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Background. Robotic systems can overcome some limitations of laparoscopic total mesorectal excision (L-TME), thus improving the quality of the surgery. So far, many studies have reported the technical feasibility and short-term oncological results of robotic total mesorectal excision (R-TME) in treating rectal cancer (RC); however, only a few evaluated the survival and long-term oncological outcomes. The following study compared the medium-term oncological data, 3-year overall survival (OS), and disease-free survival (DFS) of L-TME and R-TME in patients with rectal cancer. Methods. In this retrospective study, records of patients (patients with stage I-III rectal cancer) who underwent surgery (127 cases of L-TME and 148 cases of R-TME) at the Gansu Provincial Hospital between June 2016 and March 2018 were included in the analysis. Kaplan-Meier analysis evaluated the 3-year OS and DFS for all patients treated with curative intent. Results. The conversion rate was significantly higher, and the postoperative hospital stay was significantly longer in the L-TME group than in the R-TME group (all P<.05). Major complications were significantly lower in the robotic group (P<.05). The 3-year DFS rate (for all stages) was 74.8% for L-TME and 85.8% for R-TME (P = .021). For disease stage III, the 3-year DFS and OS were significantly higher in the R-TME group (P<.05). Conclusion. R-TME can achieve better oncological outcomes and is more beneficial for RC patients compared with L-TME, especially for those with stage III rectal cancers. Nevertheless, further randomized controlled trials and a longer follow-up period are needed to confirm these findings.
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Laparoscopía , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Estudios Retrospectivos , Laparoscopía/métodos , Neoplasias del Recto/cirugía , Resultado del TratamientoRESUMEN
PURPOSE: Transanal total mesorectal excision (TaTME) has the potential advantages for patients with low rectal cancer. The objective of this meta-analysis was to identify the pathologic outcomes between the TaTME and laparoscopic total mesorectal excision (LaTME) in rectal cancer. METHODS: The literature searches were conducted in PubMed, Cochrane Library, and EMBASE with English language restriction. The primary endpoint was circumferential margin (CRM), and the secondary endpoints were distal resection margin (DRM), mesorectal excision quality, and harvested lymph nodes. RESULTS: Our research identified 1090 articles, and 26 studies met the inclusion criteria for the meta-analysis. The positive CRM was lower in the TaTME than the LaTME (OR = 0.72; 95% CI = 0.53, 0.98; P = 0.04). There was no significant difference in the positive CRM between the TaTME and LaTME published after 2016 (OR = 0.80; 95% CI = 0.57, 1.12; P = 0.19), prospective study (OR = 2.70; 95% CI = 0.51, 14.24; P = 0.24), respective study (OR = 0.76; 95% CI = 0.55, 1.04; P = 0.09), BMI > 26 (OR = 1.00; 95% CI = 0.63, 1.58; P = 0.98), or sample size > 100 (OR = 0.84; 95% CI = 0.57, 1.23; P = 0.38). In addition, there was no significant difference observed between the TaTME and LaTME in terms of DRM, mesorectum incompleteness, and harvested lymph nodes. CONCLUSIONS: The TaTME is associated with lower positive CRM compared to the LaTME and similar pathologic outcomes including DRM, harvested lymph node, and mesorectal excision quality.
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Laparoscopía , Neoplasias del Recto , Cirugía Endoscópica Transanal , Humanos , Márgenes de Escisión , Complicaciones Posoperatorias/cirugía , Estudios Prospectivos , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Recto/cirugía , Resultado del TratamientoRESUMEN
Ribosome assembly factor URB1 is essential for ribosome biogenesis. However, its latent role in cancer remains unclear. Analysis of The Cancer Genome Atlas database and clinical tissue microarray staining showed that URB1 expression was upregulated in colorectal cancer (CRC) and prominently related to clinicopathological characteristics. Silencing of URB1 hampered human CRC cell proliferation and growth in vitro and in vivo. Microarray screening, ingenuity pathway analysis, and JASPAR assessment indicated that activating transcription factor 4 (ATF4) and X-box binding protein 1 (XBP1) are potential downstream targets of URB1 and could transcriptionally interact through direct binding. Silencing of URB1 significantly decreased ATF4 and cyclin A2 (CCNA2) expression in vivo and in vitro. Restoration of ATF4 effectively reversed the malignant proliferation phenotype of URB1-silenced CRC cells. Dual-luciferase reporter and ChIP assays indicated that XBP1 transcriptionally activated ATF4 by binding with its promoter region. X-box binding protein 1 colocalized with ATF4 in the nuclei of RKO cells, and ATF4 mRNA expression was positively regulated by XBP1. This study shows that URB1 contributes to oncogenesis and CRC growth through XBP1-mediated transcriptional activation of ATF4. Therefore, URB1 could be a potential therapeutic target for CRC.
