RESUMO
Oxygenation is necessary for aerobic metabolism, which maintains adenosine triphosphate within the graft organ. In recent years, some studies have demonstrated that subnormothermic machine perfusion (SNMP) with hemoglobin-based oxygen carriers has the potential to improve oxygen metabolism. OBJECTIVE: The aim of this study was to evaluate the effectiveness of perfusate with human-derived hemoglobin vesicles (HbV) under SNMP in a pig model of donation after cardiac death. MATERIALS AND METHODS: In this study, pig livers were procured with a warm ischemic time of 60 minutes and were preserved in 3 groups for 240 minutes. The preservation conditions were as follows: 4°C cold storage (Group 1); SNMP with University of Wisconsin perfusate alone (Group 2); and SNMP (21°C) with University of Wisconsin solution and HbV (hemoglobin, 0.6 mg/dL) perfusate (Group 3). All livers were perfused for 120 minutes using pig autologous blood machine perfusion (reperfusion phase). We investigated the aspartate transaminase level and hemodynamics (portal vein resistance and oxygen consumption) in the preservation and reperfusion phases. A histologic study (hematoxylin-eosin staining) was performed after 240 minutes of preservation. RESULTS: The portal vein resistance of Group 3 was not increased in comparison with Group 2. During preservation, the oxygen consumption of Group 3 was higher than that of Group 2. However, the level of aspartate transaminase did not differ between Groups 2 and 3. CONCLUSION: The present study revealed that perfusate with HbV increased the oxygen consumption of the donor liver during SNMP.
Assuntos
Hemoglobinas/farmacologia , Transplante de Fígado/métodos , Soluções para Preservação de Órgãos/química , Preservação de Órgãos/métodos , Animais , Morte , Humanos , Perfusão , Suínos , Doadores de Tecidos/provisão & distribuição , Transplantes/efeitos dos fármacos , Transplantes/metabolismo , Isquemia QuenteRESUMO
A 7-month-old female Japanese Black calf developed elongated, nodular mass measuring 30â¯×â¯16â¯cm extended from the retropharyngeal region to mid lateral neck region. Histological examination revealed granulomatous lymphangitis with non-septate fungal hyphae recognized throughout the lesions. Fungal culture, DNA sequencing and molecular phylogenetic tree analysis confirmed the sequence of Lichtheimia corymbifera. The lymphogenous route was speculated to be the main route of fungal spread leading to the characteristic nodular appearance of this case.
RESUMO
Malignant melanoma (MM), a well-known skin cancer with a poor prognosis, has various clinical manifestations, but vesiculobullous lesions have seldom been reported. We report a case of MM forming amelanotic vesicles at the site of an in-transit metastasis, and we also review the published reports on vesiculobullous MM. Our patient was an 87-year-old man with a history of a treated plantar MM 2 years previously, who had recurrence of the MM and development of an in-transit metastasis in his lower leg. Histopathological findings revealed vesicles caused by infiltration of the tumour. A review of the English literature revealed nine cases with various clinical presentations of the vesicles or blisters. For patients with MM with vesiculobullous lesions, an accurate medical history and examination of biopsies are of primary importance for management.
