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1.
Gastroenterol Rep (Oxf) ; 8(5): 343-348, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33163188

RESUMO

The Denonvilliers' fascia (DVF) plays an important role in rectal surgery because of its anatomic position and its relationship to the surrounding organs. It affects the surgical plane anterior to the rectum in the procedure of total mesorectal excision (TME). Anatomical and embryological studies have helped us to understand this structure to some extent, but many controversies remain. In terms of its embryonical origin, there are three mainstream hypotheses: peritoneal fusion of the embryonic cul-de-sac, condensation of embryonic mesenchyme, and mechanical pressure. Regarding its architecture, the DVF may be a single, two, or multiple layers, or a composite single-layer structure. In women, most authors deem that this structure does exist but they are willing to call it the rectovaginal septum rather than the DVF. Operating behind the DVF is supported by most surgeons. This article will review those mainstream studies and opinions on the DVF and combine them with what we have observed during surgery to discuss those controversies and consensuses mentioned above. We hope this review may help young colorectal surgeons to have a better understanding of the DVF and provide a platform from which to guide future scientific research.

2.
Cancer Cell ; 38(5): 734-747.e9, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-32888432

RESUMO

We integrate the genomics, proteomics, and phosphoproteomics of 480 clinical tissues from 146 patients in a Chinese colorectal cancer (CRC) cohort, among which 70 had metastatic CRC (mCRC). Proteomic profiling differentiates three CRC subtypes characterized by distinct clinical prognosis and molecular signatures. Proteomic and phosphoproteomic profiling of primary tumors alone successfully distinguishes cases with metastasis. Metastatic tissues exhibit high similarities with primary tumors at the genetic but not the proteomic level, and kinase network analysis reveals significant heterogeneity between primary colorectal tumors and their liver metastases. In vivo xenograft-based drug tests using 31 primary and metastatic tumors show personalized responses, which could also be predicted by kinase-substrate network analysis no matter whether tumors carry mutations in the drug-targeted genes. Our study provides a valuable resource for better understanding of mCRC and has potential for clinical application.

3.
Dig Dis Sci ; 65(12): 3660-3671, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32500285

RESUMO

BACKGROUND: The causes of chronic antibiotic refractory pouchitis (CARP) and pouch failure in inflammatory bowel disease (IBD) patients remain unknown. Our previous small study showed peripouch fat area measured by MRI was associated with pouchitis. AIMS: To explore the relationship between peripouch fat area on CT imaging and pouch outcomes. METHODS: This is a historical cohort study. Demographic, clinical, and radiographic data of IBD patients with abdominal CT scans after pouch surgery between 2002 and 2017 were collected. Peripouch fat areas and mesenteric peripouch fat areas were measured on CT images at the middle pouch level. RESULTS: A total of 435 IBD patients were included. Patients with higher peripouch fat areas had a higher prevalence of CARP. Univariate analyses demonstrated that long duration of the pouch, high weight or body mass index, the presence of primary sclerosing cholangitis or other autoimmune disorders, and greater peripouch fat area or mesenteric peripouch fat area were risk factors for CARP. Multivariable analyses demonstrated that the presence of primary sclerosing cholangitis or autoimmuned disorders, and greater peripouch fat area (odds ratio [OR] 1.031; 95% confidence interval [CI] 1.016-1.047, P < 0.001) or mesenteric peripouch fat area were independent risk factors for CARP. Of the 435 patients, 139 (32.0%) had two or more CT scans. Multivariable Cox proportional hazard analyses showed that "peripouch fat area increase ≥ 15%" (OR 3.808, 95%CI 1.703-8.517, P = 0.001) was an independent predictor of pouch failure. CONCLUSIONS: A great peripouch fat area measured on CT image is associated with a higher prevalence of CARP, and the accumulation of peripouch fat is a risk factor for pouch failure. The assessment of peripouch fat may be used to monitor the disease course of the ileal pouch.

