[Show abstract][Hide abstract] ABSTRACT: Objective:
To know the effect of age on survival outcome in operated and non-operated patients with colon cancer.
From the Surveillance, Epidemiology, and End Results database, we identified 123,356 patients with colon cancer who were diagnosed between 1996 and 2005, grouped them as older or younger than 40 years and analyzed their 5-year cancer-specific survival (CSS) data, along with some risk factors, using Kaplan-Meier methods and multivariable Cox regression models.
The younger group had significantly higher pathological grades (P<0.001), more mucinous and signet-ring histology (P<0.001), advanced AJCC stage (P<0.001), and were more likely to undergo surgery (P<0.001). For surgically treated patients, age did not significantly affect 5-year CSS (younger: 66.7%; older: 67.3%; P = 0.86). Further analysis showed that age was an independent prognostic factor in stage I-IV disease (stage I: P = 0.001; P<0.001 for stages II-IV, in both uni- and multivariate analyses), but not for patients with unknown disease stage (P = 0.52). For non-surgically treated patients, age significantly affected 5-year CSS (younger: 16.2%; older: 12.9%; P<0.001) in univariate analysis; and was an independent prognostic factor (P<0.001) in multivariate analysis.
The CSS rate for younger CC patients was at least as high as for older patients, although they presented with higher proportions of unfavorable factors and more advanced disease.
[Show abstract][Hide abstract] ABSTRACT: A recently invented duodenal-jejunal bypass sleeve (DJBS) implanted in the duodenum and proximal jejunum has exhibited good glycemic control in diabetes mellitus. However, the specific mechanism by which DJBS placement induces the remission of diabetes is not well known. Previous studies have indicated that changes in the pattern of gut hormone secretion may play a role. The aim of the present study was to explore the role of intestinal L cells and the production of glucagon-like peptide-1 (GLP-1) by these cells in DJBS implantation-induced glycemic control in diabetic rats. A DJBS was placed in the proximal small intestine of rats with diabetes induced by a high-fat diet and low-dose streptozotocin (STZ), and the effects of the DJBS on the remission of diabetes and the GLP-1 levels of plasma and intestinal tissues were investigated 12 weeks after DJBS placement. The number of intestinal GLP-1 positive cells was also counted. When the DJBS had been in place for 12 weeks, the plasma glucose level of the DJBS-implanted rats decreased significantly from 23.33±1.56 mmol/l prior to surgery to 7.70±0.84 mmol/l and the diabetes mellitus was relieved completely; however, diabetic control rats and diabetic rats subjected to sham surgery did not show any improvement. Parallel with the remission of diabetes, the plasma and distal ileum GLP-1 levels of rats in the DJBS implantation group were also higher than those of rats in the diabetic control and sham surgery groups. The number of GLP-1-positive cells in the distal ileum was also higher in the DJBS implantation group than in the diabetic control and sham surgery groups (31.0±2.6 vs. 23.5±4.4 vs. 23.0±3.2 respectively; P<0.01). DJBS implantation effectively led to the remission of diabetes in rats with diabetes induced by a high-fat diet and low-dose STZ when implanted for 12 weeks. The remission of diabetes may be associated with the increase in the number of L cells and elevation of GLP-1 levels induced by DJBS implantation.
Preview · Article · Aug 2015 · Experimental and therapeutic medicine
[Show abstract][Hide abstract] ABSTRACT: Klotho, an anti-aging gene, has recently been shown to contribute to human hepatic tumorigenesis. In addition, it is known that Wnt signaling is antagonized by the protein klotho. Because augmented Wnt signaling has an important role in tumorigenesis of human hepatocellular carcinoma (HCC), we studied the relationship of klotho expression and activity to the Wnt pathway in this malignancy. Immunohistochemical analysis performed on tissue arrays revealed that klotho expression levels were significantly lower in HCC than in adjacent noncancerous tissues, while klotho staining was inversely correlated with clinical stage and histologic grade. Patients with klotho-expressing tumors had longer survival periods than did those with klotho-negative tumors. Overexpression of klotho as well as treatment with soluble klotho protein reduced hepatoma cell growth in vitro and in vivo, whereas klotho silencing enhanced cellular proliferation. Moreover, forced expression of klotho inhibited Wnt/β-catenin signaling, as confirmed by reduced expression of β-catenin, inhibition of translocation of β-catenin from the cytoplasm to the nucleus, and reduced expression of c-myc and cyclin D1, two known target genes of the Wnt/β-catenin pathway. In contrast, activation of the Wnt/β-catenin pathway was enhanced when klotho was silenced by inhibitory RNAs. Furthermore, serum levels of soluble klotho in patients with malignant tumors were studied, and results suggested a significant increase in these levels in HCC patients. These data suggest that klotho acts as a tumor suppressor and an inhibitor of the Wnt/β-catenin pathway in HCC, and moreover, that soluble klotho is a potential serum biomarker for HCC.Laboratory Investigation advance online publication, 3 August 2015; doi:10.1038/labinvest.2015.86.
