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BACKGROUND: Anastomotic stenosis is a common complication of colorectal cancer surgery with anastomosis. Transanal minimally invasive surgery is a novel approach to the treatment of anastomotic stenosis. OBJECTIVE: This study aimed to evaluate the efficacy and safety of transanal minimally invasive surgery for anastomotic stenosis treatment. DESIGN: This was a retrospective study. SETTINGS: This study was conducted at a comprehensive cancer center. PATIENTS: This study included patients with rectal anastomotic stenosis who after undergoing colorectal surgery were admitted to the Sir Run Run Shaw Hospital between September 2017 and June 2019. MAIN OUTCOME MEASURES: The primary outcome was the operative success rate. The secondary outcomes were intraoperative variables, postoperative complications, stoma closure conditions, and stenosis recurrence risks. RESULTS: Nine patients, aged 52 to 80 years, with a history of colorectal cancer with end-to-end anastomosis underwent transanal minimally invasive surgery for anastomotic stenosis. The distance between the stenosis and the anal verge ranged from 5 to 12 cm. The mean stenosis diameter was 0.3 cm. Four patients had completely obstructed rectal lumens. Eight of 9 patients successfully underwent transanal minimally invasive surgery radial incision and cutting. The average operation time was 50 minutes. After the procedure, 1 patient had symptomatic procedure-associated perforations but recovered with conservative treatment. No perioperative mortality occurred. One patient underwent transverse colostomy 1 month after transanal minimally invasive surgery because of proximal colon ischemia induced by primary rectal surgery. Eight patients underwent protective loop ileostomy. After transanal minimally invasive surgery, stoma closure was performed in 88% of patients with no stenosis recurrence or obstruction at follow-up (21-42 mo). LIMITATIONS: This study was limited by its small sample size and single-center design. CONCLUSIONS: Transanal minimally invasive surgery provides an excellent operative field, good maneuverability, and versatile instrumentation and is a safe and effective treatment for rectal anastomotic stenosis, especially for severe fibrotic stenosis or complete obstruction. See Dynamic Article Video at http://links.lww.com/DCR/B965 .
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Neoplasias Retais , Cirurgia Endoscópica Transanal , Canal Anal/cirurgia , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/etiologia , Fístula Anastomótica/cirurgia , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Humanos , Complicações Pós-Operatórias , Neoplasias Retais/cirurgia , Reto/cirurgia , Estudos Retrospectivos , Cirurgia Endoscópica Transanal/efeitos adversosRESUMO
BACKGROUND: This study aimed to evaluate the value of chitinase activity in prognosticating the occurrence of metastasis in and prognosis of patients with colorectal cancer (CRC). METHODS: The chitinase activity in four different groups, namely 335 CRC patients without distant metastasis at their first visit (Group 1), 51 patients with CRC having synchronous liver metastasis (Group 2), 100 healthy age-matched controls (Group 3) and 40 patients with liver cancer (Group 4), were assayed using an enzyme-linked immunosorbent assay. The Cox proportional hazards ratio model and Kaplan-Meier curve were used to identify the association between chitinase activity and the clinical outcome of CRC patients without metastasis in the training set and testing set at their first visit. An in vitro Transwell experiment was performed to evaluate the migration of colon cancer cells. RESULTS: Patients with high chitinase activity had a significantly higher metastasis risk than those with low chitinase activity in the training and testing sets during follow-up, both at stage I/II and stage III. Further, multivariate analysis revealed that chitinase activity was an independent risk factor prognosticating liver metastases (P = 0.001). The combination of chitinase activity and lymph node metastasis status increased the accuracy of the prognosis of liver metastases after radical resection (P = 0.454E-011). In addition, chitinase promoted CRC cell migration in vitro. CONCLUSIONS: Chitinase activity can prognosticate the occurrence of metastasis in patients with CRC. Moreover, the combination of chitinase activity and N stage increased the power of prognosticating the occurrence of metastasis. Inhibiting chitinase activity may serve as a new strategy to treat metastases of CRC.