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Factor de Transcripción Activador 4/genética , Proliferación Celular/genética , Neoplasias Colorrectales/genética , Proteínas Nucleares/genética , Ribosomas/genética , Activación Transcripcional/genética , Línea Celular Tumoral , Transformación Celular Neoplásica/genética , Neoplasias Colorrectales/patología , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Células HCT116 , Humanos , Masculino , Persona de Mediana Edad , Transducción de Señal/genética , Regulación hacia Arriba/genética , Proteína 1 de Unión a la X-Box/genéticaRESUMEN
BACKGROUND: Robotic colorectal cancer surgery is widely accepted and applied. However, there is still no objective and comprehensive assessment on the data of nationwide multicenter series. METHOD: A total of 28 medical centers in Mainland China participated in this nationwide retrospective observational study. From the first case performed in each center to the last until December 2017, patients with robotic resection for primary tumor and pathologically confirmed colorectal adenocarcinoma were consecutively enrolled. Clinical, pathological and follow-up data were collected and analyzed. RESULTS: A total of 5389 eligible patients were finally enrolled in this study, composing 72.2% of the total robotic colorectal surgery volume of Mainland China in the same period. For resections of one bowel segment of primary tumor, the postoperative mortality rate was 0.08% (4/5063 cases), and the postoperative complication rate (Clavien-Dindo grade II or higher) was 8.6% (434/5063 cases). For multiple resections, the postoperative mortality rate was 0.6% (2/326 cases), and the postoperative complication rate was 16.3% (53/326 cases). Out of 2956 patients receiving sphincter-preserving surgery in only primary resection, 130 (4.4%) patients had anastomotic leakage. Traditional low anterior resection (tumor at middle rectum) (OR 2.384, P < 0.001), traditional low anterior resection (tumor at low rectum) (OR 1.968, P = 0.017) and intersphincteric resection (OR 5.468, P = 0.006) were significant independent risk factors for anastomotic leakage. Female gender (OR 0.557, P = 0.005), age ≥ 60 years (OR 0.684, P = 0.040), and preventive stoma (OR 0.496, P = 0.043) were significant independent protective factors. Body mass index, preoperative chemotherapy/radiotherapy, tumor size, and TNM stage did not independently affect the occurrence of anastomotic leakage. CONCLUSION: Robotic colorectal cancer surgery was safe and reliable and might have advantages in patients at high risk of anastomotic leakage.
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Procedimientos Quirúrgicos del Sistema Digestivo , Proctectomía , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Anastomosis Quirúrgica , Fuga Anastomótica , Femenino , Humanos , Persona de Mediana Edad , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Factores de Riesgo , Procedimientos Quirúrgicos Robotizados/efectos adversosRESUMEN
PURPOSE: Three-dimensional (3D) vision technology has recently been validated for the improvement of surgical skills in a simulated setting. This study assessed the current evidence regarding the efficiency and potential advantages of 3D compared with two-dimensional (2D) laparoscopic rectal surgery for rectal cancer. METHODS: We comprehensively searched PubMed, EMBASE and the Cochrane Library and performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) and non-randomized controlled trials (nRCTs) assessing the two approaches. RESULTS: Four trials including a total 331 cases were identified. The positive circumferential resection margins (CRMs) were significantly lower for the 3D group (P = 0.02). The operative time was significantly shorter in the 3D group than in the 2D group (P < 0.00001). There was less estimated blood loss (EBL) in the 3D group than in the 2D group (P = 0.02). Perioperative complication rates, conversion rate, harvested lymph nodes, first flatus, length of stay, pneumonia, wound infection, ileus, anastomotic fistula and urinary retention did not differ significantly between the two groups (P > 0.05). CONCLUSIONS: In summary, 3D laparoscopic rectal surgery appears to have advantages over 2D laparoscopic rectal surgery in terms of positive CRM and operation time; however, it is not better than 2D laparoscopic rectal surgery in terms of the conversion rate and postoperative complications.