No preview · Article · Aug 2015 · Laboratory Investigation
[Show abstract][Hide abstract] ABSTRACT: Derlin-1 is overexpressed in many types of solid tumors and plays an important role in cancer progression. However, the expression pattern and functions of Derlin-1 in human colon cancer are not fully understood. In the present study, we examined Derlin-1 expression in colon cancer cell lines and human tissues and investigated its role in colon cancer. We found that Derlin-1 expression was increased significantly in colon cancer tissues and its overexpression correlated with the tumor differentiation, Dukes stage, invasion, lymph node metastasis, distant metastasis, and poor overall survival. The silencing of Derlin-1 by shRNA led to the growth inhibition of colon cancer cells, which were associated with the promotion of apoptosis. Furthermore, Derlin-1 silencing significantly inhibited the activation of the PI3K/AKT signaling pathway. Taken together, our results showed that Derlin-1 is overexpressed in colon cancer and promotes proliferation of colon cancer cells. Derlin-1 may be a potential therapeutic target for the treatment of colon cancer.
No preview · Article · Jul 2015 · Molecular and Cellular Biochemistry
[Show abstract][Hide abstract] ABSTRACT: Background
The aim of this study was to evaluate the safety and efficacy of the intramuscular injection of either mitomycin C or dexamethasone in association with an endoscopic dilation for benign esophageal strictures after esophageal surgery or ESD (Endoscopic Submucosal Dissection).Methods
Patients with benign esophageal strictures were retrospectively analyzed in this study. These patients were divided into 3 groups, including the mitomycin C group (mitomycin C injections in association with an endoscopic dilation), the dexamethasone group (dexamethasone injections and dilation) and the dilation group (saline injections and dilation). The patients’ characteristics, locations of the lesion, number of previous dilations, diameters after dilation, dysphagia grades before and after the procedure and follow-ups were compared.ResultsA total of 74 patients were enrolled in this retrospective case control study, 25 in the mitomycin C group, 25 in the dexamethasone group and 24 in the dilation group. The mean dysphagia-free period was 4.88±1.66 months in the mitomycin C group, 4.02±1.77 months in the dexamethasone group, and 2.41±1.26 months in the dilation group (P<0.05). There were no significant differences in the three groups for the other indices.Conclusion
The intramuscular injection of either mitomycin C or dexamethasone may prolong the dysphagia-free period and decrease the frequency of repeat dilations compared with conventional endoscopic dilations in patients with benign esophageal strictures. Mitomycin C may have predominant advantages compared with the other two methods.
No preview · Article · May 2015 · Journal of Digestive Diseases
[Show abstract][Hide abstract] ABSTRACT: To evaluate the efficacy of endoscopic purse-string suture (EPSS) with metallic clips and endoloop for the gastric wall defect after postoperative perforation.
Clinical data of 25 patients with gastric tumors(1 of gastric adenocarcinoma, 24 of gastric gastrointestinal stromal tumor, GIST) undergoing EPSS in Jiangsu Province People's Hospital and The Second Affiliated Hospital of Nanjing Medical University from January 2013 to May 2014 were retrospectively analyzed. During the procedure, EPSS was performed in 8 cases with perforation after endoscopic submucosal dissection(ESD), and in 17 cases with active perforation after endoscopic full-thickness resection.
