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Hepatectomy and/or local ablation therapy have been recommended for colorectal cancer liver metastases (CRLM). However, they still lack strong evidence for their survival benefits, in addition to systemic therapy. This study aims to evaluate the survival evidence of hepatectomy and/or radiofrequency ablation (RFA) therapy in CRLM patients from a large multi-institutional database. A total of 20,251 patients with colorectal cancer, 4521 of whom were with CRLM, were screened for eligibility. Finally, 2612 patients (637 hepatectomy, 93 RFA, 92 combined hepatectomy and RFA, and 1790 non-aggressive treatment) were enrolled. Frequency matching analysis was used to adjust for baseline differences. The 5-year overall survival (OS) was as follows: hepatectomy alone was 47.8%, combined hepatectomy plus RFA was 35.9%, RFA alone was 29.2%, and the non-aggressive treatment group was 7.4%. Kaplan-Meier curves showed that hepatectomy, RFA, and combination were significantly associated with a better OS compared to those without aggressive local therapy (p < 0.001). Multivariate Cox regression analysis showed that male gender (hazard ratio (HR) 0.89; 95% confidence interval (CI), 0.81-0.97; p = 0.011), old age (≥60 years) (HR 1.20; 95% CI, 1.09-1.32; p < 0.001), high CEA level (>5 ng/mL) (HR 2.14; 95% CI, 1.89-2.42; p < 0.001), primary right-sided cancer (HR 1.35; 95% CI, 1.22-1.51; p < 0.001), extrahepatic metastasis (HR 1.46; 95% CI, 1.33-1.60; p < 0.001), systemic therapy (HR 0.7; 95% CI, 0.62-0.79; p < 0.001), and aggressive local therapy (hepatectomy vs. non-local therapy HR 0.22; 95% CI, 0.20-0.26; p < 0.001; RFA vs. non-local therapy HR 0.29; 95% CI, 0.29-0.41; p < 0.001) were independent factors associated with OS. In the frequency matching analysis, patients receiving hepatectomy and/or RFA resulted in a better OS than those without (p < 0.001). In conclusion, aggressive local treatment provides survival advantages over systemic therapy alone among CRLM patients.
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PURPOSE: NSAIDs are commonly used as opioid-sparing analgesics in colorectal surgery. Many efforts are made to elucidate the risk of NSAID-associated anastomotic leakage after colorectal surgery. However, these results still remain controversial. In this study, we applied large-scale retrospective analysis using propensity score matching to fully clarify the association between risk of anastomotic leakage and use of NSAID after colorectal surgery. METHODS: All colorectal cancer patients receiving operation during February 2008 to August 2018 in our multi-institution medical organization research database were enrolled. It is worthy to mention that only patients requiring re-operation within 21 days after colorectal surgery due to anastomotic leakage were counted as anastomosis leakage. Furthermore, a propensity score TriMatch analysis was performed to prevent from interference of confounding factors. RESULTS: A total of 10,584 patients were included in this study and divided into three groups, no NSAIDs group, non-selective NSAIDs group, and selective COX-2 inhibitors group, respectively. Before tri-matching analysis, significant differences in anastomotic leakage rate were observed. After propensity score matching analysis, the ratio of anastomotic leakage requiring re-operation occurred in 2.0%, 3.6%, and 2.0% in no NSAIDs, non-selective NSAIDs, and selective COX-2 inhibitors group, respectively. No significant difference was observed in these three groups. CONCLUSION: These results suggest that NSAIDs are not associated with incidence of anastomosis leakage following colorectal surgery. To our knowledge, it is the first study demonstrating that NSAIDs is not associated with incidence of anastomosis leakage following colorectal surgery using propensity score matching at a larger-scale retrospective study.
