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BACKGROUND: We investigated the prognostic impact of osteosarcopenia, defined as the combination of osteopenia and sarcopenia, in patients undergoing pancreatic resection for pancreatic ductal adenocarcinoma (PDAC). METHODS: The relationship of osteosarcopenia with disease-free survival and overall survival was analyzed in 183 patients who underwent elective pancreatic resection for PDAC. Computed tomography was used to measure the pixel density in the midvertebral core of the 11th thoracic vertebra for evaluation of osteopenia and in the psoas muscle area of the 3rd lumbar vertebra for evaluation of sarcopenia. Osteosarcopenia was defined as the simultaneous presence of both osteopenia and sarcopenia. The study employed a retrospective design to examine the relationship between osteosarcopenia and survival outcomes. RESULTS: Osteosarcopenia was identified in 61 (33%) patients. In the univariate analysis, disease-free survival was significantly worse in patients with male sex (p = 0.031), pathological stage ≥ III PDAC (p = 0.001), NLR, ≥ 2.71 (p = 0.041), sarcopenia (p = 0.027), osteopenia (p = 0.001), and osteosarcopenia (p < 0.001), and overall survival was significantly worse in patients with male sex (p = 0.001), pathological stage ≥ III PDAC (p = 0.001), distal pancreatectomy (p = 0.025), sarcopenia (p = 0.003), osteopenia (p < 0.001), and osteosarcopenia (p < 0.001). In the multivariate analysis, the independent predictors of disease-free survival were osteosarcopenia (p < 0.001) and pathological stage ≥ III PDAC (p = 0.002), and the independent predictors of overall survival were osteosarcopenia (p < 0.001), male sex (p = 0.006) and pathological stage ≥ III PDAC (p = 0.001). CONCLUSION: Osteosarcopenia has an adverse prognostic impact on long-term outcomes in patients undergoing pancreatic resection for PDAC.
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Enfermedades Óseas Metabólicas , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Sarcopenia , Humanos , Masculino , Pancreatectomía , Pronóstico , Estudios RetrospectivosRESUMEN
PURPOSE: The preoperative platelet-to-lymphocyte ratio (PLR) has been reported as an important prognostic index for pancreatic ductal adenocarcinoma (PDAC); however, the significance of the postoperative (post-op) PLR for this disease has not been elucidated. METHODS: We analyzed data on 118 patients who underwent pancreaticoduodenectomy for pancreatic head PDAC, collected from a prospectively maintained database. The post-op PLR was obtained by dividing the platelet count after surgery by the lymphocyte count on post-op day (POD) 14. The patients were divided into two groups according to a post-op PLR of < 310 or ≥ 310. Survival data were analyzed. RESULTS: A high post-op PLR was identified as a significant prognostic index on univariate analysis for disease-free survival (DFS) and overall survival (OS). The post-op PLR remained significant, along with tumor differentiation and adjuvant chemotherapy, on multivariate analysis for OS (hazard ratio = 2.077, 95% confidence interval: 1.220-3.537; p = 0.007). The post-op PLR was a significant independent prognostic index for poor DFS, along with tumor differentiation and lymphatic invasion, on multivariate analysis (hazard ratio = 1.678, 95% confidence interval: 1.056-2.667; p = 0.028). CONCLUSIONS: The post-op PLR in patients with pancreatic head PDAC was an independent predictor of DFS and OS after elective resection.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Pancreaticoduodenectomía , Neoplasias Pancreáticas/patología , Linfocitos/patología , Pronóstico , Plaquetas , Recuento de Linfocitos , Carcinoma Ductal Pancreático/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: The influence of fine needle aspiration (FNA) on peritoneal lavage cytology (CY) in pancreatic ductal adenocarcinoma (PDAC) is unknown. METHODS: We retrospectively analyzed 29 patients with resectable left-sided PDAC undergoing FNA prior to CY examination. We assessed clinical factors related to CY+, scored the tumor diameter (<20 mm = 0, ≥20 mm = 1) and examination interval between FNA and CY (>18 days = 0, ≤18 days = 1), and investigated the probability of CY + by the sum of each score (0-2). RESULTS: The probability of CY+ was 31%. The CY + group had larger tumors and shorter examination intervals than the CY- group. The CY + probability was 75%, 15%, and 13% for a score of 2, 1, and 0, respectively (P = 0.011). CONCLUSION: A short interval between FNA and CY examination for a large tumor may be a risk factor for CY+ in patients with left-sided PDAC.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Lavado Peritoneal , Estudios Retrospectivos , Incidencia , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/patología , Adenocarcinoma/patología , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Neoplasias PancreáticasRESUMEN
