RESUMEN
OBJECTIVE: This study aimed to compare the short-term outcomes between laparoscopic and open distal pancreatectomy for lesions of the distal pancreas from a real-world database. BACKGROUND: Reports on the benefits of laparoscopic distal pancreatectomy include 2 randomized controlled trials; however, large-scale, real-world data are scarce. METHODS: We analyzed the data of patients undergoing laparoscopic or open distal pancreatectomy for benign or malignant pancreatic tumors from April 2008 to May 2020 from a Japanese nationwide inpatient database. We performed propensity score analyses to compare the inhospital mortality, morbidity, readmission rate, reoperation rate, length of postoperative stay, and medical cost between the 2 groups. RESULTS: From 5502 eligible patients, we created a pseudopopulation of patients undergoing laparoscopic and open distal pancreatectomy using inverse probability of treatment weighting. Laparoscopic distal pancreatectomy was associated with lower inhospital mortality during the period of admission (0.0% vs 0.7%, P <0.001) and within 30 days (0.0% vs 0.2%, P =0.001), incidence of reoperation during the period of admission (0.7% vs 1.7%, P =0.018), postpancreatectomy hemorrhage (0.4% vs 2.0%, P <0.001), ileus (1.1% vs 2.8%, P =0.007), and shorter postoperative length of stay (17 vs 20 d, P <0.001). CONCLUSIONS: The propensity score analysis revealed that laparoscopic distal pancreatectomy was associated with better outcomes than open surgery in terms of inhospital mortality, reoperation rate, postoperative length of stay, and incidence of postoperative complications such as postpancreatectomy hemorrhage and ileus.
Asunto(s)
Ileus , Obstrucción Intestinal , Laparoscopía , Neoplasias Pancreáticas , Humanos , Estudios Retrospectivos , Pancreatectomía , Puntaje de Propensión , Resultado del Tratamiento , Tiempo de Internación , Obstrucción Intestinal/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/cirugíaRESUMEN
BACKGROUND: The National Kidney Foundation recently proposed a ≥ 30% decrease in urinary albumin-to-creatinine ratio (UACR) over 0.5-2 years as a surrogate endpoint for chronic kidney disease (CKD) progression in individuals with baseline UACR > 30 mg/g. This historical cohort study aimed to determine the applicability of a decrease in UACR, within as little as 1 year, as a surrogate endpoint for Japanese individuals with type 2 diabetes mellitus (T2D). METHODS: A total of 5067 individuals with T2D were divided into three groups based on 1-year change in UACR: ≥ 30% decrease (UACR decreased group), < 30% decrease and < 30% increase (UACR unchanged group), or ≥ 30% increase (UACR increased group). The primary endpoint was a composite of a ≥ 30% decline in estimated glomerular filtration rate (eGFR) or the initiation of kidney replacement therapy, whichever occurred first. RESULTS: At baseline, the proportions of individuals with normoalbuminuria, microalbuminuria, and eGFR ≥ 60 mL/min/1.73 m2 were 68.1%, 22.1%, and 75.5%, respectively. During a median follow-up of 6.8 years, 926 individuals (18.3%) reached the composite endpoint. Adjusted hazard ratios (vs. the UACR unchanged group) for the UACR decreased and increased groups were 0.758 (95% confidence interval [CI], 0.636-0.905; P = 0.002) and 1.304 (95% CI, 1.108-1.536; P = 0.001), respectively. CONCLUSIONS: These findings support the use of 1-year changes in UACR as a surrogate endpoint for the progression of CKD and the implementation of a ≥ 30% decrease in UACR as a positive efficacy endpoint in Japanese individuals with T2D and early-stage kidney disease.