Assuntos
Metástase Linfática , Melanoma/patologia , Dermatopatias Vesiculobolhosas/patologia , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Humanos , Masculino , Melanoma/secundário , Pessoa de Meia-IdadeRESUMO
MYC activation at modest levels has been frequently found in hepatocellular carcinoma. However, its significance in hepatocarcinogenesis has remained obscure. Here we examined the role of Myc activation in mouse liver tumours induced by hepatocytic expression of myristoylated AKT (AKT) and/or mutant HRASV12 (HRAS) via transposon-mediated gene integration. AKT or HRAS alone required 5 months to induce liver tumours, whereas their combination generated hepatocellular carcinoma within 8 weeks. Co-introduction of AKT and HRAS induced lipid-laden preneoplastic cells that grew into nodules composed of tumour cells with or without intracytoplasmic lipid, with the latter being more proliferative and associated with spontaneous Myc expression. AKT/HRAS-induced tumorigenesis was almost completely abolished when MadMyc, a competitive Myc inhibitor, was expressed simultaneously. The Tet-On induction of MadMyc in preneoplastic cells significantly inhibited the progression of AKT/HRAS-induced tumours; its induction in transformed cells suppressed their proliferative activity with alterations in lipid metabolism and protein translation. Transposon-mediated Myc overexpression facilitated tumorigenesis by AKT or HRAS, and when it was co-introduced with AKT and HRAS, diffusely infiltrating tumours without lipid accumulation developed as early as 2 weeks. Examination of the dose-responses of Myc in the enhancement of AKT/HRAS-induced tumorigenesis revealed that a reduction to one-third retained enhancing effect but three-times greater introduction damped the process with increased apoptosis. Myc overexpression suppressed the mRNA expression of proteins involved in the synthesis of fatty acids, and when combined with HRAS introduction, it also suppressed the mRNA expression of proteins involved in their degradation. Finally, the MYC-positive human hepatocellular carcinoma was characterized by the cytoplasm devoid of lipid accumulation, prominent nucleoli and a higher proliferative activity. Our results demonstrate that in hepatocarcinogenesis induced by both activated AKT and HRAS, activation of endogenous Myc is an enhancing factor and adequate levels of Myc deregulation further facilitate the process with alterations in cellular metabolism.
Assuntos
Carcinoma Hepatocelular/patologia , Transformação Celular Neoplásica/patologia , Neoplasias Hepáticas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Animais , Apoptose , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proliferação de Células , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos Retrospectivos , Transdução de Sinais , Células Tumorais CultivadasRESUMO
ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) can contaminate environmental surfaces that are frequently touched by the hands of patients with MRSA colonization/infection. There have been many studies in which the presence or absence of MRSA contamination was determined but no studies in which MRSA contamination levels were also evaluated in detail. We evaluated MRSA contamination of environmental surfaces (overbed tables, bed side rails, and curtains) in the rooms of inpatients from whom MRSA was isolated via clinical specimens. We examined the curtains within 7-14 days after they had been newly hung. The environmental surfaces were wiped using gauze (molded gauze for wiping of surface bacteria; 100% cotton, 4 cm × 8 cm) moistened with sterile physiological saline. The MRSA contamination rate and mean counts (range) were 25.0% (6/24 samples) and 30.6 (0-255) colony-forming units (cfu)/100 cm2, respectively, for the overbed tables and 31.6% (6/19 samples) and 159.5 (0-1620) cfu/100 cm2, respectively, for the bed side rails. No MRSA was detected in 24 curtain samples. The rate of MRSA contamination of environmental surfaces was high for the overbed tables and bed side rails but low for the curtains. Therefore, at least until the 14th day of use, frequent disinfection of curtains may be not necessary.
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Humanos , Infecções Estafilocócicas/microbiologia , Infecção Hospitalar , Microbiologia Ambiental , Staphylococcus aureus Resistente à Meticilina/isolamento & purificaçãoRESUMO
AIMS: Gastric cancer is a common and heterogeneous disease; however, global standard and biomarkers for selecting chemotherapy regimens have not been established. This study was designed retrospectively to identify molecular biomarkers for irinotecan plus S-1 (IRI-S) and S-1 therapy from subset analyses in GC0301/TOP-002, a randomised phase III trial for advanced gastric cancer. MATERIALS AND METHODS: Paraffin-embedded primary tumour specimens were collected from 126 of 326 randomised patients in GC0301/TOP-002. The mRNA was measured for thymidylate synthase, dihydropyrimidine dehydrogenase, topoisomerase I, excision repair cross-complementing gene 1 (ERCC1) and thymidine phosphorylase; categorised into low and high to analyse their association with efficacy end points. RESULTS: There was no significant difference in each mRNA between S-1 and IRI-S groups, whereas there were differences among some clinical characteristics. Multivariate analyses for overall survival showed that mRNA levels were not correlated with prognosis. By comparison, between IRI-S and S-1 arms, low thymidylate synthase, low ERCC1 and high thymidine phosphorylase were associated with better prognosis for IRI-S versus S-1 (hazard ratio = 0.653, 0.702 and 0.709, respectively; P < 0.15 for each interaction). CONCLUSION: Low thymidylate synthase, low ERCC1 and high thymidine phosphorylase are candidates for predictive biomarkers for first-line treatment in advanced gastric cancer by IRI-S. Further study is warranted to confirm these results in other clinical trials and cohort studies.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Camptotecina/análogos & derivados , Ácido Oxônico/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Tegafur/administração & dosagem , Idoso , Camptotecina/administração & dosagem , DNA Topoisomerases Tipo I/análise , Proteínas de Ligação a DNA/análise , Di-Hidrouracila Desidrogenase (NADP)/análise , Combinação de Medicamentos , Endonucleases/análise , Feminino , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/análise , Estudos Retrospectivos , Timidina Fosforilase/análise , Timidilato Sintase/análiseRESUMO
