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1.
Ann Surg Oncol ; 28(7): 3789-3797, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33244738

RESUMEN

BACKGROUND: Intractable serous (not chylous) ascites (IA) that infrequently develops early following pancreaticoduodenectomy (PD) for pancreatic cancer is a life-threatening problem. The relationship between neoadjuvant chemoradiotherapy (NACRT) for pancreatic cancer and the incidence of IA following PD has not been evaluated. This study aims to identify the risk factors associated with IA that develops early after PD for pancreatic cancer. METHODS: We retrospectively identified 94 patients who underwent PD for pancreatic cancer at the Department of General and Gastroenterological Surgery, Osaka Medical College Hospital, Osaka, Japan, from April 2012 to March 2020. Data on 29 parameters were obtained from medical records. Univariate and multivariate analyses were conducted to identify independent risk factors. Levels of serum albumin were compared before and after NACRT to analyze its effect. Survival analysis was also conducted. RESULTS: Of the 92 patients included in this study, 8 (8.70%) were categorized into the IA group. Multivariate analysis identified NACRT [odds ratio (OR) 27, 95% confidence interval (CI) 1.87-394, p = 0.016)] and hypoalbuminemia (≤ 1.6 g/dl) just after the operation (OR 50, 95% CI 1.68-1516, p = 0.024) as risk factors. The level of serum albumin was significantly decreased following NACRT. The IA group had poorer prognosis than the control group. CONCLUSIONS: IA is a serious problem that aggravates patient's prognosis. Postoperative lymphatic leak might be a trigger of IA. NACRT was a major risk factor, followed by hypoalbuminemia caused by various reasons. These factors may act synergistically and cause IA.


Asunto(s)
Terapia Neoadyuvante , Neoplasias Pancreáticas , Ascitis/etiología , Ascitis/terapia , Quimioradioterapia , Humanos , Japón/epidemiología , Terapia Neoadyuvante/efectos adversos , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía/efectos adversos , Estudios Retrospectivos
2.
Circulation ; 140(10): 846-863, 2019 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-31266349

RESUMEN

BACKGROUND: Transplantation is the treatment of choice for many patients with end-stage organ disease. Despite advances in immunosuppression, long-term outcomes remain suboptimal, hampered by drug toxicity and immune-mediated injury, the leading cause of late graft loss. The development of therapies that promote regulation while suppressing effector immunity is imperative to improve graft survival and minimize conventional immunosuppression. Notch signaling is a highly conserved pathway pivotal to T-cell differentiation and function, rendering it a target of interest in efforts to manipulate T cell-mediated immunity. METHODS: We investigated the pattern of Notch-1 expression in effector and regulatory T cells (Tregs) in both murine and human recipients of a solid-organ transplant. Using a selective human anti-Notch-1 antibody (aNotch-1), we examined the effect of Notch-1 receptor inhibition in full major histocompatibility complex-mismatch murine cardiac and lung transplant models, and in a humanized skin transplant model. On the basis of our findings, we further used a genetic approach to investigate the effect of selective Notch-1 inhibition in Tregs. RESULTS: We observed an increased proportion of Tregs expressing surface and intracellular (activated) Notch-1 in comparison with conventional T cells, both in mice with transplants and in the peripheral blood of patients with transplants. In the murine cardiac transplant model, peritransplant administration of aNotch-1 (days 0, 2, 4, 6, 8, and 10) significantly prolonged allograft survival in comparison with immunoglobulin G-treated controls. Similarly, aNotch-1 treatment improved both histological and functional outcomes in the murine lung transplant model. The use of aNotch-1 resulted in a reduced proportion of both splenic and intragraft conventional T cells, while increasing the proportion of Tregs. Furthermore, Tregs isolated from aNotch-1-treated mice showed enhanced suppressive function on a per-cell basis, confirmed with selective Notch-1 deletion in Tregs (Foxp3EGFPCreNotch1fl/fl). Notch-1 blockade inhibited the mammalian target of rapamycin pathway and increased the phosphorylation of STAT5 (signal transducer and activator of transcription 5) in murine Tregs. Notch-1low Tregs isolated from human peripheral blood exhibited more potent suppressive capacity than Notch-1high Tregs. Last, the combination of aNotch-1 with costimulation blockade induced long-term tolerance in a cardiac transplant model, and this tolerance was dependent on CTLA-4 (cytotoxic T-lymphocyte-associated antigen-4) signaling. CONCLUSIONS: Our data reveal a promising, clinically relevant approach for immune modulation in transplantation by selectively targeting Notch-1.