Long-chain-fatty-acid (LCFA) metabolism is a fundamental cellular process in bacteria that is involved in lipid homeostasis, energy production, and infection. However, the role of LCFA metabolism in Salmonella enterica serovar Typhimurium (S. Tm) gut infection remains unclear. Here, using a murine gastroenteritis infection model, we demonstrate involvement of LCFA metabolism in S. Tm gut colonization. The LCFA metabolism-associated transcriptional regulator FadR contributes to S. Tm gut colonization. fadR deletion alters the gene expression profile and leads to aberrant flagellar motility of S. Tm. Colonization defects in the fadR mutant are attributable to altered swimming behavior characterized by less frequently smooth swimming, resulting from reduced expression of the phase 2 flagellin FljB. Notably, changes in lipid LCFA composition by fadR deletion lead to reduced expression of fljB, which is restored by exogenous LCFA. Therefore, LCFA homeostasis may maintain proper flagellar motility by activating fljB expression, contributing to S. Tm gut colonization. Our findings improve the understanding of the effect of luminal LCFA on the virulence of enteric pathogens.
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Flagelina , Salmonella typhimurium , Animales , Ácidos Grasos/metabolismo , Flagelina/metabolismo , Homeostasis , Lípidos , Ratones , Salmonella typhimurium/genética , Salmonella typhimurium/metabolismoRESUMEN
AIMS: The reporting of tumour cellularity in cancer samples has become a mandatory task for pathologists. However, the estimation of tumour cellularity is often inaccurate. Therefore, we propose a collaborative workflow between pathologists and artificial intelligence (AI) models to evaluate tumour cellularity in lung cancer samples and propose a protocol to apply it to routine practice. METHODS AND RESULTS: We developed a quantitative model of lung adenocarcinoma that was validated and tested on 50 cases, and a collaborative workflow where pathologists could access the AI results and adjust their original tumour cellularity scores (adjusted-score) that we tested on 151 cases. The adjusted-score was validated by comparing them with a ground truth established by manual annotation of haematoxylin and eosin slides with reference to immunostains with thyroid transcription factor-1 and napsin A. For training, validation, testing the AI and testing the collaborative workflow, we used 40, 10, 50 and 151 whole slide images of lung adenocarcinoma, respectively. The sensitivity and specificity of tumour segmentation were 97 and 87%, respectively, and the accuracy of nuclei recognition was 99%. One pathologist's visually estimated scores were compared to the adjusted-score, and the pathologist's scores were altered in 87% of cases. Comparison with the ground truth revealed that the adjusted-score was more precise than the pathologists' scores (P < 0.05). CONCLUSION: We proposed a collaborative workflow between AI and pathologists as a model to improve daily practice and enhance the prediction of tumour cellularity for genetic tests.
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Adenocarcinoma del Pulmón , Aprendizaje Profundo , Neoplasias Pulmonares , Humanos , Patólogos , Inteligencia Artificial , Flujo de Trabajo , Adenocarcinoma del Pulmón/diagnóstico , Neoplasias Pulmonares/diagnósticoRESUMEN
INTRODUCTION: A soft remnant texture of the pancreas is commonly accepted as a risk factor for postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). However, its assessment is subjective. The aim of this study was to evaluate the significance of intraoperative amylase level of the pancreatic juice as a risk factor of POPF after PD. METHOD: This study included 75 patients who underwent PD between November 2014 and April 2020â¯at Jikei University Hospital. We investigated the relationship between pancreatic texture, intraoperative amylase level of pancreatic juice, results of the pathological evaluations, and the incidence of POPF. RESULTS: Twenty-three patients (31%) developed POPF. The significant predictors of POPF were non-ductal adenocarcinoma (pâ¯<â¯0.01), soft pancreatic remnant (pâ¯<â¯0.01), high intraoperative blood loss (pâ¯<â¯0.01), high intraoperative amylase level of pancreatic juice (pâ¯<â¯0.01), and low pancreatic fibrosis (pâ¯<â¯0.01). Multivariate analysis revealed that the significant independent predictors of POPF were high intraoperative blood loss (pâ¯<â¯0.01) and high intraoperative amylase level of pancreatic juice (pâ¯=â¯0.02). Receiver operating characteristic (ROC) analysis showed that the cut-off value for the intraoperative amylase level of pancreatic juice was 2.17â¯×â¯105 IU/L (area under the curveâ¯=â¯0.726, sensitivityâ¯=â¯95.7%, and specificityâ¯=â¯50.0%) CONCLUSIONS: The intraoperative amylase level of pancreatic juice is a reliable objective predictor for POPF after PD.
