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2.
Br J Surg ; 108(3): 286-295, 2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33793720

RESUMO

BACKGROUND: Primary infected aneurysms of the abdominal aorta and iliac arteries are potentially life-threatening. However, because of the rarity of the disease, its pathogenesis and optimal treatment strategy remain poorly defined. METHODS: A nationwide retrospective cohort study investigated patients who underwent surgical treatment for a primary infected abdominal aortic and/or common iliac artery (CIA) aneurysm between 2011 and 2017 using a Japanese clinical registry. The study evaluated the relationships between preoperative factors and postoperative outcomes including 90-day and 3-year mortality, and persistent or recurrent aneurysm-related infection. Propensity score matching was used to compare survival between patients who underwent in situ prosthetic grafting and those who had endovascular aneurysm repair (EVAR). RESULTS: Some 862 patients were included in the analysis. Preceding infection was identified in 30.2 per cent of the patients. The median duration of postoperative follow-up was 639 days. Cumulative overall survival rates at 30 days, 90 days, 1 year, 3 years and 5 years were 94.0, 89.7, 82.6, 74.9 and 68.5 per cent respectively. Age, preoperative shock and hypoalbuminaemia were independently associated with short-term and late mortality. Compared with open repair, EVAR was more closely associated with persistent or recurrent aneurysm-related infection (odds ratio 2.76, 95 per cent c.i. 1.67 to 4.58; P < 0.001). Propensity score-matched analyses demonstrated no significant differences between EVAR and in situ graft replacement in terms of 3-year all-cause and aorta-related mortality rates (P = 0.093 and P =0.472 respectively). CONCLUSION: In patients undergoing surgical intervention for primary infected abdominal aortic and CIA aneursyms, postoperative survival rates were encouraging. Eradication of infection following EVAR appeared less likely than with open repair, but survival rates were similar in matched patients between EVAR and in situ graft replacement.


Assuntos
Aneurisma Infectado/cirurgia , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma Ilíaco/cirurgia , Fatores Etários , Idoso , Aneurisma Infectado/mortalidade , Aneurisma da Aorta Abdominal/mortalidade , Prótese Vascular , Estudos de Coortes , Procedimentos Endovasculares , Feminino , Seguimentos , Humanos , Hipoalbuminemia/mortalidade , Aneurisma Ilíaco/mortalidade , Japão/epidemiologia , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Choque/mortalidade
3.
Br J Surg ; 107(5): 586-594, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32162301

RESUMO

BACKGROUND: Japan Clinical Oncology Group (JCOG) 0212 (ClinicalTrials.gov NCT00190541) was a non-inferiority phase III trial of patients with clinical stage II-III rectal cancer without lateral pelvic lymph node enlargement. The trial compared mesorectal excision (ME) with ME and lateral lymph node dissection (LLND), with a primary endpoint of recurrence-free survival (RFS). The planned primary analysis at 5 years failed to confirm the non-inferiority of ME alone compared with ME and LLND. The present study aimed to compare ME alone and ME with LLND using long-term follow-up data from JCOG0212. METHODS: Patients with clinical stage II-III rectal cancer below the peritoneal reflection and no lateral pelvic lymph node enlargement were included in this study. After surgeons confirmed R0 resection by ME, patients were randomized to receive ME alone or ME with LLND. The primary endpoint was RFS. RESULTS: A total of 701 patients from 33 institutions were assigned to ME with LLND (351) or ME alone (350) between June 2003 and August 2010. The 7-year RFS rate was 71.1 per cent for ME with LLND and 70·7 per cent for ME alone (hazard ratio (HR) 1·09, 95 per cent c.i. 0·84 to 1·42; non-inferiority P = 0·064). Subgroup analysis showed improved RFS among patients with clinical stage III disease who underwent ME with LLND compared with ME alone (HR 1·49, 1·02 to 2·17). CONCLUSION: Long-term follow-up data did not support the non-inferiority of ME alone compared with ME and LLND. ME with LLND is recommended for patients with clinical stage III disease, whereas LLND could be omitted in those with clinical stage II tumours.