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Quitinases/sangue , Neoplasias do Colo/enzimologia , Neoplasias do Colo/patologia , Neoplasias Hepáticas/secundário , Neoplasias Retais/enzimologia , Neoplasias Retais/patologia , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular , Neoplasias do Colo/mortalidade , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Retais/mortalidade , Estudos RetrospectivosRESUMO
Background: Anastomotic stricture (AS) is a common complication following rectal cancer surgery with anastomosis, but its diagnosis and management pose significant challenges due to the lack of standardized diagnostic criteria. We present a case highlighting the complexities encountered in diagnosing and managing occult AS post-rectal cancer surgery. Case presentation: A 51-year-old male patient presented with symptoms suggestive of AS following robot-assisted laparoscopic low anterior resection for rectal adenocarcinoma. Despite conventional evaluations, including colonoscopy, digital rectal examination, and radiography, AS was not identified. Following prolonged and ineffective treatment for suspected conditions such as low anterior resection syndrome (LARS), the patient underwent anal dilatation, resulting in significant symptom improvement. Conclusions: This case underscores the challenges associated with diagnosing and managing occult AS following rectal cancer surgery. The absence of standardized diagnostic criteria and reliance on conventional modalities may lead to underdiagnosis and inadequate treatment. A comprehensive diagnostic approach considering intestinal diameter, elasticity, and symptoms related to difficult defecation may enhance diagnostic accuracy. Further research is needed to refine the diagnostic and therapeutic strategies for occult AS.
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BACKGROUND: Robotic-assisted surgery (RAS) is increasingly used for treating low rectal cancer. Its comparative effectiveness against laparoscopic surgery (LAS) in enhancing long-term anal function remains uncertain. METHODS: A meta-analysis was conducted to compare long-term anal function outcomes between patients undergoing RAS and LAS. Meta-regression and sensitivity analyses were performed to assess available evidence. Studies published up to September 2023 in English or Chinese were included. RESULTS: Seven studies were identified. RAS patients exhibited lower low anterior resection syndrome (LARS) scores (standardised mean difference [SMD] = -1.39; 95% confidence interval [CI]: -2.64 to -0.15) and Wexner scores (SMD = -0.74; 95% CI: -1.20 to -0.27) compared with LAS patients. However, RAS did not significantly reduce major LARS risk (odds ratio = 0.85; 95% CI: 0.68-1.04). CONCLUSIONS: RAS slightly improved postoperative anal function compared with LAS. Further studies with large samples are warranted to confirm or update our findings.
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Canal Anal , Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Retais/cirurgia , Laparoscopia/métodos , Canal Anal/cirurgia , Resultado do Tratamento , Seguimentos , Masculino , Complicações Pós-Operatórias , Feminino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Low anterior resection syndrome (LARS) is a distressing condition that affects approximately 25-80% of patients following surgery for rectal cancer. LARS is characterized by debilitating bowel dysfunction symptoms, including fecal incontinence, urgent bowel movements, and increased frequency of bowel movements. Although biofeedback therapy has demonstrated effectiveness in improving postoperative rectal control, the research results have not fulfilled expectations. Recent research has highlighted that stimulating the pudendal perineal nerves has a superior impact on enhancing pelvic floor muscle function than biofeedback alone. Hence, this study aims to evaluate the efficacy of a combined approach integrating biofeedback with percutaneous electrical pudendal nerve stimulation (B-PEPNS) in patients with LARS through a randomized controlled trial (RCT). METHODS AND ANALYSIS: In this two-armed multicenter RCT, 242 participants with LARS after rectal surgery will be randomly assigned to undergo B-PEPNS (intervention group) or biofeedback (control group). Over 4 weeks, each participant will undergo 20 treatment sessions. The primary outcome will be the LARS score. The secondary outcomes will be anorectal manometry and pelvic floor muscle electromyography findings and the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 29 (EORTC QLQ-CR29) scores. Data will be collected at baseline, post-intervention (1 month), and follow-up (6 months). DISCUSSION: We anticipate that this study will contribute further evidence regarding the efficacy of B-PEPNS in alleviating LARS symptoms and enhancing the quality of life for patients following rectal cancer surgery. TRIAL REGISTRATION: Chinese Clincal Trials Register ChiCTR2300078101. Registered 28 November 2023.
