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PURPOSE: Whether long-term aspirin usage is associated with colorectal cancer (CRC) risk needs more evidence. The study evaluated the association between long-term aspirin use and prevalence of CRC in a large, nationally representative database. METHODS: Hospitalized patients aged ≥ 50 years during 2018 were identified in the United States (US) National Inpatient Sample (NIS). Patients without complete information of age, sex, race, income, and insurance status were excluded, as well as those with inflammatory bowel disease (IBD) or malignancies other than CRC. Propensity score matching (PSM) was applied to balance the characteristics between patients with and without long-term aspirin use. Logistic regressions were performed to determine the relationship between long-term aspirin use and the presence of CRC. CRC and aspirin use were identified through the administrative International Classification of Diseases (ICD) codes. RESULTS: Data from 3,490,226 patients were included, in which 688,018 (19.7%) had a record of long-term aspirin use. After 1:1 PSM, there remained 1,376,006 patients, representing 6,880,029 individuals in the US after weighting. After adjusting for confounders, long-term aspirin use was significantly associated with lower CRC odds (adjusted odds ratio [aOR] = 0.64, 95% confidence interval [CI] 0.62, 0.67). This association was not changed when stratified by age, sex, race, body mass index (BMI), and smoking. CONCLUSIONS: From a national inpatient dataset, US adults ≥ 50 years on long-term aspirin are less likely to have CRC, regardless of age, sex, race, BMI, and smoking status.
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Aspirina , Neoplasias Colorrectales , Adulto , Humanos , Estados Unidos/epidemiología , Pacientes Internos , Prevalencia , Neoplasias Colorrectales/epidemiologíaRESUMEN
BACKGROUND: Robot-assisted surgery has been increasingly adopted in colorectal cancer resection. OBJECTIVE: The study aimed to compare the inpatient outcomes of robot-assisted versus conventional laparoscopic colorectal cancer resection in patients aged 75 years and older. DESIGN: A retrospective, population-based study. SETTINGS: This study analyzed data from the United States Nationwide Inpatient Sample from 2005 to 2018. PATIENTS: Patients with colorectal cancer aged 75 years and older and who underwent robot-assisted or conventional laparoscopic resection. MAIN OUTCOME MEASURES: Postoperative complications, prolonged length of stay, and total hospital costs were assessed. RESULTS: Data from 14,108 patients were analyzed. After adjustment, any postoperative complications (adjusted OR = 0.87; 95% CI, 0.77-0.99; p = 0.030) and prolonged length of stay (adjusted OR = 0.78; 95% CI, 0.67-0.91; p = 0.001) were significantly less in the robotic than the laparoscopic group. In addition, robotic surgery was associated with significantly higher total hospital costs (26.06 USD greater cost; 95% CI, 21.35-30.77 USD; p < 0.001). LIMITATIONS: The analysis was limited by its retrospective and observational nature, potential coding errors, and the lack of intraoperative factors, such as operative time, laboratory measures, and information on surgeons' experience. CONCLUSIONS: In the United States, in patients with colorectal cancer aged 75 years and older who were undergoing tumor resections, compared to conventional laparoscopic surgery, robotic surgery is associated with better inpatient outcomes in terms of complication rate and risk of prolonged length of stay. This finding is especially true among patients with colon cancer. However, robotic surgery is associated with higher total hospital costs. See Video Abstract . RESULTADOS DE LA CIRUGA ASISTIDA POR ROBOT FRENTE A LA CIRUGA LAPAROSCPICA PARA EL CNCER COLORRECTAL EN ADULTOS AOS DE EDAD UN ANLISIS EMPAREJADO POR PUNTUACIN DE PROPENSIN DE LA MUESTRA NACIONAL DE PACIENTES HOSPITALIZADOS DE ESTADOS UNIDOS: ANTECEDENTES:La cirugía asistida por robot se ha adoptado cada vez más en la resección del cáncer colorrectal.OBJETIVO:El estudio tuvo como objetivo comparar los resultados hospitalarios de la resección del cáncer colorrectal asistida por robot versus la laparoscópica convencional en pacientes ≥ 75 años.DISEÑO:Estudio retrospectivo de base poblacional.AJUSTES:Este estudio analizó datos de la Muestra Nacional de Pacientes Hospitalizados de Estados Unidos de 2005 a 2018.PACIENTES:Pacientes con cáncer colorrectal ≥ 75 años y sometidos a resección laparoscópica convencional o asistida por robot.PRINCIPALES MEDIDAS DE RESULTADO:Se evaluaron las complicaciones posoperatorias, la duración prolongada de la estancia hospitalaria y los costos hospitalarios totales.RESULTADOS:Se analizaron datos de 14.108 pacientes. Después del ajuste, cualquier complicación posoperatoria (aOR = 0,87; IC del 95 %: 0,77-0,99, p = 0,030) y duración prolongada de la estancia hospitalaria (aOR = 0,78; IC del 95 %: 0,67-0,91, p = 0,001) fueron significativamente menores en el grupo robótico que el grupo laparoscópico. Además, la cirugía robótica se asoció con costos hospitalarios totales significativamente mayores ($26,06 USD mayor costo; IC 95%: 21,35-30,77 USD, p < 0,001).LIMITACIONES:El análisis estuvo limitado por su naturaleza retrospectiva y observacional, posibles errores de codificación y la falta de factores intraoperatorios como el tiempo operatorio, medidas de laboratorio e información sobre la experiencia de los cirujanos.CONCLUSIONES:En Estados Unidos, los pacientes con cáncer colorrectal ≥ 75 años que se sometieron a resecciones tumorales, en comparación con la cirugía laparoscópica convencional, la cirugía robótica se asocia con mejores resultados hospitalarios en términos de tasa de complicaciones y riesgo de estadía prolongada, especialmente entre pacientes con cáncer de colon. Sin embargo, la cirugía robótica se asocia a costes hospitalarios totales más elevados. (Traducción-Yesenia Rojas-Khalil ).
