Netrin-1-CD146 and netrin-1-S100A9 are associated with early stage of lymph node metastasis in colorectal cancer.

BACKGROUND: The netrin-1/CD146 pathway regulates colorectal cancer (CRC) liver metastasis, angiogenesis, and vascular development. However, few investigations have yet examined the biological function of netrin-1/CD146 complex in CRC. In this work, we investigated the relationship between the netrin-1/CD146 axis and S100 proteins in sentinel lymph node, and revealed a possible new clue for vascular metastasis of CRC. METHODS: The expression levels of netrin-1 and CD146 proteins in CRC, as well as S100A8 and S100A9 proteins in the sentinel lymph nodes were determined by immunohistochemistry. Using GEPIA and UALCAN, we analyzed netrin-1 and CD146 gene expression in CRC, their association with CRC stage, and their expression levels and prognosis in CRC patients. RESULTS: The expression level of netrin-1 in N1a+1b (CRC lymphatic metastasis groups, exculded N1c) was positively increased with N0 (p = 0.012). The level of netrin-1 protein was positively correlated with CD146 protein (p < 0.05). The level of S100A9 protein was positively correlated with CD146 protein (r = 0.492, p = 0.007). Moreover, netrin-1 expression was obviously correlated with S100A9 expression in the N1 stage (r = 0.867, p = 0.000). CD146 level was correlated with S100A9 level in the N2 stage (r = 0.731, p = 0.039). CD146 mRNA expression was higher in normal colorectal tissues than in CRC (p < 0.05). Netrin-1 and CD146 expression were not significantly associated with the tumor stages and prognosis of patients with CRC (p > 0.05). CONCLUSIONS: The netrin-1/CD146 and netrin-1/S100A9 axis in CRC tissues might related with early stage of lymph node metastasis, thus providing potential novel channels for blocking lymphatic metastasis and guiding biomarker discovery in CRC patients.

Shengu granules ameliorate ovariectomy-induced osteoporosis by the gut-bone-immune axis.

Introduction: Postmenopausal osteoporosis (PMOP) is a common chronic disease, and the loss of bone density and bone strength after menopause are its main symptoms. Effective treatments for PMOP are still uncertain, but Chinese medicine has some advantages in slowing down bone loss. Shengu granules are often used clinically to treat PMOP. It has been shown to be an effective prescription for the treatment of PMOP, and there is evidence that gut flora may play an important role. However, whether Shengu granules attenuate PMOP by modulating gut flora and related mechanisms remains unclear. Methods: In this study, we mainly examined the bone strength of the femur, the structure of the intestinal microbiota, SCFAs in the feces and the level of FOXP3 cells in the colon. To further learn about the inflammation response, the condition of the mucosa and the level of cytokines in the serum also included in the testing. In addition, to get the information of the protein expression, the protein expression of OPG and RANKL in the femur and the protein expression of ZO-1 and Occludin in the colon were taken into account. Results: The osteoporosis was significantly improved in the SG group compared with the OVX group, and the diversity of intestinal flora, the secretion level of SCFAs and the expression level of FOXP3 were significantly increased compared with the OVX group. In terms of inflammatory indicators, the intestinal inflammation scores of the SG group was significantly lower than those in the OVX group. Additionally, the serum expression levels of IL-10 and TGF-ß in the SG group were significantly increased compared with the OVX group, and the expression levels of IL-17 and TNF-α were significantly decreased compared with the OVX group. In terms of protein expression, the expression levels of ZO-1, Occluding and OPG were significantly increased in the SG group compared with the OVX group, and the expression level of RANKL was significantly decreased compared with the OVX group. Discussion: Shengu granules treatment can improve the imbalance of intestinal flora, increase the secretion of SCFAs and the expression of FOXP3, which reduces the inflammatory response and repairs the intestinal barrier, as well as regulates the expression of OPG/RANKL signaling axis. Overall, Shengu granules ameliorate ovariectomy-induced osteoporosis by the gut-bone-immune axis.

Meta-analysis of laparoscopic anterior resection with natural orifice specimen extraction (NOSE-LAR) versus abdominal incision specimen extraction (AISE-LAR) for sigmoid or rectal tumors.