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Biorretroalimentação Psicológica , Incontinência Fecal , Estudos Multicêntricos como Assunto , Nervo Pudendo , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Retais , Estimulação Elétrica Nervosa Transcutânea , Humanos , Biorretroalimentação Psicológica/métodos , Resultado do Tratamento , Estimulação Elétrica Nervosa Transcutânea/métodos , Incontinência Fecal/terapia , Incontinência Fecal/fisiopatologia , Incontinência Fecal/etiologia , Neoplasias Retais/cirurgia , Neoplasias Retais/terapia , Feminino , Pessoa de Meia-Idade , Síndrome , Masculino , Adulto , Diafragma da Pelve/fisiopatologia , Diafragma da Pelve/inervação , Recuperação de Função Fisiológica , China , Defecação , Idoso , Protectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Eletromiografia , ManometriaRESUMO
BACKGROUND: Conventional neoadjuvant chemoradiotherapy (nCRT) yields a pathologic complete response (pCR) rate of 15%-30% for locally advanced rectal cancer (LARC). This study ventures to shift this paradigm by incorporating short-course nCRT with immunotherapy, specifically Envafolimab, to achieve improved treatment efficacy and possibly redefine the standard of care for LARC. MATERIALS AND METHODS: The PRECAM study is a prospective, single-arm, phase 2 clinical trial for LARC in patients with microsatellite stable (MSS) tumors. Participants received short-course radiotherapy (25Gy/5f), followed by two cycles of CAPEOX chemotherapy and six weekly doses of Envafolimab, a PD-L1 antibody, before total mesorectal excision surgery. The primary endpoint was the pCR rate. RESULTS: From April to December 2022, 34 patients were enrolled, of whom 32 completed the study, each diagnosed with an MSS rectal adenocarcinoma. All patients underwent preoperative CRT combined with Envafolimab. Remarkably, a pCR rate of 62.5% (20/32) was attained, and a significant pathologic response rate of 75% (24/32) was achieved. Additionally, 21 of 32 participants achieved a neoadjuvant rectal (NAR) score below 8, suggesting an effective treatment response. Common adverse events included tenesmus (78.1%), diarrhea (62.5%), and leukocyte decrease (40.6%). Two Grade 3 adverse events were noted, one related to liver function abnormality and the other to a decrease in platelet count. Surgical procedures were performed in all cases, with minor complications, including ileus, infections, and anastomotic leakage. As of this report, there have been no reported cases of recurrence or death during the follow-up period, ranging from 12 to 20 months. CONCLUSION: In LARC patients exhibiting MSS tumors, combining short-course nCRT with Envafolimab demonstrated favorable efficacy, leading to a significant pCR rate. Minor adverse effects and surgical complications were observed. These preliminary but promising results underscore the potential of this approach and call for further exploration and validation through a randomized controlled trial.
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An association between the methylenetetrahydrofolate reductase (MTHFR) C667T genotype and the risk of colorectal cancer, as well as a link between MTHFR gene polymorphism and thrombosis, have been revealed. However, the connection between MTHFR gene polymorphism and the risk of thrombosis in patients with colorectal cancer has remained to be fully elucidated. The present study investigated the link between MTHFR gene polymorphism and basic clinical data, postoperative D-dimer (DDi), postoperative thromboelastogram and postoperative thrombosis in 591 patients who underwent surgery for colorectal cancer. Postoperative DDi, thromboelastogram and postoperative thrombosis were not significantly different among patients with colorectal cancer and different MTHFR genotypes. While the results were 'negative', the present study may help physicians understand that it is not necessary to detect MTHFR polymorphism for therapeutic purposes. Regarding the danger of venous thrombosis, more focus should be placed on the standardized procedural enforcement system for deep vein thrombosis prevention for patients undergoing pelvic and abdominal surgery.
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OBJECTIVE: Osteoporosis is a common disease in postmenopausal women. Several studies have analysed the associations between dietary supplementation with probiotics and bone health in postmenopausal women, but the results are still controversial. We conducted this meta-analysis to assess the effects of probiotics supplement on bone mineral density (BMD) and bone turnover markers for postmenopausal women. DESIGN: Systematic review and meta-analysis. METHODS: We systematically searched PubMed, EMBASE and the Cochrane Library from their inception to November 2020 for randomised controlled trials (RCTs) assessing probiotic supplements and osteoporosis in postmenopausal women. Study-specific risk estimates were combined using random-effect models. RESULTS: Five RCTs (n=497) were included. Probiotic supplements were associated with a significantly higher BMD in the lumbar spine (standardised mean difference, SMD=0.27, 95% CI 0.09 to 0.44) than in control. There was no difference between probiotic supplements and BMD in hips (SMD=0.22, 95% CI -0.07 to 0.52). Collagen type 1 cross-linked C-telopeptide levels in the treatment groups were significantly lower than those of the placebo group (SMD=-0.34, 95% CI -0.60 to -0.09). In subgroup meta-analysis, levels of bone-specific alkaline phosphatase, osteoprotegerin, osteocalcin and tumour necrosis factor did not differ between the probiotic and placebo groups. CONCLUSIONS: We conclude cautiously that supplementation with probiotics could increase lumbar BMD. More RCTs are recommended to validate or update these results.