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Amilasas/análisis , Fístula Pancreática/etiología , Jugo Pancreático/enzimología , Pancreaticoduodenectomía/efectos adversos , Complicaciones Posoperatorias/enzimología , Anciano , Pérdida de Sangre Quirúrgica , Carcinoma Ductal Pancreático/cirugía , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Fístula Pancreática/epidemiología , Neoplasias Pancreáticas/cirugía , Complicaciones Posoperatorias/epidemiología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
The imbalanced redox status in lung has been widely implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis. To regulate redox status, hydrogen peroxide must be adequately reduced to water by glutathione peroxidases (GPx). Among GPx isoforms, GPx4 is a unique antioxidant enzyme that can directly reduce phospholipid hydroperoxide. Increased lipid peroxidation products have been demonstrated in IPF lungs, suggesting the participation of imbalanced lipid peroxidation in IPF pathogenesis, which can be modulated by GPx4. In this study, we sought to examine the involvement of GPx4-modulated lipid peroxidation in regulating TGF-ß-induced myofibroblast differentiation. Bleomycin-induced lung fibrosis development in mouse models with genetic manipulation of GPx4 were examined. Immunohistochemical evaluations for GPx4 and lipid peroxidation were performed in IPF lung tissues. Immunohistochemical evaluations showed reduced GPx4 expression levels accompanied by increased 4-hydroxy-2-nonenal in fibroblastic focus in IPF lungs. TGF-ß-induced myofibroblast differentiation was enhanced by GPx4 knockdown with concomitantly enhanced lipid peroxidation and SMAD2/SMAD3 signaling. Heterozygous GPx4-deficient mice showed enhancement of bleomycin-induced lung fibrosis, which was attenuated in GPx4-transgenic mice in association with lipid peroxidation and SMAD signaling. Regulating lipid peroxidation by Trolox showed efficient attenuation of bleomycin-induced lung fibrosis development. These findings suggest that increased lipid peroxidation resulting from reduced GPx4 expression levels may be causally associated with lung fibrosis development through enhanced TGF-ß signaling linked to myofibroblast accumulation of fibroblastic focus formation during IPF pathogenesis. It is likely that regulating lipid peroxidation caused by reduced GPx4 can be a promising target for an antifibrotic modality of treatment for IPF.
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Fibrosis Pulmonar Idiopática/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Animales , Bleomicina , Diferenciación Celular , Células Cultivadas , Modelos Animales de Enfermedad , Humanos , Fibrosis Pulmonar Idiopática/inducido químicamente , Fibrosis Pulmonar Idiopática/patología , Peroxidación de Lípido , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Miofibroblastos/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/deficiencia , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
It has been known that repeat laparoscopic hepatectomy (RLH) after open hepatectomy is technically challenging because of adhesions around the hilum. It is quite often that conventional tourniquet technique for the Pringle maneuver is difficult in RLH, and we introduced Laparoscopic Satinsky Vascular Clamp (LSVC) for inflow control in RLH. The Spiegel lobe is the anatomical landmark in LSVC technique. If a space behind the hepatoduodenal ligament and the Spiegel lobe was obtained, LSVC was applied laterally from the left side of the hepatoduodenal ligament, whereas LSVC was vertically applied for those with obstruction of a space behind the hepatoduodenal ligament. We performed 14 cases of RLH for those with histories of open hepatectomies by lateral (n = 6) and vertical (n = 8) LSVC technique with successful inflow control, confirmed by intraoperative Doppler ultrasound. Five patients underwent 2 or more previous histories of hepatectomies. The RLH included segmentectomy (n = 1), subsegmentectomy (n = 2) and partial hepatectomy (n = 11). The median time for the Pringle maneuver, operative time, and blood loss was 47 min, 237.5 min, and 160 mL. All the patients completed pure laparoscopic hepatectomy. In conclusion, LSVC technique is a safe and reliable technique for the Pringle maneuver in RLH.