ANTECEDENTES: El JCOG0212 (ClinicalTrials.gov: NCT00190541) fue un ensayo fase III de no inferioridad en pacientes con cáncer de recto en estadio clínico II/III sin ganglios linfáticos aumentados de tamaño en la pared pélvica lateral. El ensayo comparó la escisión del mesorrecto (mesorectal excision, ME) con la ME con disección de los ganglios linfáticos laterales (lateral lymph node dissection, LLND), siendo el criterio de valoración principal la supervivencia libre de recidiva (recurrence free survival, RFS). El análisis primario planificado a los 5 años de seguimiento no pudo confirmar la no inferioridad de la ME frente a la ME con LLND. Este estudio tuvo como objetivo comparar la ME como procedimiento único y la ME con LLND utilizando datos de seguimiento a largo plazo del ensayo JCOG0212. MÉTODOS: En este estudio se incluyeron pacientes con cáncer de recto en estadio clínico II/III por debajo de la reflexión peritoneal sin ganglios linfáticos aumentados de tamaño en la pared pélvica lateral. Después de que los cirujanos confirmaran la resección R0 mediante la ME, los pacientes fueron asignados al azar al brazo de ME sola o al brazo de ME con LLND. El criterio de valoración principal fue la supervivencia libre de recidiva (RFS). RESULTADOS: Un total de 701 pacientes de 33 instituciones fueron asignados al azar para ser tratados mediante una ME con LLND (n = 351) o EM sola (n = 350) entre junio de 2003 y agosto de 2010. Las tasas de RFS a 7 años fueron del 71,1% para ME con LLND y 70,7 % para ME sola (cociente de riesgos instantáneos, hazard ratio, HR: 1,09 (i.c. del 95% 0,84-1,42), no inferioridad P = 0,064)). El análisis de subgrupos mostró una mejor RFS entre los pacientes en estadio clínico III que se sometieron a ME con LLND en comparación con ME sola (HR: 1,49 (i.c. del 95%: 1,02-2,17)). CONCLUSIÓN: Los datos de seguimiento a largo plazo no justificaron la no inferioridad de la ME en comparación con la ME con LLND. Se recomienda la ME con LLND para pacientes en estadio clínico III, mientras que LLND podría omitirse para pacientes en estadio clínico II.


Assuntos
Excisão de Linfonodo , Protectomia/métodos , Neoplasias Retais/cirurgia , Intervalo Livre de Doença , Estudos de Equivalência como Asunto , Seguimentos , Humanos , Linfonodos/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasias Retais/patologia
4.
BJS Open ; 3(4): 539-548, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31388647

RESUMO

Background: More extensive lymphadenectomy may improve survival after resection of colonic cancer. Nomograms were created predicting overall survival and recurrence for patients who undergo D2-D3 lymph node dissection, and their validity determined. Methods: This was a multicentre study of patients with colonic cancer who underwent resection with D2-D3 lymph node dissection in Japan. Inclusion criteria included R0 resection. A training cohort of patients operated on from 2007 to 2008 was analysed to construct prognostic models predicting survival and recurrence. Discrimination and calibration were performed using an external validation cohort from the Japanese colorectal cancer registry (procedures in 2005-2006). Results: The training cohort consisted of 2746 patients. Predictors of survival were: age (hazard ratio (HR) 1·04), female sex (HR 0·71), depth of tumour invasion (HR 1·15, 1·22, 2·96 and 3·14 for T2, T3, T4a and T4b respectively versus T1), lymphatic invasion (HR 1·11, 1·15 and 2·95 for ly1, ly2 and ly3 versus ly0), preoperative carcinoembryonic antigen (CEA) level (HR 1·21, 1·59 and 1·99 for 5·1-10·0, 10·1-20·0 and 20·1 and over versus 0-5·0 ng/ml), number of metastatic lymph nodes (HR 1·07), number of lymph nodes examined (HR 0·98) and extent of lymphadenectomy (HR 0·23, 0·13 and 0·11 for D1, D2 and D3 versus D0). Predictors of recurrence were: female sex (HR 0·82), macroscopic type (HR 3·82, 4·56, 6·66, 7·74 and 3·22 for types I, II, III, IV and V versus type 0), depth of invasion (HR 1·25, 2·66, 5·32 and 6·43 for T2, T3, T4a and T4b versus T1), venous invasion (HR 1·43, 3·05 and 4·79 for v1, v2 and v3 versus v0), preoperative CEA level (HR 1·39, 1·43, 1·56 and 1·85 for 5·1-10·0, 10·1-20·0, 20·1-40·0 and 40·1 or more versus 0-5 ng/ml), number of metastatic lymph nodes (HR 1·07) and number of lymph nodes examined (HR 0·98). The validation cohort comprised 4446 patients. The internal and external validated Harrell's C-index values for the nomogram predicting survival were 0·75 and 0·74 respectively. Corresponding values for recurrence were 0·78 and 0·75. Conclusion: These nomograms could predict survival and recurrence after curative resection of colonic cancer.


