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1.
Aging Clin Exp Res ; 36(1): 193, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39311977

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a significant health concern, particularly among older adults. Outcomes between laparoscopic and robot-assisted surgeries for right-sided colon cancers in the oldest old population have yet to be evaluated despite increased use of these surgeries. AIM: This study aimed to compare clinical outcomes after robot-assisted right hemicolectomy (RARH) versus laparoscopic right hemicolectomy (LRH) in octogenarian and nonagenarian patients. METHODS: This population-based, retrospective and observational study analyzed the data of adults ≥ 80 years old diagnosed with right-side colon cancer who received RARH or LRH. All data were extracted from the US National Inpatient Sample (NIS) database 2005-2018. Associations between type of surgery and in-hospital outcomes were determined using univariate and multivariable logistic regression and linear regression analysis. RESULTS: Data of 7,550 patients (representing 37,126 hospitalized patients in the U.S.) were analyzed. Mean age of the study population was 84.8 years, 61.4% were females, and 79.1% were non-smokers. After adjusting for relevant confounders, regression analysis showed that patients undergoing RARH had a significantly shorter LOS (adjusted Beta (aBeta), -0.24, 95% CI: -0.32, -0.15) but greater total hospital costs (aBeta, 26.54, 95% CI: 24.64, 28.44) than patients undergoing LRH. No significant differences in mortality, perioperative complications, and risk of unfavorable discharge were observed between the two procedures (p > 0.05). Stratified analyses by frailty status revealed consistent results. CONCLUSIONS: RARH is associated with a significantly shorter LOS but higher total hospital costs than LRH among octogenarians and nonagenarians. Other short-term outcomes for this population are similar between the two procedures, including in-hospital mortality, perioperative complications, and unfavorable discharge. These findings also apply to frail patients.


Assuntos
Colectomia , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Feminino , Masculino , Colectomia/métodos , Laparoscopia/métodos , Laparoscopia/estatística & dados numéricos , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Estudos Retrospectivos , Estados Unidos/epidemiologia , Pacientes Internados , Tempo de Internação , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Neoplasias do Colo/cirurgia , Neoplasias do Colo/mortalidade
2.
Cancers (Basel) ; 15(18)2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37760404

RESUMO

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.

3.
Int J Colorectal Dis ; 37(5): 1189-1197, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35476135

RESUMO

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.


Assuntos
Fístula Anastomótica , Cirurgia Colorretal , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Fístula Anastomótica/prevenção & controle , Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase 2 , Humanos , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco
4.
Cancers (Basel) ; 13(20)2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34680230

RESUMO

(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.

5.
Sci Rep ; 10(1): 6459, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32296122

RESUMO

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.


Assuntos
Neoplasias Colorretais/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Sarcopenia/epidemiologia , Abdome/diagnóstico por imagem , Idoso , Aspartato Aminotransferases/sangue , Índice de Massa Corporal , Neoplasias Colorretais/complicações , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Fígado/enzimologia , Fígado/patologia , Fígado/cirurgia , Testes de Função Hepática , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Período Pré-Operatório , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Sarcopenia/diagnóstico , Sarcopenia/etiologia , Tomografia Computadorizada por Raios X
6.
J Cell Physiol ; 234(7): 10336-10344, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30480806

RESUMO

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.


Assuntos
Celecoxib/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Anti-Inflamatórios não Esteroides/farmacologia , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Humanos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo
7.
Biomed Res Int ; 2018: 9123912, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30356463

RESUMO

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.


Assuntos
Colectomia/efeitos adversos , Mesentério/cirurgia , Complicações Pós-Operatórias/etiologia , Feminino , Seguimentos , Humanos , Obstrução Intestinal/etiologia , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Estudos Retrospectivos , Aderências Teciduais/etiologia
8.
BMJ Open ; 8(7): e020511, 2018 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-30018094

RESUMO

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.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Hiperlipidemias/complicações , Hepatopatias/complicações , Complicações Pós-Operatórias/epidemiologia , Idoso , Doença Crônica , Cirurgia Colorretal/efeitos adversos , Estudos Transversais , Bases de Dados Factuais , Feminino , Mortalidade Hospitalar , Humanos , Hiperlipidemias/epidemiologia , Tempo de Internação/estatística & dados numéricos , Hepatopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
9.
Int J Mol Sci ; 19(6)2018 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-29899208

RESUMO

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.


Assuntos
Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Flavonoides/farmacologia , Fluoruracila/farmacologia , Células HCT116 , Células HT29 , Humanos , Compostos Organoplatínicos/farmacologia , Oxaliplatina , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR/metabolismo
10.
J Investig Med ; 65(8): 1148-1154, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28735257

RESUMO

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.


Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Programa de SEER , Demografia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida
11.
Pediatr Infect Dis J ; 36(11): 1039-1043, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28650933

RESUMO

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.