BACKGROUND: Few nomograms can predict overall survival (OS) after curative resection of advanced gastric cancer (AGC), and these nomograms were developed using data from only a few large centers over a long time period. The aim of this study was to develop and externally validate an elaborative nomogram that predicts 5-year OS after curative resection for serosa-negative, locally AGC using a large amount of data from multiple centers in Japan over a short time period (2001-2003). PATIENTS AND METHODS: Of 39 859 patients who underwent surgery for gastric cancer between 2001 and 2003 at multiple centers in Japan, we retrospectively analyzed 5196 patients with serosa-negative AGC who underwent Resection A according to the 13th Japanese Classification of Gastric Carcinoma. The data of 3085 patients who underwent surgery from 2001 to 2002 were used as a training set for the construction of a nomogram and Web software. The data of 2111 patients who underwent surgery in 2003 were used as an external validation set. RESULTS: Age at operation, gender, tumor size and location, macroscopic type, histological type, depth of invasion, number of positive and examined lymph nodes, and lymphovascular invasion, but not the extent of lymphadenectomy, were associated with OS. Discrimination of the developed nomogram was superior to that of the TNM classification (concordance indices of 0.68 versus 0.61; P < 0.001). Moreover, calibration was accurate. CONCLUSIONS: We have developed and externally validated an elaborative nomogram that predicts the 5-year OS of postoperative serosa-negative AGC. This nomogram would be helpful in the assessment of individual risks and in the consideration of additional therapy in clinical practice, and we have created freely available Web software to more easily and quickly predict OS and to draw a survival curve for these purposes.
Assuntos
Adenocarcinoma/mortalidade , Nomogramas , Neoplasias Gástricas/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Gastrectomia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Adulto JovemRESUMO
BACKGROUND: S-1, an oral fluoropyrimidine, plus cisplatin (SP) is a standard regimen for advanced gastric cancer (AGC) in East Asia. To date, no studies have evaluated the efficacy and safety of trastuzumab combined with SP in patients with human epidermal growth factor receptor type 2 (HER2)-positive AGC. METHODS: Patients with HER2-positive AGC received S-1 (80-120 mg per day) orally on days 1-14, cisplatin (60 mg m(-2)) intravenously on day 1, and trastuzumab (course 1, 8 mg kg(-1); course 2 onward, 6 mg kg(-1)) intravenously on day 1 of a 21-day cycle. The primary end point was response rate (RR); secondary end points included overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), and adverse events. RESULTS: A total of 56 patients were enrolled. In the full analysis set of 53 patients, the confirmed RR was 68% (95% confidence interval (CI)=54-80%), and the disease control rate was 94% (95% CI=84-99%). Median OS, PFS, and TTF were estimated as 16.0, 7.8, and 5.7 months, respectively. Major grade 3 or 4 adverse events included neutropaenia (36%), anorexia (23%), and anaemia (15%). CONCLUSIONS: Trastuzumab in combination with SP showed promising antitumour activity and manageable toxic effects in patients with HER2-positive AGC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptor ErbB-2/biossíntese , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Receptor ErbB-2/genética , Neoplasias Gástricas/enzimologia , Tegafur/administração & dosagem , Tegafur/efeitos adversos , TrastuzumabRESUMO
BACKGROUND: Mesothelin is expressed in various types of malignant tumour, and we recently reported that expression of mesothelin was related to an unfavourable patient outcome in pancreatic ductal adenocarcinoma. In this study, we examined the clinicopathological significance of the mesothelin expression in gastric cancer, especially in terms of its association with the staining pattern. METHODS: Tissue specimens from 110 gastric cancer patients were immunohistochemically examined. The staining proportion and intensity of mesothelin expression in tumour cells were analysed, and the localisation of mesothelin was classified into luminal membrane and/or cytoplasmic expression. RESULTS: Mesothelin was positive in 49 cases, and the incidence of mesothelin expression was correlated with lymph-node metastasis. Furthermore, luminal membrane staining of mesothelin was identified in 16 cases, and the incidence of luminal membrane expression was also correlated with pT factor, pStage, lymphatic permeation, blood vessel permeation, recurrence, and poor patient outcome. Multivariate analysis showed that luminal membrane expression of mesothelin was an independent predictor of overall patient survival. CONCLUSION: We described that the luminal membrane expression of mesothelin was a reliable prognostic factor in gastric cancer, suggesting the functional significance of membrane-localised mesothelin in the aggressive behaviour of gastric cancer cells.