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Osteoporose Pós-Menopausa , Probióticos , Densidade Óssea , Suplementos Nutricionais , Feminino , Humanos , Osteoporose Pós-Menopausa/prevenção & controle , Pós-Menopausa , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Following the publication of the above paper, the authors realized that, in their followup experiments, the STAT3 and p65 antibodies they used had already expired prior to the results being published. This affected the confidence that the authors could place in the results published in Figs. 1 and 3E. In addition, the findings were also inconsistent with Fig. 4A and B, potentially causing confusion for the readers. The authors therefore repeated some of these experiments with newly purchased antibodies; they also changed the RT-qPCR results. In the published manuscript, the authors investigated the expression of LYPD8 mRNA expression in tissues from stages I, II, and III whereas in the revised manuscript they have investigated stages II and IV. In addition, the authors have supplemented the manuscript with new transwell assays. The revised figures are presented on the next two pages (Figs 1-4). Repeating these particular experiments has resulted in the following changes being necessary to the text of the published paper (changes are highlighted in bold): i) The fourth sentence in the Abstract, on p. 2389, should read as follows: "The results revealed that the expression of LYPD8 was significantly reduced in the CRC tissue compared with that in precancerous tissue and normal tissue, particularly in stage IV tissue." ('III' has been changed to 'IV'). ii) In the Materials and methods section, "Histological analysis" subsection on p. 2390, the last three sentences should be replaced with the following text: "The histological sections were then stained with the DAB Kit (cat. no. PV9000; ZSGBBIO, Beijing, China). All sections were observed under a brightfield microscope (Nikon Corporation, Tokyo, Japan)." iii) In the "Cell culture" subsection in the righthand column, the first four sentences should be revised to the following: "Four CRC cell lines (SW480, SW620, HCT116 and RKO) were used. SW480 (ATCC® CCL228™, organism, human; tissue, colon; disease, colorectal adenocarcinoma), SW620 (ATCC® CCL227™, organism, human; tissue, colon; derived from metastatic site, lymph node; disease, colorectal adenocarcinoma), HCT116 (ATCC® CCL247™, organism, human; tissue, colon; disease, colorectal carcinoma) and RKO (ATCC® CRL2577™, organism, human; tissue, colon; disease, carcinoma) cells were purchased from the American Type Culture Collection (Manassas, VA, USA). The four cell lines within passages 10 were used in all experiments, and the cell lines were maintained at 37ËC in a humidified incubator containing 5% CO2". Also, in line 8 of p. 2391, the cell lines here should be changed to "SW480, SW620 and HCT116 cells", and on line 11, "HT29 cells" should be changed to "RKO cells". iv) In the Results section, the following changes to the text are necessary: In the "Correlation of the expression of LYPD8 with STAT3/P65 phosphorylation and IL6/TNFα secretion in patients with CRC" subsection, in the second sentence, "immunofluorescence" should have been written as "immunohistochemistry", and the fourth sentence should have read as follows: "The results of the western blotting showed that the levels of pP65/P65 and pSTAT3/STAT3 gradually increased between stage II and IV (Fig. 1B and C)." Then, the three sentences starting on line 7 on p. 2391 should now read as follows: "Following this, the gene expression levels of LYWPD8 in stage II and IV CRC tissue, precancerous tissue, and normal tissue were assessed using RTqPCR analysis (Fig. 2C). Compared with the precancerous tissue and normal tissue, the gene expression of LYPD8 was significantly reduced in stage II and IV tissues. Furthermore, the expression of LYPD8 was reduced in stage IV tissue compared with that in stage II tissue." v) In the subsequent subsection, "Construction and overexpression of LYPD8 in CRC cells", the first sentence should have read as follows: "The plasmid DNA for overexpressing LYPD8 was constructed using the eukaryotic expression vector (pIRES2), as shown in Fig. 3A and B, and the relative expression levels of LYPD8 in the RTO, SW480 HCT116 and SW620 cells were examined by RT-qPCR analysis. vi) In the "Overexpression of LYPD8 inhibits CRC cell proliferation and migration" subsection, the penultimate sentence as it appears towards the foot of p. 2392 should now read as follows: "As shown in Fig. 4C and D, a more marked inhibitory effect