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Laparoscopía , Neoplasias Hepáticas , Hepatectomía , Humanos , Neoplasias Hepáticas/cirugía , Tempo OperativoRESUMEN
Glutathione peroxidase 4 (GPx4) is a unique antioxidant enzyme that directly reduces the phospholipid hydroperoxides (PLOOH) generated in biomembranes using glutathione as the reductant. We have previously reported that the Caenorhabditis elegans gpx-quad mutant, which lacks all homologous genes of GPx4 has a reduced lifespan compared with the wild-type. However, the mechanisms underlying the lifespan reduction remain unclear. By monitoring the change in PLOOH production with age, we found that PLOOH was elevated in the gpx-quad mutants compared with the wild-type during the reproductive period. Administration of vitamin E not only reduced the PLOOH content but also prolonged the lifespan of the gpx-quad mutants. In contrast, vitamin C did not extend the lifespan of the gpx-quad mutants. Interestingly, we found that the inhibition of lipid peroxidation by vitamin E during 5 to 10 days after hatching is important to extend the lifespan of C. elegans. These results suggest that production of PLOOH during the reproductive period strongly influences the lifespan of C. elegans.
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Superoxide dismutase (SOD) is a ubiquitous antioxidant enzyme that catalytically converts the superoxide radical to hydrogen peroxide (H2O2). In mammals, high SOD activity is detectable in sperm and seminal plasma, and loss of SOD activity has been correlated with male infertility; however, the underlying mechanisms of sperm infertility remain to be clarified. Here we report that the deletion of two major SOD genes in Caenorhabditis elegans, sod-1 and sod-2, causes sperm activation defects, leading to a significant reduction in brood size. By examining the reactivity to the sperm activation signals Pronase and triethanolamine, we found that sod-1;sod-2 double mutant sperm cells display defects in pseudopod extension. Neither the content nor oxidative modification of major sperm protein, an essential cytoskeletal component for crawling movement, were significantly affected in sod-1;sod-2 mutant sperm. Surprisingly, H2O2, the dismutation product of SOD, could activate sod-1;sod-2 mutant sperm treated with Pronase. Moreover, the H2O2 scavenger ebselen completely inhibited pseudopod extension in wild-type sperm treated with Pronase, and H2O2 could directly induce pseudopod extension in wild-type sperm. Analysis of Pronase-triggered sperm activation in sod-1 and sod-2 single mutants revealed that sod-2 is required for pseudopod extension. These results suggest that SOD-2 plays an important role in the sperm activation of C. elegans by producing H2O2 as an activator of pseudopod extension.
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Caenorhabditis elegans/citología , Caenorhabditis elegans/enzimología , Peróxido de Hidrógeno/metabolismo , Espermatozoides/metabolismo , Superóxido Dismutasa/metabolismo , Animales , Masculino , Superóxido Dismutasa/genéticaRESUMEN
Glutathione peroxidase 4 (Phospholipid hydroperoxide glutathione peroxidase, PHGPx) can directly reduce phospholipid hydroperoxide. Depletion of GPx4 induces lipid peroxidation-dependent cell death in embryo, testis, brain, liver, heart, and photoreceptor cells of mice. Administration of vitamin E in tissue specific GPx4 KO mice restored tissue damage in testis, liver, and heart. These results indicate that suppression of phospholipid peroxidation is essential for cell survival in normal tissues in mice. Ferroptosis is an iron-dependent non-apoptotic cell death that can elicited by pharmacological inhibiting the cystine/glutamate antiporter, system Xc- (type I) or directly binding and loss of activity of GPx4 (Type II) in cancer cells with high level RAS-RAF-MEK pathway activity or p53 expression, but not in normal cells. Ferroptosis by Erastin (Type I) and RSL3 (RAS-selective lethal 3, Type II) treatment was suppressed by an iron chelator, vitamin E and Ferrostatin-1, antioxidant compound. GPx4 can regulate ferroptosis by suppression of phospholipid peroxidation in erastin and RSL3-induced ferroptosis. Recent works have identified several regulatory factors of erastin and RSL3-induced ferroptosis. In our established GPx4-deficient MEF cells, depletion of GPx4 induce iron and 15LOX-independent lipid peroxidation at 26 h and caspase-independent cell death at 72 h, whereas erastin and RSL3 treatment resulted in iron-dependent ferroptosis by 12 h. These results indicated the possibility that the mechanism of GPx4-depleted cell death might be different from that of ferroptosis induced by erastin and RSL3.
