, and also helps remove reactive oxygen species (ROS) by recovering antioxidant enzymes inactivated by oxidation. Although its functions have been investigated extensively, little is known about the mechanism by which MSRA is regulated. Arrest defective 1 (ARD1) is an enzyme that catalyzes not only N-terminal acetylation as a cotranslational modification but also lysine acetylation as a posttranslational modification. ARD1, which is expressed in most cell types, is believed to participate in diverse biological processes, but its roles are poorly understood. Given that MSRA was hunted in a yeast two-hybrid screen with ARD1 as the bait, we here investigated whether ARD1 is a novel regulator of MSRA. ARD1 was shown to interact with and acetylate MSRA in both cells and test tubes. It specifically acetylated the K49 residue of MSRA, and by doing so repressed the enzymatic function of MSRA. ARD1 increased cellular levels of ROS, carbonylated proteins and DNA breaks under oxidative stress. Moreover, it promoted cell death induced by pro-oxidants, which was attenuated in MSRA-deficient cells. When mice were exposed to hyperoxic conditions for 2 days, their livers and kidneys were injured and protein carbonylation was increased. The oxidative tissue injury was more severe in ARD1 transgenic mice than in their wild-type littermates. In conclusion, ARD1 has a crucial role in the cellular response to oxidative stress as a bona fide regulator of MSRA. ARD1 is a potential target for ameliorating oxidative injury or for potentiating ROS-producing anticancer agents.
Assuntos
Metionina Sulfóxido Redutases/metabolismo , Acetiltransferase N-Terminal A/metabolismo , Acetiltransferase N-Terminal E/metabolismo , Estresse Oxidativo , Acetilação , Sequência de Aminoácidos , Animais , Humanos , Metionina Sulfóxido Redutases/química , Camundongos Transgênicos , Dados de Sequência Molecular , Necrose , Ligação ProteicaRESUMO
Emerging molecular studies have identified a subgroup of patients with unfavorable core-binding factor-positive (CBF)-AML who should be treated by intensified post-remission treatments. We analyzed 264 adults with CBF-AML from 2002 to 2011, and focused on 206 patients who achieved CR after standard '3+7' induction chemotherapy. Patients who achieved CR with an available donor were treated with allogeneic hematopoietic SCT (allo-HSCT, n=115) and the rest were treated with autologous (auto) HSCT (n=72) or chemotherapy alone (n=19). OS was not significantly different between CBFß/MYH11 (n=62) and RUNX1/RUNX1T1 (n=144), and auto-HSCT showed favorable OS compared with allo-HSCT or chemotherapy alone. Cytogenetic analysis identified that inv(16) without trisomy had a favorable OS and t(8;21) with additional chromosomes had an unfavorable OS, but multivariate analysis revealed those were NS. Patients with c-kit mutation showed inferior OS. For transplanted patients, residual post-transplant CBF-minimal residual disease quantitative PCR with higher WT1 expression at D+60 showed the worst OS with a higher incidence of relapse. Conclusively, we found that unfavorable CBF-AML can be defined with risk stratification using cytogenetic and molecular studies, and a careful risk-adapted treatment approach using frontline transplantation with novel therapies should be evaluated for this particular risk subgroup.
Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Inversão Cromossômica , Fatores de Ligação ao Core/metabolismo , Citogenética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mutação , Prognóstico , Recidiva , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Translocação Genética , Resultado do Tratamento , Adulto JovemRESUMO
Few studies are available that compare PBSC and BM from unrelated donors, especially in adult high-risk ALL. To determine which graft source is superior in adult high-risk ALL, we analyzed the long-term outcomes of 106 consecutive transplants from 8/8-matched or 7/8-matched unrelated donors (38 PBSC vs 68 BM). All patients received a uniform strategy of pre-transplant therapy, myeloablative conditioning and GVHD prophylaxis. At 5 years, PBSC transplants showed higher incidence of chronic GVHD than did BM transplants (74.3% vs 46.7%, P=0.001). PBSC transplants showed outcomes comparable to those of BM transplants for relapse (23.7% vs 28.1%), non-relapse mortality (18.4% vs 25.0%), disease-free survival (57.9% vs 46.9%) and OS (57.9% vs 50.0%). In a separate comparison of outcomes between the two graft sources according to the presence of a Ph chromosome, no significant advantage of PBSC over BM was found in both subgroups of patients. Our data suggest that the outcomes of unrelated donor transplantation are similar between PBSC and BM in adult high-risk ALL. Whether PBSC should be the preferred graft source for a specific subgroup of adult ALL needs to be further investigated.