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Laparoscopía , Recto/cirugía , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sesgo de Publicación , Resultado del TratamientoRESUMEN
Background. Robotic surgery has been recently used as a novel tool for rectal surgery. This study assessed the current evidence regarding the efficiency, safety, and potential advantages of robotic rectal surgery (RRS) compared with laparoscopic rectal surgery (LRS). Methods. We comprehensively searched PubMed, Embase, and the Cochrane Library databases and performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) assessing the 2 approaches. Results. Seven RCTs including a total of 1022 cases were identified. The conversion rate is significantly lower for RRS (odds ratio: 0.29; 95% confidence interval: 0.09 to 0.96; P = .04). The length of the distal margin was significantly shorter in the LRS group than in the RRS group (weighted mean difference: 0.60; 95% confidence interval: 0.09 to 1.10; P = .02). Perioperative complication rates, harvested lymph nodes, positive circumferential resection margins, complete total mesorectal excision, first flatus, and length of stay did not differ significantly between approaches (P > .05). Conclusions. This meta-analysis indicates that RRS is a safe and effective approach. It is not inferior to LRS in terms of oncologic outcomes and postoperative complications. Future large-volume, well-designed RCTs with extensive follow-up are awaited to confirm and update the findings of this analysis.
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Laparoscopía/métodos , Neoplasias del Recto/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
AIM: The robotic technique has been established as an alternative approach to laparoscopy in colorectal surgery. The aim of this study was to compare short-term outcomes of robot-assisted and laparoscopic surgery in colorectal cancer. METHODS: The cases of robot-assisted or laparoscopic colorectal resection were collected retrospectively between July 2015 and October 2017. We evaluated patient demographics, perioperative characteristics, and pathologic examination. A multivariable linear regression model was used to assess short-term outcomes between robot-assisted and laparoscopic surgery. Short-term outcomes included time to passage of flatus and postoperative hospital stay. RESULTS: A total of 284 patients were included in the study. There were 104 patients in the robotic colorectal surgery (RCS) group and 180 in the laparoscopic colorectal surgery (LCS) group. The mean age was 60.5 ± 10.8 years, and 62.0% of the patients were male. We controlled for confounding factors, and then the multiple linear model regression indicated that the time to passage of flatus in the RCS group was 3.45 days shorter than the LCS group (coefficient = -3.45, 95% confidence interval [CI] = -5.19 to -1.71; P < .001). Additionally, the drainage of tube duration (coefficient = 0.59, 95% CI = 0.3 to 0.87; P < .001) and transfers to the intensive care unit (coefficient = 7.34, 95% CI = 3.17 to 11.5; P = .001) influenced the postoperative hospital stay. The total costs increased by 15501.48 CNY in the RCS group compared with the LCS group ( P = .008). CONCLUSIONS: The present study suggests that colorectal cancer robotic surgery was more beneficial to patients because of shorter postoperative recovery time of bowel function and shorter hospital stays.
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Neoplasias Colorrectales/cirugía , Cirugía Colorrectal/métodos , Laparoscopía/métodos , Complicaciones Posoperatorias/epidemiología , Procedimientos Quirúrgicos Robotizados/métodos , Anciano , Pérdida de Sangre Quirúrgica , China , Estudios de Cohortes , Neoplasias Colorrectales/patología , Cirugía Colorrectal/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Laparoscopía/efectos adversos , Tiempo de Internación , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Tempo Operativo , Selección de Paciente , Complicaciones Posoperatorias/fisiopatología , Estudios Retrospectivos , Medición de Riesgo , Procedimientos Quirúrgicos Robotizados/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a composite inflammatory biomarker, is associated with the prognosis in patients with colorectal tumors. However, whether the NLR can be used as a predictor of symptomatic postoperative anastomotic leakage (AL) in elderly patients with colon cancer is unclear. AIM: To assess the role of the NLR in predicting the occurrence of symptomatic AL after