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Fuga Anastomótica , Cirugía Colorrectal , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Fuga Anastomótica/prevención & control , Antiinflamatorios no Esteroideos/efectos adversos , Inhibidores de la Ciclooxigenasa 2 , Humanos , Puntaje de Propensión , Estudios Retrospectivos , Factores de RiesgoRESUMEN
(1) Background: To investigate the prognostic value of cancer-inflammation prognostic index (CIPI) in patients with metastatic colorectal cancer (mCRC) on regorafenib treatment; (2) Methods: Patients with mCRC who were given regorafenib as later-line treatment at Kaohsiung and Linkou Chang-Gung Memorial Hospital between November 2014 and January 2021 were consecutively enrolled. All relevant clinicopathologic, laboratory data and survival status were recorded. Independent prognostic factors were determined by the multivariate Cox regression method; (3) Results: In total, 106 patients in the training cohort and 250 in the validation cohort were enrolled. The median OS for patients with CIPI ≥ 300 and < 300 in the training cohort was 3.8 and 9.0 months, respectively (hazard ratio (HR) 2.78, 95% confidence interval (CI) 1.82-4.23; p < 0.0001). Time to regorafenib, liver metastasis and CIPI were independent factors by multivariate Cox regression analyses. A new scoring model demonstrated a good discriminatory ability to risk stratification of a patient's survival; (4) Conclusions: We identified CIPI as a novel serum marker highly associated with overall survival in patients with mCRC receiving regorafenib treatment. Further confirmatory studies are warranted.
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The prognostic significance of sarcopenia has been widely studied in different cancer patients. This study aimed to analyze the influence of sarcopenia on long-term survival in patients with colorectal liver metastasis (CRLM) undergoing hepatic resection. A retrospective analysis of 182 patients undergoing hepatic resection for CRLM was performed. Sarcopenia was determinedusing the Hounsfield unit average calculation (HUAC), a measure of muscle quality-muscledensity at preoperative abdominal computed tomography scans. Sarcopenia was defined as an HUAC score of less than 22 HU calculated using receiver operating characteristic analysis. The prognostic relevance of clinical variables and overall survival (OS) and recurrence-free survival (RFS) was evaluated. Patients with sarcopenia were older (p < 0.001) and had higher prevalence of diabetics (p = 0.004), higher body mass index (BMI) (p < 0.001) and neutrophil-to-lymphocyte ratio (p = 0.026) compared to those without. Sarcopenia was not significantly associated with OS and RFS. Multivariate Cox's regression analysis showed that multinodularity (>3) (hazard ratio (HR) 2.736; 95% confidence interval (CI), 1.631-4.589; p < 0.001), high CEA level (≥20 ng/ml) (HR 1.793; 95% CI, 1.092-2.945; p = 0.021) and blood loss (≥300 cc) (HR1.793; 95% CI, 1.084-2.964; p = 0.023) were independent factors associated with OS. In subgroup analyses, sarcopenia was a significant factor of poor OS in the patients with multinodularity by univariate (p = 0.002) and multivariate analyses(HR 3.571; 95% CI, 1.508-8.403; p = 0.004). Multinodularity (>3) (HR 1.750; 95% CI, 1.066-2.872; p = 0.027), high aspartate aminotransferase level (HR 1.024; 95% CI, 1.003-1.046; p = 0.025) and male gender (HR 1.688; 95% CI, 1.036-2.748; p = 0.035) were independent factors of RFS. In conclusion, despite no significance in whole cohort, sarcopenia was predictive of worse OS in patients with multiple CRLM after partial hepatectomy.