BACKGROUND: Natural orifice specimen extraction surgery is a novel technique of minimally invasive surgery. The purpose of this study was to compare the safety of laparoscopic anterior resection with natural orifice specimen extraction (NOSE-LAR) and abdominal incision specimen extraction (AISE-LAR) for sigmoid or rectum tumors. METHODS: MEDLINE (PubMed), Embase, CENTRAL (Cochrane Central Register of Controlled Trials), Scopus, and ClinicalTrials databases were systematically searched for related articles up to August 2019. The primary outcomes included postoperative complications (overall postoperative complication, incision-related complication, anastomotic fistula, and severe complication) and pathologic results (lymph nodes harvested, proximal resection margin, and distal resection edge). The statistical analysis was performed on STATA 12.0 software. RESULTS: Ten studies comprising 1787 patients were used for meta-analysis. Compared with AISE-LAR, NOSE-LAR had more advantages in terms of overall postoperative complication (odds ratio (OR) = 0.65 (95% CI, 0.46 to 0.90; P = 0.01)), incision-related complication (OR = 0.13 (95% CI, 0.05 to 0.35; P < 0.01)), distal resection edge (weighted mean difference (WMD) = 0.17 cm (95% CI, 0.02 to 0.33 cm; P = 0.02)), recovery of gastrointestinal function (WMD = - 0.38 day (95% CI, - 0.70 to - 0.06 day; P = 0.02 )), pain scores in postoperative day 1 (WMD = - 1.64 (95% CI, - 2.31 to - 0.98; P < 0.01)), additional analgesics usage (OR = 0.21 (95% CI, 0.11 to 0.40; P < 0.01)) and hospital stay (WMD = - 0.71 day (95% CI, - 1.10 to - 0.32 day; P < 0.01)), while the operation time of NOSE-LAR was prolonged (WMD = 7.4 min (95% CI, 0.17 to 14.64 min; P = 0.04)). The anastomotic fistula, severe complication, lymph nodes harvested, proximal resection margin, intraoperative blood loss, and long-term outcomes in NOSE-LAR were comparable with AISE-LAR. CONCLUSIONS: The safety of NOSE-LAR was demonstrated, and it could be an alternative to conventional surgery in laparoscopic anterior resection for sigmoid and rectal tumors. However, further randomized and multi-center trials are required.

Feasibility of ambulatory surgery for anal fistula with LIFT procedure.

BACKGROUND: Ambulatory surgery maintains the advantages of a more rapid return to work and overall reduced hospital costs. The specific impact of ambulatory surgery for anal fistula using the LIFT procedure (ligation of the intersphincteric fistula tract) is presented. METHODS: A total of 218 consecutive patients with anal fistula who underwent ambulatory LIFT surgery were retrospectively compared with 386 cases managed as in-patients. Patient demographics, comorbidities, postoperative morbidity and pain as well as readmission rates within 30 days and satisfaction ratings were compared between the two groups. RESULTS: When compared with patients undergoing in-patient surgery, those in the ambulatory group were younger with a better level of education (P < 0.05). Ambulatory cases returned to work after shorter postoperative periods (P < 0.01) but experienced more frequent postoperative external hemorrhoidal thrombosis and more reported postoperative pain (P < 0.05). There were no differences in the overall rate of complications or readmissions between the two groups. Ambulatory patients reported higher satisfaction ratings than in-patients (P < 0.05). CONCLUSIONS: The LIFT procedure for anal fistula can be safely performed in the ambulatory setting resulting in an acceptable level of satisfaction and a more rapid return to work when compared with in-patient fistula management.

Predictive impact of the inflammation-based indices in colorectal cancer patients with adjuvant chemotherapy.

Increasing evidences reported that cancer-triggered inflammation was associated with survival prognosis from colorectal cancer (CRC). However, the comprehensive effects of inflammatory-based coNLR-PLR that combines neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) rarely remain to be determined during chemotherapy. We retrospectively analyzed clinical data and baseline laboratory parameters from 153 colorectal cancer patients who underwent palliative adjuvant chemotherapy between January 2009 to January 2012. Receiver operating characteristic (ROC) curves and linear regression analyzed the predictive ability of NLR, and PLR for calculating the score of coNLR-PLR. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated using the Kaplan-Meier method and analyzed by the Cox proportional hazards model in univariate and multivariate analysis. The optimal cut-off value of NLR and PLR was 2.24 and 186 by the ROC analysis. Kaplan-Meier method showed that patients with high coNLR-PLR score was associated with poorer OS and RFS (all P < .05). In univariate and multivariate analysis, it obtained that the coNLR-PLR severed as a strong independent prognostic factor for OS and RFS (all P < .05). These results highlight that coNLR-PLR index severed as a strong predictor of prognosis biomarker in CRC patients receiving adjuvant chemotherapy. Furthermore, its assessment could contribute to accurately predicting prognosis after chemotherapy in clinical practice.

[Effect of Modified Dachengqi Decoction on Recovery of Gastrointestinal Function after Surgery in Patients with Rectal Cancer].

