Risk factors for anastomotic leak and postoperative morbidity after right hemicolectomy for colon cancer: results from a prospective, multi-centre, snapshot study in China.

BACKGROUND: Right hemicolectomy is the standard treatment for right-sided colon cancer. There is variation in the technical aspects of performing right hemicolectomy as well as in short-term outcomes. It is therefore necessary to explore best clinical practice following right hemicolectomy in expert centres. METHODS: This snapshot study of right hemicolectomy for colon cancer in China was a prospective, multicentre cohort study in which 52 tertiary hospitals participated. Eligible patients with stage I-III right-sided colon cancer who underwent elective right hemicolectomy were consecutively enrolled in all centres over 10 months. The primary endpoint was the incidence of postoperative 30-day anastomotic leak. RESULTS: Of the 1854 patients, 89.9 per cent underwent laparoscopic surgery and 52.3 per cent underwent D3 lymph node dissection. The overall 30-day morbidity and mortality were 11.7 and 0.2 per cent, respectively. The 30-day anastomotic leak rate was 1.4 per cent. In multivariate analysis, ASA grade > II (P < 0.001), intraoperative blood loss > 50 ml (P = 0.044) and D3 lymph node dissection (P = 0.008) were identified as independent risk factors for postoperative morbidity. Extracorporeal side-to-side anastomosis (P = 0.031), intraoperative blood loss > 50 ml (P = 0.004) and neoadjuvant chemotherapy (P = 0.004) were identified as independent risk factors for anastomotic leak. CONCLUSION: In high-volume expert centres in China, laparoscopic resection with D3 lymph node dissection was performed in most patients with right-sided colon cancer, and overall postoperative morbidity and mortality was low. Further studies are needed to explore the optimal technique for right hemicolectomy in order to improve outcomes further.

Development and future perspectives of natural orifice specimen extraction surgery for gastric cancer.

In recent years, natural orifice specimen extraction surgery (NOSES), a novel minimally invasive surgical technique, has become a focus in the surgical field, and has been initially applied in gastric surgery in many national medical centers worldwide. In addition, this new surgical technique was launched in major hospitals in China. With an increasing number of patients who have accepted this new surgical technique, NOSES has provided new prospects for the treatment of gastric cancer (GC), which may achieve a better outcome for both patients and surgeons. More and more experts and scholars from different countries and regions are currently paying close attention to NOSES for the treatment of GC. However, there are only a few reports of its use in GC. This review focuses on the research progress in NOSES for radical gastrectomy in recent years. We also discuss the challenges and prospects of NOSES in clinical practice.

Aryl hydrocarbon receptor activation modulates γδ intestinal intraepithelial lymphocytes and protects against ischemia/reperfusion injury in the murine small intestine.

The pathogenesis of intestinal ischemia/reperfusion (I/R) is associated with dysregulation of the intestinal immune system. The aryl hydrocarbon receptor (AhR), a receptor expressed in gamma­delta (γδ) intraepithelial lymphocytes (IELs), is thought to regulate inflammation in the bowel. γδIELs are a key immunologic compartment with a capacity to modulate immune responses. In the present study, the function of the AhR in γδIELs in a mouse model of intestinal I/R injury was investigated to determine whether the AhR attenuates intestinal injury induced by intestinal I/R. Mice were assigned to three groups: sham, I/R and I/R+6­formylindolo(3,2­b)carbazole (FICZ). The sham group received no ischemia treatment, whereas the I/R and I/R+FICZ groups underwent upper mesenteric vessel ischemia for 30 min. The I/R group was injected intraperitoneally with 0.3 ml saline and the I/R+FICZ group was administered 1 µg of FICZ before a subsequent 6 h reperfusion. Then, the mice were sacrificed and the entire small intestinal tissues were collected for histologic examination. The phenotype and apoptosis of γδIELs and activation of CD4+ and CD8+ IELs were examined using flow cytometry. The cytokine mRNA and anti­apoptosis gene expression in IELs were measured by qPCR. FICZ increased the γδIEL population and anti­apoptosis genes in the γδIELs. FICZ reduced the percentage of activated CD4+ and CD8+ subpopulations and the expression of pro­inflammatory mediator genes in IELs. FICZ inhibited inflammation in the gastrointestinal tract of mice with I/R injury. These results suggest that the AhR plays an important role in protecting the small intestine from I/R and increasing the γδIEL population by decreasing apoptosis of γδIELs.