Assuntos
Neoplasias do Colo , Excisão de Linfonodo/mortalidade , Idoso , Antígeno Carcinoembrionário/sangue , Estudos de Coortes , Neoplasias do Colo/epidemiologia , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Feminino , Humanos , Excisão de Linfonodo/métodos , Masculino , Mesocolo/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Nomogramas , Prognóstico , Análise de Sobrevida
5.
Pharmazie ; 73(10): 613-616, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30223928

RESUMO

Chemotherapy is among the standard treatments for esophageal cancer. The docetaxel, 5-fluorouracil, and cisplatin (DCF) protocol yields a better response rate than 5-fluorouracil plus cisplatin. However, the incidence of side effects, such as febrile neutropenia and hematologic toxicity, is also significantly high with the DCF protocol. The granulocyte colony-stimulating factor and pegfilgrastim are prophylactically administered to prevent febrile neutropenia. This retrospective study evaluated the efficacy and safety of pegfilgrastim in patients receiving DCF therapy. Of the 65 patients who were administered DCF therapy in our hospital from 2011 through 2016, 21 received pegfilgrastim 24 hours or more after the end of chemotherapy. The protocol comprised 70 mg/m2 each of docetaxel and cisplatin on day 1 and 700 mg/m2 5-fluorouracil on days 1 to 5 via intravenous injection in a 3-week cycle. The primary endpoint was the rate of grade 3-4 neutropenia and febrile neutropenia. The mean patient age was 66.4 years. The incidence of grade 3 and 4 neutropenia was 14.2 % and 11.4 %, respectively, in the pegfilgrastim group and 31.9 % and 37.8 %, respectively, in the non-pegfilgrastim group. The incidence of febrile neutropenia in the pegfilgrastim group and non-pegfilgrastim group was 11.4 % and 40.3 %, respectively. Statistical analysis showed that the incidence of neutropenia and febrile neutropenia was significantly different (p<0.05) between the two groups. Pegfilgrastim prevents severe neutropenia and febrile neutropenia in patients with esophageal cancer who are treated according to the DCF protocol.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Filgrastim/farmacologia , Neutropenia/tratamento farmacológico , Polietilenoglicóis/farmacologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Neoplasias Esofágicas/sangue , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Estudos Retrospectivos
6.
Br J Surg ; 105(1): 48-57, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29265404

RESUMO

BACKGROUND: The postoperative pancreatic fistula (POPF) rate for duct-to-mucosa and invagination anastomosis after pancreatoduodenectomy is still debated. The aim of this RCT was to investigate the POPF rate for duct-to-mucosa versus invagination pancreaticojejunostomy. METHODS: Patients were stratified by pancreatic texture and diameter of the main pancreatic duct and randomized to the duct-to-mucosa or invagination group. The primary endpoint was the rate of clinically relevant POPF (defined as grade B or C). Secondary endpoints were suture material cost for pancreaticojejunostomy, drain insertion duration and duration of postoperative hospital stay. RESULTS: Some 120 patients undergoing pancreatoduodenectomy were included following consent. Clinically relevant POPF developed in six of 59 patients (10 per cent) in the invagination group and in 14 of 61 patients (23 per cent) in the duct-to-mucosa group (P = 0·077). Duration of drain insertion (6 versus 7 days respectively; P = 0·027) and postoperative hospital stay (19 versus 24 days; P = 0·015) were shorter in the invagination group. Subgroup analysis for 61 patients with a soft pancreas revealed a lower rate of clinically relevant POPF in the invagination group (10 per cent versus 42 per cent in the duct-to-mucosa group; P = 0·010). Among 20 patients with a clinically relevant POPF, the six patients in the invagination group had a shorter duration of drain insertion (38·5 days versus 49 days for 14 patients in the duct-to-mucosa group; P = 0·028) and postoperative hospital stay (42 versus 54·5 days respectively; P = 0·028). CONCLUSION: This study did not demonstrate a superiority of invagination over duct-to-mucosa pancreaticojejunostomy in the risk of POPF. However, in high-risk patients with a soft pancreas, invagination may reduce the risk of clinically relevant POPF compared with duct-to-mucosa. Registration number: UMIN000005890 (http://www.umin.ac.jp).


Assuntos
Fístula Pancreática/prevenção & controle , Pancreaticoduodenectomia , Pancreaticojejunostomia/métodos , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento
7.
Dis Esophagus ; 30(6): 1-8, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28475746

RESUMO

Jejunostomy, which requires the fixation of the jejunum to the abdominal wall, is commonly used as an enteral feeding access after esophagectomy. However, this procedure sometimes causes severe complications, such as mechanical bowel obstruction. In 2009, we developed a modified approach to insert an enteral feeding tube through the reconstructed gastric tube using the round ligament of the liver. The aim of this study is to investigate the usefulness of this approach as compared to the approach through jejunostomy. Between January 2005 and March 2015, 420 patients with thoracic esophageal cancer underwent esophagectomy via thoracotomy and laparotomy. Of these, 214 underwent feeding jejunostomy (FJ group) and 206 patients underwent feeding via gastric tube with round ligament of the liver (FG group). Catheter-related complications, other postoperative complications, and mortality were compared between the two groups. The incidence of catheter site infection during catheterization in the FG group was significantly lower (n = 1/206, 0.5%) compared to the FJ group (n = 11/214, 5.1%) (P < 0.01). The postoperative bowel obstruction did not occur in the FG group, while it occurred in eight patients (3.7%) in the FJ group (P < 0.01). The incidences of other catheter-related and postoperative complications were similar between the two groups. Feeding catheter gastrostomy with the round ligament of the liver can be a useful enteral feeding access after esophagectomy, because the incidence rate of severe catheter-related complications, such as surgical site infection and mechanical obstruction tend to be lower with this technique compare to jejunostomy.


