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INTRODUCTION: We evaluated the prognosis after endoscopic treatment for choledocholithiasis, particularly in patients with borderline tolerance to surgery. Stone removal and cholecystectomy are generally recommended for patients with choledocholithiasis combined with gallstones to prevent recurrent biliary events. However, the prognosis after choledocholithiasis treatment in patients with borderline tolerance to surgery, such as the elderly or those with many comorbidities, remains controversial. METHODS: We retrospectively analyzed data from patients with choledocholithiasis treated at our facility between January 2012 and December 2021. Patients who underwent endoscopic sphincterotomy were dichotomized into the cholecystectomy (CHOLE) and conservation (CONS) groups depending on whether cholecystectomy was performed, and their prognoses were subsequently compared. Furthermore, we performed a logistic regression analysis of the factors contributing to recurrent biliary events in patients with high age-adjusted Charlson Comorbidity Index (aCCI) scores. RESULTS: Of 169 participants, 110 had gallstones and were divided into the CHOLE (n=56) and CONS (n=54) groups. The CONS group was significantly ordered, had more comorbidities, and higher aCCI scores, whereas the CHOLE group had fewer recurrent biliary events, although not significant (P= 0.122). No difference was observed in the recurrent incidence of grade ≥ 2 biliary infections and mortality related to biliary events between the groups. In patients with aCCI scores ≥ 5, conservation without cholecystectomy was not an independent risk factor for recurrent biliary events. CONCLUSION: Cholecystectomy after choledocholithiasis treatment prevents recurrent biliary events, but conservation without cholecystectomy is a feasible option for patients with high aCCI scores.
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PURPOSE: Body weight loss after surgery for gastric cancer is related to S-1 compliance and it also affects the prognosis. However, it is unclear whether the preoperative skeletal muscle mass affects S-1 completion for gastric cancer. We investigated the impact of preoperative skeletal muscle mass loss on the completion of S-1 adjuvant chemotherapy for gastric cancer. METHODS: We retrospectively analyzed data from 53 patients who underwent curative gastrectomy followed by adjuvant S-1 monotherapy for pStage II-III gastric cancer between 2012 and 2021 at our hospital. The psoas muscle mass index (PMI) was used as the index for preoperative skeletal muscle mass. RESULTS: Thirty-six patients completed S-1 treatment and 17 discontinued treatment. The patients who completed S-1 treatment had a longer overall survival than those who discontinued treatment (log-rank test, p = 0.043). According to a univariate analysis, the patients in the discontinuation group had a significantly lower preoperative body mass index (< 22.9 kg/m2, p = 0.005) and a higher rate of adverse events (grade 2 or higher, p < 0.001) than those in the completion group. According to a multivariate analysis, preoperative PMI (HR 3.563, p = 0.030) was an independent predictive factor for S-1 completion. CONCLUSION: Preoperative skeletal muscle loss might therefore prevent the completion of adjuvant chemotherapy S-1 in patients with gastric cancer.
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BACKGROUND: Dropped head syndrome (DHS) is caused by dysfunction of the cervical musculature. It is classified into two groups according to the cause: one is weakness of the neck extensors and the other is hypercontraction of the cervical flexors associated with Parkinson's disease and other disorders. Although some drugs have previously been reported as suspected causes of DHS, we are unaware of any reports in which oxaliplatin was suspected. In this report, we describe a case of DHS during adjuvant chemotherapy for gastric cancer, along with a review of the relevant literature. CASE PRESENTATION: A 72-year-old man was diagnosed with gastric cancer, cT3N0M0 cStage IIB, and underwent laparoscopic total gastrectomy with D2 lymphnode dissection and Roux-en-Y reconstruction. The operative time was 311 min, intraoperative blood loss was 40 g, and he was discharged without any post-operative complications. The histopathological diagnosis was pT4aN2M0 pStage IIIA, and S-1 + oxaliplatin (SOX) therapy was started as adjuvant chemotherapy. On the 4th course of SOX, he complained of neck heaviness and a blood test revealed that his creatine kinase (CK) level was elevated to 2464 IU/L. After consultation with an orthopedic surgeon and a neurologist, DHS due to localized cervical extensor myositis was suspected. Therefore, the 6th course of SOX was postponed, and 30 mg of oral steroids were initiated. His symptoms improved, and his CK level decreased within 2 weeks. After resuming S-1 monotherapy and tapering off oral steroids, no recurrence of symptoms has been observed. CONCLUSIONS: We experienced one case of DHS during adjuvant chemotherapy for gastric cancer. If DHS develops after starting oxaliplatin, involvement of the drug should be suspected, and discontinuation of chemotherapy and introduction of oral steroids should be considered.