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Neoplasias Colorrectales , Laparoscopía , Tiempo de Internación , Complicaciones Posoperatorias , Puntaje de Propensión , Procedimientos Quirúrgicos Robotizados , Humanos , Anciano , Masculino , Femenino , Laparoscopía/métodos , Laparoscopía/economía , Laparoscopía/estadística & datos numéricos , Procedimientos Quirúrgicos Robotizados/economía , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/estadística & datos numéricos , Neoplasias Colorrectales/cirugía , Estudios Retrospectivos , Estados Unidos/epidemiología , Complicaciones Posoperatorias/epidemiología , Anciano de 80 o más Años , Tiempo de Internación/estadística & datos numéricos , Costos de Hospital/estadística & datos numéricos , Colectomía/métodos , Colectomía/economía , Resultado del TratamientoRESUMEN
Metastatic dissemination of colorectal cancer (CRC), the third most common cancer type, is responsible for CRC deaths. Understanding the transition of lymph node metastasis (LNM) from Stage II to Stage III is beneficial in the prognosis and intervention of CRC. In this study, a quantitative proteomic survey was conducted to investigate the LNM-associated proteins and evaluate the clinicopathological characteristics of these target proteins in CRC. By using the LC-MS/MS iTRAQ technology, we analysed the proteomic changes between LMN II and LMN III. Fresh tumours from the CRC specimens consisting of 12 node-negative (Stage II) and 12 node-positive (Stage III) cases were analysed by LC-MS/MS iTRAQ proteome analysis. Subsequently, tissue microarray with immunohistochemistry staining was conducted to access the clinicopathological characteristics of these proteins in 116 paraffin-embedded CRC samples, each for non-LNM and LNM CRC. To study the effects of the differentially expressed proteins on the potential mechanism, Boyden chamber assay, flow cytometry and shRNA-based assessments were conducted to examine the role of the epithelial-mesenchymal transition (EMT) and the invasiveness of CRC cells and others in vivo xenograft mouse model experiments. Forty-eight proteins were found differentially expressed between non-LNM and LNM CRC tissues. Protein abundances of chromogranin-A (CHGA) and ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) were observed in node-positive CRC (p < 0.05). Knockdown of CHGA and UCHL1 significantly regulate cancer behaviours of HCT-116, including inhibition of cell migration, invasiveness, cell cycle G1/S arrest and reactive oxygen species (ROS) generation. Mechanistically, the CHGA and UCHL1 inactivation displayed decreased levels of UCH-L1, chromogranin A, ß-catenin, cyclin E, twist-1/2, vimentin, MMP-9, N-cadherin and PCNA through the activation of the Rho-GTPase/AKT/NFκB pathways. Histone modification of H3K4 trimethylation of CHGA and UCHL1 promoter were increased to activate their transcription through the signalling transduction such as Rho-GTPase, AKT and NFκB pathways. Our results indicated that UCHL1 and chromogranin A are novel regulators in CRC lymph node metastasis to potentially provide new insights into the mechanism of CRC progression and serve as biomarkers for CRC diagnosis at the metastatic stage.
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Biomarcadores de Tumor , Neoplasias Colorrectales , Humanos , Animales , Ratones , Metástasis Linfática , Cromogranina A , Biomarcadores de Tumor/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteómica/métodos , Ubiquitina Tiolesterasa/genética , Ubiquitina Tiolesterasa/metabolismo , Cromatografía Liquida , Espectrometría de Masas en Tándem , Neoplasias Colorrectales/metabolismo , GTP Fosfohidrolasas , Transición Epitelial-Mesenquimal/genéticaRESUMEN
BACKGROUND AND AIM: Morbid obesity is associated with poorer postoperative outcomes in colorectal cancer (CRC) patients. We aimed to evaluate short-term outcomes after robotic versus conventional laparoscopic CRC resection in morbidly obese patients. METHODS: This population-based, retrospective study extracted data from the US Nationwide Inpatient Sample during 2005-2018. Adults ≥ 20 years old, with morbid obesity and CRC, and undergoing robotic or laparoscopic resections were identified. Propensity score matching (PSM) was applied to minimize the confounding. Univariate and multivariable regression was conducted to evaluate the associations between outcomes and study variables. RESULTS: After PSM, 1296 patients remained. The risks of any postoperative complication (adjusted odds ratio [aOR] = 0.99, 95% confidence interval [CI]: 0.80, 1.22), prolonged length of stay (LOS) (aOR = 0.80, 95% CI: 0.63, 1.01), death (aOR = 0.57, 95% CI: 0.11, 3.10), or pneumonia (aOR = 1.13, 95% CI: 0.73, 1.77) were not significantly different between the two procedures after adjustment. Robotic surgery was significantly associated with greater hospital cost (aBeta = 26.26, 95% CI: 16.08, 36.45) than laparoscopic surgery. Stratified analyses revealed that, in patients with tumor located at the colon, robotic surgery was associated with lower risk of prolonged LOS (aOR = 0.72, 95% CI: 0.54, 0.95). CONCLUSIONS: In patients with morbid obesity, risks of postoperative complication, death, or pneumonia are not significantly different between robotic and laparoscopic CRC resection. Among patients with tumor located at the colon, robotic surgery is associated with lower risk of prolonged LOS. These findings fill the knowledge gap and provide useful information for clinicians on risk stratification and treatment choice.