Assuntos
Transplante de Medula Óssea , Transplante de Células-Tronco de Sangue Periférico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Transplante de Medula Óssea/efeitos adversos , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Terapêutica , Condicionamento Pré-Transplante , Doadores não Relacionados , Adulto JovemRESUMO
Diabetic erectile dysfunction (ED) has multiple causative factors, such as endothelial and smooth muscle dysfunction and cavernous fibrosis. Wnt signalling is essential for normal embryonic development and for tissue homeostasis in adults. Aberrant activation of Wnt family members has been implicated in tissue fibrosis and in angiogenesis. In this study, we investigated the differential expression of Wnts in the penises of mice with streptozotocin-induced diabetic ED. We also examined the effect of transforming growth factor-ß1 (TGF-ß1) on the expression of Wnts in primary cultured fibroblasts isolated from human tunica albuginea. Among the mouse and human Wnts tested, 16 mouse Wnts and 14 human Wnts were detected in the corpus cavernosum tissue of normal mice and in fibroblasts derived from human tunica albuginea respectively. We observed up-regulation of Wnt10b (known to be involved in tissue fibrosis) and down-regulation of Wnt16 (known to be involved in vasculogenesis and hematopoiesis), both in the diabetic condition in vivo and with treatment of fibroblasts with TGF-ß1 in vitro. Wnt10b was mainly expressed in fibroblasts and Wnt16 was colocalized with smooth muscle cells in the corpus cavernosum tissue. Cavernous TGF-ß1 protein expression and the degree of cavernous fibrosis determined by the ratio of collagen to smooth muscle content were significantly higher in diabetic mice than in controls. Cavernous endothelial content was significantly decreased by the diabetic condition. Overexpression of Wnt16 with plasmid vector accelerated tube formation in primary cultured mouse cavernous endothelial cells. However, down-regulation of Wnt10b with small interfering RNA did not decrease the production of extracellular matrix protein in human fibroblasts. This is the first report demonstrating the differential expression of Wnts in diabetic mouse penis. Aberrant Wnt expression might contribute to the pathogenesis of ED.
Assuntos
Complicações do Diabetes , Diabetes Mellitus Experimental/metabolismo , Disfunção Erétil/complicações , Proteínas Proto-Oncogênicas/biossíntese , Fator de Crescimento Transformador beta1/farmacologia , Proteínas Wnt/biossíntese , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Células Cultivadas , Células Endoteliais , Proteínas da Matriz Extracelular/biossíntese , Proteínas da Matriz Extracelular/genética , Fibrose , Humanos , Masculino , Camundongos Endogâmicos C57BL , Músculo Liso/fisiopatologia , Ereção Peniana/fisiologia , Pênis/fisiopatologia , Proteínas Proto-Oncogênicas/genética , Interferência de RNA , RNA Interferente Pequeno , Estreptozocina , Fator de Crescimento Transformador beta1/biossíntese , Proteínas Wnt/genéticaRESUMO
To obtain real-time dose information in photon-beam therapy using a clinical linear accelerator, we fabricated a novel Cerenkov fiber-optic dosimeter using two plastic optical fibers without employing a scintillator. In this study, the light intensity and spectrum of Cerenkov radiation induced by a high-energy photon beam were measured as functions of the irradiation angle and the length difference between the two plastic optical fibers in the dosimeter probe. Also, we obtained a percentage depth dose curve for a 6 MV photon beam with a field size of 10 × 10 cm(2) according to the depth of the solid water phantom. Based on the results of this study, it is anticipated that the proposed Cerenkov fiber-optic dosimeter can be developed as a useful dosimeter to accurately obtain dose information prior to conducting radiotherapy.