Knockdown on aPKC-ι inhibits epithelial-mesenchymal transition, migration and invasion of colorectal cancer cells through Rac1-JNK pathway.

BACKGROUND: Atypical protein kinase C-ι (aPKC-ι) is an oncogenic factor, and required for the epithelial-mesenchymal transition (EMT) of different types of cancer. Our study aimed to investigate the role of aPKC-ι in the EMT, migration and invasion of colorectal cancer (CRC) cells. METHODS: Expression of aPKC-ι was evaluated in CRC cell lines treated with TGF-ß1 using qPCR and western blot. After aPKC-ι was knocked down using shRNA, migration and invasion abilities of CRC cell lines were evaluated by wound healing assay and transwell assay, respectively. Activation status of downstream signaling factors of aPKC-ι, including Rac1, JNK, STAT3 and ß-catenin, was measured using western blot. Furthermore, auranofin, an aPKC-ι inhibitor, was used to treat CRC cell lines to investigate its possible inhibition on the EMT of CRC cell lines, as well as on the expression of aPKC-ι and its downstream signaling factors. RESULTS: TGF-ß1 induced the expression of aPKC-ι in CRC cells, and knockdown on aPKC-ι inhibited the TGF-ß1-induced EMT, migration and invasion of CRC cells. Interestingly, Rac1 GTPase level was decreased when aPKC-ι was knocked down, and overexpression of Rac1G12V rescued the cell EMT, migration and invasion in CRC cells as inhibited by sh-aPKC-ι. Moreover, knockdown on aPKC-ι suppressed the phosphorylation of JNK and STAT3, and nuclear translocation of ß-catenin. The aPKC- ι inhibitor, Auranofin, showed similar inhibitory effects as aPKC-ι knockdown. CONCLUSION: Knockdown on aPKC-ι inhibited the EMT, migration and invasion of CRC cells through suppressing of Rac1-JNK pathway. Those findings indicate that aPKC-ι may serve as a novel therapeutic target for CRC.

Aryl Hydrocarbon Receptor Activation Modulates Intestinal Epithelial Barrier Function by Maintaining Tight Junction Integrity.

Activation of Aryl hydrocarbon receptor (AhR) is involved in the control of intestinal mucosal homeostasis. Intestinal barrier dysfunction contributes to the development of many intestinal diseases, such as inflammatory bowel disease (IBD). In this study, we investigated the mechanisms of AhR activation in the maintenance of intestinal barrier function. Adult C57BL/6 mice were treated with dextran sulphate sodium (DSS) for 7 days, with or without 6-Formylindolo(3,2-b)carbazole (FICZ), a ligand of AhR. We found that AhR activation by FICZ attenuated the decreased TJ protein expression in the colonic mucosa of the DSS-induced mice. Further, the increase of both MLC phosphorylation and MLCK expression in the mice with DSS-induced colitis was also significantly inhibited by FICZ induced AhR activation. For in vitro experiments, Caco-2 cells were treated with tumour necrosis factor alpha (TNF-α)/interferon gamma (IFN-γ) for 48 h, with or without FICZ. AhR activation prevented TNF-α/IFN-γ-induced decrease in TER and morphological disruption of the TJs in Caco-2 monolayers. It also inhibited TNF-α/IFN-γ-induced increase in MLCK expression and MLC phosphorylation by suppression of NF-κB p65 signaling pathway. Thus, AhR-activating factors might have potential as therapeutic agents for the treatment of patients with IBD.

A new intracorporeal Billroth II stapled anastomosis technique in totally laparoscopic distal gastrectomy.