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Muerte Celular/fisiología , Ciclohexilaminas/metabolismo , Glutatión Peroxidasa/metabolismo , Hierro/metabolismo , Peroxidación de Lípido/fisiología , Fenilendiaminas/metabolismo , Animales , Carbolinas/farmacología , Caspasas/metabolismo , Humanos , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Piperazinas/farmacologíaRESUMEN
BACKGROUND: Blood transfusion has been reported to be associated with immunomodulation and poor oncologic outcomes in several malignancies. The aim of the study is to investigate the influence of the use of fresh frozen plasma (FFP) on long-term outcomes in patients with colorectal liver metastases (CRLM) after hepatic resection. MATERIALS AND METHODS: The study comprised 127 patients who had undergone first hepatic resection for CRLM between April 2000 and December 2013. We retrospectively investigated the influence of the use of FFP on disease-free survival as well as overall survival and assessed the impact of such a practice on postoperative inflammation markers. RESULTS: In multivariate analysis, more than four lymph node metastases of the primary cancer (P = 0.001), bilobar distribution (P = 0.002), and perioperative FFP transfusion (P = 0.005) were independent risk factors for cancer recurrence, while more than four lymph node metastases of the primary cancer (P < 0.001), presence of neoadjuvant chemotherapy (P = 0.002), and perioperative FFP transfusion (P = 0.004) were independent risk factors for poor overall survival. In patients who underwent FFP transfusion, tumor size (P = 0.004), anatomic resection (P < 0.001), duration of operation (P = 0.039), and intraoperative blood loss (P < 0.001) were significantly greater. Moreover, FFP transfusion was associated with a higher white blood cell level on postoperative day 3 (P < 0.001) and day 5 (P = 0.010) and lower serum C-reactive protein level on postoperative day 1 (P < 0.001) and day 3 (P = 0.017). CONCLUSIONS: Perioperative FFP transfusion is independently associated with poor long-term outcomes in patients with CRLM after hepatic resection. FFP may have an influence on postoperative inflammation because of its immunosuppressive effects.
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Transfusión de Componentes Sanguíneos/métodos , Pérdida de Sangre Quirúrgica , Neoplasias Colorrectales/patología , Inflamación/diagnóstico , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Supervivencia sin Enfermedad , Femenino , Hepatectomía/efectos adversos , Humanos , Inflamación/sangre , Inflamación/etiología , Inflamación/inmunología , Hígado/cirugía , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Tempo Operativo , Periodo Perioperatorio , Plasma/inmunología , Estudios Retrospectivos , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
BACKGROUND: Duodenal adenocarcinoma (DA) is a rare disease, and the optimal extent of lymphadenectomy and the role of limited resection remain controversial. OBJECTIVE: The aim of our study was to assess the pattern of regional lymph node spread of DA and to determine the optimal extent of resection. METHODS: A total of 65 patients who underwent curative resection for DA at our institution from 1989 through 2015 were included in this study. Clinicopathologic factors associated with long-term outcomes and the patterns of regional node spread per primary tumor location were evaluated. RESULTS: Fifty-one patients (78%) underwent pancreaticoduodenectomy (PD), with the remainder undergoing limited resection. The median number of retrieved lymph nodes was 24 (range 1-63) and 48% of patients had regional node metastasis. The 5-year overall survival (OS) rate was 67%. In the multivariate analysis, regional node and para-aortic lymph node metastasis were risk factors associated with poorer OS (hazard ratio [HR] 12.1 [p = 0.025], and HR 3.2 [p = 0.045], respectively). While pancreaticoduodenal (#13) and superior mesenteric (#14) lymph node stations were commonly involved by both distal and proximal DA (33 vs. 39% for #13, p = 0.39; and 33 vs. 22% for #14, p = 0.27), the pyloric lymph node station was much less involved by distal DA than proximal DA (0 vs. 37%, p = 0.036). CONCLUSION: The pancreaticoduodenal lymph node station was the most commonly involved lymph node in DA, and PD should be the standard operation for DA. Segmental resection should only be reserved for patients with distal DA who are physically unfit for PD.