surgery in elderly patients with colon cancer. METHODS: Data from elderly colon cancer patients who underwent elective radical colectomy with anastomosis at three centers between 2018 and 2022 were retrospectively analyzed. Receiver operating characteristic curve analysis was performed to determine the best predictive cutoff value for the NLR. Twenty-two covariates were matched using a 1:1 propensity score matching method, and univariate and multivariate logistic regression analyses were used to determine risk factors for the development of postoperative AL. RESULTS: Of the 577 patients included, 36 (6.2%) had symptomatic AL. The optimal cutoff value of the NLR for predicting AL was 2.66. After propensity score matching, the incidence of AL was significantly greater in the ≥ 2.66 NLR subgroup than in the < 2.66 NLR subgroup (11.5% vs 2.5%; P = 0.012). Univariate logistic regression analysis revealed statistically significant correlations between blood transfusion intraoperatively and within 2 d postoperatively, preoperative albumin concentration, preoperative prognostic nutritional index, and preoperative NLR and AL occurrence (P < 0.05); multivariate logistic regression analysis revealed that an NLR ≥ 2.66 [odds ratio (OR) = 5.51; 95% confidence interval (CI): 1.50-20.26; P = 0.010] and blood transfusion intraoperatively and within 2 d postoperatively (OR = 2.52; 95%CI: 0.88-7.25; P = 0.049) were risk factors for the occurrence of symptomatic AL. CONCLUSION: A preoperative NLR ≥ 2.66 and blood transfusion intraoperatively and within 2 d postoperatively are associated with a higher incidence of postoperative symptomatic AL in elderly patients with colon cancer. The preoperative NLR has predictive value for postoperative symptomatic AL after elective surgery in elderly patients with colon cancer.
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OBJECTIVE: It remains controversial whether primary tumor resection (PTR) improves survival in patients with asymptomatic, unresectable metastatic colorectal cancer (mCRC). Therefore, we conducted a meta-analysis to assess the latest evidence on clinical outcomes. MATERIALS AND METHODS: We systematically searched PubMed, Web of Science, Cochrane Library, and Embase databases for eligible studies published between database inception and May 2022. RevMan 5.4 and Stata 16.0 were used for the meta-analysis. RESULTS: A total of nine studies were included, including four randomized controlled trials (RCTs) and five retrospective cohort studies. Meta-analysis showed that overall survival (OS) [HR = 0.89, 95%CI (0.74, 1.06), P = 0.19] and progression-free survival (PFS) [HR = 0.87, 95%CI (0.71, 1.06), P = 0.17] were not significantly different between the PTR and non-PTR groups. In the subgroup analysis, all subgroups showed no significant difference in OS between the two groups. CONCLUSION: PTR may not provide additional survival benefits over chemotherapy in asymptomatic, unresectable mCRC patients. However, in view of the limitations of this study, more well-designed RCTs are needed to validate our conclusions.
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Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Humanos , Neoplasias Colorrectales/patologíaRESUMEN
OBJECTIVE: Our objective was to estimate the effect of flexible sigmoidoscopy (FS)-based screening on colorectal cancer (CRC) incidence and mortality by conducting an updated meta-analysis of randomized controlled trials (RCTs). METHODS: PubMed, Web of Science, Embase, and Cochrane Library searched for RCTs from database inception to December 2022. The methodological quality of the RCTs was assessed using the Cochrane Collaboration Risk of Bias Tool. RevMan 5.4 was used for this meta-analysis. RESULTS: Four RCTs involving 457, 871 patients were included. This meta-analysis revealed that FS-based screening was associated with a 20% relative risk reduction in CRC incidence [RR = 0.80; 95% CI (0.75, 0.86); P < 0.00001], and a 24% reduction in CRC mortality [RR = 0.76; 95% CI (0.70, 0.82); P < 0.00001]. In addition, this meta-analysis revealed that FS-based screening reduced the incidence[RR = 0.68; 95% CI (0.60, 0.77); P < 0.00001] and mortality[RR = 0.64; 95% CI (0.49, 0.83); P = 0.0007] of distal CRC, but had no significant effect on proximal colon cancer. CONCLUSION: FS-based screening appeared to be effective in reducing distal CRC incidence and mortality in patients at average risk compared to no intervention, but had no significant effect on proximal colon cancer.