Assuntos
Nutrição Enteral/métodos , Gastrostomia/métodos , Obstrução Intestinal/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Ligamento Redondo do Fígado/cirurgia , Idoso , Nutrição Enteral/efeitos adversos , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Feminino , Humanos , Incidência , Obstrução Intestinal/epidemiologia , Obstrução Intestinal/etiologia , Jejunostomia/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
8.
Biofabrication ; 8(3): 035016, 2016 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-27579855

RESUMO

A novel engineering methodology for organizing a large liver tissue equivalent was established by intergrating both 'top down' and 'bottom up' approaches. A three-dimensional (3D) scaffold was engineered comprising 43 culture chambers (volume: 11.63 cm(3)) assembled in a symmetrical pattern on 3 layers, a design which enables further scaling up of the device to a clinically significant size (volume: 500 cm(3)). In addition, an inter-connected flow channel network was designed and proved to homogenously deliver culture medium to each chamber with the same pressure drop. After fabrication using nylon-12 and a selective laser sintering process, co-cultured cellular aggregates of human hepatoma Hep G2 and TMNK-1 cells were loosely packed into the culture chambers with biodegradable poly-L-lactic acid fibre pieces for 9 days of perfusion culture. The device enabled increased hepatic function and well-maintained cell viability, demonstrating the importance of an independent medium flow supply for cell growth and function provided by the current 3D scaffold. This integrative methodology from the macro- to the micro-scale provides an efficient way of arranging engineered liver tissue with improved mass transfer, making it possible to further scale up to a construct with clinically relevant size while maintaining high per-volume-based physiological function in the near future.


Assuntos
Técnicas de Cultura de Células/métodos , Fígado Artificial , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Albuminas/metabolismo , Técnicas de Cultura de Células/instrumentação , Linhagem Celular , Sobrevivência Celular , Técnicas de Cocultura , Desenho Assistido por Computador , Glucose/metabolismo , Células Hep G2 , Humanos , Modelos Biológicos , Poliésteres/química , Engenharia Tecidual/instrumentação
9.
Eur J Surg Oncol ; 42(12): 1851-1858, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27519616

RESUMO

BACKGROUND: We conducted a randomized controlled trial (JCOG0212) to determine whether the outcome of mesorectal excision (ME) alone for rectal cancer is not inferior to that of ME with lateral lymph node dissection (LLND). The present study focused on male sexual dysfunction after surgery. METHODOLOGY: Eligibility criteria included clinical stage II/III rectal cancer, the lower margin of the lesion below the peritoneal reflection, the absence of lateral pelvic lymph node enlargement, and no preoperative radiotherapy. After confirmation of R0 resection by ME, patients were intraoperatively randomized. Questionnaires using the International Index of Erectile Function (IIEF-5) about the sexual function of men were collected before and 1 year after surgery. Sexual dysfunction incidence was defined as the ratio of patients showing sexual dysfunction after surgery relative to the number who had no erectile dysfunction before surgery. RESULTS: Among 701 patients enrolled between June 2003 and August 2010, 472 males were included. Among them, 343 (73%) completed preoperative and postoperative questionnaires. According to the study protocol, the incidences of sexual dysfunction in patients who underwent ME alone and ME with LLND were 68% (17/25; 95%CI, 47-85%) and 79% (23/29; 95%CI, 60-92%), respectively (p = 0.37). Incidences of sexual dysfunction in patients with no or only mild erectile dysfunction before surgery who underwent ME alone and ME with LLND were 59% (48/81) and 71% (67/95), respectively (p = 0.15). Multivariate analysis identified age as the only risk factor for sexual dysfunction after surgery (p = 0.02). CONCLUSIONS: LLND may not increase sexual dysfunction incidence after rectal cancer surgery. This incidence is associated with increased age. This trial is registered with ClinicalTrials.gov, number NCT00190541 and University Hospital Medical Information Network Clinical Trials Registry, number C000000034.