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Adenocarcinoma/mortalidad , Neoplasias Duodenales/mortalidad , Escisión del Ganglio Linfático/mortalidad , Ganglios Linfáticos/patología , Pancreaticoduodenectomía/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Neoplasias Duodenales/patología , Neoplasias Duodenales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Ganglios Linfáticos/cirugía , Metástasis Linfática , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
A 61-year-old man visited our hospital for treatment of a retroperitoneal tumor. The patient had undergone distal gastrectomy for gastric cancer in the past. At 5 years after distal gastrectomy, a retroperitoneal tumor with a large diameter of 30mm was detected by computed tomography and the patient underwent chemotherapy for suspected lymph node metastasis from gastric cancer at a local hospital. However, the retroperitoneal tumor gradually increased, and it was diagnosed finally as asymptomatic paraganglioma. The patient underwent tumor resection and made a satisfactory recovery. He was discharged 11 days after the surgery in a good general condition. Here, we report a case of successful resection of asymptomatic paraganglioma in a patient 5 years after distal gastrectomy for gastric cancer.
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Diagnóstico Diferencial , Paraganglioma/diagnóstico por imagen , Neoplasias Gástricas/diagnóstico por imagen , Gastrectomía , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Persona de Mediana Edad , Paraganglioma/cirugía , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the feasibility and efficacy of anatomical liver resection (ALR) guided by fused images comprising a macroscopic view and indocyanine green fluorescence imaging (fusion IGFI). BACKGROUND: ALR is established in treating hepatocellular carcinoma or other malignancies to achieve curability and functional preservation. However, the conventional demarcation technique (CDT) marks only the organ surface and sometimes fails to execute a completely valid demarcation. METHODS: Twenty-four consecutive ALRs for focal liver malignancy were studied using fusion IGFI. Indocyanine green was administered systemically after selective inflow clamping in 12 patients or by portal puncture and direct injection in 12 patients, and we compared demarcation findings between fusion IGFI and CDT. The strength of contrast between target and nontarget areas was quantitatively calculated as contrast index and compared between IGFI and CDT according to injection technique or state of the liver surface. RESULTS: Fusion IGFI achieved valid demarcation in 23 of 24 patients (95.8%), whereas CDT achieved valid demarcation in only 10 patients (41.7%) (P < 0.0001). The contrast index of fusion IGFI was 0.81 (0.18-2.51), which was significantly higher than that of CDT at 0.12 (0.01-0.42) (P < 0.0001), and the same result was obtained regardless of the injection method or liver surface state used. ALR was conducted referring to 3-dimensional staining of target parenchyma, with no related perioperative adverse events. CONCLUSIONS: Fusion IGFI is a safe imaging technique for ALR that attained valid 3-dimensional parenchymal demarcation with better feasibility and clearer demarcation than CDT.