on cell migration was observed in the LYPD8 OE group compared with that in the control, LYPD8 OE + IL6 and LYPD8 OE + TNFα groups." vi) In the Discussion, the sentence starting on p. 2394, righthand column, line 10 should read as follows: "By contrast, the expression of LYPD8 was significantly reduced in stage II and IV CRC tissues." vii) Finally, some revisions were necessary to the descriptions in the figure legends for Figs. 1, 2 and 4, as follows (only the affected text is included, and the changes are indicated in bold): Figure 1. STAT3 and P65 are activated in colonic tumor tissues from patients. (A) Representative immunohistochemistry images revealing activated STAT3 and P65 in colonic cancer tissue and precancerous tissue. Scale bar, 100 µm. (B) Representative western blotting revealing the expression of pP65, P65, pSTAT3 and STAT3 in stages II and IV colonic tumor tissues. GAPDH was used as a control. (C) Band intensities of western blotting for pP65/P65 and pSTAT3/STAT3 in stage II and IV tissues were analyzed. The data are reported as the mean ± standard deviation of experiments (n=4). **P<0.05, phosphorylation levels of STAT3 in stage II tissues vs. in stage IV tissues. Figure 2. Association between IL6/TNFα and the expression of LYPD8 in colonic tumor tissue, precancerous tissue and normal tissue at different stages. (A) IL6 and (B) TNFα secretion were analyzed by ELISA in stage II and IV colonic tumor tissue and precancerous tissue. (C) Gene expression of LYPD8 in stage II and IV colonic tumor tissue and precancerous tissue. ßactin was used as a control. The data are reported as the mean ± standard deviation of experiments (n=6). **P<0.01, LYPD8 mRNA expression of normal tissue, precancerous tissue vs. colonic tumor tissue in stage II and IV tissues. Figure 4. Effects of the overexpression of LYPD8 on SW480 cell proliferation and migration. (A) Cell viability of the Control, LYPD, LYPD8 OE + IL6 and LYPD8 OE + TNFα groups of SW480 cells. (B) SW480 cells were treated with different concentrations (0.5, 1 and 2 µM) of niclosamide and different concentrations (5, 15 and 30 µM) of JSH23, respectively. (C) Numbers of migratory SW480 cells from the Control, LYPD8, LYPD8 OE + IL6 and LYPD8 OE + TNFα groups. (D) Transwell assay of SW480 cells from the (a) Control, (b) LYPD8 OE, (c) LYPD8 OE + IL6 and (d) LYPD8 OE + TNFα groups (magnification, ×200). Note that the replacement of the original figures and these revisions made to the text do not drastically alter the overall conclusions reported in the study. The authors are very grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum; furthermore, they apologize for any inconvenience caused to the readership of the Journal. [the original articles was published in Oncology Reports 41: 23892395, 2019; DOI: 10.3892/or.2019.7034].
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AIM: This study aimed to compare clinical and oncological outcomes of robot-assisted and laparoscopic surgery for rectal cancer. MATERIALS AND METHODS: We searched PubMed/Medline, Embase, the Cochrane Library, Yahoo, and Google Scholar databases for relevant articles published up to 2017. Studies based on comparability between robot-assisted and laparoscopic surgery for rectal cancer were designated. Clinical outcomes included operative time, conversion to open surgery, estimated blood loss (EBL), bowel function recovery time, length of hospital stay (LOS), anastomosis leak, and postoperative complications. Oncological outcomes comprised the number of lymph nodes extracted, the positive circumferential margin (PCRM), and the distal resection margin (DRM). RESULTS: Twenty studies were designated totaling 5496 patients, comprising a robot-assisted surgery patient group (n = 2168, 39.4%) and a laparoscopic surgery patient group (n = 3328, 60.6%). The robot-assisted surgery group was associated with longer operative time (odds ratio [OR] 0.48, 95% confidence interval [CI]; 0.14, 0.82), lower conversion to open surgery rate (OR 0.55, 95% CI; 0.44, 0.69), shorter LOS (OR - 0.15, 95% CI; -0.30, 0.00), faster bowel function recovery (OR - 0.38, 95% CI; -0.74, -0.02), and lower postoperative complications (OR 0.79, 95% CI; 0.65, 0.97). EBL, anastomosis leak rate, and oncological outcomes including the number of lymph nodes extracted, the DRM, and the PCRM showed no significant differences between groups. CONCLUSION: Robot-assisted surgery for rectal cancer showed longer operative time, lower conversion, faster bowel function recovery rates, and shorter hospital stay, and similar oncological outcomes compared to laparoscopic surgery.