Assuntos
Radioterapia/instrumentação , Estudos de Viabilidade , Tecnologia de Fibra Óptica , Humanos , Fibras Ópticas , Imagens de Fantasmas , Radiometria/instrumentaçãoRESUMO
Hepatic veno-occlusive disease (VOD) remains one of the most severe complications of hematopoietic SCT (HSCT). Anticoagulation and thrombolytic therapies using tissue-plasminogen activator (t-PA) have been used, but are reported to be ineffective and are associated with significant bleeding complications. We analyzed 56 moderate-to-severe post HSCT hepatic VOD cases treated with t-PA. We analyzed clinical outcomes according to the maximal daily dose of t-PA (t-PAmax) and the severity of VOD. Patients were stratified by t-PAmaxîº10 mg (n=37) vs t-PAmax>10 mg (n=19). A higher t-PAmax was associated with increased mortality. Bleeding complications were more likely at higher t-PAmax in both moderate and severe VOD (P=0.036, 0.063), especially if patients had concomitant use of anticoagulants (36.4% vs 13.3%). In moderate VOD, the response rate was 86.4% for t-PAmaxîº10 mg/day and 80% for t-PAmax>10 mg compared with 33.3% and 7.1%, respectively, for severe VOD (P=0.106). The 5-year OS in moderate and severe VOD was 49% and 7%, respectively, and it was 32% for t-PAmaxîº10 mg and 18% for t-PAmax>10 mg. Our data demonstrate that lower bleeding complications and bleeding-related deaths may result from strict limitations on the t-PAmax without concomitant use of anticoagulation therapy. However, the overall response and survival outcomes should be re-evaluated by a well-validated study in the future.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Hepatopatia Veno-Oclusiva/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Adolescente , Adulto , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Autólogo , Adulto JovemRESUMO
Clear cell sarcoma (CCS), also known as malignant melanoma of soft parts, is a rare malignancy constituting approximately 1% of all soft-tissue sarcomas. It occurs predominantly in the lower extremities of young adults, manifesting as a deep, painless, slow-growing mass. CCS is sometimes confused with other types of melanoma because of its melanocytic differentiation. Although BRAF and KIT mutations are well-known melanocytic tumour-promoting mutations frequently found in cutaneous melanoma, they are rare or absent in CCS. We present two cases of CCS with different clinical and genetic features. Both female patients, aged 25 and 20 years, presented with a palpable nodule on a lower extremity. Biopsies of both tumours revealed features diagnostic of CCS. Each tumour cell was positive for S100 protein and HMB-45. However, one patient's tumour was localized to the dermis, with many multinucleated giant cells, whereas the other was located in the deep subcutaneous fat layer near bone. Fluorescence in situ hybridization demonstrated the presence of a characteristic Ewing sarcoma RNA-binding protein (EWSR)1 gene rearrangement in both cases. Reverse-transcription polymerase chain reaction (PCR) and sequencing of the PCR product revealed an EWSR1-activating transcription factor 1 type 1 fusion transcript in both cases. In addition, we detected BRAF mutation in the dermal type and KIT mutation in the subcutaneous type. It is of interest that the BRAF and KIT mutations are known to be very rare in CCS. On the basis of our observations, we suggest that mutation inhibitors may be useful in selected patients with mutated CCS lineages.
Assuntos
Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-kit/genética , Sarcoma de Células Claras/genética , Neoplasias Cutâneas/genética , Adulto , Evolução Fatal , Feminino , Humanos , Canal Inguinal , Metástase Linfática , Adulto JovemRESUMO
Treatment of intracranial giant aneurysms presents is challenging. In the case of pediatric giant aneurysm, more challenges arise. We describe our experience with a 17-year-old pediatric patient who presented with severe headache. She was diagnosed as having a giant fusiform aneurysm at the right P1-P2-Pcom junction. The aneurysm was treated with superficial temporal artery-posterior cerebral artery bypass and subsequent coil embolization of the aneurysm with parent artery occlusion. The patient had an excellent outcome at one-year follow-up. Our case suggests a combined approach of surgical and endovascular management may yield a better outcome than surgery or endovascular management alone in the treatment of pediatric giant aneurysm.