Assuntos
Proteínas Ligadas por GPI/metabolismo , Neoplasias Gástricas/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Células Epiteliais/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Linfonodos/metabolismo , Metástase Linfática , Masculino , Mesotelina , Pessoa de Meia-Idade , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de SobrevidaRESUMO
BACKGROUND: There is no consensus on the most appropriate treatment for patients with large to giant congenital melanocytic naevi (CMN) because of the risk of melanoma development. Surgical excision followed by skin grafting or expanded skin coverage may cause unfavourable scarring. There is a balance to be achieved between minimizing the disfiguring appearance and the risk of malignant change. The pulsed dye laser (PDL) is commonly used for vascular lesions and is highly absorbed by melanin and haemoglobin. Its pulse duration is longer than that of Q-switched ruby lasers (QsRL), which can have nonspecific photothermolytic effects on surrounding nonpigmented naevus cells. OBJECTIVES: To investigate the effectiveness of combined treatment with the PDL and QsRL for large to giant CMN. METHODS: Six patients with large to giant CMN were enrolled in this study. Treatment consisted of one pass of PDL treatment followed by one pass of QsRL treatment. Multiple rounds of treatment were applied to all patients. RESULTS: All patients responded to this combined regimen, and the lesional colour was effectively reduced. The mean number of rounds of laser treatment required to achieve skin lightening was 7·7. No patients suffered severe hypertrophic scarring. No cases of recurrence or malignant transformation were observed. The histological results from the patient who underwent the most laser therapy in this study showed a remarkable reduction in the number of melanocytic naevus cells after treatment. CONCLUSIONS: This technique may enable the removal of most of the pigmented lesion and melanocytic naevus cells with minimal scarring.
Assuntos
Terapia a Laser/métodos , Lasers de Corante/uso terapêutico , Lasers de Estado Sólido/uso terapêutico , Nevo Pigmentado/cirurgia , Neoplasias Cutâneas/cirurgia , Adulto , Criança , Pré-Escolar , Cicatriz/prevenção & controle , Feminino , Humanos , Masculino , Nevo Pigmentado/congênito , Neoplasias Cutâneas/congênito , Resultado do Tratamento , Adulto JovemRESUMO
Blockade of the CD40-CD154 costimulatory signal is an attractive strategy for immunosuppression and tolerance induction in organ transplantation. Treatment with anti-CD154 monoclonal antibodies (mAbs) results in potent immunosuppression in nonhuman primates (NHPs). Despite plans for future clinical use, further development of these treatments was halted by complications. As an alternative approach, we have been focusing on the inhibition of the counter receptor, CD40 and have shown that a novel human anti-CD40 mAb, ASKP1240, markedly prolongs renal allograft survival in NHPs, although allografts eventually underwent chronic allograft nephropathy. On the basis of our previous findings that a CD40-CD154 costimulation blockade induces tolerance to hepatic, but not cardiac, allografts in rodents, we tested here our hypothesis that a blockade of CD40 by ASKP1240 allows acceptance of hepatic allografts in NHPs. A 2-week ASKP1240 induction treatment prolonged liver allograft survival in NHPs; however, the graft function deteriorated due to chronic rejection. In contrast, a 6-month ASKP1240 maintenance monotherapy efficiently suppressed both cellular and humoral alloimmune responses and prevented rejection on the hepatic allograft. No serious side effects, including thromboembolic complications, were noted in the ASKP1240-treated monkeys. We conclude that CD40 blockade by ASKP1240 would be a desirable immunosuppressant for clinical liver transplantation.