4.
Front Oncol ; 10: 310, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32232001

RESUMO

Background: Next generation sequencing (NGS)-based multi-gene panel tests have been performed to predict the treatment response and prognosis in patients with colorectal cancer (CRC). Whether the multi-gene mutation results of formalin-fixed paraffin-embedded (FFPE) tissues are identical to those of fresh frozen tissues remains unknown. Methods: A 22-gene panel with 103 hotspots was used to detect mutations in paired fresh frozen tissue and FFPE tissue from 118 patients with CRC. Results: In our study, 117 patients (99.2%) had one or more variants, with 226 variants in FFPE tissue and 221 in fresh frozen tissue. Of the 129 variants identified in this study, 96 variants were present in both FFPE and fresh frozen tissues; 27 variants were found in FFPE tissues only; 6 variants were found only in fresh frozen tissues. The mutation results demonstrated >94.0% concordance in all variants, with Kappa coefficient >0.500 in 64.3% (83/129) of variants. At the gene level, concordance ranged from 73.8 to 100.0%, with Kappa coefficient >0.500 in 81.3% (13/16) of genes. Conclusions: The results of mutation analysis performed with a multi-gene panel and FFPE and fresh frozen tissue were highly concordant in patients with CRC, at both the variant and gene levels. There were, however, some important differences in mutation results between the two tissue types. Therefore, fresh frozen tissue should not routinely be replaced with FFPE tissue for mutation analysis with a multi-gene panel. Rather, FFPE tissue is a reasonable alternative for fresh frozen tissue when the latter is unavailable.

5.
Int J Colorectal Dis ; 35(4): 665-674, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32020266

RESUMO

BACKGROUND: Pouch prolapse is a rare pouch complication which often leads to pouch failure in inflammatory bowel disease (IBD) patients. Its exact cause remains unknown. Floppy pouch complex (FPC) was defined as the presence of any one of the following pouch disorders: pouch prolapse, afferent limb syndrome (ALS), redundant loop, and pouch folding. We aimed to explore the role of peripouch fat area in the occurrence of pouch prolapse and FPC. METHODS: Pouch patients with available pouchoscopy and abdominal CT scans who were followed up between 2011 and 2017 in Cleveland Clinic were reviewed. Peripouch fat was measured on CT images. RESULTS: Of the 93 included patients, 31 were females; 87 had J pouches and 6 had S pouches. The median duration of pouch was 8.0 (interquartile range [IQR] 5.0-16.5) years. A total of 18 cases (19.4%, 18/93) were identified as FPC, including 12 pouch prolapse, 5 ALS, 1 redundant loop, and 3 pouch folding. Patients with pouch prolapse had lower peripouch fat area (13.6 (9.3-18.5) vs. 27.6 (11.0-46.2)cm2, P = 0.022) than those without. Patients with FPC had lower peripouch fat area (15.4 (11.4-20.6) vs. 27.6 (11.0-46.9)cm2, P = 0.040) than those without. Univariate and multivariate analyses demonstrated that lower peripouch fat area, lower weight, and family history of IBD were independent predictors of pouch prolapse and FPC. CONCLUSIONS: A lower peripouch fat area was observed in inflammatory bowel disease patients with pouch prolapse and FPC. Longitudinal studies are needed to further elucidate the role of peripouch fat in the pathogenesis of pouch prolapse and FPC.

6.
Surg Oncol ; 31: 67-74, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31541909

RESUMO

The molecular mechanisms governing the metastasis of colorectal cancer (CRC) are incompletely understood. In the present study, we found NOVA1 to be expressed at higher levels in CRC cell lines and tissue samples, and this upregulation was positively correlated with TNM stage (p = 0.034), poor differentiation (p = 0.001), and lymph node metastasis (p = 0.008). Both overall survival (OS) and relapse-free survival (RFS) were both significantly decreased in patients with high NOVA1 expression relative to those with low expression. Through a multivariate analysis, we determined that NOVA1 independently predicted poor outcomes in those with CRC. In further functional studies, we found that NOVA1 expression controlled the proliferation and invasive characteristics of CRC cells via a mechanism wherein NOVA1 bound and stabilized the IL6 mRNA, enhancing IL-6/JAK2/STAT3 signaling to in turn upregulate matrix metalloproteinases (MMPs) 2, 7, and 9. NOVA1 therefore plays key functional roles in regulating CRC progression, and our results further indicate that it serve as a valuable prognostic biomarker and potentially a target for therapeutic treatment in individuals with CRC.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Interleucina-6/genética , Janus Quinase 2/metabolismo , Neoplasias Pulmonares/secundário , Proteínas de Ligação a RNA/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Janus Quinase 2/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico , Estabilidade de RNA , Proteínas de Ligação a RNA/genética , Fator de Transcrição STAT3/genética , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Int J Clin Oncol ; 24(2): 141-152, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30612269