Asunto(s)
Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/orina , Creatinina/orina , Estudios de Cohortes , Pueblos del Este de Asia , Riñón , Insuficiencia Renal Crónica/diagnóstico , Tasa de Filtración Glomerular , Biomarcadores , Progresión de la Enfermedad , Albúminas , AlbuminuriaRESUMEN
BACKGROUND: The number of overweight gastric cancer patients who are undergoing laparoscopic gastrectomy (LG) has increased in Japan. However, the relationship between obesity and surgical outcomes of LG remains unclear. Therefore, this study aimed to evaluate the effect of visceral fat area (VFA) on surgical outcomes of LG for gastric cancer compared to the body mass index (BMI). METHODS: This study was a retrospective, cohort study that included 587 patients who underwent LG in our institution between January 2015 and December 2019. The patients were divided into two groups according to VFA (< 100 cm2 and ≥ 100 cm2) and BMI (< 25 kg/m2 and ≥ 25 kg/m2) values, respectively. Surgical outcomes and postoperative complications were compared between the low and high groups for each VFA and BMI value. Propensity score matching was used to minimize potential selection bias. RESULTS: After propensity score matching, 144 pairs of patients in the VFA group and 82 pairs of patients in the BMI group were extracted. Operative time (p = 0.003), intraoperative blood loss (p = 0.0006), and CRP levels on postoperative day 1 (p = 0.002) and on postoperative day 3 (p = 0.004) were significantly higher in the high-VFA group than in the low-VFA group. However, these surgical outcomes were not significantly different between the high-BMI and low-BMI groups. There was no strong correlation between VFA and BMI (R2 = 0.64). There were no significant differences in postoperative complications between the high and low groups for both VFA and BMI values. On multivariate analysis, high VFA was an independent predictor of operative time, but it was not significantly associated with the incidence of postoperative complications. CONCLUSION: VFA is a better indicator of longer operative time than BMI. However, increased VFA did not affect postoperative complications.
Asunto(s)
Laparoscopía , Neoplasias Gástricas , Índice de Masa Corporal , Estudios de Cohortes , Gastrectomía/efectos adversos , Humanos , Grasa Intraabdominal , Laparoscopía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Puntaje de Propensión , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/cirugía , Resultado del TratamientoRESUMEN
PURPOSE: The efficacy of pre or postoperative chemotherapy for resectable colorectal cancer liver metastases (CRLM) is disputed. This study aimed to examine the risk factors for time to surgical failure (TSF) and analyze the efficacy of pre or postoperative chemotherapy prior to liver resection for CRLM. METHODS: The clinicopathological factors of 567 patients who underwent initial hepatectomy for CRLM at 7 university hospitals between April 2007 and March 2013 were retrospectively analyzed. The prognostic factors were identified and then stratified into two groups according to the number of preoperative prognostic factors: the high-score group (H-group, score 2-4) and the low-score group (L-group, score 0 or 1). RESULTS: Patients who experienced unresectable recurrence within 12 months after initial treatment had a significantly shorter prognosis than other patients (p < 0.001). Multivariate analysis identified age ≥ 70 (p = 0.001), pT4 (p = 0.015), pN1 (p < 0.001), carbohydrate antigen 19-9 ≥ 37 U/ml (p = 0.002), Clavien-Dindo grade ≥ IIIa (p = 0.013), and postoperative chemotherapy (p = 0.006) as independent prognostic factors. In the H-group, patients who received chemotherapy had a better prognosis than those who did not (p = 0.001). CONCLUSION: Postoperative chemotherapy is beneficial in colorectal cancer patients with more than two of the following factors: age ≥ 70, carbohydrate antigen 19-9-positivity, pT4, and lymph node metastasis.
Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Quimioterapia Adyuvante , Neoplasias Colorrectales/patología , Hepatectomía , Humanos , Neoplasias Hepáticas/secundario , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: This retrospective study aimed to compare long-term oncological outcomes between laparoscopic-assisted colectomy (LAC) with extracorporeal anastomosis (EA) and totally laparoscopic colectomy (TLC) with intracorporeal anastomosis (IA) for colon cancers, including right- and left-sided colon cancers. METHODS: Patients with stage I-III colon cancers who underwent elective laparoscopic colectomy between January 2013 and December 2017 were analyzed retrospectively. Patients converted from laparoscopic to open surgery and R1/R2 resection were excluded. Propensity score matching (PSM) analysis (1:1) was performed to overcome patient selection bias. RESULTS: A total of 388 patients were reviewed. After PSM, 83 patients in the EA group and 83 patients in the IA group were compared. Median follow-up was 56.5 months in the EA group and 55.5 months in the IA group. Estimated 3-year overall survival (OS) did not differ significantly between the EA group (86.6%; 95% confidence interval (CI), 77.4-92.4%) and IA group (84.8%; 95%CI, 75.0-91.1%; P = 0.68). Estimated 3-year disease-free survival (DFS) likewise did not differ significantly between the EA group (76.4%; 95%CI, 65.9-84.4%) and IA group (81.0%; 95%CI, 70.1-88.2%; P = 0.12). CONCLUSION: TLC with IA was comparable to LAC with EA in terms of 3-year OS and DFS. TLC with IA thus appears to offer an oncologically feasible procedure.