Assuntos
Anticorpos Monoclonais/imunologia , Antígenos CD40/imunologia , Transplante de Fígado , Animais , Anticorpos Monoclonais Humanizados , Humanos , Memória Imunológica , Teste de Cultura Mista de Linfócitos , Macaca fascicularis , Masculino , Transplante HomólogoRESUMO
BACKGROUND: Perioperative enteral immunonutrition is thought to reduce postoperative morbidity in patients undergoing major gastrointestinal surgery. This study assessed the clinical effects of preoperative enteral immunonutrition in well nourished patients with gastric cancer undergoing total gastrectomy. METHODS: Well nourished patients with primary gastric cancer, fit for total gastrectomy, were randomized to either a control group with regular diet, or an immunonutrition group that received regular diet supplemented with 1000 ml/day of immunonutrients for 5 consecutive days before surgery. The primary endpoint was the incidence of surgical-site infection (SSI). Secondary endpoints were rates of infectious complications, overall postoperative morbidity and C-reactive protein (CRP) levels on 3-4 days after surgery. RESULTS: Of 244 randomized patients, 117 were allocated to the control group and 127 received immunonutrition. SSIs occurred in 27 patients in the immunonutrition group and 23 patients in the control group (risk ratio (RR) 1.09, 95 per cent confidence interval 0.66 to 1.78). Infectious complications were observed in 30 patients in the immunonutrition group and 27 in the control group (RR 1.11, 0.59 to 2.08). The overall postoperative morbidity rate was 30.8 and 26.1 per cent respectively (RR 1.18, 0.78 to 1.78). The median CRP value was 11.8 mg/dl in the immunonutrition group and 9.2 mg/dl in the control group (P = 0.113). CONCLUSION: Five-day preoperative enteral immunonutrition failed to demonstrate any clear advantage in terms of early clinical outcomes or modification of the systemic acute-phase response in well nourished patients with gastric cancer undergoing elective total gastrectomy. REGISTRATION NUMBER: ID 000000648 (University Hospital Medical Information Network (UMIN) database).
Assuntos
Nutrição Enteral/métodos , Gastrectomia/métodos , Imunoterapia/métodos , Complicações Pós-Operatórias/etiologia , Neoplasias Gástricas/terapia , Adulto , Idoso , Proteína C-Reativa/metabolismo , Terapia Combinada/métodos , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/etiologia , Resultado do TratamentoRESUMO
BACKGROUND: The aim of this study was to evaluate the efficacy and feasibility of preoperative chemotherapy with S-1 plus cisplatin in patients with initially unresectable locally advanced gastric cancer. METHODS: We enrolled patients with initially unresectable locally advanced gastric cancer because of severe lymph node metastases or invasion of adjacent structures. Preoperative chemotherapy consisted of S-1 at 80 mg/m(2) divided in two daily doses for 21 days and cisplatin at 60 mg/m(2) intravenously on day 8, repeated every 35 days. If a tumor decreased in size, patients received 1 or 2 more courses. Surgery involved radical resection with D2 lymphadenectomy. RESULTS: Between December 2000 and December 2007, 27 patients were enrolled on the study. No CR was obtained, but PR was seen in 17 cases, and the response rate was 63.0%. Thirteen patients (48.1%) had R0 resections. There were no treatment related deaths. The median overall survival time (MST) and the 3-year overall survival (OS) of all patients were 31.4 months and 31.0%, respectively. Among the 13 patients who underwent curative resection, the median disease-free survival (DFS) and the 3-year DFS were 17.4 months and 23.1%, respectively. The MST and the 3-year OS were 50.1 months and 53.8%, respectively. The most common site of initial recurrence after the R0 resection was the para-aortic lymph nodes. CONCLUSIONS: Preoperative S-1 plus cisplatin can be safely delivered to patients undergoing radical gastrectomy. This regimen is promising as neoadjuvant chemotherapy for resectable gastric cancer. For initially unresectable locally advanced gastric cancer, new trials using more effective regimens along with extended lymph node dissection are necessary.