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Neoplasias del Colon , Neoplasias Colorrectales , Humanos , Sigmoidoscopía , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Incidencia , Detección Precoz del Cáncer , Ensayos Clínicos Controlados Aleatorios como Asunto , Tamizaje MasivoRESUMEN
OBJECTIVE: It remains controversial which targeted monoclonal antibodies combined with chemotherapy can provide better efficacy in wild-type KRAS/RAS metastatic colorectal cancer (mCRC) patients. Therefore, we used this meta-analysis to assess the latest evidence of clinical outcomes. MATERIALS AND METHODS: We systematically searched PubMed, Web of Science, Cochrane Library and Embase databases for eligible studies published from database inception to May 2022. RevMan 5.4 was used to conduct the meta-analysis. RESULTS: 11 RCTs involving a total of 3575 patients were included. Meta-analysis showed that EGFR inhibitors significantly prolonged the overall survival (OS) [HR = 0.83, 95%CI (0.73, 0.94), P = 0.003] and overall response rate (ORR) [RR = 1.11, 95%CI (1.05, 1.18), P = 0.0003] compared to VEGF inhibitors in wild-type KRAS/RAS mCRC patients, but no significant difference in progression-free survival (PFS) [HR = 0.96, 95%CI (0.87, 1.07), P = 0.50]. In subgroup analysis, the survival benefit of EGFR inhibitors was limited to first-line treatment. CONCLUSION: Our study showed that EGFR inhibitors were superior to VEGF inhibitors in wild-type KRAS/RAS mCRC patients, especially in patients with first-line treatment. However, subsequent large sample, multi-center RCTs are needed to further verify our conclusions.
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Neoplasias Colorrectales , Factor A de Crecimiento Endotelial Vascular , Humanos , Bevacizumab/farmacología , Cetuximab/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Panitumumab , Proteínas Proto-Oncogénicas p21(ras)/genéticaRESUMEN
Transformation Induced Plasticity (TRIP)-assisted annealed martensitic (TAM) steel sheets with various microalloying additions such as niobium, vanadium, or titanium were prepared on laboratory scale and subjected to a double-quenching and austempering heat treatment cycle. Slow strain rate tensile (SSRT) was tested on the investigated TAM steels with and without hydrogen charging to reveal their tensile behaviors and hydrogen induced embrittlement effects. Microstructure observations by scanning electron microscope (SEM) are composed of a principal annealed martensitic matrix and 11.0-13.0% volume fraction of retained austenite, depending on the type of microalloying addition in the different steels. SSRT results show that these TRIP-assisted annealed martensitic steels under air media conditions combine high tensile strength (>1000 MPa) and good ductility (~25%), while under hydrogen charging condition, both tensile strength and ductility decrease where tensile strength ranges between 680 and 760 MPa, down from 1000-1100 MPa, and ductility loss ratio is between 78.8% and 91.1%, along with a total elongation of less than 5%. Hydrogen charged into steel matrix leads to the appearance of cleavage fractures, implying the occurrence of hydrogen induced embrittlement effect in TAM steels. Thermal hydrogen desorption results show that there are double-peak hydrogen desorption temperature ranges for these microalloyed steels, where the first peak corresponds to a high-density dislocation trapping effect, and the second peak corresponds to a hydrogen trapping effect exerted by microalloying precipitates. Thermal desorption analysis (TDS) in combination with SSRT results demonstrate that microalloying precipitates act as irreversible traps to fix hydrogen and, thus, retard diffusive hydrogen motion towards defects, such as grain boundaries and dislocations in microstructure matrix, and eventually reduce the hydrogen induced embrittlement tendency.
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BACKGROUND: The robotic technique has been established as an alternative approach to laparoscopy for colorectal surgery. The aim of this study was to compare the short-term outcomes of robot-assisted and laparoscopic surgery in colorectal cancer. METHODS: The cases of robot-assisted or laparoscopic colorectal resection were collected retrospectively between July 2015 and September 2018. We evaluated patient demographics, perioperative characteristics, and pathologic examinations. Short-term outcomes included time to passage of flatus and length of postoperative hospital stay. RESULTS: A total of 580 patients were included in the study. There were 271 patients in the robotic colorectal surgery (RCS) group and 309 in the laparoscopic colorectal surgery (LCS) group. The time to passage of flatus in the RCS group was 3.62 days shorter than the LCS group. The total costs were increased by 2,258.8 USD in the RCS group compared to the LCS group (P < 0.001). CONCLUSION: The present study suggests that colorectal cancer robotic surgery was more beneficial to patients because of a shorter postoperative recovery time of bowel function and shorter hospital stays.