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Neoplasias Colorrectales , Laparoscopía , Obesidad Mórbida , Procedimientos Quirúrgicos Robotizados , Robótica , Adulto , Humanos , Adulto Joven , Estudios Retrospectivos , Pacientes Internos , Obesidad Mórbida/complicaciones , Obesidad Mórbida/epidemiología , Obesidad Mórbida/cirugía , Puntaje de Propensión , Procedimientos Quirúrgicos Robotizados/efectos adversos , Procedimientos Quirúrgicos Robotizados/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/complicaciones , Laparoscopía/efectos adversos , Laparoscopía/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Metabolic syndrome (MetS) is a worldwide pandemic and complex disorder associated with colorectal cancer (CRC). This study aims to identify the influence of number of MetS components on CRC incidence and mortality, using a national, longitudinal dataset of hospital care in Taiwan. METHODS: Patient data from the Taiwan National Health Insurance Research Database (NHIRD) from 2001 to 2008 were extracted. Individuals with at least one inpatient diagnosis or 2 outpatient visits with any MetS component found within one year were identified and included. Subjects died within 12 months after the presence of MetS components or had any prior cancer were excluded. The study cohort were then divided into two groups: subjects who had more (i.e., 3 to 4) MetS components and those who had fewer (i.e., 1 to 2) MetS components. An 2:1 propensity score (PS) matching were performed to balance the baseline characteristics between the groups. Cox regression analyses were conducted to compare the CRC incidence and all-cause mortality at follow-up between subjects with more MetS components versus fewer components. RESULTS: After matching, a total of 119,843 subjects (78,274 with 1-2 and 41,569 with 3-4 MetS components) were analyzed. After adjusting for confounders, subjects with 3-4 MetS components had a significantly higher risk of CRC [adjusted hazard ratio (aHR), 1.28; 95% confidence interval (CI), 1.15-1.43, p < 0.001) and all-cause mortality (aHR, 1.13; 95% CI, 1.08-1.17, p < 0.001) than those with only 1-2 MetS components. In stratified analyses, the greatest increased risk of CRC incidence that 3-4 MetS components posed as compared to 1-2 MetS components was seen in subjects without CHD history (aHR, 1.41, 95% CI, 1.23-1.62, p < 0.001). In addition, 3-4 MetS components (vs. 1-2) led to greater all-cause mortality among the subjects < 65y, both genders, with or without CHD, subjects without CKD hisotry, both aspirin users and non-users, users of nonsteroidal anti-inflammatory drugs (NSAIDs), and users of statin. CONCLUSION: Compared with 1-2 components, subjects with 3-4 MetS components are at greater risk of CRC and death at follow-up. This study also demonstrates the risks for CRC and all-cause mortality in certain subgroups of individuals with 3-4 MetS components compared to 1-2 components. These findings may help clinicians on the CRC risk stratification according to individuals' characteristics, as well as to optimize the strategy of MetS surveillance and control in order to prevent CRC.
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Neoplasias Colorrectales , Síndrome Metabólico , Humanos , Femenino , Masculino , Síndrome Metabólico/complicaciones , Síndrome Metabólico/epidemiología , Incidencia , Factores de Riesgo , Neoplasias Colorrectales/etiología , HospitalesRESUMEN
PURPOSE: Obesity is an independent risk factor for worse outcomes in various surgical settings. Whether obesity is a prognostic factor for postoperative morbidity and mortality of colorectal cancer (CRC) is inconclusive. This study aimed to determine the impact of obesity on short-term postoperative outcomes in CRC patients undergoing laparoscopic surgery. METHODS: Data of a total of 23,898 CRC patients aged ≥ 20 years and undergoing laparoscopic resection were extracted from the US National Inpatient Sample (NIS) database and analyzed. The study endpoints were in-hospital mortality, any postoperative complications, infection/sepsis, acute kidney injury (AKI), deep vein thrombosis (DVT)/pulmonary embolisms (PE), and extended hospital stay. Univariate and multivariate logistic regression analyses were performed to examine the associations between patients' obesity status (morbid obese: BMI > = 40 kg/m2; obese: BMI 30-39.9 kg/m2) and the study outcomes. RESULTS: In 23,898 CRC patients undergoing laparoscopic resection, the prevalence of obesity prevalence was 11.8%. After adjustment, the results revealed that morbid obesity was significantly associated with increased risk for in-hospital mortality (aOR = 2.06, 95%CI: 1.11-3.83), AKI (aOR = 1.78, 95%CI = 1.34-2.36), DVT/PE (aOR = 2.88, 95%CI = 1.70-4.88), and extended LOS (aOR = 1.21, 95%CI = 1.02-1.43), while non-morbid obesity was significantly associated with more DVT/PE (aOR = 2.12, 95%CI = 1.32-3.41) as compared with non-obesity. CONCLUSION: In patients with CRC undergoing laparoscopic surgery, morbid obesity is strongly associated with worse postoperative outcomes, including increased in-hospital mortality, postoperative AKI and DVT/PE, and extended LOS. The findings of the present study highlight the importance of obesity status in risk stratification for laparoscopic CRC surgery.