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INTRODUCTION: The right intersectional plane and the right hepatic hilum were noted too often exhibit anatomical variations, making difficult the laparoscopic right anterior sectionectomy (LRAS). METHODS: We analyzed the anatomical features employing 3D-CT images of 55 patients, and evaluated these features according to the course of ventral branches of segment VI of the portal vein (PV, P6a) relative to the right hepatic vein (RHV). RESULTS: P6a run on the dorsal side of RHV in 32 patients (58%, Dorsal-P6a) and the ventral side of RHV in 23 (42%, Ventral-P6a). Ventral-P6a had more patients with S6 partially drained by middle hepatic vein (MHV, 39% vs. 0%, P < 0001), the narrower angle between the anterior and posterior branches of PV (73.1° vs. 93.8°, P = 0.006), the wider angle between the RHV and inferior vena cava (54.3° vs. 44.3°, P < 0.001), and more steeply pitched angle between S6 and S7 along the RHV (140.6° vs. 162.0°, P < 0.001) compared to Dorsal-P6a. CONCLUSION: In LRAS for Dorsal-P6a patients, the transection surface was relatively flat. In LRAS for Ventral-P6a patients, the narrow space between anterior and posterior glissons makes difficult the glissonean approach. The transection plane was steeply pitched, and RHV was partially exposed. S6 was often partially drained to MHV in 39% of the Ventral-P6a patients, which triggers congestion during liver transection of a right intersectional plane after first splitting the confluence of this branch.
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Hepatectomía , Venas Hepáticas , Imagenología Tridimensional , Laparoscopía , Vena Porta , Tomografía Computarizada por Rayos X , Humanos , Vena Porta/cirugía , Vena Porta/anatomía & histología , Vena Porta/diagnóstico por imagen , Femenino , Venas Hepáticas/diagnóstico por imagen , Venas Hepáticas/anatomía & histología , Venas Hepáticas/cirugía , Masculino , Laparoscopía/métodos , Persona de Mediana Edad , Hepatectomía/métodos , Anciano , Adulto , Estudios RetrospectivosRESUMEN
Objectives: A total mesenteric excision (TME) with lateral pelvic lymph node dissection (LLND) is the standard treatment for advanced low rectal cancer in Japan. Recently, neoadjuvant (chemo)radiotherapy (n(C)RT) has been used with LLND to improve outcomes at multiple Japanese institutes. This study evaluates the benefits of adding nCRT to TME with LLND. Methods: Seventy-two consecutive patients who underwent TME and LLND with or without nCRT between 2006-2019 to treat advanced low rectal cancer were retrospectively reviewed. The clinicopathological data were compared and the risk factors for local recurrence were evaluated. Results: Fifty-seven patients (79.1%) underwent TME and LLND with nCRT, and 15 patients (20.9%) without nCRT. There was no significant difference in the clinicopathological characteristics except the clinical T stage. The occurrence of postoperative complications was statistically insignificant. The 5-year local recurrence rate of patients with nCRT was significantly lower than those without (4.0% versus 26.6%, in all patients, p=0.002). Multivariate analysis revealed that the absence of nCRT was an independent risk factor for local recurrences in patients who underwent TME with LLND (hazard ratio: 6.04, p=0.04). Conclusions: The administration of nCRT prevented local recurrences more effectively in patients with advanced low rectal cancer who underwent TME with LLND.