Objective To observe the effect of Modified Dachengqi Decoction on recovery of gastrointestinal function after closure of protective ileostomy of rectal cancer. Methods Seventy pa- tients with rectal cancer, scheduled to receive protective ileostomy were enrolled and randomized into treatment group (35 cases) and control group (35 cases). The treatment group was subjected to ante-grade enema with Modified Dachengqi Decoction (500 mL) once a day before ileostomy, the therapeutic course was 2 weeks ,and the control group received ileostomy alone. The oral feeding time, anal exhaust time, ileus rate and length of hospital stay were observed. Results Compared with the control group, the oral feeding time(h,22 ±6 vs.41 ±8), anal exhaust time(h,27 ±5 vs.48 ±8), ileus rate(2. 85% vs. 14. 29%) and length of hospital stay ( d,5. 5 ± 1. 0 vs.7. 6 ± 1. 2) were decreased in the treatment group (P <0. 01 , P <0. 05).Conclusion Modified Dachengqi Decoction could promote the recovery of gastroin- testinal function after surgery in patients with rectal cancer.

[Clinical analysis of 31 cases with rectal prolapse undergoing modified Gant-Miwa procedure and anal encircling].

OBJECTIVE: To evaluate the efficacy of modified Gant-Miwa procedure with anal encircling for adults with rectal prolapse. METHODS: Clinical and follow-up data of 31 adult patients with rectal prolapse undergoing modified Gant-Miwa procedure with anal encircling procedure between September 2005 and January 2012 were retrospectively analyzed. RESULTS: Operations were successfully performed in these 31 cases. The mean operation time was 75 (range 50-165) minutes. The mean estimated blood loss during operation was 50 (range 20-80) ml. There were no postoperative complications, such as hemorrhage, perianal abscess, anal fistula, intra-abdominal infection, or urogenital dysfunction, while only 7 patients developed urinary retention postoperatively. Rate of postoperative constipation improvement was 61.5% (8/13) and defecation difficulty improvement was 69.6% (16/23). Twenty-eight patients received anal manometry 2 months after operation and the result showed that rectal sensation threshold and rectal maximal tolerance decreased significantly, while anal resting pressure and anal squeeze pressure did not change significantly as compared to preoperative values. Six months after operation, anal function was Kirwan grade I in 22 cases and grade II in 8 cases. During a mean postoperative follow-up of 2.5 years (3 months-6.3 years), 2 of 26 patients developed recurrent prolapse. CONCLUSIONS: Modified Gant-Miwa procedure with anal encircling for adults of rectal prolapse is a simple and safe procedure with low recurrence rate, minimal invasion, no serious complication and mortality, especially suitable for the elderly patients, accompanied with underlying diseases or reluctant to undergo transabdominal operation.

[Association of CD133 expression and sensitivity of rectal cancer to preoperative radiotherapy].

OBJECTIVE: To determine the association of CD133 expression with the sensitivity to radiotherapy among rectal cancer patients. METHODS: The clinical data of 32 rectal cancer patients was retrospectively collected for patients who received a short-term preoperative radiotherapy(5 Gy/d,×5 d) from 2008 to 2010. Pretreatment tumor biopsies were immunostained for CD133 expression. Rectal cancer regression grade (RCRG) was used to evaluate the sensitivity of the rectal cancer to preoperative radiotherapy. The correlation of CD133 expression and sensitivity to radiotherapy was analyzed. RESULTS: CD133 differentially expressed in rectal cancer tissue with 17 high expression and 15 low expression. The expression of CD133 was associated with the differentiation of rectal cancer with higher expression of CD133 among poorly differentiated rectal cancers(P<0.05). Among the CD133-high patients, two patients showed 1st RCRG, five patients showed 2nd RCRG and ten patients showed 3rd RCRG. For the CD133-low patients, there were five 1st RCRG, seven 2nd RCRG and three 3rd RCRG. There was a significant association between CD133 expression and sensitivity to radiotherapy (P=0.037). Multivariate logistic regression analysis showed that the expression level of CD133(P=0.027) and the differentiation of rectal cancer(P=0.046) were independent predictive factors for the sensitivity of rectal cancer to radiotherapy. CONCLUSIONS: Correlation between CD133 expression and sensitivity to radiotherapy of rectal cancer may exist, which may be helpful in predicting the sensitivity of rectal cancer to preoperative radiotherapy.

[Multi-gene methylation detection increases positive methylation rate in colorectal cancer].