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Neoplasias Colorrectales , Obesidad Mórbida , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/cirugía , Bases de Datos Factuales , Humanos , Tiempo de Internación , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: As one of the most popular methods for treating hemorrhoidal diseases, hemorrhoidectomy with LigaSure devices has been proven to have less postoperative pain and has gained in popularity among surgeons. However, our previous study found higher incidence of delayed post-hemorrhoidectomy bleeding (DPHB) in patients who underwent LigaSure hemorrhoidectomy compared to those who underwent the traditional Ferguson's method. This follow-up study aimed to reveal the relationship between DPHB and the surgeon's experience. METHODS: This retrospective study included 437 consecutive patients with symptomatic grade II to IV hemorrhoids who received hemorrhoidectomy by LigaSure devices from March 2009 to December 2017. Twenty-two patients who experienced DPHB were analyzed to identify risk factors. Cumulative incidence of DPHB were calculated and visualized to assess the improvement of DPHB rate by time. RESULTS: All operations were performed by a single surgeon. The most common postoperative complication was constipation, followed by urinary retention. DPHB developed in 22 patients (5%). Multivariate analysis showed that the male sex was an independent risk factor for DPHB in patients who underwent hemorrhoidectomy with LigaSure devices. The cumulative incidence was initially higher (about 10%) in the earlier cases and stabilized at around 5% with more cases. The change in cumulative incidence indicated a lower complication rate as the surgeon's experience increased. CONCLUSION: Male sex is an independent risk factor for DHBP. The risk of DPHB is higher in patients undergoing hemorrhoidectomy with LigaSure in a surgeon's earlier cases, and decreases to a rate similar to that for the traditional hemorrhoidectomy once the surgeon becomes more familiar with the procedure and postoperative care.
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Hemorreoidectomía , Hemorroides , Butanonas , Estudios de Seguimiento , Hemorragia/etiología , Hemorreoidectomía/efectos adversos , Hemorreoidectomía/métodos , Hemorroides/cirugía , Humanos , Masculino , Dolor Postoperatorio/etiología , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
Ailanthoidol (ATD) has been isolated from the barks of Zanthoxylum ailanthoides and displays anti-inflammatory, antioxidant, antiadipogenic, and antitumor promotion activities. Recently, we found that ATD suppressed TGF-ß1-induced migration and invasion of HepG2 cells. In this report, we found that ATD exhibited more potent cytotoxicity in Huh7 hepatoma cells (mutant p53: Y220C) than in HepG2 cells (wild-type p53). A trypan blue dye exclusion assay and colony assay showed ATD inhibited the growth of Huh7 cells. ATD also induced G1 arrest and reduced the expression of cyclin D1 and CDK2. Flow cytometry analysis with Annexin-V/PI staining demonstrated that ATD induced significant apoptosis in Huh7 cells. Moreover, ATD increased the expression of cleaved PARP and Bax and decreased the expression of procaspase 3/8 and Bcl-xL/Bcl-2. In addition, ATD decreased the expression of mutant p53 protein (mutp53), which is associated with cell proliferation with the exploration of p53 siRNA transfection. Furthermore, ATD suppressed the phosphorylation of the signal transducer and activator of transcription 3 (STAT3) and the expression of mevalonate kinase (MVK). Consistent with ATD, the administration of S3I201 (STAT 3 inhibitor) reduced the expression of Bcl-2/Bcl-xL, cyclin D1, mutp53, and MVK. These results demonstrated ATD's selectivity against mutp53 hepatoma cells involving the downregulation of mutp53 and inactivation of STAT3.
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Benzofuranos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Ácidos Aminosalicílicos , Apoptosis/fisiología , Bencenosulfonatos , Benzofuranos/farmacología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclina D1/metabolismo , Regulación hacia Abajo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteínas Mutantes/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
BACKGROUND: Approximately, 22.6% of colorectal cancer surgeries were performed on patients aged 80 or over. The present study aimed to evaluate the use of laparoscopic resection and its short-term surgical outcomes in patients who were aged 80 and older and diagnosed with colon cancer or rectal cancer in parallel. METHODS: In this retrospective population-based study, colon and rectal cancer patients ≥ 80 years undergoing laparoscopic resection or open resection were identified from the United States National Inpatient Sample (2005-2014). Primary outcomes were postoperative complication and in-hospital mortality. Logistic regression analyses were performed to assess the short-term effectiveness of laparoscopic and open resection. RESULTS: In this study, 40,451 colon cancer patients and 1117 rectal cancer patients were included. Multivariate analysis revealed that laparoscopic resection was significantly associated with lower risks for developing postoperative complications (aOR = 0.67; 95%, CI 0.64-0.71) and in-hospital mortality (aOR = 0.37; 95% CI 0.32-0.43) compared to open resection in colon cancer patients. For rectal cancer patients, multivariate analysis indicated that laparoscopic resection was significantly associated with a lower risk of developing postoperative complications (aOR = 0.41; 95% CI 0.32-0.52) but was not associated with in-hospital mortality. CONCLUSION: Compared to open resection, laparoscopic resection has better or similar short-term surgical outcomes in colon and rectal cancer patients ≥ 80 years.