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BACKGROUND: Pancreatic fistula (PF) is one of the most serious postoperative complications of gastrectomy. Misidentification of the boundary between the pancreas and the dissected fat is a primary concern. In this study, we focused on differences in the appearance of the pancreas and the dissected fat in actual surgical images and statistically analyzed the relationship between the pancreas and the dissected fat. METHODS: We analyzed data from 109 gastric cancer patients who underwent curative gastrectomy between November 2018 and March 2023. Intraoperative images were taken from videos of lymph node dissections of Nos.6 and 8a regions, and the mean gray value of the areas was measured using ImageJ software for analysis. The visceral fat area (VFA) was evaluated by preoperative axial CT at the umbilical level using Ziostation software. RESULTS: A significant correlation was observed between the fat/pancreas gray value ratio in the No.8a lymph node region and the drain/serum amylase ratio (P < 0.001). The fat/pancreas gray value ratio in the No.6 lymph node region correlated with VFA (P < 0.001). The VFA and drain/serum amylase ratio were significantly higher in the group with intra-abdominal complications (P = 0.004). CONCLUSIONS: We revealed significant relationships between the fat/pancreas gray value ratio with drain/serum amylase and VFA. Detecting differences in gray values between the pancreas and the dissected fat may lead to a decrease in the drain/serum amylase ratio and PF.
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Gastrectomía , Laparoscopía , Fístula Pancreática , Procedimientos Quirúrgicos Robotizados , Neoplasias Gástricas , Humanos , Fístula Pancreática/etiología , Fístula Pancreática/epidemiología , Gastrectomía/métodos , Gastrectomía/efectos adversos , Masculino , Laparoscopía/métodos , Laparoscopía/efectos adversos , Femenino , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Persona de Mediana Edad , Anciano , Medición de Riesgo/métodos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Escisión del Ganglio Linfático/métodos , Escisión del Ganglio Linfático/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/etiología , Grasa Intraabdominal/diagnóstico por imagen , Páncreas/diagnóstico por imagen , Páncreas/cirugía , Páncreas/patología , Estudios Retrospectivos , AdultoRESUMEN
Postoperative hepatobiliary enzyme abnormalities often present as postoperative liver dysfunction in patients with gastric cancer (GC). This study aimed to identify the risk factors for postoperative liver dysfunction and their clinical impact after GC surgery. We retrospectively analyzed the data of 124 patients with GC who underwent laparoscopic or robotic surgery at Kyoto Prefectural University of Medicine between 2017 and 2019. Twenty (16.1%) patients with GC developed postoperative liver dysfunction (Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 ≥ Grade 3). Univariate analyses identified robotic surgery as a risk factor for postoperative liver dysfunction (P = 0.005). There was no correlation between the postoperative liver dysfunction status and postoperative complications or postoperative hospital stays. Patients with postoperative liver dysfunction did not have significantly worse overall survival (P = 0.296) or recurrence-free survival (P = 0.565) than those without postoperative liver dysfunction. Robotic surgery is a risk factor for postoperative liver dysfunction; however, postoperative liver dysfunction does not affect short or long-term outcomes.
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Laparoscopía , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/etiología , Estudios Retrospectivos , Gastrectomía/efectos adversos , Relevancia Clínica , Resultado del Tratamiento , Laparoscopía/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Factores de RiesgoRESUMEN
PURPOSE: In recent years, clinicians have focused on the importance of preventing hypoglycemia. We evaluated the impact of different reconstruction procedures after proximal gastrectomy on glycemic variability in non-diabetic patients with gastric cancer. METHODS: This prospective observational study was conducted between April 2020 and March 2023. Flash continuous glucose-monitoring, a novel method for assessing glycemic control, was used to evaluate the glycemic profiles after gastrectomy. A flash continuous glucose-monitoring sensor was placed subcutaneously at the time of discharge, and glucose trends were evaluated for 2 weeks. RESULTS: The anastomotic methods for proximal gastrectomy were esophagogastrostomy in 10 patients and double-tract reconstruction in 10 patients. The time below this range (glucose levels < 70 mg/dL) was significantly higher in the double-tract reconstruction group than in the esophagogastrostomy group (p = 0.049). A higher nocturnal time below this range was significantly correlated with an older age and double-tract reconstruction (p = 0.025 and p = 0.025, respectively). CONCLUSION: These findings provide new insights into reconstruction methods after proximal gastrectomy by assessing postoperative hypoglycemia in non-diabetic patients with gastric cancer.