Asunto(s)
Rechazo de Injerto/metabolismo , Receptor Notch1/antagonistas & inhibidores , Subgrupos de Linfocitos T/inmunología , Linfocitos T Reguladores/inmunología , Animales , Anticuerpos Bloqueadores/farmacología , Células Cultivadas , Regulación de la Expresión Génica , Rechazo de Injerto/inmunología , Rechazo de Injerto/mortalidad , Humanos , Tolerancia Inmunológica , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Transgénicos , Trasplante de Órganos , Receptor Notch1/genética , Receptor Notch1/metabolismo , Factor de Transcripción STAT5/metabolismo , Transducción de Señal , Análisis de Supervivencia
3.
Ann Surg Oncol ; 27(11): 4143-4152, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32500344

RESUMEN

BACKGROUND: The effectiveness of adjuvant transcatheter arterial chemo- or/and chemoembolization therapy after curative hepatectomy of initial hepatocellular carcinoma (HCC) is controversial. This study aimed to evaluate whether hepatectomy combined with adjuvant transcatheter arterial infusion therapy (TAI) for initial HCC has better long-term survival outcomes than hepatectomy alone. METHODS: From January 2012 to December 2014, a prospective randomized controlled trial of patients with initial HCC was conducted. Then, 114 initial HCC patients were recruited to undergo hepatectomy with adjuvant TAI (TAI group, n = 55) or hepatectomy alone (control group, n = 59) at our institution. The TAI therapy was performed twice, at 3 and 6 months after curative hepatectomy (UMIN 000011900). RESULTS: The patients treated with TAI had no serious side effects, and operative outcomes did not differ between the two groups. No significant differences were found in the pattern of intrahepatic recurrence or time until recurrence between the two groups. Moreover, no significant differences were found in the relapse-free survival or overall survival. Low cholinesterase level (< 200) had been identified as a risk factor affecting relapse-free survival. Furthermore, compared with surgery alone, adjuvant TAI with hepatectomy improved the overall survival for lower-cholinesterase patients. CONCLUSIONS: Adjuvant TAI is safe and feasible, but it cannot reduce the incidence of postoperative recurrence or prolong survival for patients who underwent curative hepatectomy for initial HCC.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Quimioterapia Adyuvante , Hepatectomía , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Tasa de Supervivencia , Resultado del Tratamiento
4.
Surg Today ; 50(4): 413-418, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31673783

RESUMEN

Patients who undergo pancreatectomy for pancreatic ductal adenocarcinoma (PDA) develop relatively early recurrence, but pulmonary metastasis from PDA is rare. Between January 2008 and December 2016, a total of 120 consecutive patients underwent pancreatectomy for primary PDA at Osaka Medical College Hospital. Among these, 13 patients developed pulmonary metastasis and 6 patients underwent pulmonary metastasectomy. Among these patients, the median disease-free survival following initial pancreatic surgery was 26.1 months, and the median overall survival (OS) interval was 39 months. On the other hand, seven patients did not undergo pulmonary resection. The median OS interval of these patients was 33 months. The 1-, 3-, and 5-year OS rates were 100%, 80%, and 60%, respectively, for patients who underwent pulmonary metastasectomy and 100.0%, 42.8%, and 0%, respectively, for those who did not undergo the procedure. Our experience has shown that surgical resection may lengthen the survival time of patients who tolerate surgery.


Asunto(s)
Carcinoma Ductal Pancreático/cirugía , Neoplasias Pulmonares/secundario , Pancreatectomía , Neoplasias Pancreáticas/cirugía , Carcinoma Ductal Pancreático/mortalidad , Humanos , Neoplasias Pancreáticas/mortalidad , Tasa de Supervivencia , Factores de Tiempo
5.
BMC Surg ; 20(1): 28, 2020 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-32041579