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Neoplasias del Colon/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Laparoscopía/métodos , Neoplasias del Recto/cirugía , Anciano de 80 o más Años , Procedimientos Quirúrgicos del Sistema Digestivo/mortalidad , Femenino , Humanos , Pacientes Internos , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Colorectal cancers (CRCs) is the most commonly diagnosed and deadly cancer types in the world. Despite advances in chemotherapy for CRCs, drug resistance remains a major challenge to high incurable and eventually deadly rates for patients. CPT-11 is one of the current chemotherapy agents for CRC patients and the CPT-11 resistance development of CRCs is also inevitable. Recently, accumulating data has suggested that DNA repair system might be an inducer of chemotherapy resistance in cancer cells. Thus, this study was aimed to examine whether MutS homolog (MSH) 2, one member of DNA repair system, plays a role to affect the cytotoxicity of CPT-11 to CRCs. Human DLD-1 CRC cells were used in this study. It was shown that MSH2 gene and protein expression could be upregulated in DLD-1 cells under CPT-11 treatment and this upregulation subsequently attenuates the sensitivity of DLD-1 cells to CPT-11. Moreover, ERK1/2 and Akt signaling and AP-1 transcription factor have been found to modulate these effects. These results elucidate the drug resistance role of MSH2 upregulation in the CPT-11-treated DLD-1 CRC cells. Our findings may provide a useful thought for new adjuvant drug development by controlling the DNA repair system.
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Neoplasias Colorrectales/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , Irinotecán/farmacología , Proteína 2 Homóloga a MutS/genética , Inhibidores de Topoisomerasa I/farmacología , Línea Celular Tumoral , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Reparación del ADN/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Humanos , Irinotecán/uso terapéutico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/genética , Proteína 2 Homóloga a MutS/metabolismo , Inhibidores de Topoisomerasa I/uso terapéutico , Regulación hacia Arriba/efectos de los fármacosRESUMEN
INTRODUCTION: Duplications of the alimentary tract are a rare congenital malformation. Most of the cases are symptomatic and diagnosed before 2 years of age. Here, we report a young female presented with a huge abdominal mass, and colonic duplication was confirmed during laparotomy. CASE PRESENTATION: A 29-year-old female had chronic constipation treated with laxative agents. She presented to the emergency room with abdominal cramping for 3 days, accompanied with intermittent fever and vomiting. A huge movable abdominal mass was noted during physical examination. Computerized tomography showed a long segmental dilated bowel lumen with stool impaction and bowel wall thickening of the dilated lumen in the left abdomen, highly suggestive of a long tubular colon duplication. The patient underwent subtotal colectomy. Specimen subsequently confirmed the diagnosis for colonic duplication from cecum to sigmoid colon, and the duplicated colon was found on the antimesenteric side of the native colon. She had a stable postoperative course and was discharged 9 days later. DISCUSSION: Duplications of the alimentary tract are a rare congenital anomaly. Colonic duplication is an even more unusual malformation of this type. It can be classified into cystic or tubular type according to the gross morphology and may or may not be associated with other congenital anomalies. Most common presentation includes abdominal distention, refractory constipation, and bowel obstruction like many other colorectal conditions. Thus, its indistinct symptoms make it difficult to be diagnosed preoperatively. The recommended treatment is surgical resection of the duplicated lumen along with the attached native colon.
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Colon/anomalías , Adulto , Bario , Colon/diagnóstico por imagen , Enema , Femenino , Humanos , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: Delayed post-hemorrhoidectomy bleeding (DPHB) is a rare but serious complication. We investigated the incidence and risk factors of DPHB in patients undergoing hemorrhoidectomy using the LigaSure device or the Ferguson procedure. METHODS: This retrospective study included 382 consecutive patients with symptomatic grades II to IV hemorrhoids who received either LigaSure (184 patients) or Ferguson (198 patients) hemorrhoidectomy procedures. Thirty-two patients who experienced DPHB after discharge were followed up. RESULTS: Significantly fewer Ferguson group patients had DPHB compared to the LigaSure group (5.1% vs. 11.9%; P = 0.015). In the overall population, the risk of DPHB was higher in (1) males compared to that of females (OR = 3.39; 95% CI 1.50-7.69, P = 0.003); (2) in the LigaSure group compared to the Ferguson group (OR = 2.77; 95% CI 1.23-6.24, P = 0.01); and (3) in patients with constipation (OR = 6.59; 95% CI 2.73-15.89, P < 0.0001). Males in the LigaSure group had a significantly higher rate of delayed bleeding than those in the Ferguson group (20% vs. 5.8%, P = 0.004); no significant differences were found in females (4.9% vs. 4.5%, P = 0.878). Subgroup analysis showed that in males, risk of DPHB increased significantly with postoperative constipation (OR = 4.73, 95% CI 1.45-15.43, P = 0.010) and the LigaSure procedure (OR = 3.99, 95% CI 1.37-11.62, P = 0.011). In females, the risk of DPHB was significantly associated with postoperative constipation (OR = 8.80, 95% CI 2.24-34.54, P = 0.002). CONCLUSIONS: The LigaSure procedure and constipation are independent risk factors for DPHB in patients undergoing hemorrhoidectomy and can be used as predictors of outcome.