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Neoplasias Colorrectales/mortalidad , Cirugía Colorrectal/mortalidad , Laparoscopía/mortalidad , Procedimientos Quirúrgicos Robotizados/mortalidad , Anciano , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: To compare the clinical efficacy and safety between laparoscopic complete mesocolic excision (CME) and traditional radical operation for colon cancer in the treatment of stage III colon cancer. METHODS: A total of 196 patients with stage III colon cancer treated in out hospital from January 2014 to February 2016 were selected and divided into two groups using a random number table. One group (CME group, n=98) received laparoscopic CME, while another group (Traditional group, n=98) underwent traditional radical operation for colon cancer. The surgery-related indexes and perioperative complications were compared between the two groups, the pathological diagnosis of the patient's surgical specimens was recorded, and the survival of all patients was followed up. RESULTS: The general clinical characteristics of the patients were comparable between the two groups, and no perioperative death occurred. The operation time had no statistically significant difference between the two groups (p=0.190). There was overtly less intraoperative blood loss and shorter postoperative hospital stay in the CME group than those in the Traditional group (129.35±34.54 mL vs. 162.43±38.16 mL, p<0.001, 13.8±3.1 days vs. 15.2±3.4 days, p=0.003). There were no statistically significant differences in the indwelling time of drainage tube after operation, the time of liquid diet after operation and the recovery time of normal diet after operation between the two groups (p>0.05). The time for passage of flatus after operation was significantly shorter in the CME group than that in the Traditional group (p=0.016). The incidence rate of postoperative complications was lower in the CME group (12.2%) than that in the Traditional group (17.3%), but the difference was not statistically significant (p=0.421). The comparisons of surgical specimens revealed that there were no statistically significant differences in tumor size, stage, histopathological classification and differentiation grade between the two groups (p>0.05). The number of lymph nodes dissected and the number of positive lymph nodes detected were clearly greater in the CME group than in the Traditional group (p<0.001). At the end of the follow-up, the overall survival rate and tumor-free survival rate were notably higher in the CME group than in the Traditional group (p=0.046, p=0.038). CONCLUSION: In comparison with traditional radical operation for colon cancer, laparoscopic CME has higher yield of lymph nodes dissected, smaller intraoperative blood loss, no increase in perioperative complications, and higher overall survival and tumor-free survival of patients, demonstrating it as safe and applicable in the treatment of stage III colon cancer.
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Neoplasias del Colon/cirugía , Laparoscopía/métodos , Mesocolon/cirugía , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de NeoplasiasRESUMEN
Mammalian target of rapamycin complex 1 (mTORC1) is evolutionally conserved and frequently activated in various tumors, including colorectal cancer (CRC). It has been reported that the ribosome assembly factor Urb1 acts downstream of mTORC1/raptor signaling and contributes to digestive organ development in zebrafish. Previously, we highlighted that URB1 was overexpressed in CRC. Here, we assessed the mTORC1/regulatory associated protein with mTOR (RAPTOR)-URB1 axis in CRC tumorigenesis. We found that RAPTOR was overexpressed in CRC tissues and cell lines, was a favorable predictor in patients with CRC, and positively correlated with URB1. Silencing of RAPTOR suppressed CRC cell proliferation and migration and induced cell cycle arrest and apoptosis in vitro and inhibited xenograft growth in vivo. Moreover, ectopic overexpression of RAPTOR exerted an inverse biological phenotype. Knockdown of RAPTOR quenched mTORC1 activity and reduced the expression of URB1 and cyclinA2 (CCNA2). In contrast, overexpression of RAPTOR activated mTORC1 and upregulated URB1 and CCNA2. Furthermore, URB1 and CCNA2 expression were also impeded by rapamycin, which is a specific inhibitor of mTORC1. Thus, RAPTOR promoted CRC proliferation, migration, and cell cycle progression by inducing mTORC1 signaling and transcriptional activation of both URB1 and CCNA2. Taken together, we concluded that RAPTOR has the potential to serve as a novel biomarker and therapeutic target for CRC.