RESUMEN

BACKGROUND: Total pancreatectomy is performed for chronic pancreatitis, tumors involving the entire pancreas or remnant pancreas after pancreatectomy. Gastric venous congestion and bleeding may be associated with total pancreatectomy. We report the case of a patient who underwent left gastric vein to splenic vein bypass to relieve gastric venous congestion during total pancreatectomy for remnant pancreatic cancer. CASE PRESENTATION: A 60-year-old woman underwent subtotal stomach-preserving pancreaticoduodenectomy for cancer of the pancreatic head. A follow-up computed tomography revealed a low-density tumor of the remnant pancreas. The pathological diagnosis was adenocarcinoma on endoscopic ultrasound-fine needle aspiration. Total resection of the remnant pancreas was performed for the tumor 3 years after the initial surgery. We ligated the splenic vein at the point of distal side of the left gastric vein confluent. Immediately, the vein congestion around the stomach was confirmed. We found the stenosis of the confluent between the left gastric vein and splenic vein. We subsequently anastomosed the left gastric vein and splenic vein, following which the gastric venous congestion was relieved. CONCLUSION: In cases wherein all the drainage veins from the stomach are removed, an anastomosis between the left gastric vein and splenic vein can be effectively used to prevent gastric venous congestion and bleeding after total pancreatectomy.


Asunto(s)
Adenocarcinoma/cirugía , Pancreatectomía/métodos , Neoplasias Pancreáticas/cirugía , Femenino , Humanos , Hiperemia/etiología , Persona de Mediana Edad , Pancreaticoduodenectomía/métodos , Vena Porta/cirugía , Vena Esplénica/cirugía , Estómago/cirugía , Tomografía Computarizada por Rayos X
6.
BMC Surg ; 20(1): 86, 2020 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-32366237

RESUMEN

BACKGROUND: Double aortic arch (DAA) is a congenital anomaly of the aorta. Esophageal cancer with DAA is rare, and consequently, the appropriate surgical approach has not been standardized. Herein, we report the utilization of intraoperative neurological monitoring (IONM) system to preserve the function of the recurrent laryngeal nerve. CASE PRESENTATION: A 79-year-old man with esophageal cancer was diagnosed with DAA incidentally. The descending aorta was located on the right side of the thoracic vertebrae. Safe dissection of the mediastinal lymph nodes was difficult using the right transthoracic approach because of the anatomical abnormalities. During surgery, we used cervical mediastinoscopy combined with the IONM system to preserve the bilateral recurrent laryngeal nerves. Severe complications, including recurrent nerve palsy, were not observed postoperatively. CONCLUSION: IONM may be useful for evaluation of the function of the recurrent laryngeal nerve, and it would be suitable for atypical cases of esophageal cancer.


Asunto(s)
Neoplasias Esofágicas/cirugía , Monitoreo Intraoperatorio/métodos , Anillo Vascular/diagnóstico , Anciano , Aorta/anomalías , Aorta Torácica/anomalías , Humanos , Ganglios Linfáticos/patología , Masculino , Mediastinoscopía , Nervio Laríngeo Recurrente/fisiología
7.
Surg Today ; 49(1): 82-89, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30255329

RESUMEN

PURPOSE: Neoadjuvant chemotherapy (NAC) for resectable liver metastasis from colorectal cancer (CRLM) is used widely, but its efficacy lacks clear evidence. This study aimed to clarify its worth and develop appropriate treatment strategies for CRLM. METHODS: We analyzed, retrospectively, the clinicopathological factors and outcomes of 137 patients treated for resectable CRLM between 2006 and 2015, with upfront surgery (NAC- group; n = 117) or initial NAC treatment (NAC+ group; n = 20). RESULTS: The time to surgical failure (TSF) and overall survival (OS) after initial treatment were significantly worse in the NAC+ group than in the NAC- group (P = 0.002 and P = 0.032, respectively). At hepatectomy, the NAC+ group had a lower median prognostic nutrition index (PNI), higher rates of a positive Glasgow Prognostic Score (P = 0.002) and more perioperative blood transfusions (P = 0.027) than the NAC- group. Moreover, the serum albumin (P = 0.006), PNI (P ≤ 0.001) and lymphocyte-to-monocyte ratio (P ≤ 0.001) were significantly decreased and the GPS positive rate was increased from 15 to 35% in the NAC+ group. The OS rates did not differ significantly according to the NAC response (5-year OS rates-CR/PR 67%, SD 60%, PD 38%). CONCLUSIONS: Patients with resectable CRLM should undergo upfront hepatectomy because NAC did not improve OS after initial treatment in these patients.