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Hemorragia/etiología , Hemorreoidectomía/efectos adversos , Complicaciones Posoperatorias/etiología , Femenino , Humanos , Ligadura , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
The shear force effect on human chondrocytes is time and magnitude dependent. Recently, kruppel-like factor (KLF) 4 has been identified as a pleiotropic protein and its activity in cells is dependent on different stimuli and/or cell types. The role of KLF4 in chondrocytes is still unclear and there has been no report determining whether shear force regulates KLF4 levels in chondrocytes. Hence, this study was carried out to investigate the role of KLF4 in human chondrocytes under shear force stimulation and the underlying mechanism. Human primary and SW1353 chondrocytes were used in this study. The shear forces at 2, 5, or 15 dyn/cm2 intensity were applied to both types of human chondrocytes. The specific small interfering RNAs, activators, and inhibitors were used to study the detailed mechanism of shear force. The presented results showed that 2, but not 5 and 15, dyn/cm2 shear force increases KLF4 expression in human primary and SW1353 chondrocytes. Extracellular signal-regulated kinase 5 induced peroxisome proliferator-activated receptor γ transcription activity to increase KLF4 transcription. Moreover, the KLF4 induction in human chondrocytes in response to 2 dyn/cm2 shear force could attenuate interleukin (IL)-1ß-stimulated nuclear factor-κB activation. These results elucidate the role of KLF4 in antagonizing the effect of IL-1ß in human chondrocytes under 2 dyn/cm2 shear force stimulation and provide a possible mechanism to demonstrate the protection of moderate forces or exercises in cartilage.
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Condrocitos/citología , Interleucina-1beta/genética , Factores de Transcripción de Tipo Kruppel/genética , Osteoartritis/genética , Cartílago/crecimiento & desarrollo , Cartílago/metabolismo , Condrocitos/metabolismo , Regulación del Desarrollo de la Expresión Génica/genética , Humanos , Factor 4 Similar a Kruppel , Proteína Quinasa 7 Activada por Mitógenos/genética , FN-kappa B/genética , Osteoartritis/patología , PPAR gamma/genética , Cultivo Primario de Células , ARN Interferente Pequeño/genética , Estrés Mecánico , Activación Transcripcional/genéticaRESUMEN
Gastric cancer is the third leading cause of cancer mortality all over the world. The combination therapy of surgery with chemotherapy, that is, 5-fluorouracil (5-FU) and platinum-containing anticancer drugs, is becoming a current clinical strategy for patients with gastric cancer because of the lower curative rate and higher cancer recurrence rate of patients treated with only surgery. However, the development of drug resistance in cancer cells is still the most challenge in clinical chemotherapy. Excision repair cross-complementing 1 (ERCC1), an essential member of nucleotide excision repair system, recently has been suggested to be a predictive biomarker of treatment evaluation and might affect the outcomes of chemotherapy. Thus, this study was aimed to investigate whether ERCC1 expression could be regulated, and its role in gastric cancer cells treated with 5-FU and the underlying mechanism. Human AGS gastric cancer cells were used in this study. It was shown that ERCC1 expression could be upregulated in AGS cells treated with 5-FU and this upregulation could subsequently attenuate the cytotoxicity of 5-FU in AGS cells. Moreover, 5-FU-upregulated ERCC1 expression was regulated by extracellular signal-regulated kinase (ERK) 1/2 and p38 signaling through activating the transcription factor c-jun/activator protein (AP)-1. These results indicated the role of ERCC1 in the development of drug resistance to 5-FU in AGS cells. The mechanism elucidation concerning the ERK1/2 and p38 kinases and transcription factor c-jun/AP-1 might contribute another idea to the development of chemotherapy strategy for the gastric cancers in the future.
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Antimetabolitos Antineoplásicos/uso terapéutico , Reparación del ADN/efectos de los fármacos , Proteínas de Unión al ADN/genética , Endonucleasas/genética , Fluorouracilo/uso terapéutico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Gástricas/tratamiento farmacológico , Regulación hacia Arriba/genética , Análisis de Varianza , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Humanos , Sistema de Señalización de MAP Quinasas , Proteínas Proto-Oncogénicas c-jun/metabolismo , Factor de Transcripción AP-1/metabolismo , TransfecciónRESUMEN
Colorectal cancer (CRC) is the fourth most common cause of cancer death worldwide. Chemotherapy has been the major strategy for treating patients with advanced CRC. Oxaliplatin (OXA) is used as both an adjuvant and neoadjuvant anticancer agent available to treat advanced CRC. High-mobility group box 1 protein (HMGB1) is a critical regulator of cell death and survival. HMGB1 overexpression has been shown to be resistant to cytotoxic agents. In addition, Metformin, a widely used drug for diabetes, has emerged as a potential anticancer agent. In this study, we examined whether HMGB1 plays a role in the OXA- and/or metformin-induced cytotoxic effect on CRC cells. The results showed that treatment with OXA increased HMGB1 expression in the ERK1/2- and Akt-dependent manners in DLD-1 cells. HMGB1 gene knockdown enhanced the cytotoxicity and cell growth inhibition of OXA. Moreover, OXA-increased HMGB1 expression was by inducing NF-κB-DNA-binding activity to in DLD-1 cells. Compared to a single agent, OXA combined with metformin administration resulted in cytotoxicity and cell growth inhibition synergistically, accompanied with reduced HMGB1 level. These findings may have implications for the rational design of future drug regimens incorporating OXA and metformin for the treatment of CRC.