Twenty-five patients underwent EPSS successfully. The procedure time was 35.0-75.0(49.8±10.1) min. No severe operational and postoperative complications occurred. Tumor resection margin were all negative. Time to withdraw gastrointestinal decompression drainage tube was 1-3(1.3±0.8) d. Postoperative hospital stay was 2-10(4.8±2.1) d and total cost was 10-31(19±0.5) thousand Yuan. One month after the procedure, all the patients received follow-up with no complaint of discomfort, and endoscopy confirmed that all the lesions healed.
EPSS with metallic clips and endoloop is effective and safe to close the gastric wall defect after full-thickness resection.
No preview · Article · Feb 2015 · Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery
[Show abstract][Hide abstract] ABSTRACT: Long noncoding RNA (lncRNA) have been proved to participate in the oncogenesis or development of gastrointestinal tumors. In this study, we aimed to identify the function of lncRNAs in the differentiation of peripheral blood T cells especially the distribution of regulatory T cells (T-reg) in gastric cancer. The distribution of T-reg was detected by flow cytometry. Peripheral blood T-reg cells were significantly up-regulated in plasma samples of gastric cancer patients. LncRNA microarray detection indicated an aberrant expression profiling of lncRNAs in T-reg cells between gastric cancer patients and controls in which linc-POU3F3 was selected as a potential biomarker with the highest fold change value as well as the most stable expression level in each group. In addition, over-expression of linc-POU3F3 elevated Treg distribution in vitro and promoted tumor cell proliferation in the co-culture system. We further found that linc-POU3F3 could recruit TGF-beta which increased the phosphorylation of SMAD2/3. In conclusion, we found that linc-POU3F3 could promote the distribution of Tregs in peripheral blood T cell which caused an enhanced cell proliferation of gastric cancer cells by recruiting TGF-beta as well as activating TGF-beta signal pathway. This finding may provide a theoretical basis for the further exploration of lncRNAs function in immune cell cells of gastric cancer.
No preview · Article · Jan 2015 · American Journal of Translational Research
[Show abstract][Hide abstract] ABSTRACT: Recently, more and more evidence are rapidly accumulating that long noncoding RNAs (lncRNAs) are involved in human tumorigenesis and misregulated in many cancers, including colon cancer. LncRNA could regulate essential pathways that contribute to tumor initiation and progression with their tissue specificity, which indicates that lncRNA would be valuable biomarkers and therapeutic targets. Colon cancer-associated transcript 1 (CCAT1) is a 2628 nucleotide-lncRNA and located in the vicinity of a well-known transcription factor c-Myc. CCAT1 has been found to be upregulated in many cancers, including gastric carcinoma and colonic adenoma-carcinoma. However, its roles in colon cancer are still not well documented and need to be investigated. In this study, we aim to investigate the prognostic value and biological function of CCAT1 and discover which factors may contribute to the deregulation of CCAT1 in colon cancer. Our results revealed that CCAT1 was significantly overexpressed in colon cancer tissues when compared with normal tissues, and its increased expression was correlated with patients' clinical stage, lymph nodes metastasis, and survival time after surgery. Moreover, c-Myc could promote CCAT1 transcription by directly binding to its promoter region, and upregulation of CCAT1 expression in colon cancer cells promoted cell proliferation and invasion. These data suggest that c-Myc-activated lncRNA CCAT1 expression contribute to colon cancer tumorigenesis and the metastatic process and could predict the clinical outcome of colon cancer and be a potential target for lncRNA direct therapy.
[Show abstract][Hide abstract] ABSTRACT: AbstactBackground and AimThe gut microbiota plays a pivotal role in the intestinal diseases. Fecal microbiota transplantation (FMT) might be a rescue therapy for refractory inflammatory bowel disease. This study aimed to evaluate the safety, feasibility and efficacy of FMT through mid-gut for refractory Crohn's disease (CD).Methods
We established standardized laboratory protocol and clinical work flow for FMT. Only refractory CD patients with Harvey-Bradshaw Index (HBI) score ≥ 7 were enrolled for this study. All included patients were treated with single FMT through mid-gut and assessed during follow-up.ResultsMetagenomics analysis showed a high concordance between feces sample and purified fecal microbiota from same donors. Standardized fecal microbiota preparation and clinical flow significantly simplified the practical aspects of FMT. Totally 30 patients were qualified for the present analysis. The rate of clinical improvement and remission based on clinical activity at the first month was 86.7 % (26/30) and 76.7 % (23/30) respectively, which was higher than other assessment points within 15-month follow-up. Patients’ body weight increased after FMT, and the lipid profile improved as well. FMT also showed a fast and continuous significant effect in relieving the sustaining abdominal pain associated with sustaining CD.Conclusions
This is a pilot study with the largest sample of patients with refractory CD underwent single FMT. The results demonstrated that FMT through mid-gut might be a safe, feasible, and efficient rescue therapy for refractory CD.