Asunto(s)
Neoplasias del Colon , Laparoscopía , Anastomosis Quirúrgica/métodos , Colectomía/métodos , Neoplasias del Colon/cirugía , Humanos , Laparoscopía/métodos , Puntaje de Propensión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Non-alcoholic steatohepatitis (NASH) has pathological characteristics similar to those of alcoholic hepatitis, despite the absence of a drinking history. The greatest threat associated with NASH is its progression to cirrhosis and hepatocellular carcinoma. The pathophysiology of NASH is not fully understood to date. In this study, we investigated the pathophysiology of NASH from the perspective of glycolysis and the Warburg effect, with a particular focus on microRNA regulation in liver-specific macrophages, also known as Kupffer cells. We established NASH rat and mouse models and evaluated various parameters including the liver-to-body weight ratio, blood indexes, and histopathology. A quantitative phosphoproteomic analysis of the NASH rat model livers revealed the activation of glycolysis. Western blotting and immunohistochemistry results indicated that the expression of pyruvate kinase muscle 2 (PKM2), a rate-limiting enzyme of glycolysis, was upregulated in the liver tissues of both NASH models. Moreover, increases in PKM2 and p-PKM2 were observed in the early phase of NASH. These observations were partially induced by the downregulation of microRNA122-5p (miR-122-5p) and occurred particularly in the Kupffer cells. Our results suggest that the activation of glycolysis in Kupffer cells during NASH was partially induced by the upregulation of PKM2 via miR-122-5p suppression.
Asunto(s)
Neoplasias Hepáticas , MicroARNs , Enfermedad del Hígado Graso no Alcohólico , Piruvato Quinasa/metabolismo , Animales , Modelos Animales de Enfermedad , Regulación hacia Abajo , Glucólisis , Macrófagos del Hígado/metabolismo , Neoplasias Hepáticas/metabolismo , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Músculos/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Piruvato Quinasa/genética , RatasRESUMEN
Commercially available laparoscopic instruments are not designed for female surgeons. We redesigned the endoscopic flexible head purse-string suture instrument for improved use by female surgeons. The weight, total length, and diameter of the swing head handle and clump handle were reduced (786 to 565 g, 715 to 700 mm, 70 to 50 mm, and 30 to 25 mm, respectively). Stroke of the slide for firing and release of the lever was reduced from 92 to 83 mm. This is the first step toward an ergonomic surgical device that considers physical differences related to sex.
Asunto(s)
Laparoscopía , Cirujanos , Femenino , Humanos , Técnicas de Sutura , SuturasRESUMEN
In humans, mutations in genes encoding homologs of the DNA mismatch repair endonuclease MutL cause a hereditary cancer that is known as Lynch syndrome. Here, we determined the crystal structures of the N-terminal domain (NTD) of MutL from the thermophilic eubacterium Aquifex aeolicus (aqMutL) complexed with ATP analogs at 1.69-1.73 Å. The structures revealed significant structural similarities to those of a human MutL homolog, postmeiotic segregation increased 2 (PMS2). We introduced five Lynch syndrome-associated mutations clinically found in human PMS2 into the aqMutL NTD and investigated the protein stability, ATPase activity, and DNA-binding ability of these protein variants. Among the mutations studied, the most unexpected results were obtained for the residue Ser34. Ser34 (Ser46 in PMS2) is located at a previously identified Bergerat ATP-binding fold. We found that the S34I aqMutL NTD retains ATPase and DNA-binding activities. Interestingly, CD spectrometry and trypsin-limited proteolysis indicated the disruption of a secondary structure element of the S34I NTD, destabilizing the overall structure of the aqMutL NTD. In agreement with this, the recombinant human PMS2 S46I NTD was easily digested in the host Escherichia coli cells. Moreover, other mutations resulted in reduced DNA-binding or ATPase activity. In summary, using the thermostable aqMutL protein as a model molecule, we have experimentally determined the effects of the mutations on MutL endonuclease; we discuss the pathological effects of the corresponding mutations in human PMS2.