Assuntos
Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/diagnóstico , Aneurisma Intracraniano/terapia , Procedimentos Neurocirúrgicos/métodos , Procedimentos Cirúrgicos Vasculares/métodos , Adolescente , Terapia Combinada , Feminino , Humanos , Resultado do TratamentoRESUMO
BACKGROUNDS: A pegylated form of recombinant granulocyte-colony stimulating factor (G-CSF) was developed for prophylactic use in breast cancer. The aim of this study was to evaluate the efficacy and safety of once-per-cycle DA-3031 in patients receiving chemotherapy for breast cancer. METHODS: A total of 61 patients receiving docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy were randomized in cycle 1 to receive daily injections of filgrastim (100 µg/m(2)) or a single subcutaneous injection of pegylated filgrastim DA-3031 at a dose of either 3.6 mg or 6 mg. RESULTS: The mean duration of grade 4 neutropenia in cycle 1 was comparable among the treatment groups (2.48, 2.20, and 2.05 days for filgrastim, DA-3031 3.6 mg and 6 mg, respectively; P=0.275). No statistically significant differences were observed in the incidence of febrile neutropenia between the treatment groups (9.5 %, 15.0 %, and 5.0 % for filgrastim, DA-3031 3.6 mg and 6 mg, respectively; P=0.681) in cycle 1. The incidences of adverse events attributable to G-CSF were similar among the treatment groups. CONCLUSIONS: Fixed doses of 3.6 mg or 6 mg DA-3031 have an efficacy comparable to that of daily injections of filgrastim in ameliorating grade 4 neutropenia in patients receiving TAC chemotherapy.
Assuntos
Medicamentos Biossimilares/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Neutropenia/tratamento farmacológico , Polietilenoglicóis/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medicamentos Biossimilares/efeitos adversos , Neoplasias da Mama/sangue , Ciclofosfamida/administração & dosagem , Docetaxel , Doxorrubicina/administração & dosagem , Feminino , Filgrastim , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Contagem de Leucócitos , Pessoa de Meia-Idade , Neutropenia/sangue , Neutropenia/induzido quimicamente , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Taxoides/administração & dosagem , Resultado do TratamentoRESUMO
In-stent restenosis is the primary failure mode of endovascular treatment of occlusive disease in the femeropopliteal segment. Cryoplasty has been proposed to reduce intimal hyperplasia through induction of apoptosis. We sought to evaluate the efficacy of cryoplasty for treatment of in-stent restenosis compared to conventional balloon angioplasty (CBA). After IRB approval, a retrospective record review was performed of reinterventions for in-stent restenosis by a single vascular surgery group at a university hospital. Reinterventions involving cryoplasty and CBA were evaluated at 1, 3, 6 and 12 months after intervention with duplex imaging to identify significant recurrent stenosis utilizing established velocity criteria. Data collected included basic demographic information and comorbidities as well as time to restenosis. Statistical analysis was performed using KaplanMeier survival curves with the log rank test, Wilcoxon rank test, and Cox proportional hazards models. From December 2004 to November 2007, 76 reinterventions were performed using CBA (n = 39) or cryoplasty (n = 37) for in-stent restenosis without placement of additional stents. Periprocedural technical success (>30% residual stenosis) was 100% for both groups, with no complications. The two cohorts were statistically similar in mean age, gender, comorbidities, tobacco use and use of statins, aspirin and Plavix. However, the mean lesion length was significantly longer in the cryoplasty cohort (CBA: 140.9 mm, Cyro: 191.7 mm; P = 0.032). The mean time to recurrent stenosis or need for additional secondary intervention was significantly shorter for the cyroplasty cohort than for the CBA, 4.09 and 10.79 months, respectively (P = .0001). Recurrent stenosis-free survival was significantly lower in the cyroplasty cohort at 3 months (CBA: 96.9%, Cyro: 88.9%) and 6 months (CBA: 84.0%, Cyro: 43.8%; P = .0089). Cyroplasty as a modality for treatment of in-stent stenosis in the femoropopliteal segment offers no benefit over CBA.