OBJECTIVE: To study whether combined detection of the methylation status of vimentin, sFRP1, and HPP1 gene can increase the positive methylation rate in colorectal cancer. METHODS: Tissue samples were collected from 90 patients with colorectal cancer, 60 patients with adenomatous polyp, and 20 healthy controls. DNA was extracted and the methylation status of vimentin, sFRP1, and HPP1 gene was detected by Methylation-specific PCR (MSP). The relationship between clinicopathologic features of colorectal cancer and gene methylation was analyzed. RESULTS: The methylation rates of vimentin, sFRP1, and HPP1 were 66.7%, 68.9%, and 72.2% in colorectal cancer, 53.3%, 55.0%, and 50.0% in colorectal adenomas, and 0, 0, and 5.0% in healthy controls, respectively. The methylation of each of the three genes in colorectal cancer tissues was higher than colorectal adenomas and healthy controls(P<0.05). The diagnostic sensitivity by combining three methylation markers was 93.3% in colorectal cancer, 76.7% in colorectal adenomas, which was higher than the sensitivity using single gene testing(P<0.05). No significant associations existed between the methylation status of the three genes and clinical characteristics including sex, age, tumor location, lymph node metastases, distant metastasis, and TNM stage(P>0.05). CONCLUSIONS: DNA methylation levels of vimentin, sFRP1 and HPP1 are significantly higher in colorectal cancer tissue. Combined detection significantly improves the positive rate of methylation, and may be used as early diagnosis method for colorectal cancer.

Clinical evaluation of oligonucleotide microarrays for the detection of HBV mutants associated with lamivudine resistance.

OBJECTIVES: Long-term lamivudine administration in hepatitis B virus (HBV)-infected patients induces the emergence of HBV mutants with lamivudine resistance. The aim of the present study was to evaluate the clinical application of an oligonucleotide microarray in detecting HBV mutants associated with lamivudine resistance. METHODS: 947 HBV DNA-positive sera from: 388 patients receiving lamivudine treatment, 559 chronic hepatitis B patients not receiving lamivudine treatment, and 359 from HBV DNA-negative controls, were assayed for HBV mutations using the oligonucleotide microarray. Furthermore, follow-up studies were performed using 255 clinical samples from 51 patients treated with lamivudine at various periods. The results were compared with sequencing and real-time polymerase chain reaction (PCR). RESULTS: The HBV DNA polymerase Tyr-Met-Asp-Asp motif (YMDD) mutation was detected in all 388 samples containing lamivudine-resistant mutations identified by microarray. For the codons rt180, rt204 and rt207, the agreements between the microarray and sequencing data are 96.6, 98.5 and 100%, respectively. Two previously unreported mutants were also found in those samples. In the 947 samples collected from different patients, which were detected positive for HBV DNA by quantitative PCR, all but three weak-positive samples were positive by the microarray, demonstrating an agreement of 99.7%. In all the positive samples, mutations could be detected in the relevant loci of HBV DNA polymerase with lamivudine resistance. All of the 359 HBsAg-negative samples were shown to be negative for HBV DNA using the microarray method. Follow-up detection of the clinical samples from 51 patients treated with lamivudine demonstrated that the microarray method was able to detect mutations in mixed viruses that were infecting prior to sequencing. CONCLUSION: The oligonucleotide microarray can be conveniently utilized to detect mutant HBV in clinical serum samples.

Correlation of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function in Chinese patients with chronic hepatitis C virus infection.

AIM: To determine serum leptin levels and investigate their correlations with anthropometric and metabolic parameters and biochemical liver function in patients with chronic hepatitis C virus (HCV) infection and their potential clinical implications. METHODS: Forty-two chronic HCV-infected patients without anti-viral treatment were enrolled in this study, 30 patients had chronic hepatitis C, 10 had cirrhosis, and 2 had hepatocellular carcinoma (HCC). Thirty age- and sex-matched healthy individuals served as controls. Serum leptin levels were determined by ELISA. The biochemical liver function and serum lipids were determined at the same time. The height and body weight of patients and controls were measured, and body mass index (BMI) and body fat were calculated simultaneously. The correlations of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function were assessed statistically. RESULTS: The mean of serum leptin levels in patients with chronic hepatitis C, HCV-associated cirrhosis, HCV-associated HCC and control groups was (6.13+/-3.94), (5.25+/-4.21), (4.17+/-0.28), and (3.59+/-3.44) ng/mL, respectively. The serum leptin level in patients with chronic hepatitis C was significantly higher than that in controls. The serum leptin levels between cirrhotic patients and controls and between male and female cirrhotic patients had no significant difference. Serum leptin levels were positively-correlated with body fat, BMI, and apolipoprotein B (Apo B) in patients with chronic HCV infection. The serum alanine aminotransferase (ALT) levels were closely-correlated with BMI in patients with chronic hepatitis C. CONCLUSION: HCV infection interferes with fat and lipid metabolism in patients with chronic HCV infection and leptin may play a role in hepatosteatosis.