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Neoplasias Colorrectales/cirugía , Hepatectomía , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia/epidemiología , Sarcopenia/epidemiología , Abdomen/diagnóstico por imagen , Anciano , Aspartato Aminotransferasas/sangre , Índice de Masa Corporal , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Hígado/enzimología , Hígado/patología , Hígado/cirugía , Pruebas de Función Hepática , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/prevención & control , Periodo Preoperatorio , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Sarcopenia/diagnóstico , Sarcopenia/etiología , Tomografía Computarizada por Rayos XRESUMEN
Cyclooxygenase-2 (COX-2) is frequently overexpressed and enhances colorectal cancer (CRC) tumorigenesis, including cancer stem cell (CSC) regulation. Accordingly, nonsteroidal anti-inflammatory drugs (NSAIDs), inhibiting COX-1/2 activity, are viewed as potential drugs for CRC treatment. Accumulated evidence indicates that celecoxib has the most potency for antitumor growth among NSAIDs and the underlying mechanism is only partly dependent on COX-2 inhibition. However, the potency of these NSAIDs on CSC inhibition is still not known. In this study, we found that among these NSAIDs, celecoxib has the most potency for CSC inhibition of CRC cells, largely correlating to inhibition of c-Met, not COX-2. Further analysis reveals that c-Met activity was required for basal CSC property. Silence of c-Met blocked whereas overexpression of c-Met enhanced the celecoxib-inhibited CSC property. Collectively, these results not only first elucidate the mechanism underlying celecoxib-inhibited CSC but also indicate c-Met as a critical factor for the CSC property of CRC cells.
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Celecoxib/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Antiinflamatorios no Esteroideos/farmacología , Línea Celular Tumoral , Neoplasias Colorrectales/metabolismo , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/farmacología , Humanos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismoRESUMEN
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
BACKGROUND: There are still discrepancies among general/colorectal surgeons regarding closure of mesenteric defect in scientific literature. This study aimed to assess the long-term consequences of nonclosure of the mesenteric defect after open right colectomy. METHODS: A 7-year retrospectively collected and continuous database revealed 212 consecutive patients who had undergone traditional right colectomy without closing the mesenteric defects at Kaohsiung Chung-Gung Memorial Hospital; all patients were operated by a single surgeon. Among these patients, 17 were excluded (those who died within 30 days after surgery or those who received an end ileostomy). The mean age of the 195 patients (58% men and 42% women) was 61.6 ± 12.6 years, and the follow-up period was 4.1 ± 2.8 years (interquartile range 0.09 ~ 10.4). RESULTS: Forty-four patients (22.5%) encountered intestinal obstruction. Nine (20.4%) required surgical intervention. The cause of intestinal obstruction was adhesion (n=1), ventral hernia (n=1), and cancer recurrence (n=7). Conservative treatment was successful in 35 patients. The intestinal obstruction group (n = 44) were similar to the no-intestinal obstruction group (n = 151) in terms of the following parameters: age, sex, previous abdominal surgery, indication for colectomy, and procedure related complications. Carcinomatosis was found to increase the incidence of intestinal obstruction. No patient developed intestinal obstruction because of the nonclosure of mesenteric defects after right colectomy. CONCLUSION: This study suggested that routine procedure of closing the mesenteric defect after open right colectomy might not be beneficial. Additional studies with extended long-term follow-up periods are needed to confirm the benefits of the nonclosure.