Assuntos
Adenocarcinoma/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Disfunção Erétil/epidemiologia , Excisão de Linfonodo/métodos , Mesentério/cirurgia , Complicações Pós-Operatórias/epidemiologia , Neoplasias Retais/cirurgia , Reto/cirurgia , Adenocarcinoma/patologia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Disfunções Sexuais Fisiológicas/epidemiologia
10.
Eur J Vasc Endovasc Surg ; 48(6): 695-702, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25281532

RESUMO

OBJECTIVE: To assess and risk-stratify the medium-term clinical outcomes after infrainguinal bypass grafting (IBG) to treat critical limb ischaemia (CLI) in patients with end-stage renal disease. METHODS: This was a retrospective single-centre study. Between April 2007 and March 2011, 112 limbs from 89 patients were studied. In particular, amputation-free survival (AFS), 30 day mortality, freedom from major adverse limb events (MALE), limb salvage, and overall survival were examined. The aim was to identify outcome predictors. RESULTS: Eight patients (9%) died within 30 days of IBG. The only positive predictor of 30-day mortality was an ejection fraction (EF) < 40% (hazard ratio [HR] 5.57, 95% confidence interval [CI] 1.16-26.83; p = .03). The mean follow-up duration was 14 months. The 1- and 2-year AFS rates were 64% and 43%, respectively, and the rates of freedom from MALE were 81% and 77%, respectively. In addition, the 1- and 2-year limb salvage rates were 89% and 85%, and the survival rates were 68% and 50%, respectively. Non-ambulatory status was negatively associated with AFS (HR 3.04, 95% CI 1.59-5.82; p < .01), freedom from MALE (HR 4.98, 95% CI 1.91-12.96; p < .01), and limb salvage (HR 5.18, 95% CI 1.47-18.30; p = .01). The other negative predictors of overall survival were a serum albumin level <3.0 g/dL (HR 2.26, 95% CI 1.12-4.58; p = .02) and an EF <40% (HR 2.24, 95% CI 1.05-4.79; p = .04). CONCLUSION: Patients with CLI on dialysis enjoyed satisfactory freedom from MALE and limb salvage, but survival and AFS were significantly less than reported for IBG in patients with CLI who did not receive dialysis. In addition, patients with an EF <40%, lower serum albumin (<3.0 g/dL), or non-ambulatory status experienced particularly poor clinical outcomes after IBG.


Assuntos
Isquemia/cirurgia , Falência Renal Crônica/terapia , Diálise Renal , Enxerto Vascular , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Biomarcadores/sangue , Estado Terminal , Intervalo Livre de Doença , Feminino , Humanos , Isquemia/complicações , Isquemia/diagnóstico , Isquemia/mortalidade , Isquemia/fisiopatologia , Japão , Estimativa de Kaplan-Meier , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Salvamento de Membro , Masculino , Modelos de Riscos Proporcionais , Diálise Renal/efeitos adversos , Diálise Renal/mortalidade , Reoperação , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Albumina Sérica/metabolismo , Albumina Sérica Humana , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento , Enxerto Vascular/efeitos adversos , Enxerto Vascular/mortalidade
11.
Eur J Vasc Endovasc Surg ; 43(1): 62-5, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21852163

RESUMO

OBJECTIVES: Cilostazol is known to be a selective inhibitor of phosphodiesterase 3 and is generally used to treat intermittent claudication caused by peripheral arterial disease. However, there is little information concerning the effect of cilostazol on angiogenesis. Here, we investigated whether cilostazol modulates the angiogenic process in vivo employing a hindlimb model of ischaemia-induced angiogenesis. DESIGN: This was an experimental study. MATERIALS AND METHODS: Wild-type (WT) mice were randomly divided into two groups and were treated with or without cilostazol. One week later, the mice were subjected to unilateral hindlimb ischaemia. Angiogenesis was determined by laser Doppler analysis and capillary density stained with CD31. The expression of endothelial nitric oxide synthase (eNOS) was assessed by immunoblotting. RESULTS: WT mice treated with cilostazol showed accelerated neo-vascularisation following hindlimb ischaemic surgery on post-operative day 14 based upon laser Doppler measurements of blood flow (cilostazol-treated group, 0.54 ± 0.13 vs. control group, 0.38 ± 0.11; P-<-0.05). The capillary density in the ischaemic hindlimb was also significantly greater in WT mice treated with cilostazol than in non-treated WT mice (cilostazol-treated group, 1.63 ± 0.10 vs. control group, 1.15 ± 0.12; P-<-0.01). Cilostazol stimulated an ischaemia-induced increase in the phosphorylation of eNOS in the ischaemic limbs. Administration of NOS inhibitor N-nitro-l-arginine methyl ester (l-NAME) abolished cilostazol-induced increase in limb perfusion. CONCLUSIONS: Our observations indicate that cilostazol can promote neo-vascularisation in response to tissue ischaemia via an eNOS-dependent mechanism. Cilostazol could be useful for treatment of ischaemic limb diseases.