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Neoplasias Colorrectales/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proteína HMGB1/biosíntesis , Metformina/farmacología , Proteínas de Neoplasias/biosíntesis , Oxaliplatino/farmacología , Línea Celular Tumoral , Neoplasias Colorrectales/dietoterapia , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Proteína HMGB1/genética , Humanos , Metformina/agonistas , Proteínas de Neoplasias/genética , Oxaliplatino/agonistasRESUMEN
The induction of bone morphogenetic protein (BMP)2 in injured and arthritis articular cartilage has been proposed, but the precise mechanism has not been clearly clarified. Our previous study has found that leptin could stimulate the BMP2 autocrine effect to increase the anabolic collagen II expression when it initiates the catabolic response in human chondrocytes. It has been suggested that this BMP2 autocrine effect contributes to a reparative role in leptin-stimulated human chondrocytes. In this study, we further determined whether this BMP2 autocrine effect also affect the expressions of catabolic matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS). Human primary and SW1353 chondrocytes were used in this study. It was shown that leptin could induce the expressions of MMP1, 3, and 13 and ADAMTS4 and 5 in both human primary and SW1353 chondrocytes. Leptin-increased MMP1/13 (not MMP3) and ADAMTS4 (not ADAMTS5) expressions were affected by the leptin-upregulated BMP2 and its specific downstream Smad1/5 signaling. Moreover, both HDAC3 and 4 are involved in regulating leptin-induced BMP2 upregulation and then affect MMP1 and 13 and ADAMTS4 expression. Both HDAC3 and 4 also affect leptin-increased MMP3 mRNA expression but not through BMP2 autocrine effect of leptin induction. Our results further elucidated the role of BMP2 autocrine effect in matrix-degrading enzymes expressions under leptin stimulation. The findings in this study provide new insights into the possible mechanism of BMP2 induction in leptin-stimulated chondrocytes and in leptin-induced OA development.
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Proteína ADAMTS4/metabolismo , Proteína Morfogenética Ósea 2/metabolismo , Condrocitos/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , Metaloproteinasa 1 de la Matriz/metabolismo , Proteína ADAMTS4/genética , Western Blotting , Proteína Morfogenética Ósea 2/genética , Ensayo de Inmunoadsorción Enzimática , Humanos , Leptina , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 13 de la Matriz/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteína Smad1/genética , Proteína Smad1/metabolismo , Proteína Smad5/genética , Proteína Smad5/metabolismoRESUMEN
BACKGROUND/AIMS: Inflammation is one of the main contributors to chronic diseases such as cancer. It is of great value to identify the potential activity of various medicinal plants for regulating or blocking uncontrolled chronic inflammation. We investigated whether the root extract of Morus australis possesses antiinflammatory and antioxidative stress potential and hepatic protective activity. METHODS: The microwave-assisted extractionwere was used to prepare the ethanol extract from the dried root of Morus australis (MRE), including polyphenolic and flavonoid contents. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells was examined the anti-inflammatory and anti-oxidative potential of MRE. CCl4-induced mouse hepatic damage were performed to detect the hepatic protective potential in vivo. Immunohistochemistry (IHC) and western blot assays were used to detect target proteins. RESULTS: MRE contained approximately 23% phenolic compounds and 3% flavonoids. The major flavonoid component of MRE was morusin. MRE and morusin inhibited lipopolysaccharide-induced production of nitrite and prostaglandin E2 in RAW264.7 cells. MRE and morusin also suppressed the formation of intracellular reactive oxygen species and the expression of iNOS and COX-2. In an in vivo study, a thiobarbituric acid reactive substances assay showed that MRE inhibited CCl4-induced oxidative stress and expression of nitrotyrosine. MRE also decreased CCl4-induced hepatic iNOS and COX-2 expression, as well as CCl4-induced hepatic inflammation and necrosis in mice. CONCLUSION: MRE exhibited antiinflammatory and hepatic protective activity.