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Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/genética , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Proteínas Nucleares/genética , Proteína Reguladora Asociada a mTOR/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Biomarcadores de Tumor/genética , Carcinogénesis/efectos de los fármacos , Carcinogénesis/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Colon/patología , Colon/cirugía , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/cirugía , Ciclina A2/genética , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Humanos , Estimación de Kaplan-Meier , Masculino , Diana Mecanicista del Complejo 1 de la Rapamicina/antagonistas & inhibidores , Ratones , Persona de Mediana Edad , Recto/patología , Recto/cirugía , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Sirolimus/farmacología , Regulación hacia Arriba/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
To assess the clinical efficacy and safety of robotic-assisted right colectomy (RRC) with conventional laparoscopic right colectomy (LRC) by performing a systematic review and meta-analysis of the published studies. All published literature for comparative studies reporting preoperative outcomes of RRC and LRC were searched. We searched the databases included Cochrane Library of Clinical Comparative Trials, MEDLINE, Embase, Web of Science and Chinese Biomedical Database (CBM) from 1973 to 2018. The censor date was up to January 2018. Operative time, estimated blood loss, length of hospital stay, conversion rates to open surgery, postoperative complications, and related outcomes were evaluated. All calculations and statistical tests were performed using Stata 12.0 software. A total of 7769 patients with colon cancer enrolled in 13 trials were divided into a study group (n = 674) and a control group (n = 7095). Meta-analysis suggested significantly greater length of hospital stay in the LRC group [MD = -0.85; 95% CI: -1.07 to -0.63; P < 0.00001]. Robotic surgery was also associated with a significantly lower complication rate [OR = 0.73; 95% CI: 0.52 to 1.01; P = 0.05]. There were statistically significant differences between the groups in estimated blood loss [MD = -16.89; 95% CI: -24.80 to -8.98; P < 0.00001] and the rate of intraoperative conversion to open surgery [OR = 0.34, 95% CI: 0.15 to 0.75; P = 0.008)], but these differences were not clinically relevant. The recovery of bowel function in two groups is no significant differences [MD = -0.58, 95% CI: -0.96 to -0.20, P = 0.0008]. However, operation times [MD = 43.61, 95% CI: 39.11 to 48.10, P < 0.00001] were longer for RRC than for LRC. Compared to LRC, RRC was associated with reduced estimated blood loss, reduced postoperative complications, longer operation times. Recovery of bowel function and other perioperative outcomes were equivalent between the two surgeries.
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Colectomía/métodos , Laparoscopía/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Bases de Datos Bibliográficas , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Tempo Operativo , Recuperación de la Función , Factores de Tiempo , Resultado del TratamientoRESUMEN
The aim of this study was to evaluate and compare the intestinal function recovery time and other short-term outcomes between robotic-assisted total mesorectal excision (R-TME) and laparoscopic total mesorectal excision (L-TME) for rectal cancer. This is a retrospective study using a prospectively collected database. Patients' records were obtained from Gansu Provincial Hospital between July 2015 and October 2017. Eighty patients underwent R-TME, and 116 with the same histopathological stage of the tumor underwent an L-TME. Both operations were performed by the same surgeon, comparing intra- and postoperative outcomes intergroups. The time to the first passage of flatus (P < 0.001), the time to the first postoperative oral fluid intake (P < 0.001), and the length of hospital stay (P < 0.01) of the R-TME group were about three days faster than those in the L-TME group. The rate of conversion to open laparotomy (P = 0.038) and postoperative urinary retention (P = 0.016) were significantly lower in the R-TME group than in the L-TME group. Intraoperative blood loss of the R-TME group was more than that of the L-TME group (P < 0.01).The operation time, number of lymph nodes harvested, and rate of positive circumferential resection margin were similar intergroup. The total cost of the R-TME group was higher than that of the L-TME group, but with a lack of statistical significance (85,623.91 ± 13,310.50 vs 67,356.79 ± 17,107.68 CNY, P = 0.084). The R-TME is safe and effective and has better postoperative short-term outcomes and faster intestinal function recovery time, contrasting with the L-TME. The large, multicenter, prospective studies were needed to validate the advantages of robotic surgery system used in rectal cancer.