Asunto(s)
Neoplasias Colorrectales/patología , Hepatectomía , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Terapia Neoadyuvante , Anciano , Transfusión Sanguínea/estadística & datos numéricos , Quimioterapia Adyuvante , Femenino , Escala de Consecuencias de Glasgow , Humanos , Neoplasias Hepáticas/mortalidad , Recuento de Linfocitos , Masculino , Evaluación Nutricional , Atención Perioperativa , Pronóstico , Estudios Retrospectivos , Albúmina Sérica , Tasa de Supervivencia
8.
Surg Innov ; 26(1): 46-49, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30191768

RESUMEN

INTRODUCTION: A recent development in minimally invasive surgery (MIS) is single-port surgery, where a single large multiport trocar is placed in the umbilicus. All medical schools require that students complete an anatomy course as part of the medical curriculum. However, there is limited instruction regarding the detailed parts of the "umbilicus." In several famous anatomy atlases, the umbilicus is not dissected at all and is merely represented as a button. Until now, the true nature of the umbilicus has not been anatomically demonstrated. METHODS: Five cadavers were obtained from the Osaka Medical College medical student anatomy class. The umbilicus was dissected in the anatomy laboratory, to demonstrate all the layers. A detailed dissection was performed, focusing on the exact center of the umbilicus, in order to ascertain whether there exists a "natural orifice" or a fascial defect. RESULTS: In all cadavers, a small defect of fascia was identified just below the center of the umbilicus. Yellow fatty tissue was present just below the skin in the exact center of the umbilicus. A probe placed exactly in the middle of this defect passes easily through into the abdominal cavity. CONCLUSIONS: With the widespread use of MIS, umbilical incision is commonly used to reduce pain and improve cosmetic results. This study consistently revealed a natural defect of fascia in the center of the umbilicus. Therefore, the umbilicus can be called a concealed "natural orifice." It is important to recognize and utilize this defect effectively to minimize unnecessary tissue trauma during MIS.


Asunto(s)
Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Cirugía Endoscópica por Orificios Naturales/métodos , Ombligo/anatomía & histología , Ombligo/cirugía , Cadáver , Disección , Femenino , Humanos , Japón , Laparoscopios , Masculino , Facultades de Medicina , Sensibilidad y Especificidad
9.
World J Surg ; 42(4): 1100-1110, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-28929234

RESUMEN

BACKGROUND: There is no consensus about remnant liver regeneration associated with middle hepatic vein (MHV) resecting. METHODS: Seventy-five patients who underwent hemihepatectomy were retrospectively analysed with respect to remnant liver regeneration. The liver remnant volume (LRV) and each sectional volume were postoperatively measured with multidetector computed tomography at day 7 and months 1, 2, 5, and 12 after the operation. RESULTS: In right hemihepatectomy cases, the regeneration rate of LRV in the MHV preservation group was significantly higher than that of the MHV resection group at months 5 and 12. In particular, the regeneration rate of remnant segment IV peaked at day 7 and was shrunk after 1 month, and was significant higher in the MHV preservation group. In left hemihepatectomy cases, the regeneration rate of LRV at month 12 was significantly higher in the MHV preservation group. The regeneration rate of the remnant anterior section peaked at 1 month and was shrunk. CONCLUSION: In this study, the MHV should be preserved or reconstructed whenever possible during hepatic hemihepatectomy. Hepatic regeneration in the MHV perfusion region becomes poor within 7 days to 1 month after surgery (UMIN000023714).


Asunto(s)
Carcinoma Hepatocelular/cirugía , Hepatectomía , Venas Hepáticas/cirugía , Regeneración Hepática , Hígado/irrigación sanguínea , Hígado/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Femenino , Humanos , Hiperplasia , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector , Periodo Posoperatorio , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo
10.
World J Surg ; 42(10): 3316-3330, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29549511

RESUMEN

BACKGROUND: Various chemotherapy regimens have been shown to improve outcomes when administered before tumor excision surgery. However, there is no consensus on the utility of multidisciplinary treatment with preoperative chemotherapy for treating colorectal liver metastasis (CLM). MATERIALS AND METHODS: Two hundred-fifty patients who underwent hepatectomy were retrospectively analyzed using propensity score matching. Postoperative outcomes were evaluated with a focus on the effect of pre-hepatectomy chemotherapy on regeneration of the remnant liver in patients with CLM. The remnant liver volumes (RLVs) were postoperatively measured with multidetector computed tomography on days 7 and months 1, 2, 5, and 12 after the operation. RESULTS: RLV regeneration and blood test results did not significantly differ between patients who underwent preoperative chemotherapy versus those who did not immediately after surgery or at any time point from postoperative day 7 to postoperative month 12. The 1-, 2-, and 3-year overall survival (OS) rates for all patients were 94.6, 86.2, and 79.9%, respectively; the corresponding disease-free survival (RFS) rates were 49.3, 38.6, and 33.7%, respectively. There were no significant differences in OS and RFS between the two groups after hepatic resection. The recurrence rates, including marginal and intrahepatic recurrences, as well as resection frequency of the remnant liver were not significantly different between the two groups. CONCLUSION: Preoperative chemotherapy may have no appreciable benefit for patients with CLM in terms of perioperative and long-term outcomes.