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BACKGROUND: Lymphovascular invasion (LVI) is a poor prognostic factor in various malignancies. However, its prognostic effect in remnant gastric cancer (RGC) remains unclear. We examined the correlation between LVI and disease prognosis in patients with T1N0-3 or T2-3N0 RGC in whom adjuvant chemotherapy was not indicated and a treatment strategy was not established. METHODS: We retrospectively analyzed patients with T1N0-3 and T2-3N0 RGC who underwent curative surgery at the Kyoto Prefectural University of Medicine between 1997 and 2019 and at the Kyoto Chubu Medical Center between 2009 and 2019. RESULTS: Fifteen of 38 patients (39.5%) with RGC were positive for LVI. Patients with LVI had a significantly poorer prognosis for both overall survival ([OS]: P = 0.006) and recurrence-free survival ([RFS]: P = 0.001) than those without LVI. Multivariate analyses using the Cox proportional hazards model revealed LVI as an independent prognostic factor affecting OS (P = 0.024; hazard ratio 8.27, 95% confidence interval:1.285-161.6) and RFS (P = 0.013; hazard ratio 8.98, 95% confidence interval:1.513-171.2). CONCLUSIONS: LVI is a prognostic factor for patients with T1N0-3 or T2-3N0 RGC. Evaluating LVI may be useful for determining treatment strategies for RGC.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Estudios Retrospectivos , Estadificación de Neoplasias , Metástasis Linfática , Pronóstico , Invasividad Neoplásica/patologíaRESUMEN
PURPOSE: The Global Leader Initiative on Malnutrition (GLIM) criteria were developed in 2018 as a global indicator of malnutrition, and the term 'malnutrition-sarcopenia syndrome' was established. Recently, it has been reported that fluctuations in blood glucose are related to sarcopenia. In this study, we investigated the effects of glucose fluctuations on malnutrition after gastrectomy using a continuous glucose monitoring (CGM) device. METHODS: We analyzed the data of 69 patients with gastric cancer (GC) who underwent curative gastrectomy between November 2017 and December 2020. CGM was performed over a 2-week period at 1 month and 1 year after surgery. The GLIM criteria included weight loss, the body mass index (BMI), and the psoas muscle mass index (PMI). RESULTS: One year after surgery, 25 and 35 patients had severe and moderate malnutrition, respectively. The time below range (TBR) (percent of time the glucose concentration was < 70 mg/dL) and nocturnal (00:00-06:00) TBR were significantly higher in the severe malnutrition group than in the other groups (TBR: normal/moderate 17.9% vs. severe 21.6%, P = 0.039, nocturnal TBR; normal/moderate 30.6% vs. severe 41.1%, P = 0.034). CONCLUSIONS: Post-gastrectomy hypoglycemia, including long nocturnal hypoglycemia, was higher in severely malnourished patients than in other patients even 1 year after surgery. Prevention of nocturnal hypoglycemia may be the key to improving malnutrition following gastrectomy.
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Gastrectomía , Hipoglucemia , Desnutrición , Complicaciones Posoperatorias , Sarcopenia , Neoplasias Gástricas , Humanos , Gastrectomía/efectos adversos , Desnutrición/etiología , Hipoglucemia/etiología , Hipoglucemia/prevención & control , Estudios Retrospectivos , Neoplasias Gástricas/cirugía , Masculino , Femenino , Anciano , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Sarcopenia/etiología , Persona de Mediana Edad , Índice de Masa Corporal , Glucemia/análisis , Pérdida de Peso , Factores de Tiempo , Índice de Severidad de la Enfermedad , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Calcium voltage-gated channel auxiliary subunit alpha 2/delta 1 (CACNA2D1), a gene encoding a voltage-gated calcium channel, has been reported as an oncogene in several cancers. However, its role in colon cancer (CC) remains unclear. This study aimed to investigate the function of CACNA2D1 and its effect on the microenvironment in CC. METHODS: Immunohistochemistry (IHC) analysis was performed on samples collected from 200 patients with CC who underwent curative colectomy. Knockdown experiments were performed using CACNA2D1 siRNA in the human CC cell lines HCT116 and RKO, and cell proliferation, cycle, apoptosis, and migration were then analyzed. The fibroblast cell line CCD-18Co was co-cultured with CC cell lines to determine the effect of CACNA2D1 on fibroblasts and the relationship between CACNA2D1 and the cancer microenvironment. Gene expression profiles of cells were analyzed using microarray analysis. RESULTS: IHC revealed that high CACNA2D1 expression was an independent poor prognostic factor in patients with CC and that CACNA2D1 expression and the stroma are correlated. CACNA2D1 depletion decreased cell proliferation and migration; CACNA2D1 knockdown increased the number of cells in the sub-G1 phase and induced apoptosis. CCD-18Co and HCT116 or RKO cell co-culture revealed that CACNA2D1 affects the cancer microenvironment via fibroblast regulation. Furthermore, microarray analysis showed that the p53 signaling pathway and epithelial-mesenchymal transition-associated pathways were enhanced in CACNA2D1-depleted HCT116 cells. CONCLUSIONS: CACNA2D1 plays an important role in the progression and the microenvironment of CC by regulating fibroblasts and may act as a biomarker for disease progression and a therapeutic target for CC.