Asunto(s)
Proteínas Bacterianas/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Proteínas MutL/genética , Mutación , Adenosina Trifosfato/metabolismo , Secuencia de Aminoácidos , Aquifex/química , Aquifex/genética , Proteínas Bacterianas/química , Sitios de Unión , Cristalografía por Rayos X , Reparación de la Incompatibilidad de ADN , Humanos , Modelos Moleculares , Proteínas MutL/química , Conformación Proteica , Dominios ProteicosRESUMEN
Understanding of the microRNAs (miRNAs) regulatory system has become indispensable for physiological/oncological research. Tissue and organ specificities are key features of miRNAs that should be accounted for in cancer research. Further, cancer-specific energy metabolism, referred to as the Warburg effect, has been positioned as a key cancer feature. Enhancement of the glycolysis pathway in cancer cells is what primarily characterizes the Warburg effect. Pyruvate kinase M1/2 (PKM1/2) are key molecules of the complex glycolytic system; their distribution is organ-specific. In fact, PKM2 overexpression has been detected in various cancer cells. PKM isoforms are generated by alternative splicing by heterogeneous nuclear ribonucleoproteins. In addition, polypyrimidine tract-binding protein 1 (PTBP1) is essential for the production of PKM2 in cancer cells. Recently, several studies focusing on non-coding RNA elucidated PTBP1 or PKM2 regulatory mechanisms, including control by miRNAs, and their association with cancer. In this review, we discuss the strong relationship between the organ-specific distribution of miRNAs and the expression of PKM in the context of PTBP1 gene regulation. Moreover, we focus on the impact of PTBP1-targeting miRNA dysregulation on the Warburg effect.
Asunto(s)
Empalme Alternativo/genética , Proteínas Portadoras/genética , Metabolismo Energético/genética , Proteínas de la Membrana/genética , MicroARNs/genética , Proteína de Unión al Tracto de Polipirimidina/genética , Hormonas Tiroideas/genética , Redes Reguladoras de Genes/genética , Humanos , Piruvato Quinasa/genética , Proteínas de Unión a Hormona TiroideRESUMEN
Delta-like canonical Notch ligand 3 (DLL3) is a member of the Delta/Serrate/Lag2 (DSL) Notch receptor ligand family and plays a crucial role in Notch signaling, which influences various cellular processes including differentiation, proliferation, survival, and apoptosis. DLL3 is expressed throughout the presomitic mesoderm and is localized to the rostral somatic compartments; mutations in DLL3 induce skeletal abnormalities such as spondylocostal dysostosis. Recently, DLL3 has attracted interest as a novel molecular target due to its high expression in neuroendocrine carcinoma of the lung. Moreover, a DLL3-targeting Ab-drug conjugate, rovalpituzumab tesirine (ROVA-T), has been developed as a new treatment with proven antitumor activity. However, the development of ROVA-T was suspended because of shorter overall survival compared to topotecan, the second-line standard treatment. Thus, several studies on the mechanism and function of DLL3 in several malignancies are underway to find a new strategy for targeting DLL3. In this review, we discuss the roles of DLL3 in various malignancies and the future perspectives of DLL3-related research, especially as a therapeutic target.