Asunto(s)
Neoplasias Colorrectales/patología , Hepatectomía , Neoplasias Hepáticas/tratamiento farmacológico , Regeneración Hepática , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Neoplasias del Colon/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Premedicación , Pronóstico , Puntaje de Propensión , Estudios Retrospectivos , Tasa de Supervivencia
11.
Surg Today ; 48(9): 894-898, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29752530

RESUMEN

Pancreatic complex deep injury extending to the main pancreatic duct (MPD), caused by strong external forces such as traffic accidents, is lethal without emergency surgery. However, the best surgical procedure for this serious injury has not been established. The Bracey procedure is a relatively simple reconstructive technique involving pancreaticogastrostomy, but it is often followed by postoperative complications, such as dilatation of the MPD caused by anastomotic stenosis, as well as subsequent serious sequela such as repetitive pancreatitis and new-onset pancreatic diabetes. It is possible that the combination of ductal mucosal pancreaticogastrostomy (DMPG) and an internal stent might prevent anastomotic stenosis of the MPD. We found that the Bracey procedure was a safe and effective reconstructive procedure for five patients who suffered a pancreatic complex deep injury with MPD involvement. In three of these patients, postoperative dilatation of the MPD was prevented by combining the Bracey procedure with DMPG including an internal stent. Our experience suggests that this procedure is one of the best techniques for treating pancreatic complex deep injury extending to the MPD.


Asunto(s)
Gastrostomía/métodos , Páncreas/lesiones , Páncreas/cirugía , Conductos Pancreáticos/lesiones , Conductos Pancreáticos/cirugía , Procedimientos de Cirugía Plástica/métodos , Stents , Anastomosis Quirúrgica/efectos adversos , Constricción Patológica/etiología , Constricción Patológica/prevención & control , Dilatación Patológica/etiología , Dilatación Patológica/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Conductos Pancreáticos/patología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Índices de Gravedad del Trauma , Resultado del Tratamiento
12.
World J Surg ; 41(5): 1340-1346, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28097410

RESUMEN

BACKGROUND: Laparoscopic resection of posterosuperior (PS) tumors of the liver is more difficult than that of anterolateral (AL) tumors, owing to the narrow surgical field in the PS location. In this retrospective cohort study, our aim was to determine if port insertion through the intercostal space would lead to improved outcomes for laparoscopic resection of tumors in PS liver segments 7 and 8. METHOD: Between January 2006 and December 2015, 153 patients underwent laparoscopic resection of solitary liver tumors at Osaka Medical College Hospital. Of these, 107 patients had AL lesions, and 46 had PS lesions. Of the 46 patients with a PS lesion, 23 underwent an abdominal-only approach, and 23 underwent the intercostal trocar approach. Multivariate analyses were performed to investigate outcomes. RESULTS: Conventional abdominal-only laparoscopic resection of PS liver tumors resulted in prolonged surgical time (P = 0.031), increased bleeding (P = 0.012), and a higher open conversion rate (P = 0.022) compared with AL tumors. Among patients with PS tumors, the open conversion rate was significantly higher for those treated with the abdominal-only approach than with the intercostal trocar approach (P = 0.047). Appropriate surgical margins were obtained equally using the intercostal trocar approach (P = 0.648). There was no significant difference in occurrence of complications between the abdominal-only group and the intercostal trocar group. CONCLUSION: Using the intercostal trocar approach for PS liver lesions is a safe and effective method, which significantly reduced the open conversion rate compared with the conventional abdominal-only approach.


Asunto(s)
Laparoscopía/métodos , Neoplasias Hepáticas/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pérdida de Sangre Quirúrgica , Estudios de Cohortes , Conversión a Cirugía Abierta/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Estudios Retrospectivos , Adulto Joven
13.
Cytokine ; 83: 206-209, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27155819

RESUMEN

Early recovery from shock improves prognosis in patients with severe sepsis and septic shock. During this period, cytokine imbalances mediate the development of organ damage and mortality. In Japan, we have access to hemoperfusion using an immobilized polymyxin B fiber column for endotoxin removal (PMX-DHP) and continuous hemodiafiltration (CHDF) as artificial support for patients with septic shock, with the aim of improving hemodynamics and organ dysfunction caused by elevated inflammatory cytokines and mediators. In this Short communication, we discuss recent findings showing anti-inflammatory treatment following these continuous renal replacement therapies in sepsis.