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Colectomía/efectos adversos , Mesenterio/cirugía , Complicaciones Posoperatorias/etiología , Femenino , Estudios de Seguimiento , Humanos , Obstrucción Intestinal/etiología , Laparoscopía/métodos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/etiología , Estudios Retrospectivos , Adherencias Tisulares/etiologíaRESUMEN
OBJECTIVE: Patients with colorectal carcinoma (CRC) with pre-existing chronic liver disease (CLD) had a significantly higher 30-day mortality after CRC surgery compared with healthy controls. This study investigated the factors associated with postoperative complications and in-hospital mortality in patients with CRC with coexisting CLD (excluding cirrhosis) who underwent colorectal surgery. DESIGN: A retrospective, observational, population-based study. SETTING: Data were sourced from the National Inpatient Sample database, a part of the Healthcare Cost and Utilisation Project. PARTICIPANTS: This study analysed 7463 inpatients with CRC who underwent colorectal surgery on admission between 2005 and 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint of this study was the prevalence of postoperative complications, and the secondary endpoint was in-hospital mortality. RESULTS: In the CLD group, 36.27% of patients had chronic hepatitis C, 28.36% had non-alcoholic fatty liver disease and 31.19% had other types of CLD. The median hospital stay was 7.0 (5.0-10.0) days in patients with no postoperative complications vs 17.0 (10.0-26.0) days, 8.0 (6.0-12.0) days, 8.0 (6.0-17.0) days, 9.0 (8.0-14.0) days and 10.5 (7.0-17.0) days for patients with postoperative infection, postoperative bleeding, cardiac arrest/heart failure, respiratory complications and digestive complications, respectively (all p<0.05). The presence of CLD was significantly associated with higher risk of postoperative bleeding (adjusted OR (aOR)=1.64, 95% CI 1.15 to 2.34, p=0.007). The presence of CLD (aOR=1.98, 95% CI 1.39 to 2.82, p<0.001) and length of hospital stay (aOR=1.06, 95% CI 1.04 to 1.08, p<0.001) were significantly associated with higher risk of in-hospital mortality. However, hyperlipidaemia was associated with a significantly lower risk of mortality (aOR=0.46, 95% CI 0.28 to 0.75, p=0.002). CONCLUSIONS: Postoperative complications prolonged the length of hospital stay. The presence of CLD and hyperlipidaemia were important factors impacting postoperative complications and in-hospital mortality in patients with CRC with underlying CLD.
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Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/cirugía , Hiperlipidemias/complicaciones , Hepatopatías/complicaciones , Complicaciones Posoperatorias/epidemiología , Anciano , Enfermedad Crónica , Cirugía Colorrectal/efectos adversos , Estudios Transversales , Bases de Datos Factuales , Femenino , Mortalidad Hospitalaria , Humanos , Hiperlipidemias/epidemiología , Tiempo de Internación/estadística & datos numéricos , Hepatopatías/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Chemotherapeutic 5-fluorouracil (5-FU) combined with oxaliplatin is often used as the standard treatment for colorectal cancer (CRC). The disturbing side effects and drug resistance commonly observed in chemotherapy motivate us to develop alternative optimal therapeutic options for CRC treatment. Chrysin, a natural and biologically active flavonoid abundant in propolis, is reported to have antitumor effects on a few CRCs. However, whether and how chrysin achieves similar effectiveness to the 5-FU combination is not clear. In this study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), western blotting, fluorescence microscopy, and reactive oxygen species (ROS) production were assayed. We found that chrysin exhibited similar inhibition of cell viability as the 5-FU combination in a panel of human CRC cells. Furthermore, the results showed that chrysin significantly increased the levels of LC3-II, an autophagy-related marker, in CRC cells, which was not observed with the 5-FU combination. More importantly, blockage of autophagy induction restored chrysin-attenuated CRC cell viability. Further mechanistic analysis revealed that chrysin, not the 5-FU combination, induced ROS generation, and in turn, inhibited the phosphorylation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR). Collectively, these results imply that chrysin may be a potential replacement for the 5-FU and oxaliplatin combination to achieve antitumor activity through autophagy for CRC treatment in the future.
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Antineoplásicos/farmacología , Autofagia/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/metabolismo , Flavonoides/farmacología , Fluorouracilo/farmacología , Células HCT116 , Células HT29 , Humanos , Compuestos Organoplatinos/farmacología , Oxaliplatino , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Black garlic has been reported to show multiple bioactivities against the development of different diseases. In the present study, the hepatoprotective effect of black garlic on injured liver cells was investigated. Rat clone-9 hepatocytes were used for all experiments; tert-Butyl hydroperoxide (tBHP) was used to induce injury of rat clone-9 hepatocytes. The contents of malondialdehyde (MDA) and glutathione (GSH); anti-oxidative enzyme activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx); and mRNA expression levels of interleukin (IL)-6 and IL-8 in rat clone-9 hepatocytes were determined to evaluate the level of cell damage. Black garlic extracts were demonstrated to significantly attenuate tBHP-induced cell death of rat clone-9 hepatocytes (P<0.05). Pretreatment with black garlic extracts antagonized GSH depletion, tBHP-increased MDA accumulation and the mRNA expression level of IL-6/IL-8, and tBHP-decreased antioxidative enzyme activities (all P<0.05). Moreover, the present study revealed that c-Jun N-terminal kinase signaling regulated black garlic-inhibited tBHP effects in rat clone-9 hepatocytes. Our findings demonstrate that black garlic has the hepatoprotective potential to block tBHP-damaged effects on cell death, lipid peroxidation, oxidative stress, and inflammation in rat clone-9 hepatocytes. Thus, the present study indicates that black garlic may be an excellent natural candidate in the development of adjuvant therapy and healthy foods for liver protection.