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Apoptosis , Canales de Calcio , Neoplasias del Colon , Progresión de la Enfermedad , Microambiente Tumoral , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Canales de Calcio/genética , Canales de Calcio/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Técnicas de Cocultivo , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Transición Epitelial-Mesenquimal/genética , Fibroblastos/metabolismo , Fibroblastos/patología , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Células HCT116 , Pronóstico , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: Laparoscopic cholecystectomy is the gold standard treatment for benign gallbladder disease. However, few studies have reported the difficulty of interval cholecystectomy after cholecystitis because early cholecystectomy is recommended for acute cholecystitis. In this study, we evaluated the difficulties associated with interval cholecystectomy for cholecystitis with gallstones. METHODS: We retrospectively analyzed patients with gallstones who underwent interval laparoscopic cholecystectomy for cholecystitis at our institution between January 2012 and December 2021. Patients were classified into laparoscopic total cholecystectomy and bailout procedure groups depending on whether they were converted to a bailout procedure, and their characteristics and outcomes were subsequently compared. Additionally, a logistic regression analysis of the preoperative factors contributing to bailout procedure conversion was performed. RESULTS: Of the 269 participants, 39 converted to bailout procedure, and bile duct injury occurred in one case (0.4%). In patient characteristics comparison, patients in the bailout procedure group were significantly older, had more impacted stones, had higher post-treatment choledocholithiasis, had severe cholecystitis, and had a higher rate of percutaneous transhepatic gallbladder drainage. There were no differences in the bile duct injury or perioperative complications between the two groups. In logistic regression multivariate analysis of the factors contributing to the bailout procedure, post-treatment of choledocholithiasis (P < .001), impacted stone (P = .002), and age ≥71 (P = .007) were independent risk factors. CONCLUSION: Impacted stones and choledocholithiasis are risk factors for conversion to bailout procedure and high difficulty in interval cholecystectomy. For such patients, interval cholecystectomy should be performed cautiously.
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Colecistectomía Laparoscópica , Cálculos Biliares , Humanos , Colecistectomía Laparoscópica/efectos adversos , Colecistectomía Laparoscópica/métodos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Cálculos Biliares/cirugía , Cálculos Biliares/complicaciones , Anciano , Adulto , Colecistitis Aguda/cirugía , Resultado del Tratamiento , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiologíaRESUMEN
This work reports localized in vivo gene transfer by biodegradation of the adeno-associated virus-encapsulating alginate microspheres (AAV-AMs) loaded in collagen gel carriers. AAV-AMs are centrifugally synthesized by ejecting a mixed pre-gel solution of alginate and AAV to CaCl2 solution to form an ionically cross-linked hydrogel microsphere immediately. The AAV-AMs are able to preserve the AAV without diffusing out even after spreading them on the cells, and the AAV is released and transfected by the degradation of the alginate microsphere. In addition, AAV-AMs can be stored by cryopreservation until use. By implanting this highly convenient AAV-encapsulated hydrogel, AAV-AMs can be loaded into collagen gel carriers to fix the position of the implanted AAV-AMs and achieve localized gene transfer in vivo. In vivo experiments show that the AAV-AMs loaded in collagen gel carriers are demonstrated to release the encapsulated AAV for gene transfer in the buttocks muscles of mice. While conventional injections caused gene transfer to the entire surrounding tissue, the biodegradation of AAV-AMs shows that gene transfer is achieved locally to the muscles. This means that the proposed AAV-loaded system is shown to be a superior method for selective gene transfer.