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Gastrectomia , Terapia Neoadjuvante/métodos , Ácido Oxônico/administração & dosagem , Pré-Medicação , Neoplasias Gástricas/terapia , Tegafur/administração & dosagem , Adulto , Idoso , Terapia Combinada , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Combinação de Medicamentos , Feminino , Seguimentos , Gastrectomia/métodos , Gastrectomia/mortalidade , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Medição de Risco , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Cholangiocarcinoma (CC) is a highly malignant carcinoma. We attempted to clarify the prognostic significance of c-Met overexpression and its association with clinicopathological factors in patients with CC. PATIENTS AND METHODS: One hundred and eleven patients with intrahepatic CC (IHCC) and 136 patients with extrahepatic CC (EHCC) who had undergone curative surgery were divided immunohistologically into c-Met(high) and c-Met(low) groups. Clinicopathological factors and outcomes were compared between the groups. c-Met and epidermal growth factor receptor (EGFR) expression was also examined in 10 CC cell lines. RESULTS: The positivity of c-Met was 45.0% in IHCC and 68.4% in EHCC; c-Met(high) expression was demonstrated in 11.7% of IHCC and 16.2% of EHCC. c-Met(high) expression was significantly correlated with the 5-year survival rate for CC overall (P=0.0046) and for IHCC (P=0.0013), histopathological classification in EHCC, and for EGFR overexpression in both IHCC and EHCC. Coexpression and coactivation of c-Met and EGFR were also observed in CC cell lines. Multivariate analysis revealed that c-Met(high) expression was an independent predictor of poor overall and disease-free survival in patients with IHCC. CONCLUSIONS: c-Met overexpression is associated with EGFR expression and is a poor prognostic factor in CC.
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Neoplasias dos Ductos Biliares/metabolismo , Ductos Biliares Extra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/metabolismo , Colangiocarcinoma/metabolismo , Receptores ErbB/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Extra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/patologia , Western Blotting , Colangiocarcinoma/patologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
A 63-year-old woman was diagnosed as having severe aortic stenosis (AS) with 98 mmHg peak pressure gradient detected by echocardiography. Since, preoperative enhanced 64-row multislice computed tomography (MSCT) showed bicuspid aortic valve with only 2 sinuses of Valsalva, congenital aortic stenosis was suspected. The left and right coronary arteries originated from respective sinus of Valsalva, and severely thickened cusps of aortic valve were detected clearly by preoperative 64-row MSCT. Aortic valve replacement with a 21 mm ATS mechanical bileaflet prosthesis was performed without aortic annulus enlargement. The postoperative course was uneventful and postoperative 64-row MSCT indicated good performance of the ATS valve. Preoperative 64-row MSCT could be useful to detect complex aortic valve disease in detail. Moreover. 64-row MSCT might be a reliable tool to evaluate valvular heart disease.
Assuntos
Estenose da Valva Aórtica/congênito , Estenose da Valva Aórtica/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Estenose da Valva Aórtica/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Cuidados Pré-OperatóriosRESUMO
Soft tissue sarcomas of the head and neck region are rare, and very little has been described about the reconstructive methods used after sarcoma resection of cheek soft tissue sarcomas. Reconstructive methods for cheek defects after sarcoma resection are presented and the possibilities, advantages, disadvantages, and expected results are described. A series of 3 patients with cheek soft tissue sarcomas were examined. Reconstructive methods included; one skin graft, a free forearm flap and a cervicofacial flap. All patients had lesions < 5 cm and low-grade tumours, and no case presented local recurrence or metastases. The choice of reconstructive methods depends mostly on the complexity of the defect. In cases comprising comparatively small or minor defects, reconstructions using local flaps, such as the cervicofacial flap, provide better aesthetic and functional results than either free flaps or skin graft.