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The benefits of radiotherapy for colorectal cancer are well documented, but the impact of adjuvant radiotherapy on early-stage rectal adenocarcinoma remains unclear. This study aimed to identify predictors of overall survival (OS) and cancer-specific survival (CSS) in patients with stage II rectal adenocarcinoma treated with preoperative or postoperative radiation therapy. Patients with early-stage rectal adenocarcinoma in the postoperative state were identified using the Surveillance, Epidemiology, and End Results database. The primary endpoints were OS and overall CSS. Stage IIA patients without radiotherapy had significantly lower OS and CSS compared with those who received radiation before or after surgery. Stage IIB patients with radiotherapy before surgery had significantly higher OS and CSS compared with patients in the postoperative or no radiotherapy groups. Patients with signet ring cell carcinoma had the poorest OS among all the groups. Multivariable analysis showed that ethnicity (HR, 0.388, p=0.006) and radiation before surgery (HR, 0.614, p=0.006) were favorable prognostic factors for OS, while age (HR, 1.064, p<0.001), race (HR, 1.599, p=0.041), stage IIB (HR, 3.011, p=0.011), and more than one tumor deposit (TD) (HR, 2.300, p=0.001) were unfavorable prognostic factors for OS. Old age (HR, 1.047, p<0.00 L), stage IIB (HR, 8.619, p=0.005), circumferential resection margin between 0.1 mm and 10 mm (HR, 1.529, p=0.039), and more than one TD (HR, 2.688, p=0.001) were unfavorable prognostic factors for CSS. This population-based study identified predictors of OS and CSS in patients with early-stage resected rectal adenocarcinoma, which may help to guide future management of this patient population.
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Adenocarcinoma/patología , Adenocarcinoma/cirugía , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Programa de VERF , Demografía , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de SupervivenciaRESUMEN
BACKGROUND: Kawasaki disease (KD) is an acute febrile systemic vasculitis that disturbs coronary arteries. Patients' risks of adverse cardiovascular events and subclinical atherosclerosis have been found to significantly increase with polymorphisms of the human cytochrome P450. This current study aims to research the possible relationship between cytochrome P450, family 2, subfamily E and polypeptide 1 (CYP2E1) polymorphisms with KD. METHODS: We selected 6 tag single-nucleotide polymorphisms (SNPs) of the CYP2E1 gene for TaqMan allelic discrimination assay in 340 KD patients and performed analysis on the clinical phenotypes and coronary artery lesions (CALs). CAL associations of tag SNPs were adjusted for age and gender in the logistic regression. RESULTS: The KD patients with a CC genotype of rs915906 demonstrated a greater proportion of CAL formation (P = 0.009). Furthermore, the GG genotype frequencies of rs2070676 showed a significantly greater risk for CAL formation in KD patients (P = 0.007). However, the SNPs of the CYP2E1 gene did not influence CAL formation in the participating KD patients either with or without high-dose acetylsalicylic acid. Using the expression quantitative trait locus analyses, we found that the SNPs associated with CAL formation in KD also affected CYP2E1 expression in certain cell types. CONCLUSION: This study is the first to find that the risk of CAL formation is related to CYP2E1 gene polymorphisms in KD patients.