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Alginatos , Colágeno , Dependovirus , Microesferas , Dependovirus/genética , Alginatos/química , Animales , Colágeno/química , Ratones , Técnicas de Transferencia de Gen , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Humanos , Hidrogeles/química , Geles/químicaRESUMEN
BACKGROUND AND AIMS: This retrospective study aimed to compare the short- and long-term outcomes of endoscopic submucosal dissection and laparoscopic and endoscopic cooperative surgery in patients with superficial non-ampullary duodenal epithelial tumors. PATIENTS AND METHODS: We investigated consecutive patients with SNADETs > 10 mm in size who underwent ESD (ESD group) or LECS (LECS group) between January 2015 and March 2021. The data was used to analyze the clinical course, management, survival status, and recurrence between the two groups. RESULTS: A total of 113 patients (100 and 13 in the ESD and LECS groups, respectively) were investigated. The rates of en bloc resection and curative resection were 100% vs. 100% and 93.0% vs. 77.0% in the ESD and LECS groups, respectively, with no significant difference. The ESD group had shorter resection and suturing times than the LECS group, but there were no significant difference after propensity score matching. There were also no differences in the rates of postoperative adverse event (7.0% vs. 23.1%; P = 0.161). The 3-year overall survival (OS) rate was high in both the ESD and LECS groups (97.6% vs. 100%; P = 0.334). One patient in the ESD group experienced recurrence due to liver metastasis; however, no deaths related to SNADETs were observed. CONCLUSION: ESD and LECS are both acceptable treatments for SNADETs in terms of a high OS rate and a low long-term recurrence rate, thereby achieving a comparable high rate of curative resection. Further studies are necessary to compare the outcomes of ESD and LECS for SNADETs once both techniques are developed further.
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Resección Endoscópica de la Mucosa , Laparoscopía , Neoplasias Glandulares y Epiteliales , Humanos , Estudios Retrospectivos , Resección Endoscópica de la Mucosa/métodos , Resultado del Tratamiento , Laparoscopía/métodosRESUMEN
BACKGROUND: Recent studies have identified that low levels of some tumour suppressor microRNAs (miRNAs) in the blood contribute to tumour progression and poor outcomes in various cancers. However, no study has proved these miRNAs are associated with cancer immune mechanisms. METHODS: From a systematic review of the NCBI and miRNA databases, four tumour suppressor miRNA candidates were selected (miR-5193, miR-4443, miR-520h, miR-496) that putatively target programmed cell death ligand 1 (PD-L1). RESULTS: Test-scale and large-scale analyses revealed that plasma levels of miR-5193 were significantly lower in gastric cancer (GC) patients than in healthy volunteers (HVs). Low plasma levels of miR-5193 were associated with advanced pathological stages and were an independent prognostic factor. Overexpression of miR-5193 in GC cells suppressed PD-L1 on the surface of GC cells, even with IFN-γ stimulation. In the coculture model of GC cells and T cells stimulated by anti-CD3/anti-CD28 beads, overexpression of miR-5193 increased anti-tumour activity of T cells by suppressing PD-L1 expression. Subcutaneous injection of miR-5193 also significantly enhanced the tumour-killing activity and trafficking of T cells in mice. CONCLUSIONS: Low blood levels of miR-5193 are associated with GC progression and poor outcomes and could be a target of nucleic acid immunotherapy in GC patients.