Assuntos
Indutores da Angiogênese/farmacologia , Capilares/efeitos dos fármacos , Isquemia/tratamento farmacológico , Músculo Esquelético/irrigação sanguínea , Neovascularização Fisiológica/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Inibidores da Fosfodiesterase 3/farmacologia , Tetrazóis/farmacologia , Animais , Western Blotting , Capilares/enzimologia , Capilares/fisiopatologia , Cilostazol , Modelos Animais de Doenças , Membro Posterior , Imuno-Histoquímica , Isquemia/enzimologia , Isquemia/fisiopatologia , Fluxometria por Laser-Doppler , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/deficiência , Óxido Nítrico Sintase Tipo III/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Fatores de Tempo
13.
Oncogene ; 28(8): 1142-50, 2009 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-19137017

RESUMO

O(6)-Methylguanine produced in DNA induces mutation due to its ambiguous base-pairing properties during DNA replication. To suppress such an outcome, organisms possess a mechanism to eliminate cells carrying O(6)-methylguanine by inducing apoptosis that requires the function of mismatch repair proteins. To identify other factors involved in this apoptotic process, we performed retrovirus-mediated gene-trap mutagenesis and isolated a mutant that acquired resistance to a simple alkylating agent, N-methyl-N-nitrosourea (MNU). However, it was still sensitive to methyl methanesulfonate, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea, etoposide and ultraviolet irradiation. Moreover, the mutant exhibited an increased mutant frequency after exposure to MNU. The gene responsible was identified and designated Mapo1 (O(6)-methylguanine-induced apoptosis 1). When the expression of the gene was inhibited by small interfering RNA, MNU-induced apoptosis was significantly suppressed. In the Mapo1-defective mutant cells treated with MNU, the mitochondrial membrane depolarization and caspase-3 activation were severely suppressed, although phosphorylation of p53, CHK1 and histone H2AX was observed. The orthologs of the Mapo1 gene are present in various organisms from nematode to humans. Both mouse and human MAPO1 proteins expressed in cells localize in the cytoplasm. We therefore propose that MAPO1 may play a role in the signal-transduction pathway of apoptosis induced by O(6)-methylguanine-mispaired lesions.


Assuntos
Apoptose/genética , Pareamento Incorreto de Bases/genética , DNA/genética , Regulação da Expressão Gênica/fisiologia , Guanina/análogos & derivados , Camundongos Knockout/genética , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Animais , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Caspase 3/metabolismo , Metilases de Modificação do DNA/fisiologia , Enzimas Reparadoras do DNA/fisiologia , Etoposídeo/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Guanina/metabolismo , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/efeitos da radiação , Metanossulfonato de Metila/farmacologia , Metilnitrosoureia/farmacologia , Camundongos , Proteína 1 Homóloga a MutL , Mutagênese , Mutação/genética , Proteínas Nucleares/fisiologia , RNA Interferente Pequeno/farmacologia , Proteínas Supressoras de Tumor/fisiologia , Raios Ultravioleta
14.
Eur J Vasc Endovasc Surg ; 35(6): 694-7, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18295515

RESUMO

BACKGROUND AND AIM: We assessed serum procalcitonin (PCT) as a screening test for early detection of ischemic colitis. PATIENTS AND METHODS: Ninety-three patients (81 men and 12 women) undergoing elective aortic surgery were enrolled in this study. Their mean age was 70.3+/-8.1 years old. Serum procalcitonin was measured postoperatively. RESULTS: Four patients suffered from colon ischemia. Based on a cut off value of serum PCT>/=2.0 ng/ml, fourteen patients had a false positive but none had a false negative result. Sensitivity was 100%, and specificity was 83.9% in detecting ischemic colitis. Negative predictive vale was 100%. CONCLUSION: Serum PCT is a non-invasive test that has a high negative predictive vale in ruling out colon ischemia after aortic surgery.


Assuntos
Doenças da Aorta/cirurgia , Calcitonina/sangue , Colite Isquêmica/diagnóstico , Precursores de Proteínas/sangue , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Doenças da Aorta/sangue , Biomarcadores/sangue , Peptídeo Relacionado com Gene de Calcitonina , Colite Isquêmica/sangue , Colite Isquêmica/etiologia , Diagnóstico Precoce , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento
15.
Int J Colorectal Dis ; 22(8): 911-7, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17318555