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Angiografía con Fluoresceína/métodos , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Hígado/diagnóstico por imagen , Estudios de Factibilidad , Colorantes Fluorescentes/administración & dosificación , Humanos , Imagenología Tridimensional , Verde de Indocianina/administración & dosificación , Hígado/anatomía & histología , Hígado/cirugía , Neoplasias Hepáticas/diagnóstico , Radiografía , Coloración y Etiquetado , Resultado del TratamientoRESUMEN
The glutathione peroxidase (GPx) family is a major antioxidant enzyme family that catalyzes the reduction of a variety of hydroperoxides. GPxs are divided into selenium- and nonselenium-containing GPxs. Because of their efficient antioxidant activity, which depends on the presence of the amino acid residue selenocysteine, selenium-containing GPxs have been the subject of many studies. However, the physiological roles of the nonselenium GPxs remain unclear. Here, we report that the deletion of phospholipid hydroperoxide glutathione peroxidase (PHGPx) homologues causes accelerated aging that leads to a shortened lifespan in Caenorhabditis elegans. PHGPx is an antioxidant enzyme that directly reduces the phospholipid hydroperoxides generated in biomembranes. The quadruple phgpx mutant gpx-1; gpx-2; gpx-6; gpx-7 developed normally, reached adulthood and reproduced as well as the wild type. However, a lifespan analysis showed that the quadruple phgpx mutant had a short maximum lifespan, with an age-related increase in its mortality rate. The intestine is the primary tissue expressing gpx-1, gpx-2, gpx-6 and gpx-7 in C. elegans, and the expression of gpx-6 is greatly enhanced under starvation conditions. These results suggest that the C. elegans PHGPx homologues have important functions in the regulation of aging, probably by reducing oxidative damage in the intestine.
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Caenorhabditis elegans/fisiología , Eliminación de Gen , Glutatión Peroxidasa/genética , Envejecimiento/genética , Envejecimiento/metabolismo , Animales , Animales Modificados Genéticamente , Caenorhabditis elegans/genética , Glutatión Peroxidasa/metabolismo , Mucosa Intestinal/metabolismo , Oxidación-Reducción , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Fosfolípidos/metabolismo , Inanición/metabolismoRESUMEN
Growing evidence indicates that the intake of trans fatty acids (TFAs) increases the risk of numerous diseases, such as cardiovascular diseases. Recently, our group found that certain natural sulfur compounds (allyl isothiocyanate [AITC] and diallyl disulfide [DADS]) promote cis to trans isomerization of fatty acid esters during heat treatment. However, little information is available on the fatty acid isomerization with them. In this study, we investigated the effects of oxygen and α-tocopherol (antioxidant) on isomerization of oleic acid (18:1) methyl ester (OA-ME) in the presence of AITC and DADS. Furthermore, the effect of the simultaneous use of AITC and DADS was evaluated. Our results indicate that oxygen enhances the AITC-induced trans isomerization, and DADS was found to promote trans isomerization but inhibit AITC-induced trans isomerization during heating. Both AITC- and DADS-induced trans isomerization were inhibited by α-tocopherol. These results indicate that the trans isomerization of fatty acids induced by sulfur compounds can be controlled by devising a cooking process and the food ingredients used together.
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Disulfuros , Isotiocianatos , Ácidos Oléicos , alfa-Tocoferol , Isomerismo , alfa-Tocoferol/química , Disulfuros/química , Ácidos Oléicos/química , Isotiocianatos/química , Compuestos Alílicos/química , Oxígeno/química , Antioxidantes/química , Calor , Compuestos de Azufre/química , Culinaria , Ácido Oléico/química , Ácidos Grasos trans/química , Ésteres/química , Estereoisomerismo , Cisteína/análogos & derivadosRESUMEN
BACKGROUND/AIM: With the aging of the population, there is a rising proportion of elderly patients undergoing liver resection. However, the safety and efficacy of laparoscopic liver resection (LLR) in the elderly have not yet been established. In this study, we compared the short-term results of LLR and open liver resection (OLR) in elderly patients using propensity score matched (PSM) analysis. PATIENTS AND METHODS: The study comprised 237 elderly patients aged 65 years and older who had undergone liver resection between 2015 to 2021, excluding biliary and vascular reconstruction and simultaneous surgeries other than liver resection. We conducted PSM analysis for baseline characteristics (age, sex, BMI, ASA-PS, disease, procedure, tumor size, and number of tumors) to eliminate potential selection bias. We then compared short-term postoperative outcomes between LLR and OLR groups in patients selected by PSM analysis. RESULTS: Applying PSM analysis, 90 cases each were selected for the LLR and OLR groups. The LLR group had a significantly lower complication rate (Clavien-Dindo: CD ≥II) (19% vs. 33%, p=0.03), especially bile leakage (CD ≥II) (0% vs. 6.7%, p=0.03) compared with those in the OLR group. In addition, a shorter operation time (244 min vs. 351 min, p<0.01), less blood loss (150 ml vs. 335 ml, p<0.01), and shorter hospital stay (8 days vs. 12 days, p<0.01) were observed in the LLR group. No operative or in-hospital deaths were observed in both groups. CONCLUSION: LLR can be safely performed in elderly patients and offers better short-term outcomes.