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MicroARNs , Neoplasias Gástricas , Humanos , Animales , Ratones , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Antígeno B7-H1 , MicroARNs/metabolismo , Genes Supresores de Tumor , InmunoterapiaRESUMEN
BACKGROUND/AIM: The membrane transporters activated in cancer stem cells (CSCs) are the target of novel cancer therapies for hepatocellular carcinoma (HCC). The present investigation demonstrated the expression profiles of ion channels in CSCs of HCC. MATERIALS AND METHODS: Cells that highly expressed aldehyde dehydrogenase 1 family member A1 (ALDH1A1) were separated from HepG2 cells, a human HCC cell line, by fluorescence-activated cell sorting, and CSCs were identified based on the formation of tumorspheres. Gene expression profiles in CSCs were investigated using microarray analysis. RESULTS: Among HepG2 cells, ALDH1A1 messenger RNA level was higher in CSCs than in non-CSCs. Furthermore, CSCs exhibited resistance to cisplatin and had the capacity to redifferentiate. The results of the microarray analysis of CSCs showed the up-regulated expression of several genes related to ion channels, such as calcium voltage-gated channel auxiliary subunit gamma 4 (CACNG4). The cytotoxicity of the CACNG4 inhibitor amlodipine was higher at lower concentrations in CSCs than in non-CSCs, and markedly decreased the number of tumorspheres. The cell population among HepG2 cells that highly expressed ALDH1A1 was also significantly reduced by this inhibitor. CONCLUSION: CACNG4 plays a role in maintaining CSCs, and its inhibitor, amlodipine, could potentially be a targeted therapeutic agent against HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Canales de Calcio/genética , Células Madre Neoplásicas , Amlodipino/farmacologíaRESUMEN
BACKGROUND: Although a 3-5 cm surgical margin distance is recommended for advanced gastric cancer (GC) in Japanese guidelines, little is known about the clinical effects of the surgical margin, especially the distal resection margin (DM). This study aims to clarify the clinical significance of DM in GC. METHODS: A total of 415 GC patients who underwent curative distal gastrectomy between 2008 and 2018 were analyzed retrospectively. RESULTS: The DM significantly stratified recurrence-free survival (P = 0.002), and a DM < 30 mm was an independent factor of a poor prognosis (P = 0.023, hazard ratio: 1.91). Lymphatic recurrence occurred significantly more frequently in the DM < 30 mm group than in the DM ≥ 30 mm group (P = 0.019, 6.9% vs. 1.9%). Regarding the station No.6 lymph node metastases in advanced GC (DM < 30 mm vs. 30 mm ≤ DM ≤ 50 mm vs. DM > 50 mm), the number (P < 0.001, 1.42 ± 1.69 vs. 1.18 ± 1.80 vs. 0.18 ± 0.64), the positive rate (P < 0.001, 59.0% vs. 46.7% vs. 11.3%) and therapeutic value index (43.3 vs. 14.5 vs. 8.0) were significantly higher in the DM < 30 mm group. By subdivision using the DM distance of 30 mm, more segmented prognostic stratifications were possible (P < 0.001). CONCLUSIONS: A DM of less than 30 mm could be a surrogate marker of poor RFS, especially increasing nodal recurrence. More intensive treatment strategies, including lymphadenectomy and chemotherapy, are needed for patients with this condition.
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Márgenes de Escisión , Neoplasias Gástricas , Humanos , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias Gástricas/patología , Gastrectomía , Recurrencia Local de Neoplasia/patología , Pronóstico , Escisión del Ganglio Linfático , BiomarcadoresRESUMEN
Although the average life span differs between males and females, little is known about differences in clinical features and short and long-term outcomes between elderly male and female gastric cancer patients. This study was designed to clarify these issues to identify the possibility for sex-based treatment strategies in elderly gastric cancer patients. This study included 295 consecutive elderly gastric cancer patients (75 years or older) who underwent curative gastrectomy between 1997 and 2016. We defined postoperative complications as Clavien-Dindo classification grade II or higher. Comorbidities were present in 67% of all patients. Males tended to have more comorbidities than females (P = 0.077). Male patients had significantly more upper gastric cancers (P = 0.001), a higher incidence of postoperative complications (P = 0.045), and poorer prognoses than females (P = 0.003). Multivariate analysis revealed that being male was an independent risk factor for postoperative complications (Odds ratio 2.5, P = 0.045) and a poor prognostic factor (Hazard ratio 1.81, P = 0.008). Patients who underwent limited surgery without postoperative complications tended to have a better prognosis than patients receiving standard surgery with postoperative complications (3-year overall survival: 78% vs. 55%, P = 0.156). Male was an independent risk factor for postoperative complications and an independent poor prognostic factor in elderly gastric cancer patients. To avoid postoperative complications, the limited surgery might be justified for high-risk elderly male patients.