RESUMO

BACKGROUND: Simultaneous detection of multiple molecular biomarkers is helpful in the prediction of treatment response and prognosis for colorectal cancer (CRC) patients. METHODS: A 22-gene panel consisting of 103 hotspot regions was utilized in the formalin-fixed paraffin-embedded (FFPE) tissue samples of 207 CRC patients, using the next-generation sequencing (NGS)-based multiplex PCR technique. Those 22 genes included AKT1, ALK, BRAF, CTNNB1, DDR2, EGFR, ERBB2, ERBB4, FBXW7, FGFR1, FGFR2, FGFR3, KRAS, MAP2K1, MET, NOTCH1, NRAS, PIK3CA, PTEN, SMAD4, STK11, and TP53. RESULTS: Of the 207 patients, 193 had one or more variants, with 170, 20, and 3 having one, two, and three mutated genes, respectively. Of the total 414 variants identified in this study, 384, 25, and 5 were single-nucleotide variants, deletion, and insertion. The top four frequently mutated genes were TP53, KRAS, PIK3CA, and FBXW7. There was high consistency between the results of NGS-PCR technique and routine ARMS-PCR in KRAS and BRAF mutation detection. Univariate and multivariate analyses demonstrated that advanced TNM stage, elevated serum CEA, total variants number ≥ 2, AKT1 and PTEN mutation were independent predictors of shorter DFS; poor differentiation, advanced TNM stage, total variants number ≥ 2, BRAF, CTNNB1 and NRAS mutation were independent predictors of shorter OS. CONCLUSIONS: It is feasible to detect multiple gene mutations with a 22-gene panel in FFPE CRC specimens. TNM stage and total variants number ≥ 2 were independent predictors of DFS and OS. Detection of multiple gene mutations may provide additional prognostic information to TNM stage in CRC patients.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , Inclusão em Parafina , Transcriptoma , Idoso , Neoplasias Colorretais/genética , Feminino , Formaldeído , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
8.
J Dig Dis ; 19(11): 685-692, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30345716

RESUMO

OBJECTIVE: Over the past decades, carbohydrate antigen 72-4 (CA72-4) was thought to be a tumor marker that was elevated in healthy individuals and patients with malignancies, including gastrointestinal (GI), ovarian, endometrial and lung malignancies. Furthermore, studies found that elevated serum CA72-4 might predict digestive tumors, especially gastric tumors, although there was still neither a sensitive nor specific tumor biomarker for gastric cancer (GC). This study aimed to evaluate the diagnostic accuracy of CA72-4 in predicting malignancies, especially GC. METHODS: Altogether 403 patients underwent a CA72-4 test after admission to the Department of Gastroenterology in Changhai Hospital, the Second Military Medical University, from 1 June 2015 to 31 October 2015. Their age and sex, main symptoms, and final diagnoses were summarized. RESULTS: The positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of CA72-4 for diagnosing GC were 31.58%, 79.17%, 1.70, and 0.97, respectively. In the receiver operating characteristic (ROC) curve analysis, the area under the ROC curve for discriminating between patients with GC and those without was 0.62. CONCLUSION: Performing a CA72-4 test on its own is of little use for predicting malignances, especially GC, in patients with GI diseases.


Assuntos
Antígenos Glicosídicos Associados a Tumores/sangue , Biomarcadores Tumorais/sangue , Neoplasias Gastrointestinais/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade , Adulto Jovem
9.
Biomed Res Int ; 2018: 7469197, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30105243