No preview · Article · Aug 2014 · Journal of Gastroenterology and Hepatology
[Show abstract][Hide abstract] ABSTRACT: Esophageal perforation is a rare complication of endoscopic retrograde cholangiopancreatography and the perforation is usually too large to close with endoclips. We developed an endoscopic procedure for the perforations.
A gastroscope fitted with a cap was inserted into the esophagus to perform the clip closure. The closure procedure was divided in 3 steps: step 1 is large clip closure; step 2 is small clip closure; and step 3 is the nasogastric tube placement for drainage.
A total of 4 patients underwent a cap-assisted clip closure and the procedures were completed successfully within 30 minutes. The cure was achieved in all the 4 patients after a relatively short period of hospital stay and no patient complained of closure-related complication.
The cap-assisted clip closure procedure is effective, safe, and easy to carry out for the closure of large esophageal perforations. It may also be applied to perform the closure of large perforations at other sites of the digestive tract.
[Show abstract][Hide abstract] ABSTRACT: To explore the feasibility, safety, efficacy, and cosmetic outcomes of transvaginal endoscopic salpingectomy for tubal ectopic pregnancy.
From May 2009 to May 2012, we prospectively enrolled 40 patients, each of whom had been scheduled for a salpingectomy because of a tubal ectopic pregnancy, and randomized them into two groups: transvaginal endoscopic surgery and laparoscopic approach. We recorded the estimated blood loss, time of anal exhaust, postoperative pain score, length of stay, and scar assessment scale associated with transvaginal endoscopic access (n = 18) (natural orifice transluminal endoscopic surgery) and laparoscopic salpingectomy (n = 20) (control group) for tubal ectopic pregnancy. The transvaginal salpingectomy was performed with a double-channel endoscope through a vaginal puncture. A single surgeon performed the surgical procedures in patients in both groups.
The group that underwent the transvaginal endoscopic procedure reported lesser pain at all postoperative visits than the group that underwent the laparoscopic approach. The duration of time for transvaginal endoscopic surgery was slightly longer than that for the laparoscopic approach. However, there was no statistically significant difference between the two groups in the duration of operative time. The group that underwent transvaginal endoscopic surgery was more satisfied with the absence of an external scar than the group that underwent the laparoscopic procedure, which left a scar. The estimated blood loss, time of anal exhaust, and length of stay were the same in both groups.
The safety and efficacy of transvaginal endoscopic salpingectomy for tubal ectopic pregnancy are equivalent to those of the laparoscopic procedure. Lesser postoperative pain and a more satisfactory cosmetic outcome were found with the transvaginal endoscopic procedure, making it the more preferred method and superior to the laparoscopic approach.
[Show abstract][Hide abstract] ABSTRACT: Stents are recommended in patients with dysphagia caused by esophageal stricture, but an ideal stent does not currently exist. Thus, studies on new esophageal stents are necessary, and suitable animal models are desperately needed for these studies. The aim of this study was to establish a model of malignant esophageal stricture in rabbit for studies on stent innovation.
A total of 38 New Zealand white rabbits were used in this study. Using the endoscopic submucosal injection technique, VX2 fragments were inoculated into the submucosal layer of the rabbit thoracic esophagus, and an endoscopic follow-up was subsequently performed to observe the tumor development and progression. The self-expandable metal stents were randomly deployed in rabbits with severe esophageal stricture to investigate the safety and feasibility of the animal models for stenting.