Asunto(s)
Proteína HMGB1/sangre , Hemodiafiltración , Terapia de Reemplazo Renal , Sepsis/sangre , Sepsis/terapia , Femenino , Humanos , Masculino
14.
J Am Soc Nephrol ; 26(10): 2341-7, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25833841

RESUMEN

A high-salt diet (HSD) in humans is linked to a number of complications, including hypertension and cardiovascular events. Whether a HSD affects the immune response in transplantation is unknown. Using a murine transplantation model, we investigated the effect of NaCl on the alloimmune response in vitro and in vivo. Incremental NaCl concentrations in vitro augmented T cell proliferation in the settings of both polyclonal and allospecific stimulation. Feeding a HSD to C57BL/6 wild-type recipients of bm12 allografts led to accelerated cardiac allograft rejection, despite similar mean BP and serum sodium levels in HSD and normal salt diet (NSD) groups. The accelerated rejection was associated with a reduction in the proportion of CD4(+)Foxp3(+) regulatory T cells (Tregs) and a significant decrease in Treg proliferation, leading to an increased ratio of antigen-experienced CD4(+) T cells to Tregs in mice recipients of a HSD compared with mice recipients of a NSD. Because serum- and glucocorticoid-regulated kinase-1 (SGK1) has been proposed as a potential target of salt in immune cells, we fed a HSD to CD4(Cre)SGK1(fl/fl) B6-transplanted recipients and observed abrogation of the deleterious effect of a HSD in the absence of SGK1 on CD4(+) cells. In summary, we show that NaCl negatively affects the regulatory balance of T cells in transplantation and precipitates rejection in an SGK1-dependent manner.


Asunto(s)
Rechazo de Injerto/inducido químicamente , Proteínas Inmediatas-Precoces/efectos de los fármacos , Proteínas Inmediatas-Precoces/fisiología , Proteínas Serina-Treonina Quinasas/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/fisiología , Cloruro de Sodio Dietético/efectos adversos , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/fisiología , Animales , Ratones , Ratones Endogámicos C57BL , Factores de Tiempo
15.
J Immunol ; 191(8): 4447-55, 2013 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-24038092

RESUMEN

Dendritic cells (DCs) are the central architects of the immune response, inducing inflammatory or tolerogenic immunity, dependent on their activation status. As such, DCs are highly attractive therapeutic targets and may hold the potential to control detrimental immune responses. TIM-4, expressed on APCs, has complex functions in vivo, acting both as a costimulatory molecule and a phosphatidylserine receptor. The effect of TIM-4 costimulation on T cell activation remains unclear. In this study, we demonstrate that Ab blockade of DC-expressed TIM-4 leads to increased induction of induced regulatory T cells (iTregs) from naive CD4(+) T cells, both in vitro and in vivo. iTreg induction occurs through suppression of IL-4/STAT6/Gata3-induced Th2 differentiation. In addition, blockade of TIM-4 on previously activated DCs still leads to increased iTreg induction. iTregs induced under TIM-4 blockade have equivalent potency to control and, upon adoptive transfer, significantly prolong skin allograft survival in vivo. In RAG(-/-) recipients of skin allografts adoptively transferred with CD4(+) T cells, we show that TIM-4 blockade in vivo is associated with a 3-fold prolongation in allograft survival. Furthermore, in this mouse model of skin transplantation, increased induction of allospecific iTregs and a reduction in T effector responses were observed, with decreased Th1 and Th2 responses. This enhanced allograft survival and protolerogenic skewing of the alloresponse is critically dependent on conversion of naive CD4(+) to Tregs in vivo. Collectively, these studies identify blockade of DC-expressed TIM-4 as a novel strategy that holds the capacity to induce regulatory immunity in vivo.