Asunto(s)
Antineoplásicos/farmacología , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas de la Membrana/genética , Neoplasias/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Benzodiazepinonas/farmacología , Benzodiazepinonas/uso terapéutico , Ensayos Clínicos como Asunto , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Inmunoconjugados/farmacología , Inmunoconjugados/uso terapéutico , Péptidos y Proteínas de Señalización Intracelular/efectos de los fármacos , Masculino , Proteínas de la Membrana/efectos de los fármacos , Terapia Molecular Dirigida , Mutación , Neoplasias/genéticaRESUMEN
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 RetrospectivosRESUMEN
BACKGROUND: The short- and long-term efficacy of laparoscopic surgery for elderly patients with gastric cancer has not been evaluated. We aimed to use propensity score matching to clarify the efficacy of laparoscopic gastrectomy (LG) for elderly patients with gastric cancer aged ≥80 years. METHODS: We retrospectively collected data from 159 consecutive patients with gastric cancer aged ≥80 years who underwent gastrectomy with curative intent at our institution between 2004 and 2015. Propensity score matching was applied to compare the open gastrectomy (OG) and LG. Short- and long-term outcomes were evaluated between the propensity-matched groups. RESULTS: Patients' backgrounds and surgical factors were similar in both groups except for blood loss. The median time to first flatus was significantly shorter in the LG group than in the OG group (P = 0.002). The postoperative hospital stay was significantly shorter in the LG group (P = 0.014). The complication rate of Clavien-Dindo grade III or higher was significantly lower in the LG group (3% vs. 23%, P = 0.023). The 5-year overall survival and 5-year disease-specific survival rates were better in the LG group than in the OG group, but the differences were not significant (45% vs. 42% and 67% vs 57%, respectively). CONCLUSION: LG was associated with good short-term outcomes and acceptable oncologic outcomes compared with OG in these propensity-matched patients aged ≥80 years.
Asunto(s)
Laparoscopía , Neoplasias Gástricas , Anciano , Gastrectomía , Humanos , Puntaje de Propensión , Estudios Retrospectivos , Neoplasias Gástricas/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: The incidence of remnant gastric cancer (RGC) after distal gastrectomy is 1-5%. However, as the survival rate of patients with gastric cancer improves due to early detection and treatment, more patients may develop RGC. There is no consensus on the surgical and postoperative management of RGC, and the clinicopathological characteristics correlated with the long-term outcomes remain unclear. Therefore, we investigated the clinicopathological factors associated with the long-term outcomes of RGC. METHODS: We included 65 consecutive patients who underwent gastrectomy for RGC from January 2000 to December 2015 at the Osaka Medical and Pharmaceutical University Hospital, Japan. The Kaplan-Meier method was used to create survival curves, and differences in survival were compared between the groups (clinical factors, pathological factors, and surgical factors) using the log-rank test. Multivariate analyses using the Cox proportional hazard model were used to identify factors associated with long-term survival. RESULTS: No significant differences were noted in the survival rate based on clinical factors (age, body mass index, diabetes mellitus, hypertension, cardiovascular disease, pulmonary complications, liver disease, diet, history of alcohol drinking, and history of smoking) or the type of remnant gastrectomy. Significant differences were noted in the survival rate based on pathological factors and surgical characteristics (intraoperative blood loss, operation time, and the number of positive lymph nodes). Multivariate analysis revealed that the T stage (hazard ratio, 5.593; 95% confidence interval [CI], 1.183-26.452; p = 0.030) and venous invasion (hazard ratio, 3.351; 95% CI, 1.030-10.903; p = 0.045) were significant independent risk factors for long-term survival in patients who underwent radical resection for RGC. CONCLUSIONS: T stage and venous invasion are important prognostic factors of long-term survival after remnant gastrectomy for RGC and may be keys to managing and identifying therapeutic strategies for improving prognosis in RGC.
Asunto(s)
Muñón Gástrico , Neoplasias Gástricas , Estudios de Cohortes , Gastrectomía , Muñón Gástrico/patología , Humanos , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugíaRESUMEN
Good short-term outcomes of intracorporeal ileocolic anastomosis (IIA) in totally laparoscopic colectomy for right-sided colon cancer (TLRC) have been shown in many reports, but no standardized technique for enterotomy closure after stapled side-to-side ileocolic anastomosis has so far been established. We retrospectively compared the short-term outcomes between 13 consecutive patients receiving either TLRC with IIA by conventional enterotomy closure (n = 6) or closure of the enterotomy using two barbed sutures (CEBAS) (n = 7) from July 2019 to April 2020. No anastomotic bleeding or leakage was observed in either group. Time to enterotomy closure was significantly shorter with the CEBAS method (16.5 ± 3.7 min) than with the conventional method (24.5 ± 4.7 min, p = 0.0059). The CEBAS method in TLRC with IIA was thus found to be technically feasible and it might reduce the stress associated with intracorporeal enterotomy closure.