Asunto(s)
Adenocarcinoma/cirugía , Laparoscopía , Neoplasias del Recto/cirugía , Procedimientos Quirúrgicos Robotizados , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Tiempo de Internación , Persona de Mediana Edad , Tempo Operativo , Recuperación de la Función , Neoplasias del Recto/patología , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Recently, in order to overcome the shortcomings of laparoscopic surgery in the treatment of low rectal cancer, a new kind of surgical procedure, transanal total mesorectal excision (TaTME), has rapidly become a research hotspot in the field of rectal cancer surgery study. Our study aimed to evaluate the efficacy and safety of transanal total mesorectal excision (TaTME) for the patients with rectal cancer. METHODS: Relevant studies were searched from the databases of the Cochrane Library, PubMed, Embase, Web of science. All relevant studies were collected to evaluate the efficacy and safety of TaTME for patients with rectal cancer. The quality of the included studies was assessed by the Newcastle-Ottawa Quality Assessment Scale (NOS) and Cochrane Library Handbook 5.1.0. Data analysis was conducted using the Review Manager 5.3 software. RESULTS: Thirteen studies including 859 patients were included in our analysis. In terms of efficacy, compared with laparoscopic total mesorectal excision (LaTME), meta-analysis showed that the rate of complete tumor resection increased and the risk of positive circumferential margins decreased in the TaTME group. For complete tumor resection and positive circumferential margins in the TaTME group, the odds ratios (ORs) and 95% confidence intervals (CIs) were 1.93 and 1.09 to 3.42 (Pâ=â.02) and 0.43 and 0.22 to 0.82 (Pâ=â.01), respectively. Concerning safety, results showed that the rates of postoperative complications were similar in the 2 groups, and differences in the risk of ileus and anastomotic leakage were not statistically significant (ORâ=â0.75, 95%CIâ=â0.51-1.09, Pâ=â.13; ORâ=â0.91, 95%CIâ=â0.46-1.78, Pâ=â.78; ORâ=â0.79, 95%CIâ=â0.45-1.38, Pâ=â.40). CONCLUSIONS: The results of this meta-analysis show that TaTME is associated with a reduced positive circumferential resection margin (CRM) rate, and could achieve complete tumor resection and improved the long-term survival in patients with mid- and low-rectal cancer.
Asunto(s)
Neoplasias del Recto/cirugía , Cirugía Endoscópica Transanal/métodos , Humanos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Complicaciones Posoperatorias , Neoplasias del Recto/patología , Recto/patología , Recto/cirugía , Cirugía Endoscópica Transanal/efectos adversosRESUMEN
Neoadjuvant chemoradiotherapy (nCRT) following surgery significantly improves the survival rate of patients with rectal cancer. However, nCRT is associated with significant adverse symptoms and high medical costs. Therefore, it is important to investigate potential biomarkers for the prediction of the response to nCRT in patients with rectal cancer. The present study identified candidate biomarkers for predicting a complete response (CR) to nCRT in patients with rectal cancer and investigated the associated mechanisms. Microarray data (accession no. GSE29298) was downloaded from the Gene Expression Omnibus database. Differentially expressed microRNAs (miRNAs/miR) were screened between the pathological CR (pCR) group and no pCR (incomplete response) group. miRNA target genes were predicted using the miRWalk 2.0 online tool and subjected to Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Furthermore, a miRNA coregulatory network was constructed and diseaseassociated genes were predicted. The results demonstrated that a total of 36 upregulated and 5 downregulated miRNAs were identified between the two groups. Among these differentially expressed miRNAs, miR548c5p, miR548d5p and miR663a were significantly associated with a CR to nCRT. The coregulatory network and pathway analysis indicated that miR548c5p and miR548d5p may function together through stem cell pluripotency and ubiquitinmediated proteolysis signaling pathways. Furthermore, the prediction of diseaseassociated genes demonstrated that miR548c5p/miR548d5p and miR663a may regulate genes associated with rectal cancer, including mutated in colorectal cancers (MCC) and adenomatous polyposis coli (APC), and colorectal neoplasms, including interleukin6 signal transducer (IL6ST), cell cycle checkpoint kinase 2 (CHEK2), marker of proliferation Ki67 (MKI67), cadherin 7 (CDH7), calreticulin (CALR) and transforming growth factor ß1 (TGFB1). Therefore, miR548c5p, miR548d5p and miR663a are promising candidate biomarkers for predicting a CR to nCRT. miR548c5p/miR548d5p may be associated with a CR by regulating IL6ST, CHEK2, MKI67 and MCC. In addition, it may function through the pluripotency of stem cells and ubiquitinmediated proteolysis signaling pathways. miR663a may be associated with a CR to nCRT by targeting CDH7, CALR, APC and TGFß1. Thus, the miRNA biomarkers investigated in the present study may represent novel therapeutic targets for the prediction and eventual improvement of the response to nCRT in patients with rectal cancer.