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Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/genética , Citocromo P-450 CYP2E1/genética , Síndrome Mucocutáneo Linfonodular/epidemiología , Síndrome Mucocutáneo Linfonodular/genética , Polimorfismo de Nucleótido Simple/genética , Preescolar , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Humanos , Lactante , MasculinoRESUMEN
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.
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Neoplasias Colorrectales/metabolismo , Diterpenos/farmacología , Proteoma/metabolismo , Factores Despolimerizantes de la Actina/metabolismo , Animales , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Femenino , Células HCT116 , Humanos , Quinasas Lim/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Profilinas/metabolismo , Proteómica/métodos , Especies Reactivas de Oxígeno/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Quinasas Asociadas a rho/metabolismoRESUMEN
BACKGROUND/AIMS: The study aimed to perform a meta-analysis comparing laparoscopic and open surgery for diverticulitis. METHODS: Studies comparing the outcomes of laparoscopic surgery versus open surgery for diverticulitis that reported quantitative data were included. Outcome measures were mortality and morbidity rates and length of hospital stay. RESULTS: Four randomized controlled trials - 3 prospective and 21 retrospective - were included in the analysis. The total numbers of patients ranged from 5 to 14,562 in the laparoscopic groups and from 4 to 110,172 in the open surgery groups, and the mean patient age ranged from 38.9 to 78 years. Overall analysis revealed that laparoscopic surgery was associated with lower mortality (pooled OR 0.40, 95% CI 0.25-0.63, p < 0.001) and a lower overall morbidity rate (pooled OR 0.65, 95% CI 0.51-0.82, p < 0.001) than open surgery. Laparoscopic surgery was associated with a higher anastomotic bleeding rate, but lower rates of ileus, anastomotic leakage, small bowel obstruction, wound infection, fascial dehiscence and intra-abdominal abscesses. Length of hospital stay was less with laparoscopic surgery. CONCLUSIONS: The current meta-analysis supports the use of laparoscopy for the treatment of diverticulitis. The results, however, should be interpreted with caution.
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Colectomía/métodos , Colon/cirugía , Diverticulitis del Colon/cirugía , Laparoscopía/efectos adversos , Complicaciones Posoperatorias/etiología , Absceso Abdominal/etiología , Anastomosis Quirúrgica/efectos adversos , Fuga Anastomótica/etiología , Colectomía/mortalidad , Diverticulitis del Colon/mortalidad , Humanos , Ileus/etiología , Laparoscopía/mortalidad , Tiempo de Internación , Dehiscencia de la Herida Operatoria/etiología , Infección de la Herida Quirúrgica/etiologíaRESUMEN
BACKGROUND: Hericium erinaceus is an edible mushroom; its various pharmacological effects which have been investigated. This study aimed to demonstrate whether efficacy of oral administration of H. erinaceus mycelium (HEM) and its isolated diterpenoid derivative, erinacine A, can act as an anti-neuroinflammatory agent to bring about neuroprotection using an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson's disease, which results in motor disturbances, in addition to elucidating the mechanisms involved. METHODS: Mice were treated with and without HEM or erinacine A, after MPTP injection for brain injuries by the degeneration of dopaminergic nigrostriatal neurons. The efficacy of oral administration of HEM improved MPTP-induced loss of tyrosine hydroxylase positive neurons and brain impairment in the substantia nigra pars compacta as measured by brain histological examination. RESULTS: Treatment with HEM reduced MPTP-induced dopaminergic cell loss, apoptotic cell death induced by oxidative stress, as well as the level of glutathione, nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE). Furthermore, HEM reversed MPTP-associated motor deficits, as revealed by the analysis of rotarod assessment. Our results demonstrated that erinacine A decreases the impairment of MPP-induced neuronal cell cytotoxicity and apoptosis, which were accompanied by ER stress-sustained activation of the IRE1α/TRAF2, JNK1/2 and p38 MAPK pathways, the expression of C/EBP homologous protein (CHOP), IKB-ß and NF-κB, as well as Fas and Bax. CONCLUSION: These physiological and brain histological changes provide HEM neuron-protective insights into the progression of Parkinson's disease, and this protective effect seems to exist both in vivo and in vitro.