Asunto(s)
Células Dendríticas/inmunología , Supervivencia de Injerto , Proteínas de la Membrana/metabolismo , Trasplante de Piel , Linfocitos T Reguladores/inmunología , Traslado Adoptivo , Aloinjertos/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Diferenciación Celular/inmunología , Células Cultivadas , Factor de Transcripción GATA3/inmunología , Proteínas de Homeodominio/genética , Interleucina-4/inmunología , Activación de Linfocitos , Proteínas de la Membrana/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Factor de Transcripción STAT6/inmunología , Transducción de Señal , Linfocitos T Reguladores/metabolismo , Células TH1/inmunología , Células Th2/inmunología
16.
Surg Endosc ; 29(2): 458-65, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24993176

RESUMEN

BACKGROUND: Laparoscopic hepatectomy (Lap-Hx) has been increasingly performed for patients with liver tumors as surgical techniques and devices have progressed. However, the long-term outcomes of Lap-Hx for malignant liver tumors are not oncologically guaranteed. This study compared the short- and long-term outcomes between Lap-Hx and open hepatectomy (Open-Hx) for malignant liver tumors by matched-pair analysis. METHODS: The indications for Lap-Hx at our department are a tumor size of <5 cm and fewer than two lesions without macroscopic vascular invasion or the need for biliary reconstruction. In total, 135 patients underwent Lap-Hx for malignant liver tumors through December 2013. We compared the short- and long-term outcomes between Lap-Hx and Open-Hx in patients who met the above-mentioned indications. RESULTS: With respect to short-term outcomes, the operation time, blood loss, postoperative hospital stay, white blood cell count, and C-reactive protein level after Lap-Hx were significantly better than those after Open-Hx in both the patients who underwent partial resection and those who underwent lateral sectionectomy. In patients who underwent partial resection, the incidence of postoperative complications after Lap-Hx was significantly lower than that after Open-Hx; in particular, wound infection and respiratory complications were significantly lower. Furthermore, when the tumor was located in the posterosuperior segments, the operation time for Lap-Hx was not shorter than that for Open-Hx. With respect to long-term outcomes of hepatocellular carcinoma, neither overall nor disease-free survival differed between the two groups. With respect to long-term outcomes of colorectal liver metastases, the disease-free survival rate was similar between Lap-Hx and Open-Hx; however, the overall survival rate was significantly better for Lap-Hx than for Open-Hx. CONCLUSIONS: Lap-Hx is a good option for selected patients with malignant liver tumors. The short- and long-term outcomes of Lap-Hx also are considered to be acceptable.


Asunto(s)
Hepatectomía/métodos , Laparoscopía/métodos , Laparotomía/métodos , Neoplasias Hepáticas/cirugía , Estadificación de Neoplasias , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Japón/epidemiología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Factores de Tiempo , Resultado del Tratamiento
17.
Am J Emerg Med ; 33(3): 473.e1-2, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25633531

RESUMEN

Clamping the descending aorta by emergency thoracotomy is a well-known effective procedure to stop bleeding from lesions under the diaphragm. We successfully treated a case of cardiopulmonary arrest resulting from a massive duodenal ulcer hemorrhage using an intraaortic balloon occlusion (IABO) catheter instead of the conventional technique. Our experience suggests that IABO catheters can be used to treat patients with hemorrhagic shock regardless of the presence of cardiopulmonary arrest. This can be a life-saving procedure, which prevents ischemic brain injury. This article describes the advantages of using IABO catheters and our experience with this case.


Asunto(s)
Aorta , Oclusión con Balón/métodos , Úlcera Duodenal/terapia , Úlcera Péptica Hemorrágica/terapia , Choque Hemorrágico/terapia , Anciano , Úlcera Duodenal/complicaciones , Femenino , Humanos , Úlcera Péptica Hemorrágica/complicaciones , Choque Hemorrágico/etiología
18.
Hepatogastroenterology ; 62(137): 111-7, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25911879

RESUMEN

BACKGROUND/AIMS: The optimal indications, including timing, for resection of liver metastases from colorectal cancer (CRCLM) remain controversial. The Japanese Society of Cancer of the Colon and Rectum has proposed "H-classification" based on the maximum size and number of CRCLM, and has advocated the "CRCLM-grade system", which involves adding the presence of primary lymph node metastasis status to H-classification. We evaluated clinicopathological factors in order to elucidate the optimal indications for and timing of hepatectomy. METHODOLOGY: Ninety-six patients who underwent initial hepatectomy for CRCLM between August 1995 and May 2009 were retrospectively analyzed with respect to characteristics of primary colorectal metastatic hepatic tumors, operation details and prognosis. RESULTS: Multivariate analysis identified depth of invasion in primary colorectal cancer (within sub-serosal (non-se) vs. beyond serosal (se)) and CRCLM-grade as independent risk factors. We then performed analyses using the combination of non-se/se and CRCLM-grade. Kaplan-Meier analysis identified significant differences between non-se+gradeA and se+gradeA, between non-se+gradeB and se+gradeB, and between non-se+gradeC and se+gradeC groups. CONCLUSIONS: We could retrospectively predict survival in CRCLM patients by adopting this new simple classification. This method may allow more precise assessment of operative indications and timing for both operations and perioperative adjuvant treatment.