Assuntos
Bochecha , Neoplasias Faciais/cirurgia , Procedimentos de Cirurgia Plástica , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Adulto , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Blockade of CD40-CD154 signaling pathway is an attractive strategy to induce potent immunosuppression and tolerance in organ transplantation. Due to its strong immunosuppressive effect shown in nonhuman primate experiments, anti-CD154 monoclonal antibodies (mAbs) have been tried in clinical settings, but it was interrupted by unexpected thromboembolic complications. Thus, inhibition of the counter molecule, CD40, has remained an alternative approach. In the previous preliminary study, we have shown that 4D11, a novel fully human anti-CD40 mAb, has a fairly potent immunosuppressive effect on kidney allograft in nonhuman primates. In this study, we aimed to confirm the efficacy and untoward events of the 2-week induction and 180-day maintenance 4D11 treatments. In both, 4D11 significantly suppressed T-cell-mediated alloimmune responses and prolonged allograft survival. Addition of weekly 4D11 administration after the induction treatment further enhanced graft survival. Complete inhibition of both donor-specific Ab and anti-4D11 Ab productions was obtained only with higher-dose maintenance therapy. No serious side effect including thromboembolic complications was noted except for a transient reduction of hematocrit in one animal, and decrease of peripheral B-cell counts in all. These results indicate that the 4D11 appears to be a promising candidate for immunosuppression in clinical organ transplantation.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígenos CD40/imunologia , Rejeição de Enxerto/prevenção & controle , Transplante de Rim/imunologia , Animais , Anticorpos Monoclonais/sangue , Anticorpos Monoclonais/imunologia , Antígenos CD40/antagonistas & inibidores , Ligante de CD40/antagonistas & inibidores , Ligante de CD40/imunologia , Rejeição de Enxerto/imunologia , Humanos , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Macaca fascicularis , Masculino , Modelos Animais , Transdução de Sinais/imunologiaRESUMO
A 63-year-old woman with severe aortic valve insufficiency and bilateral subclavian artery occlusion underwent ascending aorta-to-biaxillary artery bypass and aortic valve replacement, simultaneously. Because of severe aortic calcification, a hand-made aortic occluder was utilized to prevent embolic stroke. We believe that the new technique of aortic occllusion might be very useful for patients with severe aortic calcification.
Assuntos
Doenças da Aorta/cirurgia , Calcinose/cirurgia , Insuficiência da Valva Aórtica/cirurgia , Procedimentos Cirúrgicos Cardiovasculares/métodos , Feminino , Próteses Valvulares Cardíacas , Humanos , Pessoa de Meia-IdadeRESUMO
In Japan, organ donation has been still limited because of the strict donor criteria. The aim of this study was to show the effectiveness of pancreas transplantation (PTx) by analyzing the outcomes even under poor donor conditions. Thirty-six cases of PTx (32 simultaneous pancreas and kidney transplantations [SPK], 4 pancreas after kidney transplantations) performed during the last 8 years were examined especially for donor characteristics. Mean donor age of 41.4 +/- 11.9 years was considerably older compared with that in the United States and Europe; donors aged over 40 years comprised 67% of the total. According to the criteria described by Kapur, 29 cases (81%) in our series would be considered marginal. Thus, to increase blood supply into the pancreatic head, the gastroduodenal artery (GDA) was anastomosed using donor artery to common hepatic artery or iliac Y graft. These procedures were performed in 16 of the 24 cases in which there was liver procurement. Eventually, 34 cases (94%) preserved GDA continuity. Mean total cold ischemic time of pancreatic grafts was 12 hours 15 minutes. Of 214 registrants, 17 patients on the waiting list for SPK died of diabetic complications. To date, patient survival remains 100% with a mean follow-up period of 33 months. Pancreas graft survivals at 1, 3, and 5 years posttransplantation were 92%, 80%, and 80%, respectively. In contrast, kidney survivals were 91%, 91%, and 91%, respectively. The integrity of the pancreas head and duodenum by preservation of the GDA continuity might have decreased the risk associated with the marginal donors.