RESUMO

BACKGROUND AND AIMS: The aim of this study was to determine the incidence of isolated tumor cells (ITC) and micrometastasis in lateral lymph nodes of patients with rectal cancer and its possible correlation with prognosis. MATERIALS AND METHODS: One hundred seventy-seven rectal cancer patients who underwent curative resection with lateral lymph node dissection were enrolled. Dissected lymph nodes were examined using hematoxylin-eosin staining (HE) and immunohistochemistry (IHC) with anti-keratin antibody (AE1/AE3). States of lymph node metastasis were divisible into three groups: detectable with HE (HE+), detectable with only IHC (HE-/IHC+), and undetectable even with IHC (IHC-). Almost all the HE-/IHC+ group was classified as ITC consisting of a few tumor cells according to the UICC criteria (ITC+). Survival rates were compared among HE+, ITC+, and IHC-. RESULTS: ITC+ were detected in 24.1% of patients with HE-negative lateral lymph nodes. No significant difference in overall 5-year survival was observed between ITC+ and IHC- patients (76.1 and 82.9%, respectively, p = 0.25). Multivariate analysis showed that perirectal HE+ lymph nodes, but not ITC+ lateral lymph nodes, was an independent prognostic factor. CONCLUSIONS: ITC in lateral lymph nodes does not contribute to the prognosis of rectal cancer in patients who undergo extended lateral lymph node dissection, unlike HE+ lateral lymph node metastasis.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Excisão de Linfonodo , Linfonodos/patologia , Neoplasias Retais/patologia , Adulto , Idoso , Amarelo de Eosina-(YS) , Feminino , Seguimentos , Hematoxilina , Humanos , Imuno-Histoquímica , Incidência , Estimativa de Kaplan-Meier , Queratinas/análise , Linfonodos/química , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Neoplasias Retais/mortalidade , Neoplasias Retais/cirurgia , Coloração e Rotulagem/métodos , Resultado do Tratamento
16.
Water Sci Technol ; 53(11): 51-63, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16862774

RESUMO

Understanding of the fate of oestrogen and oestrogenic compounds is important in improving the removal efficiency for oestrogens in wastewater treatment plants (WWTPs). In this study an attempt was made to clarify the fate of oestrogen, oestrogen sulphates, and oestrogenic compounds (synthetic oestrogen, nonylphenol and its relatives) by an instrumental analysis, and the fate of oestrogenicity by an in vitro assay. The investigation was conducted in an activated sludge WWTP in winter and summer, focusing on identification of the primary substances that induce oestrogenicity. Wastewater samples were analysed by employing the silica-gel fractionation technique in conjunction with two-step column chromatography. The results revealed that, in winter, the WWTP efficiencies for the removal of nitrogen and oestrogens decreased and the oestrone level increased with the progress of the treatment. Oestrone and oestrogenic substances are likely to circulate between the aeration tank and the final sedimentation tank. In summer, however, these compounds were effectively removed in the WWTP. The results of the column chromatography coupled with the bioassay suggested that E1 and E2 are the predominant contributors to the oestrogenicity in the influent, return sludge and effluent of the WWTP. The measurement by the instrumental analysis supported these findings.


Assuntos
Estrogênios/análise , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Bioensaio , Reatores Biológicos , Cromatografia/métodos , Estrona/química , Nitrogênio/análise , Estações do Ano , Solventes , Fatores de Tempo , Água/análise , Leveduras/metabolismo
17.
Br J Surg ; 93(5): 609-15, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16607682

RESUMO

BACKGROUND: The aim of this study was to assess the impact of inferior mesenteric artery (IMA) root nodal dissection before high ligation of the artery on survival in patients with sigmoid colon or rectal cancer. METHODS: Data on 1188 consecutive patients who underwent resection for sigmoid colon or rectal cancer, with high ligation of the IMA, were identified from a prospective database (April 1965 to December 1999). Survival of patients with involvement of nodes along the IMA proximal to the origin of the left colic artery (root nodes, station 253) through the bifurcation of the superior rectal artery (trunk nodes, station 252) was determined. RESULTS: Twenty patients (1.7 per cent) had metastatic involvement of station 253 lymph nodes and 99 (8.3 per cent) had metastases to station 252. The 5- and 10-year survival rates of patients with metastases to station 253 were 40 and 21 per cent, and those for patients with metastases to station 252 were 50 and 35 per cent, respectively. CONCLUSION: High ligation of the IMA allows curative resection and long-term survival in patients with cancer of the sigmoid colon or rectum and nodal metastases at the origin of the IMA.


Assuntos
Excisão de Linfonodo/métodos , Artéria Mesentérica Inferior/cirurgia , Neoplasias Retais/cirurgia , Neoplasias do Colo Sigmoide/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Ligadura/métodos , Excisão de Linfonodo/mortalidade , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias Retais/mortalidade , Neoplasias do Colo Sigmoide/mortalidade , Taxa de Sobrevida , Resultado do Tratamento
18.
Br J Surg ; 93(6): 745-51, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16609954