An endoscopic implantation procedure for VX2 tumors was completed in 34/38 rabbits, and tumor development was confirmed in 30/34 animals. The success rate of the endoscopic implantation and tumor development were 89.4% (95% CI, 79.6% to 99.2%) and 88.2% (95% CI, 76.9% to 99.5%) respectively. During the endoscopic follow-up period, severe esophageal stricture occurred in 22/30 rabbits with a rate of 73.3% (95%CI, 57.5% to 89.1%), and 12/22 models received stent placement. During and after stent implantation, no severe stent-related complication or mortality occurred in the animal models. The rabbits that received stent placement survived longer than those without stent implantation (the mean survival time: 53.9 days versus 40.3 days, P = 0.016).
The endoscopic method is a safe and effective method for establishing a malignant esophagostenosis model in rabbits. This model can simulate the human body environment for stent deployment and is an excellent tool for the study of stent innovation for the treatment of esophageal cancer.
Full-text · Article · Feb 2014 · Journal of Translational Medicine
[Show abstract][Hide abstract] ABSTRACT: This study was undertaken to establish a rabbit esophageal tumor model for mimicking human esophageal squamous carcinoma (ESC) by endoscopic and surgical implantation of VX2 tumors.
Fragments of a VX2 tumour were endoscopically implanted in the submucosal layer of the thoracic esophagus of 32 New Zealand white rabbits, while 34 animals received surgical implantation into the muscular layer. Then, the animals were studied endoscopically and pathologically. The safety and efficiency of the two methods and the pathological features of the animal models were analyzed.
Both the endoscopic and the surgical method had a relatively high success rate of tumor implantation [93.7% (30/32) vs. 97.1% (33/34)] and tumor growth [86.7% (26/30) vs. 81.8% (27/33)], and the variation in the results was not statistically significant (P>0.05). Compared with those produced by the surgical method, the models produced by the endoscopic method had a higher rate of severe esophageal stricture [61.5% (16/26) vs. 29.6% (8/27)] and of intra-luminal tumor growth [73.1% (19/26) vs. 37.0% (10/27)], and had a lower rate of tumor invasion of adjacent organs [53.8% (14/26) vs. 81.5% (22/27)]; all of these results were statistically significant (P<0.05). However, the difference in the survival time and the rates of tumor regional/distant metastasis [38.5% (10/26) vs. 51.8% (14/27)] between the two methods were not statistically significant (P>0.05).
The endoscopic and surgical methods are both safe and effective for establishment of VX2 tumors in the rabbit esophagus. The models produced by the two methods have different pathologic features mimicking that of human ESC. We recommend the models for studies on surgical procedures and minimally invasive treatments.
[Show abstract][Hide abstract] ABSTRACT: Gastric submucosal tumors (SMTs) originating from the muscularis propria layer are treated endoscopically. Successful closure of the wall defect is a critical step. This study evaluated the safety and feasibility of the endoscopic purse-string suture (EPSS) method using an endoloop and several metallic clips after endoscopic full-thickness resection (EFTR) or perforation due to endoscopic submucosal dissection (ESD).
From December 2009 to April 2013, 30 patients with SMTs originating from the muscularis propria layer who received EFTR or ESD were retrospectively analyzed. After successful tumor resection, an endoloop was anchored onto the circumferential margin of the gastric defect with several metallic clips and tightened gently. Patient characteristics, tumor size, en bloc resection, and postoperative complications were evaluated.
For all 30 patients, EPSS was successfully performed after EFTR or perforation due to ESD. The mean diameter of the resected specimen was 1.9 cm. No severe complications occurred during or after the procedure. The lesions were healed 1 month after the procedure, as confirmed endoscopically.
The EPSS method using an endoloop and clips is an effective and safe technique for closing the gastric defect after EFTR or perforation due to ESD.
No preview · Article · Jan 2014 · Surgical Endoscopy
[Show abstract][Hide abstract] ABSTRACT: Pancreaticobiliary maljunction (PBM) is an unusual anomalous condition in which the pancreatic duct and bile duct merge outside the duodenal wall and form a long common channel. Pancreas divisum (PD) is a congenital anomaly in which the dorsal and ventral pancreatic ducts fail to fuse. Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard for diagnosing PD and magnetic resonance cholangiopancreatography (MRCP) is the non-invasive choice. In this study, four cases of patients with unusual PBM in addition to PD are described. The patients presented with abdominal pain, which was caused by distal biliary stricture diagnosed by MRCP. The patients received ERCP and had a good prognosis.
Preview · Article · Jan 2014 · Experimental and therapeutic medicine