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Hepatectomía , Laparoscopía , Neoplasias Hepáticas , Complicaciones Posoperatorias , Puntaje de Propensión , Humanos , Femenino , Masculino , Laparoscopía/métodos , Laparoscopía/efectos adversos , Anciano , Hepatectomía/métodos , Hepatectomía/efectos adversos , Hepatectomía/mortalidad , Resultado del Tratamiento , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Anciano de 80 o más Años , Tempo Operativo , Tiempo de Internación , Estudios RetrospectivosRESUMEN
OBJECTIVES: Signal intensity ratio of pancreas to spleen (SI ratio p/s ) on fat-suppressed T1-weighted images of magnetic resonance imaging has been associated with pancreatic exocrine function. We here investigated the predictive value of the SI ratio p/s for the development of nonalcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD). MATERIALS AND METHODS: This study comprised 208 patients who underwent PD. NAFLD was defined as a liver-to-spleen attenuation ratio of <0.9 calculated by a computed tomography 1 year after surgery. SI ratio p/s was calculated by dividing the average pancreas SI by the spleen SI. We retrospectively investigated the association of clinical variables including the SI ratio p/s and NAFLD by univariate and multivariate analyses. RESULTS: NAFLD after 1 year was developed in 27 patients (13%). In multivariate analysis, the SI ratio p/s < 1 ( P < 0.001) was an independent predictor of incidence of NAFLD. The SI ratio p/s < 1 was associated with low amylase level of the pancreatic juice ( P < 0.001) and progressed pancreatic fibrosis ( P = 0.017). According to the receiver operating characteristics curve, the SI ratio p/s had better prognostic ability of NAFLD than the remnant pancreas volume. CONCLUSIONS: The SI ratio p/s is useful to predict NAFLD development after PD. Moreover, the SI ratio p/s can be a surrogate marker, which represents exocrine function of the pancreas.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Pancreaticoduodenectomía/efectos adversos , Bazo/diagnóstico por imagen , Estudios Retrospectivos , Páncreas/diagnóstico por imagen , Páncreas/cirugía , Páncreas/patología , Imagen por Resonancia Magnética/métodos , Factores de RiesgoRESUMEN
AIM: Pancreatic ductal adenocarcinoma treatment is mainly based on the anatomical resectability classification. However, prognosis-based classification may be more reasonable. In this study, we stratified resectable pancreatic ductal adenocarcinoma according to preoperative factors and reconsidered treatment strategies. METHODS: We retrospectively evaluated 131 patients who underwent upfront surgery for resectable pancreatic ductal adenocarcinoma between 2007 and 2019. Recurrence within 1 year after surgery was defined as early recurrence, and the risk factors for early recurrence were identified using preoperative factors. Subsequently, we calculated the scores and stratified the participant groups. RESULTS: Fifty-five (42 %) patients who relapsed within 1 year showed significantly poorer survival than those without recurrence (median overall survival, 14.0 vs. 80.6 months; p < 0.01). Multivariate analysis revealed that a tumor diameter of ≥24 mm (p < 0.01) and preoperative serum carbohydrate antigen 19-9 level of ≥380 U/mL (p = 0.04) were the independent risk factors for early recurrence. Early recurrence score was created using these factors, stratifying the participant group into three groups of 0-2 points, and the prognosis was significantly different (median overall survival, 49.3 vs. 31.2 vs. 16.0 months; p < 0.01). CONCLUSION: We stratified the upfront surgical cases of resectable pancreatic ductal adenocarcinoma. The group with a score of 0 had a good prognosis, and upfront surgery was possibly not futile on patients in poor general condition. The group with a score of 2 had a poor prognosis and may require stronger preoperative treatment.