RESUMO

BACKGROUND: Macroscopic volume changes after portal vein embolization (PVE) can be assessed accurately by computed tomography, but histological changes remain poorly understood. The aim of this study was to clarify hepatocyte morphology and kinetics after PVE. METHODS: The resected livers from 25 patients who underwent extended hepatectomy after PVE and five normal livers were examined using hepatocyte paraffin 1 staining for histomorphometric analysis of hepatocytes. Cell kinetics were determined by Ki-67 staining and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labelling assay. Kupffer cells were examined by CD68 immunostaining. RESULTS: The number of hepatocytes was similar in the embolized lobe, non-embolized lobe and normal liver, but hepatocyte volume was greater in the non-embolized lobe than in the embolized lobe (P = 0.017). The Ki-67 labelling index was higher in the non-embolized lobe (P < 0.001) whereas the apoptotic index was higher in the embolized lobe (P < 0.001). There were more Kupffer cells per unit area in the embolized lobe (P < 0.001). CONCLUSION: Hepatocyte hypertrophy and replication leads to volume enlargement of the non-embolized hepatic lobe, whereas hepatocyte atrophy and apoptosis causes a decrease in volume of the embolized lobe.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Embolização Terapêutica/métodos , Neoplasias da Vesícula Biliar/patologia , Hepatócitos/patologia , Veia Porta/cirurgia , Adulto , Idoso , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Feminino , Neoplasias da Vesícula Biliar/cirurgia , Hepatectomia , Humanos , Antígeno Ki-67 , Cinética , Masculino , Pessoa de Meia-Idade
19.
Eur J Vasc Endovasc Surg ; 31(3): 280-3, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16376120

RESUMO

OBJECTIVES: To evaluate the ability of the retroperitoneum to serve as a barrier, against bacterial contamination, between the peritoneal cavity to the retroperitoneal space. METHODS: Seventy rats had a small piece of knitted Dacron graft placed in the retroperitoneal space and 10(6)-10(9) colony forming unit (cfu) Enterococcus faecalis was injected into the peritoneal cavity. In half the retroperitoneal (RP) group, the retroperitoneum was preserved and in the remainder, the open peritoneal (OP) group, needle holes were created. Grafts were harvested after 1, 4, or 7 days and cultured for E. faecalis. A blood sample was collected from three rats in each group for culture before the graft was harvested. RESULTS: Graft infection did not develop in any rat injected with 10(6) or 10(7) cfu in the RP group, while seven out of the 10 graft cultures of the OP group grew E. faecalis (P = 0.003). In rats injected with 10(8) or 10(9) cfu, five out of the 10 graft cultures in the RP group and eight out of 10 in the OP group grew E. faecalis. All blood cultures were negative when the injected bacterial count was 10(7) cfu or less. One out of the three blood cultures was positive at 10(8) cfu, and all were positive at 10(9) cfu. CONCLUSIONS: These results suggest that an intact retroperitroneum acts as a protective barrier against intraperitoneal bacterial contamination, particularly when blood cultures are negative.


Assuntos
Prótese Vascular/efeitos adversos , Infecções por Bactérias Gram-Positivas/fisiopatologia , Infecções Relacionadas à Prótese/fisiopatologia , Espaço Retroperitoneal/fisiologia , Animais , Enterococcus faecalis , Infecções por Bactérias Gram-Positivas/prevenção & controle , Masculino , Peritônio/microbiologia , Infecções Relacionadas à Prótese/prevenção & controle , Ratos , Ratos Sprague-Dawley , Espaço Retroperitoneal/microbiologia
20.
Water Sci Technol ; 50(5): 93-100, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15499675

RESUMO

This paper describes an analytical procedure for free estrogens and their conjugates in domestic wastewater. The procedure demonstrated in this study is innovative in terms of levels of detection and quantification of the following substances: estrone (E1); 17beta-estradiol (E2); 17alpha-ethynylestradiol (EE2); estriol (E3); estrone-3-sulfate (E1-S); beta-estradiol 3-sulfate (E2-S); estriol 3-sulfate (E3-S); estrone beta-D-glucuronide (E1-G); beta-estradiol 17-(beta-D)-glucuronide (E2-G); estriol 3-(beta-D)-glucuronide (E3-G); beta-estradiol 3-sulfate 17-glucuronide (E2-SandG); and estradiol 3,17-disulfate (E2-diS). The detection limits of this method ranged from 0.1 to 1.4 ng/l. The recovery efficiencies of the estrogens in the analysis from influent and effluent of the secondary settling tank in a wastewater treatment plant (WWTP) were higher than 94% for the free estrogens, but were less than 50% for the conjugated estrogens. The field study using this method was conducted at twenty WWTPs in Japan. The median concentrations of the estrogens ranged from ND to as high as >100 ng/l. In the influent and secondary effluent samples, the concentrations of E1, E2 and E3 were the same levels as those previously reported. We found that the conjugated estrogens exist at higher concentrations in the influent and the secondary effluent than in the other studies, and that the concentrations of the conjugated estrogens were higher than those of the free estrogens.


Assuntos
Estradiol/análise , Estrogênios/análise , Esgotos/análise , Poluentes Químicos da Água/análise , Poluentes Ambientais/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Japão , Esgotos/química
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