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Laparoscopia/métodos , Tempo de Internação/estatística & dados numéricos , Duração da Cirurgia , Complicações Pós-Operatórias , Neoplasias Retais/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Humanos , Margens de Excisão , Neoplasias Retais/patologia , Resultado do TratamentoRESUMO
Great value in the early identification and treatment of adenomatous polyps or early canceration using colonoscopy has been recognized. A clear colonoscopic vision brought by good intestinal preparation will become crucial. Several studies have completed using the low-residue diet (LRD) versus a clear liquid diet (CLD) the day before colonoscopy that presenting contradictory results. Therefore, a more comprehensive and updated meta-analysis is needed to summarize the findings on the effects of LRD and CLD on intestinal preparation and the quality of coloscopy.The comprehensive search was performed in PubMed/MEDLINE, Scopus, Cochrane databases (February 2020). LRD vs CLD before colonoscopy were included in this study. Mantel-Haenszel or DerSimonian and Laird models with the relative risk (RR) to evaluate differences in intestinal preparation, tolerance, readiness to repeat preparation, detected of a polyp, and overall adverse reactions.Total 16 studies (Nâ=â3413) were eligible. Patients with LRD compared with CLD indicated significantly better of tolerability (RR 0.92;95% CI,0.85-0.99; Pâ<â.05) and willingness to repeat intestinal preparation (RR 0.86; 95% CI 0.79-0.93; Pâ<â.05), but no differences with adequate intestinal preparations, detected polyp or overall adverse reactions (all Pâ>â.05).Patients with LRD the day before colonoscopy show better tolerance and willingness to repeat intestinal preparation, and no difference with adequate intestinal preparations compared with CLD, but the recommended level of evidence is weak. However, in terms of the detection rate of intestinal adenomas, the LRD group is not weaker than the CLD group, for its evidence level is high, and can significantly reduce the hunger experience of patients.
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Colonoscopia , Dieta/métodos , Cuidados Pré-Operatórios/métodos , Catárticos/uso terapêutico , Humanos , Satisfação do Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
PURPOSE: 5-Fluorouracil (5-Fu) is used as a conventional chemotherapy drug in chemotherapy for patients with advanced colorectal cancer, but many patients still suffer from treatment failure due to 5-Fu resistance. Emerging observations revealed the important role of chemokine (C-X-C motif) ligand 13 (CXCL-13) in tumor microenvironment and its relationship with prognosis in patients with colorectal cancer. This study is designed to reveal the important role of CXCL-13 in causing colorectal cancer resistance to 5-Fu. MATERIALS AND METHODS: CXCL-13 levels of patient's serum or cell culture supernatants were measured separately by enzyme-linked immunosorbent assay. In cell assays, cell viability is detected by Cell Counting Kit-8. Therefore, the recombinant human CXCL-13 was used to simulate its high expression in cells while its antibody and siRNA were used to reduce CXCL-13 expression in cells. RESULTS: In this study, we demonstrated that CXCL-13 is associated with 5-Fu resistance by culture medium exchange experiments and cytokine arrays of colorectal cancer resistant and nonresistant cells. Clinical studies showed that CXCL-13 is highly expressed in the serum of 5-Fu-resistant patients. High levels of serum CXCL-13 also predict a worse clinical outcome. The addition of recombinant CXCL-13 cytokine resulted in 5-Fu resistance, while its antibody overcame 5-Fu resistance, and knockdown of CXCL-13 expression by siRNA also reduced 5-Fu resistance, which can be saved by added recombination CXCL-13. CONCLUSION: These results not only identify a CXCL-13 mediated 5-Fu resistance mechanism but also provide a novel target for 5-Fu-resistant colorectal cancer in prevention and treatment strategies.