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Agaricales/química , Apoptosis/efectos de los fármacos , Diterpenos/aislamiento & purificación , Estrés del Retículo Endoplásmico/efectos de los fármacos , Intoxicación por MPTP/tratamiento farmacológico , Micelio/química , Neuroprotección/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/administración & dosificación , Animales , Conducta Animal , Encéfalo/efectos de los fármacos , Encéfalo/patología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Diterpenos/química , Endorribonucleasas/metabolismo , Intoxicación por MPTP/fisiopatología , Ratones Endogámicos C57BL , Modelos Biológicos , Actividad Motora/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/patología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Neurotoxinas/toxicidad , Proteínas Serina-Treonina Quinasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
This study attempted to purify eutrophic landscape water under a low pollutant concentration and high hydraulic volume loading using an embedded subsurface flow (SSF) constructed wetland (CW). Three species of aquatic plants (i.e., Cyperus alternifolius subsp. flabelliformis, Canna indica, and Hydrocotyle verticillata) were found to be conducive to the requirements of purifying the low-polluted water. Field results of nearly 2 years of experiments showed that SSF CW purified the eutrophic water and maintained the landscape water in a visibly clear condition. In an environment approaching the SSF CW background concentration, pollutant removal processes were divided into modulation and optimum performance periods. Average concentrations of biochemical oxygen demand (BOD), ammonium-nitrogen (NH4 (+)-N), and total phosphorous (TP) in the optimum performance period were 0.69-1.00, 0.35-1.42, and 0.19-0.23 mg/L, respectively. Almost 500 days of BOD and NH4 (+)-N removals were necessary to perform optimally. A shorter period, 350 days, was required for TP optimum removal. This feature of two stage removals was not found in chlorophyll-a (Chl-a) and suspended solids (SS), whose averages were 11.86-17.98 and 13.30 µg/L, respectively. Filter cleaning and water replacement were unnecessary, while only water recharging was needed to compensate for the water lost by evapotranspiration. The field SSF CW has maintained its performance level for over 7 years.
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Centella/metabolismo , Cyperus/metabolismo , Restauración y Remediación Ambiental/métodos , Contaminantes Químicos del Agua/metabolismo , Zingiberales/metabolismo , Biodegradación Ambiental , Ambiente , Nitrógeno/metabolismo , Fósforo/metabolismo , HumedalesRESUMEN
A high level of serum resistin has recently been found in patients with a number of cancers, including colorectal cancer (CRC). Hence, resistin may play a role in CRC development. Fulvic acid (FA), a class of humic substances, possesses pharmacological properties. However, the effect of FA on cancer pathophysiology remains unclear. The aim of this study was to investigate the effect of resistin on the endothelial adhesion of CRC and to determine whether FA elicits an antagonistic mechanism to neutralize this resistin effect. Human HCT-116 (p53-negative) and SW-48 (p53-positive) CRC cells and human umbilical vein endothelial cells (HUVECs) were used in the experiments. Treatment of both HCT-116 and SW-48 cells with resistin increases the adhesion of both cells to HUVECs. This result indicated that p53 may not regulate this resistin effect. A mechanistic study in HCT-116 cells further showed that this resistin effect occurs via the activation of NF-κB and the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Co-treating cells with both FA and resistin revealed that FA significantly attenuated the resistin-increased NF-κB activation and ICAM-1/VCAM-1 expression and the consequent adhesion of HCT-116 cells to HUVECs. These results demonstrate the role of resistin in promoting HCT-116 cell adhesion to HUVECs and indicate that FA might be a potential candidate for the inhibition of the endothelial adhesion of CRC in response to resistin.