RESUMO

Background: Osteoarthritis (OA) is a common degeneration disease characterized with joint pain. The aim of the present study was to systemically review the effects of LIPUS on pain relief and functional recovery in patients with knee osteoarthritis (OA). Methods: PubMed, Embase, and Cochrane Library were searched manually for researches on LIPUS treatment in patients with knee OA from 1945 to July 2017. Two investigators independently selected the studies according to the inclusion and exclusion criteria, extracted the concerned data, and assessed the included studies. Meta-analysis was performed to evaluate VAS, WOMAC, and ambulation speed between control and LIPUS groups. Results: Five studies were selected in this study. Compared with control group, LIPUS group received a decrease of pain intensity with moderate heterogeneity (-0.79, 95% CI, -1.57 to 0.00; I2 = 65%, P = 0.04) by VAS and improvement in knee function by WOMAC (-5.30, 95% CI, -2.88 to -7.71; I2 = 44%, P = 0.17). No significant improvement was found in ambulation speed (0.08 m/s, 95% CI, -0.02 to 0.18 m/s; I2 = 68%, P = 0.03). Conclusion: The present study includes 5 high quality randomized controlled trials. The result indicated that LIPUS, used to treat knee OA without any adverse effect, had a beneficial effect on pain relief and knee functional recovery. More evidence is needed to prove whether LIPUS is effective in improving walking ability.


Assuntos
Osteoartrite do Joelho/terapia , Terapia por Ultrassom/métodos , Artralgia , Humanos , Articulação do Joelho , Ensaios Clínicos Controlados Aleatórios como Assunto , Ondas Ultrassônicas
10.
Sci Rep ; 7(1): 7882, 2017 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-28801584

RESUMO

To compare protein expression levels, gene mutation and survival among Right-Sided Colon Cancer (RSCC), Left-Sided Colon Cancer (LSCC) and rectal cancer patients, 57 cases of RSCC, 87 LSCC and 145 rectal cancer patients were included retrospectively. Our results demonstrated significant differences existed among RSCC, LSCC and rectal cancer regarding tumor diameter, differentiation, invasion depth and TNM stage. No significant difference was identified in expression levels of MLH1, MSH2, MSH6, PMS2, ß-Tubulin III, P53, Ki67 and TOPIIα, and gene mutation of KRAS and BRAF among three groups. Progression Free Survival (PFS) of RSCC was significantly lower than that of LRCC and rectal cancer. In univariate analyses, RSCC, preoperative chemoradiotherapy, poor differentiation, advanced TNM stage, elevated serum CEA and CA19-9 level, tumor deposit, perineural and vascular invasion were found to be predictive factors of shorter PFS. In multivariate analyses, only differentiation and TNM stages were found to be independent predictors of PFS. In conclusion, compared with LSCC and rectal cancer, RSCC has larger tumor size, poor differentiation, advanced TNM stage and shorter survival. The shorter survival in RSCC might be attributed to the advanced tumor stage caused by its inherent position feature of proximal colon rather than genetic difference.


Assuntos
Neoplasias do Colo/metabolismo , Proteoma/metabolismo , Proteômica/métodos , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Neoplasias Retais/metabolismo , Idoso , Colo/metabolismo , Colo/patologia , Neoplasias do Colo/genética , Neoplasias do Colo/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mutação , Estadiamento de Neoplasias , Prognóstico , Intervalo Livre de Progressão , Proteoma/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Retais/genética , Neoplasias Retais/terapia , Estudos Retrospectivos
11.
Endoscopy ; 47(6): 525-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25590177

RESUMO

BACKGROUND AND STUDY AIMS: We developed a novel magnetic-controlled capsule endoscopy (MCE) system for use in the human stomach. The aim of the current study was to compare the diagnostic accuracy of MCE with that of standard gastroscopy for gastric diseases. PATIENTS AND METHODS: A total of 68 patients were enrolled in this self-controlled trial. Patients were evaluated by both MCE and gastroscopy. Gastroscopy was performed 4 ­â€Š24 hours after completion of the MCE examination. RESULTS: The positive percent agreement between MCE and gastroscopy was 96.0 %, and the negative percent agreement was 77.8 %. The overall agreement was 91.2 % with a kappa value of 0.765 (P < 0.001). A total of 68 pathological findings were detected, of which 53 were identified by both methods. The MCE and standard gastroscopy missed seven and eight findings, respectively. CONCLUSIONS: MCE showed a diagnostic accuracy similar to that of standard gastroscopy. These results suggest that MCE is a promising alternative to gastroscopy for noninvasive screening of gastric diseases.Clinical trial registration number: NCT01903629.


Assuntos
Endoscopia por Cápsula/métodos , Gastroscopia , Magnetismo , Gastropatias/diagnóstico , Adulto , Idoso , Endoscopia por Cápsula/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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