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Quimiocina CXCL13/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Idoso , Animais , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Fluoruracila/uso terapêutico , Humanos , Camundongos , Pessoa de Meia-IdadeRESUMO
Ly6/Plaur domaincontaining 8 (LYPD8) contributes to the segregation of intestinal microbiota and intestinal epithelia and is critical for the prevention of intestinal inflammation. However, its relevance in cancer biology remains to be fully elucidated. The present study aimed to clarify the biological effects of LYPD8 on colon cancer tissue from patients and colorectal cancer (CRC) cells. The results revealed that the expression of LYPD8 was significantly reduced in the CRC tissue compared with that in precancerous tissue and normal tissue, particularly in stage III tissue. The results also revealed increased levels of P65 and signal transducer and activator of transcription 3 (STAT3) phosphorylation and increased secretion of interleukin6 (IL6) and tumor necrosis factorα (TNFα) in CRC tissue compared with levels in precancerous tissue. Supporting these findings, the levels of secreted TNFα and IL6 were significantly reduced when LYPD8 was overexpressed in human CRC cells, and the secretion of TNFα and IL6 were positively associated with the phosphorylation of STAT3 and P65. However, this trend was restored upon supplementation with TNFα and IL6 in CRC cells. Furthermore, the overexpression of LYPD8 in CRC cells significantly inhibited CRC cell proliferation and migration. Overall, the LYPD8mediated tumorinhibiting role involves a direct effect on the secretion of IL6/TNFα in CRC cells by reducing the phosphorylation of STAT3 and P65.
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Neoplasias Colorretais/patologia , Proteínas Ligadas por GPI/metabolismo , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Idoso , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Mucosa Intestinal/patologia , Pessoa de Meia-Idade , Fosforilação , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição RelA/metabolismoRESUMO
The role of palliative primary tumor resection (PPTR) in improving survival in patients with synchronous unresectable metastatic colorectal cancer (mCRC) is controversial. In this study, we aimed to evaluate whether our novel scoring system could predict survival benefits of PPTR in mCRC patients.In this retrospective cohort study consecutive patients with synchronous mCRC and unresectable metastases admitted to Sir Run Run Shaw Hospital between January 2005 and December 2013 were identified. A scoring system was established by the serum levels of carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), neutrophil/lymphocyte ratio (NLR), and lactate dehydrogenase (LDH). Patients with scores of 0, 1-2, or 3-4 were considered as being in the low, intermediate, and high score group, respectively. Primary outcome was overall survival (OS).A total of 138 eligible patients were included in the analysis, of whom 103 patients had undergone PPTR and 35 had not. The median OS of the PPTR group was better than that of the Non-PPTR group, with 26.2 and 18.9 months, respectively (Pâ<â.01). However, the subgroup of PPTR with a high score (3-4) showed no OS benefit (13.3 months) compared with that of the Non-PPTR group (18.9 months, Pâ=â.11). The subgroup of PPTR with a low score (52.1 months) or intermediate score (26.2 months) had better OS than that of the Non-PPTR group (Pâ<â.001, Pâ=â.017, respectively).A novel scoring system composed of CEA, CA19-9, NLR, and LDH values is a feasible method to evaluate whether mCRC patients would benefit from PPTR. It might guide clinical decision making in selecting patients with unresectable mCRC for primary tumor resection.
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Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Metástase Neoplásica/terapia , Cuidados Paliativos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Projetos de Pesquisa , Estudos Retrospectivos , Adulto JovemRESUMO
The objective of this study was to investigate associations between carbohydrate intake/glycemic index (GI)/glycemic load (GL) and stroke risk. A literature search of MEDLINE, Embase, Web of Science, and CBM databases was performed to retrieve eligible studies published up to March 2014. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were used to evaluate the strength of this association. Publication bias was assessed by the Egger's regression asymmetry test and Begg's rank correlation test with Begg's funnel plot. All analyses were conducted using software STATA 12.0 (StataCorp LP, College Station, TX) and SAS version 9.1 (SAS Institute Inc, Cary, NC). We identified 7 prospective studies that met the inclusion criteria and processed data from cohort studies to update available evidence. There were 25 independent estimates and 225 000 participants free of diabetes from 6 different countries; 3046 stroke events were included; and the follow-up range was 5 to 18 years. High GI was not associated with risk of stroke events (pooled RR = 1.10; 95% CI: 0.99-1.21); GL was a risk factor for stroke (pooled RR = 1.19; 95% CI: 1.05-1.36). There was no significant association between high carbohydrate intake and stroke risk (RR = 1.12; 95% CI: 0.93-1.35). A daily high GL diet is the risk factor of stroke event, and further researches need to verify the meta-analyses results and study associated mechanisms.