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Tetracloruro de Carbono , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Flavonoides/uso terapéutico , Lipopolisacáridos/inmunología , Macrófagos/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/inmunología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Flavonoides/química , Flavonoides/farmacología , Mediadores de Inflamación/inmunología , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Morus/química , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Células RAW 264.7RESUMEN
BACKGROUND/AIMS: Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related deaths worldwide. PRDXs are antioxidant enzymes that play an important role in cell differentiation, proliferation and apoptosis and have diverse functions in malignancy development. However, the mechanism of aberrant overexpression of PRDX6 in CRC remains unclear. METHODS: Boyden chamber assay, flow cytometry and a lentiviral shRNA targeting PRDX6 and transient transfection with pCMV-6-PRDX6 plasmid were used to examine the role of PRDX6 in the proliferation capacity and invasiveness of CRC cells. Immunohistochemistry (IHC) with tissue array containing 40 paraffin- embedded CRC tissue specimens and Western blot assays were used to detect target proteins. RESULTS: PRDX6 was significantly up-expressed in different comparisons of metastasis of colorectal adenomas in node-positive CRC (P = 0.03). In in vitro HCT-116, PRDX6 silencing markedly suppressed CRC cell migration and invasiveness while also inducing cell cycle arrest as well as the generation of reactive oxygen species (ROS); specific overexpression of PRDX6 had the opposite effect. Mechanistically, the PRDX6 inactivation displayed decreased levels of PRDX6, N-cadherin, ß-catenin, Vimentin, Slug, Snail and Twist-1 through the activation of the PI3K/ AKT/p38/p50 pathways, but they were also significantly inhibited by PRDX6 transfectants. There was also increased transcriptional activation of dimethylation of histone H3 lysine 4 (H3K4me3) of PRDX6 promoter via the activation of the PI3K/Akt/NFkB pathways. CONCLUSION: Our findings demonstrated that PRDX6 expression plays a characteristic growth-promoting role in CRC metastasis. This study suggests that PRDX6 may serve as a biomarker of node-positive status and may have a role as an important endogenous regulator of cancer cell tumorigenicity in CRC. PRDX6 may also be an effective therapeutic target.
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Neoplasias Colorrectales/genética , Regulación Neoplásica de la Expresión Génica , Invasividad Neoplásica/genética , Peroxiredoxina VI/genética , Adulto , Anciano , Anciano de 80 o más Años , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Movimiento Celular , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Peroxiredoxina VI/análisis , Peroxiredoxina VI/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de SeñalRESUMEN
PURPOSE: Temporary loop colostomy is a common surgical procedure used to avoid complications in high-risk distal anastomosis as well as pelvic inflammation. Issues regarding postoperative outcomes of colostomy takedown have been widely discussed in the literature, wound infection especially. Temporary closure of colostomy with suture before takedown was adopted in our study, which provided excellent traction to aid mobilization of stomy and avoided stool spillage to downgrade the wound classification to "clean contamination." We aimed to determine the effects of the procedure on postoperative outcomes. METHODS: This was a prospective case-control study at a single tertiary medical center. Patients presenting for elective colostomy takedown were included. Allis clamp (n = 50) or silk suture (n = 60) was applied to mobilize the colostomy, and results were compared. Operative time and wound infection rate were measured as primary postoperative outcomes. Univariate and multivariate analyses were used to demonstrate the association between the two groups and outcomes. RESULTS: In univariate analyses, significantly shorter operative time (median = 57 min, p = 0.003) and lower postoperative wound infection rate (3%, p = 0.03) were noted in the group receiving silk suture. Multivariate analyses results showed that silk suture was significantly associated with both operative time (B = - 8.5, p = 0.01) and wound infection (odds ratio = 0.18, p = 0.04). CONCLUSION: With the advantage of enhancing traction and decreasing contamination, the temporary closure of colostomy with suture improved takedown outcomes, including a shorter operative time and lower wound infection rate.
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Colostomía , Suturas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Tempo Operativo , Periodo Posoperatorio , Análisis de Regresión , Infección de la Herida Quirúrgica/patología , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Erinacine A, a major active component of a diterpenoid derivative isolated from Hericium erinaceus mycelium, has been demonstrated to exert anticancer effects. Herein, we present an investigation of the molecular mechanism of erinacine A induction associated with cancer cells' aggressive status and death. A proteomic approach was used to purify and identify the differentially expressed proteins following erinacine A treatment and the mechanism of its action in apoptotic and the targets of erinacine A. Our results demonstrate that erinacine A treatment of HCT-116 and DLD-1 cells increased cell cytotoxicity and reactive oxygen species (ROS) production as well as decreased cell proliferation and invasiveness. Ten differentially displayed proteins were determined and validated in vitro and in vivo between the erinacine A-treated and untreated groups. In addition, erinacine A time-dependent induction of cell death and inhibitory invasiveness was associated with sustained phosphorylation of the PI3K/mTOR/p70S6K and ROCK1/LIMK2/Cofilin pathways. Furthermore, we demonstrated that erinacine A-induced HCT-116 and DLD-1 cells viability and anti-invasion properties by up-regulating the activation of PI3K/mTOR/p70S6K and production of ROS. Experiments involving specific inhibitors demonstrated that the differential expression of cofilin-1 (COFL1) and profilin-1 (PROF1) during erinacine A treatment could be involved in the mechanisms of HCT-116 and DLD-1 cells death and decreased aggressiveness, which occurred via ROCK1/LIMK2/Cofilin expression, with activation of the PI3K/mTOR/p70S6K signalling pathway. These findings elucidate the mechanism of erinacine A inhibiting the aggressive status of cells by activating PI3K/mTOR/p70S6K downstream signalling and the novel protein targets COF1 and PROF1; this could be a good molecular strategy to limit the aggressiveness of CRC cells.