Assuntos
Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Citocromo P-450 CYP2E1/genética , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Síndrome de Linfonodos Mucocutâneos/genética , Polimorfismo de Nucleotídeo Único/genética , Pré-Escolar , Estudos de Coortes , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Humanos , Lactente , Masculino
12.
J Cell Mol Med ; 21(3): 588-599, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27709782

RESUMO

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.


Assuntos
Neoplasias Colorretais/metabolismo , Diterpenos/farmacologia , Proteoma/metabolismo , Fatores de Despolimerização de Actina/metabolismo , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Células HCT116 , Humanos , Quinases Lim/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Profilinas/metabolismo , Proteômica/métodos , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Quinases Associadas a rho/metabolismo
13.
Dig Surg ; 34(3): 203-215, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27941315

RESUMO

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.


Assuntos
Colectomia/métodos , Colo/cirurgia , Doença Diverticular do Colo/cirurgia , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Abscesso Abdominal/etiologia , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/etiologia , Colectomia/mortalidade , Doença Diverticular do Colo/mortalidade , Humanos , Íleus/etiologia , Laparoscopia/mortalidade , Tempo de Internação , Deiscência da Ferida Operatória/etiologia , Infecção da Ferida Cirúrgica/etiologia
14.
Int J Mol Sci ; 16(12): 29370-82, 2015 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-26690142

RESUMO

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.


Assuntos
Benzopiranos/farmacologia , Neoplasias Colorretais/metabolismo , Células Endoteliais da Veia Umbilical Humana/fisiologia , Resistina/fisiologia , Adesão Celular , Quimiocinas/genética , Quimiocinas/metabolismo , Quimiocinas CXC , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , NF-kappa B/metabolismo , Ativação Transcricional
15.
Hepatogastroenterology ; 62(140): 811-6, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26902007

RESUMO

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.


Assuntos
Anestésicos Locais/uso terapêutico , Bupivacaína/uso terapêutico , Colectomia/métodos , Dor Pós-Operatória/prevenção & controle , Adulto , Idoso , Analgésicos Opioides/uso terapêutico , Neoplasias do Colo , Feminino , Humanos , Laparoscopia/métodos , Masculino , Meperidina/uso terapêutico , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/tratamento farmacológico
16.
Int J Colorectal Dis ; 30(1): 31-41, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25346004

RESUMO

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.


Assuntos
Colonoscopia , Disenteria Amebiana/diagnóstico , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
17.
Int J Mol Sci ; 16(1): 159-77, 2014 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-25547486

RESUMO

Toll-like receptors (TLRs) not only form an important part of the innate immune system but also serve to activate the adaptive immune system in response to cancer. Real-time PCR; immunohistochemical stain and Western blotting analyses were performed to clarify molecular alterations in colorectal cancer (CRC) patients. We identified Toll-like receptor 1 (TLR1), TLR2, TLR4 and TLR8 gene expression levels and downstream gene, i.e., interleukin-6 (IL-6), IL-8, interferon-α (IFN-α) and myeloid differentiation primary-response protein-88 (MyD88), expression levels in CRC patients and in cancer cell lines. CRC tissues have higher TLR1, TLR2, TLR4, TLR8, IL-6 and IL-8 gene expression levels than do the normal colon mucosa (p < 0.05). TLR2 expression varied in different cell types (mucosa and lymphocytes). There was no difference in the MyD88 and IFN-α gene expression levels between cancerous and normal colon mucosa. CRC patients had higher levels of IL-6 (p = 0.002) and IL-8 (p = 0.038) expression than healthy volunteers did; and higher IL-6 and IL-8 expression was also found to signify a higher risk of recurrence. CL075 (3M002) treatments can reduce the production of IL-8 in different cancer cell lines. The signaling pathway of TLRs in cancer tissue is different from that in normal cells; and is MyD88-independent. Higher expression levels of TLR1, TLR2, TLR 4 and TLR 8 mRNA were related to upregulation inflammatory cytokines IL-6 and IL-8 gene expression in tissue and to the upregulation of IL-6 in blood. The concentration of IL-6 in serum can be used as an indicator of the possibility of CRC recurrence. Treatment with 3M002 can reduce IL-6 production in vitro and may prevent CRC recurrence. Our findings provide evidence that TLR1, TLR2, TLR4 and TLR8 gene expression induce downstream IL-6 and IL-8 gene expression; detection of these expression levels can serve as a CRC marker.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Interleucina-6/metabolismo , Receptores Toll-Like/metabolismo , Regulação para Cima , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-6/genética , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Toll-Like/genética
18.
J Laparoendosc Adv Surg Tech A ; 24(9): 606-11, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25079975