Asunto(s)
Anastomosis Quirúrgica/métodos , Colectomía/métodos , Colon/cirugía , Neoplasias del Colon/cirugía , Enterostomía , Íleon/cirugía , Laparoscopía/métodos , Suturas , Técnicas de Cierre de Heridas , Anciano , Anciano de 80 o más Años , Animales , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
MicroRNAs (miRNAs) are small RNAs present in extracellular vesicles (EVs) that, when transferred to a target cell, affect its biological functions. Plant miRNAs regulate the expression of certain mammalian genes. Here, we characterized EVs in fruit and vegetable juice, and their miRNA cargo, and investigated whether such miRNA-containing EVs could be taken up by mammalian enterocytes in vitro. Using filtration and ultra-centrifugation methods, EVs were purified from commercially available and manually squeezed plant juice. EV morphological features and subcellular localization were analyzed using the NanoSight tracking system and electron microscopy. Plant EV miRNA levels were evaluated using quantitative reverse transcription PCR. For the in vitro EV uptake experiments, rat intestinal epithelial cells (IEC6) were used. Plant EVs shared morphological features with mammalian EVs and contained miR156a-5p, miR166a-3p, and miR168a-5p. EVs were present in the cell sap-filled central vacuoles and were taken up by IEC6 cells. Edible plant cells produce EVs that contain various miRNAs and release them into the central vacuole. The exogenous plant EVs are taken up by mammalian enterocytes in vitro. These findings suggest the possibility that exogenous plant miRNAs carried by EVs can be absorbed via the gastrointestinal tract.
Asunto(s)
Enterocitos/metabolismo , Exosomas/química , Jugos de Frutas y Vegetales , MicroARNs , Nanopartículas , Animales , Línea Celular , Enterocitos/citología , MicroARNs/farmacocinética , MicroARNs/farmacología , Nanopartículas/química , Nanopartículas/uso terapéutico , RatasRESUMEN
Acute pancreatitis is still a life-threatening disease without an evidenced therapeutic agent. In this study, the effect of chymase in acute pancreatitis and the possible effect of a chymase inhibitor in acute pancreatitis were investigated. Hamsters were subcutaneously administered 3.0 g/kg of L-arginine to induce acute pancreatitis. Biological markers were measured 1, 2, and 8 h after L-arginine administration. To investigate the effect of a chymase inhibitor, a placebo (saline) or a chymase inhibitor TY-51469 (30 mg/kg) was given 1 h after L-arginine administration. The survival rates were evaluated for 24 h after L-arginine administration. Significant increases in serum lipase levels and pancreatic neutrophil numbers were observed at 1 and 2 h after L-arginine administration, respectively. Significant increases in pancreatic neutrophil numbers were observed in the placebo-treated group, but they were significantly reduced in the TY-51469-treated group. A significant increase in the pancreatic tumor necrosis factor-α mRNA level was observed in the placebo-treated group, but it disappeared in the TY-51469-treated group. Chymase activity significantly increased in the placebo-treated group, but it was significantly reduced by treatment with TY-51469. The survival rate significantly improved in the TY-51469-treated group. A chymase inhibitor may become a novel therapeutic agent for acute pancreatitis.
Asunto(s)
Quimasas/antagonistas & inhibidores , Quimasas/metabolismo , Pancreatitis/tratamiento farmacológico , Pancreatitis/mortalidad , Sulfonamidas/administración & dosificación , Tiofenos/administración & dosificación , Animales , Arginina/efectos adversos , Cricetinae , Modelos Animales de Enfermedad , Recuento de Leucocitos , Lipasa/sangre , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Neutrófilos/metabolismo , Pancreatitis/sangre , Pancreatitis/inducido químicamente , ARN Mensajero/genética , Transducción de Señal/efectos de los fármacos , Tasa de Supervivencia , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
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 TratamientoRESUMEN
BACKGROUND: Neoadjuvant chemotherapy for advanced gastric cancer is expected to improve prognoses. However, as there is no method to evaluate neoadjuvant chemotherapeutic efficacy before gastrectomy, some patients at high risk for a poor prognosis undergo gastrectomy. The aim of the present study was to investigate whether endoscopy could be useful for assessing the efficacy of neoadjuvant chemotherapy. METHODS: In this retrospective study, we analyzed the data of 41 patients who received neoadjuvant chemotherapy followed by gastrectomy at our institution to investigate whether responsiveness to neoadjuvant chemotherapy, as assessed with endoscopy, can serve as a surrogate marker for histological grades 1b or higher in the Japanese Classification of Gastric Carcinoma (JCGC) scheme. RESULTS: There were 32 (78.0%) responders and 9 (22.0%) nonresponders to neoadjuvant chemotherapy, as observed in endoscopic evaluations. Among the endoscopic responders, 24 (75.0%) had cancer of histological grade 1b or higher, and 15 (46.9%) had cancer of grade 2 or higher. Among the endoscopic nonresponders, 1 (11.1%) patient had histological grade 1b cancer. Compared with endoscopic nonresponders, endoscopic responders were more likely to show a histological response (chi-square test: p = 0.0005 for JCGC grade 1b or higher; p = 0.0099 for JCGC grade 2 or higher). CONCLUSIONS: Most endoscopic responders showed JCGC histological responses. Evaluation of neoadjuvant chemotherapeutic efficacy by endoscopy in gastric cancer may be useful before gastrectomy. As this was a retrospective study, further investigations are required. The protocol was approved by the ethics review committee at Osaka Medical College (No. 2422) and was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN000033088).