BACKGROUND: We introduced a new, safe and simple intracorporeal Billroth II (B-II) gastrojejunostomy technique using laparoscopic linear staplers with totally laparoscopic distal gastrectomy (TLDG) for gastric cancer. We further compared the short-term operative outcomes between intracorporeal B-II gastrojejunostomy with TLDG and extracorporeal B-II gastrojejunostomy with laparoscopy-assisted distal gastrectomy (LADG). METHODS: From January 01, 2012 to January 31, 2013, a total of 36 patients with gastric cancer underwent TLDG and LADG. Overall, 11 patients underwent intracorporeal B-II gastrojejunostomy with TLDG, and 25 patients underwent a mini-laparotomy incision for extracorporeal B-II anastomosis with LADG. Perioperative parameters, including patient and tumor characteristics, short-term postoperative outcomes, and anastomosis-related complications, were analyzed to compare the two operations. RESULTS: The time to first flatus, the time on a liquid diet, and the mean postoperative length of hospital stay were significantly different between the groups (P < 0.05). In the TLDG group, the postoperative time to first flatus and the mean postoperative length of hospital stay were significantly shorter than in the LADG group (2.6 ± 0.20 vs. 3.8 ± 0.1 days; 10 ± 1.84 vs. 12.7 ± 3.35 days). However, the operation-related costs were significantly greater for totally laparoscopic distal gastrectomy (P < 0.001). The mean number of staples used in TLDG was six compared with four in LADG. CONCLUSION: Our new intracorporeal B-II anastomosis method using laparoscopic linear staplers with TLDG was safe, feasible, and minimally invasive compared with extracorporeal B-II gastrojejunostomy with LADG. At the same time, one of its characteristics of our technique is to avoid stricturing of the efferent loop or afferent loop of the jejunum when the entry hole is closed with a stapler.

[Comparison of the outcomes of microscopic varicocelectomy and laparoscopic varicocelectomy].

OBJECTIVE: To compare and analyze semen quality improvement between the patients with microscopic varicocelectomy and laparoscopic varicocelectomy. METHODS: A total of 291 patients with varicocele were included in this study, of whom 176 underwent microscopic varicocelectomy and 115 laparoscopic varicocelectomy. The improvement rates of semen quality and pregnancy rates between the two groups were compared. RESULTS: The improvement rate of sperm density in microscopic group was significantly higher than that of laparoscopic group (87.6% vs. 73.7%, P = 0.006). Spouse pregnancy rate of microscopic group was significantly higher than that of laparoscopic group (45.4% vs. 30.3%, P = 0.017). CONCLUSION: The effect of microscopic varicocelectomy was superior to that of laparoscopic varicocelectomy.

Molecularly targeted drugs for metastatic colorectal cancer.

The survival rate of patients with metastatic colorectal cancer (mCRC) has significantly improved with applications of molecularly targeted drugs, such as bevacizumab, and led to a substantial improvement in the overall survival rate. These drugs are capable of specifically targeting the inherent abnormal pathways in cancer cells, which are potentially less toxic than traditional nonselective chemotherapeutics. In this review, the recent clinical information about molecularly targeted therapy for mCRC is summarized, with specific focus on several of the US Food and Drug Administration-approved molecularly targeted drugs for the treatment of mCRC in the clinic. Progression-free and overall survival in patients with mCRC was improved greatly by the addition of bevacizumab and/or cetuximab to standard chemotherapy, in either first- or second-line treatment. Aflibercept has been used in combination with folinic acid (leucovorin)-fluorouracil-irinotecan (FOLFIRI) chemotherapy in mCRC patients and among patients with mCRC with wild-type KRAS, the outcomes were significantly improved by panitumumab in combination with folinic acid (leucovorin)-fluorouracil-oxaliplatin (FOLFOX) or FOLFIRI. Because of the new preliminary studies, it has been recommended that regorafenib be used with FOLFOX or FOLFIRI as first- or second-line treatment of mCRC chemotherapy. In summary, an era of new opportunities has been opened for treatment of mCRC and/or other malignancies, resulting from the discovery of new selective targeting drugs.

[Expression of circulating microRNAs in patients with bladder urothelial carcinoma].

OBJECTIVE: To search for differentially expressed microRNAs in circulation and to explore their potential application as non-invasive biomarkers for bladder urothelial carcinoma. METHODS: Six bladder urothelial carcinoma patients were recruited into this study, and blood from seven non-tumor patients was included as the controls. Total small RNAs were isolated from the blood. By using high-throughput sequencing technologies, we provided microRNA expression profiles of bladder urothelial carcinoma patients and the control group. The data were analyzed using T test of the SPSS17.0 software to study the expression differences of microRNAs between the two groups. RESULTS: The work identified some microRNAs with differential expression in circulation between the bladder urothelial carcinoma patients and the non-tumor patients. Five microRNAs (hsa-miR-378g, hsa-miR-942, hsa-miR-106a-5p, hsa-miR-142-3p and hsa-miR-374a) were identified to be upregulated in the patients, and the expressions of many other microRNAs were significantly downregulated. CONCLUSION: The study reveals that there is a variance of microRNA expression profile in circulation between bladder urothelial and non neoplastic populations,The results need further study by large samples.