RESUMO

BACKGROUND: Single-incision laparoscopic colectomy (SILC) is one of several promising operation choices. Our previous study demonstrated that SILC with a self-made glove-port system both improves the feasibility of SILC and decreases the cost expense of surgery. Because the incision site for SILC could be made at either the umbilicus or McBurney's point, we are interested in whether the incision site affects the outcomes of patients, which is a less explored topic. The purpose of this study is not only to show the results of SILC with a self-made glove-port system for supporting its feasibility, but also to compare the short-term surgical outcomes between SILC with the incision made at the umbilicus and at McBurney's point. SUBJECTS AND METHODS: We collected and reviewed the medical records of patients who received SILC with a self-made glove-port system for tumors in the left side of the colon from August 2009 to March 2011. All operations were performed by a single surgeon. Comparisons of the demographic characteristics, perioperative data, and clinical outcomes between umbilical and McBurney's SILCs were performed. Postoperative pain was assessed by a visual analog scale and opiate demand. RESULTS: In total, 61 patients were enrolled in this retrospective study. Five of 48 (10.4%) tumors in the umbilical SILC group and 5 of 13 (38.5%) tumors in the McBurney's SILC group were located below the peritoneal reflection. The tumor location was significantly different between these two groups (P=.015). Patients in the umbilical SILC group had significantly higher frequency of opiate demand than those in the McBurney's SILC group (0.4±0.7 versus 1.4±1.8, respectively; P=.002). CONCLUSIONS: This study further provides evidence for supporting the safety and feasibility of SILC in treating colorectal diseases. More important is that McBurney's SILC not only alleviates the patient response to wound pain, but also provides the same site for a diverting enterostomy to avoid creating an additional wound.


Assuntos
Colectomia/métodos , Neoplasias do Colo/cirurgia , Laparoscopia/métodos , Dor Pós-Operatória/prevenção & controle , Umbigo , Abdome , Idoso , Analgésicos Opioides/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/tratamento farmacológico , Estudos Retrospectivos
19.
Int J Mol Sci ; 15(9): 15073-89, 2014 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-25167134

RESUMO

Hericium erinaceus, an edible mushroom, has been demonstrated to potentiate the effects of numerous biological activities. The aim of this study was to investigate whether H. erinaceus mycelium could act as an anti-inflammatory agent to bring about neuroprotection using a model of global ischemic stroke and the mechanisms involved. Rats were treated with H. erinaceus mycelium and its isolated diterpenoid derivative, erinacine A, after ischemia reperfusion brain injuries caused by the occlusion of the two common carotid arteries. The production of inflammatory cytokines in serum and the infracted volume of the brain were measured. The proteins from the stroke animal model (SAM) were evaluated to determine the effect of H. erinaceus mycelium. H. erinaceus mycelium reduced the total infarcted volumes by 22% and 44% at a concentration of 50 and 300 mg/kg, respectively, compared to the SAM group. The levels of acute inflammatory cytokines, including interleukin-1ß, interleukin-6 and tumor necrosis factor á, were all reduced by erinacine A. Levels of nitrotyrosine-containing proteins, phosphorylation of p38 MAPK and CCAAT enhancer-binding protein (C/EBP) and homologous protein (CHOP) expression were attenuated by erinacine A. Moreover, the modulation of ischemia injury factors present in the SAM model by erinacine A seemed to result in the suppression of reactive nitrogen species and the downregulation of inducible NO synthase (iNOS), p38 MAPK and CHOP. These findings confirm the nerve-growth properties of Hericium erinaceus mycelium, which include the prevention of ischemic injury to neurons; this protective effect seems to be involved in the in vivo activity of iNOS, p38 MAPK and CHOP.


Assuntos
Basidiomycota/química , Isquemia Encefálica/tratamento farmacológico , Diterpenos/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Morte Celular , Citocinas/genética , Citocinas/metabolismo , Diterpenos/uso terapêutico , Masculino , Micélio/química , Neurônios/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo
20.
J Laparoendosc Adv Surg Tech A ; 23(11): 932-7, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24117036

RESUMO

PURPOSE: The instrument crowding derived from commercially available access devices in single-incision laparoscopic surgery (SILS) is a challenge to overcome. This study was designed to evaluate the short-term surgical outcomes of SILS by applying a self-made device in patients with benign colon diseases. PATIENTS AND METHODS: We collected and reviewed the medical records of patients who received SILC by using a self-made glove-port system from March 2007 to July 2012. All operations were performed by a single surgeon. Sixty-four patients (36 males and 28 females) were enrolled for this study. Among them, 15 patients received right-side colon resection, 31 patients received left-side colon resection, and 18 patients received total colectomy. RESULTS: In the analysis of medical records from these groups of patients, we found that there was no significant difference of gender, body mass index, tumor size, incision length, and blood loss among these three groups. Furthermore, no significant difference of the pain scores, average length of hospital stay, and average duration of bowel return was observed among these three groups. However, it was notable that younger age, longer duration of operation, and longer bowel resection were indeed significantly found in the patients undergoing total colectomy. On the other hand, curved instruments were used in 5 (16.1%) of 31 patients with left-side colon resection. CONCLUSIONS: A simple self-made glove-port device was proven as a practical method of SILS for colorectal diseases. These findings suggested that single-incision laparoscopic total colectomy provides compatible clinical outcome in the patients with benign colon diseases compared with the other two surgical procedures used in this study.


Assuntos
Colectomia/instrumentação , Doenças do Colo/cirurgia , Luvas Cirúrgicas , Laparoscopia/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças do Colo/patologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
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