Asunto(s)
Quimioterapia Adyuvante/métodos , Monitoreo de Drogas/métodos , Endoscopía/métodos , Gastrectomía , Cuidados Preoperatorios/métodos , Neoplasias Gástricas/terapia , Adulto , Anciano , Antineoplásicos/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Estudios Retrospectivos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Total mesorectal excision (TME) has decreased the local recurrence rate and improved the overall survival of rectal cancer patients. However, urinary dysfunction remains a clinical problem after rectal cancer surgery. The aim was to assess the risk factors for postoperative urinary dysfunction. METHODS: This study was a single-center, retrospective analysis of 104 patients who underwent laparoscopic rectal surgery between November 2016 and October 2017. Postoperative urinary dysfunction was defined as the need for urinary catheter re-insertion or the presence of residual urine (≥ 150 mL) postoperatively. RESULTS: Postoperative urinary dysfunction was seen in 18 patients (17%). Multivariate analysis showed that male sex (odds ratio 3.89, p = 0.034) and anterior wall tumor location (odds ratio = 4.07, p = 0.037) were the predictors of postoperative urinary dysfunction. Compared with patients without risk factors, those with the two risk factors needed longer hospital stays (16 days vs. 30 days, p = 0.0022). CONCLUSION: Male sex and anterior wall tumor location were the risk factors for urinary dysfunction after laparoscopic rectal surgery.
Asunto(s)
Laparoscopía , Complicaciones Posoperatorias/epidemiología , Recto/cirugía , Trastornos Urinarios/epidemiología , Femenino , Humanos , Laparoscopía/efectos adversos , Laparoscopía/estadística & datos numéricos , Masculino , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Factores de Riesgo , Cateterismo Urinario/estadística & datos numéricos , Trastornos Urinarios/etiologíaRESUMEN
BACKGROUND: Hepatectomy is currently recommended as the most reliable treatment for colorectal liver metastases. However, the association between the choice of treatment for recurrence and the timing of recurrence remains controversial. METHODS: Two-hundred ninety-five patients who underwent hepatectomy were retrospectively analyzed for the risk factors and the outcomes for early recurrence within 6 months. The remnant liver volumes (RLVs) and laboratory data were measured postoperatively using multidetector computed tomography on days 7 and months 1, 2, and 5 after the operation. RESULTS: Early recurrence developed in 88/295 patients (29.8%). Colorectal cancer lymph node metastasis, synchronous liver metastasis, and multiple liver metastases were independent risk factors for the occurrence of early recurrence (p < 0.001, 0.032, and 0.019, respectively). Patients with early recurrence had a poorer prognosis than did patients who developed later recurrence (p < 0.001). Patients who underwent surgery or other local treatment had better outcomes. The changes in RLV and laboratory data after postoperative month 2 were not significantly different between the 2 groups. CONCLUSION: Patients with early recurrence within 6 months had a poorer prognosis than did patients who developed later recurrence. However, patients who underwent repeat hepatectomy for recurrence had a better prognosis than did those who underwent other treatments, with good prospects for long-term survival.