Asunto(s)
Neoplasias Colorrectales/patología , Técnicas de Apoyo para la Decisión , Neoplasias Hepáticas/secundario , Clasificación del Tumor/métodos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/mortalidad , Femenino , Hepatectomía , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Metástasis Linfática , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral
19.
Hepatogastroenterology ; 62(137): 164-8, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25911889

RESUMEN

BACKGROUND/AIMS: The prevention of recurrence is important for improving long-term outcome for HCC. To identify candidates for postoperative adjuvant therapy after curative hepatectomy for HCC in Child-Pugh classification A (Child A). METHODOLOGY: Of 157 patients who underwent initial hepatectomy for Child A HCC, 93 had recurrence and were divided into 2 groups: group A, ≤2 tumors, each <3 cm in size at the time of intrahepatic recurrence; group B, ≥3 tumors or tumor ≥3 cm in size at the time of intrahepatic recurrence and/or extrahepatic recurrence. Clinicopathological and survival data were analyzed retrospectively in each group to identify poor prognostic factors. RESULTS: The 1-year recurrence rate was 50%, and the time to recurrence was shorter in group B (10 months) than in group A (20 months) Overall 1-, 3-, and 5-year survival rates were poorer in group B (83%, 52%, and 35% respectively; p < 0.001) than in group A (100%, 96%, and 71% respectively) Cancer spread (vascular invasion and/or intrahepatic metastasis) was significantly affecting the recurrence pattern of Group B (p=0.0238) on multivariate analysis. CONCLUSIONS: Systemic adjuvant chemotherapy af ter curative hepatectomy for HCC in Child A should be given to patients with microscopic vascular invasion and/or intrahepatic metastasis.


Asunto(s)
Carcinoma Hepatocelular/secundario , Carcinoma Hepatocelular/cirugía , Hepatectomía/efectos adversos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/mortalidad , Quimioterapia Adyuvante , Distribución de Chi-Cuadrado , Supervivencia sin Enfermedad , Femenino , Hepatectomía/mortalidad , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral
20.
Ann Surg Oncol ; 21(1): 139-46, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24121880

RESUMEN

BACKGROUND: The effectiveness of perioperative adjuvant chemotherapy for colorectal cancer liver metastasis (CRLM) remains a matter of debate. Despite the lack of clear evidence supporting its effectiveness after curative hepatectomy, adjuvant chemotherapy has been widely used clinically. The purpose of this study was to clarify the indications for adjuvant chemotherapy in order to develop an appropriate treatment strategy for CRLM. METHODS: The clinicopathological factors of 110 patients who underwent initial hepatectomy for CRLM between April 2000 and March 2010 were retrospectively analyzed. The prognostic factors of CRLM were identified and then CRLM was stratified according to the number of prognostic factors into the high-score group (H-group: score 2 or 3) and the low-score group (L-group: score 0 or 1), and the effectiveness of adjuvant chemotherapy was analyzed in each group. RESULTS: Multivariate analysis identified pT4 (p = 0.0047), lymph node metastasis in colorectal cancer (CRC) (p = 0.0165), and H2-classification (p = 0.0051) as factors related to a poor prognosis. The overall 5-year survival rate was markedly higher in the L-group (68 %) than in the H-group (26 %, p < 0.0001). Moreover, in the L-group, patients who did not receive adjuvant chemotherapy had the same prognosis as those who received adjuvant chemotherapy. As for recurrence, tumor relapse more often was treated by resection in the L-group than in the H-group (p = 0.0339). CONCLUSIONS: Adjuvant chemotherapy did not improve overall survival and disease-free survival in patients with no more than two factors of the H2-classification, invasion depth pT4, and lymph node metastasis in CRC.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Neoplasias Colorrectales/terapia , Hepatectomía , Neoplasias Hepáticas/terapia , Anciano , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Estadificación de Neoplasias , Pronóstico , Tasa de Supervivencia
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