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Benzopiranos/farmacología , Neoplasias Colorrectales/metabolismo , Células Endoteliales de la Vena Umbilical Humana/fisiología , Resistina/fisiología , Adhesión Celular , Quimiocinas/genética , Quimiocinas/metabolismo , Quimiocinas CXC , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Células HCT116 , Humanos , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , FN-kappa B/metabolismo , Activación TranscripcionalRESUMEN
BACKGROUND/AIMS: Minimally invasive laparoscopy provides faster recovery, less pain, fewer complications, and better cosmesis than laparotomy. We aimed to evaluate outcomes of postoperative local anesthesia infiltration at the single-incision laparoscopic surgery (SILS) wound. METHODOLOGY: This prospective, non-randomized controlled study evaluated outcomes of 58 colorectal cancer cases receiving SILS from May 2010 to December 2010. Twenty-nine patients received postoperative infiltration of local anesthesia at the wound site; another 29 patients did not. Demographic, intra- and postoperative data were compared. Postoperative pain was assessed by visual analogue scale and analgesic usage. RESULTS: Local anesthesia group included 16 males, 13 females (mean age, 62.0 ± 15.1 years); no local anesthesia group included 14 males, 15 females (mean age, 58.1 ± 12.7 years). There were no significant differences between groups at baseline (i.e., age, gender, disease stage, tumor location or size) except BMI (25.2 ± 2.8 vs. 23.5 ± 3.4, p = 0.041) was significantly higher. Postoperative pain scores were significantly lower in local anesthesia group than in no local anesthesia group (median VAS score 2.0, IQR 2.0-3.0 vs. VAS score 3.0, IQR 3.0-4.0, respectively, P = 0.024). CONCLUSIONS: Our results provide further evidence of SILS safety. Local anesthesia infiltration at SILS wounds decreases postoperative wound pain and analgesic usage.
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Anestésicos Locales/uso terapéutico , Bupivacaína/uso terapéutico , Colectomía/métodos , Dolor Postoperatorio/prevención & control , Adulto , Anciano , Analgésicos Opioides/uso terapéutico , Neoplasias del Colon , Femenino , Humanos , Laparoscopía/métodos , Masculino , Meperidina/uso terapéutico , Persona de Mediana Edad , Dimensión del Dolor , Dolor Postoperatorio/tratamiento farmacológicoRESUMEN
PURPOSE: Nonspecific gastrointestinal symptoms make diagnosis of amebiasis difficult. Certain colonoscopic findings predict amebic colitis while others suggest different diagnoses. We aimed to evaluate the diagnostic capability of colonic evaluation of amebiasis. METHODS: We retrospectively reviewed data of all amebiasis cases admitted to our institution between 2003 and 2012. Cases were diagnosed by clinical presentation, laboratory examinations, and colonoscopy with biopsy and microscopic examination. Patients were stratified as right-sided colitis and proctosigmoiditis. A systematic review was conducted by searching Medline, Cochrane, EMBASE, and Google Scholar using key words amebiasis, amebic colitis, amebic proctosigmoiditis, colonoscopy, and Entamoeba histolytica. Data were extracted from articles meeting the inclusion criteria. Colonoscopic findings were described and studies were assessed for quality. RESULTS: The current series included 20 patients (5 male, 15 female, median age 51), 7 with amebic liver abscess and 13 with amebic colitis. Colonoscopic findings of right-sided colitis included aphthae or erosions, ulcers, exudates, or edematous swollen mucosa in cecum, and findings for proctosigmoiditis were edematous swollen mucosa with bloody exudate. In 25 studies, colonoscopic findings of 41 patients (36 male, 5 female, median age 43.39 years) included mainly ulcers in the cecum and rectum, ulcerated mass, and edematous mucosa; and in fewer patients, submucosal invasion suggestive of colon cancer, bleeding ulcers, proctitis, and ulcers with aphthae in rectum. CONCLUSIONS: Colonic evaluation of suspected amebiasis is of diagnostic value when accompanied by biopsy and microscopic identification of Entamoeba species. Colonoscopic manifestations vary between right-sided colitis and proctosigmoiditis.