Search

Recent literature undeniably supports the idea that the microbiota has a strong influence on the healing process of an intestinal anastomosis. Understanding the mechanisms by which the bacterial community of the gut influences intestinal healing could open the door for new preventive and therapeutic approaches. Among the different mechanisms, data have shown that the production of specific reactive oxygen species (ROS) and the activation of specific formyl peptide receptors (FPRs) regulate intestinal wound healing. Evidence suggests that specific gut microbes such as Lactobacillus spp and Akkermansia muciniphila help to regulate healing processes through both ROS-dependent and FPR-dependent mechanisms. In this review, we will discuss the current knowledge and future perspectives concerning the impact of microbiota on wound healing. We will further review available evidence on whether mechanical bowel preparation and the use of specific antibiotics are beneficial or harmful procedures, an ongoing matter of debate. These practices have a profound effect on the gut microbiota composition at the level of both the mucosal and the luminal compartments. Therefore, a key question remains unanswered: should we continue to prepare the gut before surgical intervention? Current knowledge and data do not clearly support the use of one technique or another to avoid complications such as anastomotic leak. There is an urgent need for appropriate interventions with a deep microbiota analysis to investigate both the surgical technical benefits of a proper anastomosis compared with the potential effect of the gut microbes (beneficial vs harmful) on the processes of wound healing and anastomotic leakage reduction., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: To investigate the incidence of colorectal cancer among familial adenomatous polyposis (FAP) patients by phenotype using the latest modalities., Methods: We collected data on 303 patients who underwent surgery for FAP at one of 23 institutions between 2000 and 2012. The incidence of colorectal cancer was investigated by phenotype., Results: Colorectal cancer was diagnosed in 115 (38.0 %) of the 303 patients. Overall, colorectal cancer with the attenuated, sparse, and profuse phenotypes was diagnosed at 30, 31, and 28 years of age, respectively, in 10 % of the patients and at 59, 48, and 41 years of age, respectively, in 50 % of the patients (P = 0.013). The patients with colorectal cancer were older than those without colorectal cancer for all phenotypes. The optimal cut-off age for predicting the development of colorectal cancer in the attenuated, sparse, and profuse phenotypes was 46, 31, and 27 years, respectively., Conclusions: Patients with profuse and sparse phenotypes should undergo prophylactic proctocolectomy before their mid-to-late 20 s. On the other hand, the timing and type of surgery for patients with attenuated FAP (AFAP) should be decided individually with reference to the colonoscopic findings.

Aim: To detect the expression of Arpin, and determine its correlation with clinicopathological characteristics and the prognosis of gastric cancer (GC) patients., Methods: A total of 176 GC patients were enrolled as study subjects and classified into groups according to different clinicopathological variables. GC mucosal tissues were obtained via surgery. Another 43 paraffin-embedded tissue blocks of normal gastric epithelium (> 5 cm away from the edge of the tumor) were included in the control group. Immunohistochemistry (IHC) for the Arpin and Arp3 proteins was performed on the formalin-fixed, paraffin-embedded GC tissues. Additionally, expression of the Arpin protein in 43 normal gastric tissues was also determined using IHC., Results: Expression of the Arpin protein in GC was lower than that in normal gastric mucosa (30.68% vs 60.47%, P < 0.001). A χ 2 test of the 176 GC samples used for IHC showed that decreased Arpin expression was associated with advanced TNM stage ( P < 0.01) and the presence or absence of lymph node metastasis (80.92% vs 35.56%, P < 0.001). Additionally, a significant correlation was observed between the expression of Arpin and the presence of the Arp2/3 complex in GC tissues ( χ 2 = 30.535, P < 0.001). Moreover, a multivariate Cox regression analysis revealed that Arpin expression [hazard ratio (HR) = 0.551, P = 0.029] and TNM stage (HR = 5.344, P = 0.001) were independent prognostic markers for overall survival of GC patients. Regarding the 3-year disease-free survival (DFS), the recurrence rate of GC patients with low Arpin expression levels (median DFS 19 mo) was higher than that in the high-Arpin-expression group (median DFS 34 mo, P = 0.022)., Conclusion: Low Arpin levels are associated with clinicopathological variables and a poor prognosis in GC patients. Arpin may be regarded as a potential prognostic indicator in GC., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest.

Background: The outcome of colon cancer patients without lymph node metastasis is heterogeneous. Searching for new prognostic markers is warranted., Methods: One hundred twenty stage I-II colon cancer patients who received complete surgical excision during 1995-2004 were selected for this biomarker study. Immunohistochemical method was used to assess p53, epidermal growth factor receptor, MLH1, and MSH2 status. KRAS mutation was examined by direct sequencing., Results: Thirty three patients (27.5%) developed metachronous metastasis during follow up. By multivariate analysis, only female gender (p = 0.03), high serum carcinoembryonic antigen (CEA) level (≧5 ng/ml) (p = 0.04), and MLH1 overexpression (p = 0.003) were associated with the metastasis group. The 5-year-survival rate were also significantly lower for female gender (71.7% versus 88.9%, p = 0.025), high CEA level (64.9% versus 92.4%, p < 0.001), and MLH1 overexpression (77.5% versus 94.4%, p = 0.039). In contrast, MSH2 overexpression was associated with better survival, 95.1% versus 75.5% (p = 0.024)., Conclusions: The reversed prognostic implications in the overexpression of MLH1 and MSH2 for stage I-II colon cancer patients is a novel finding and worthy of further confirmation., (Copyright © 2017 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Purpose: Familial adenomatous polyposis (FAP) is a genetic disorder. Some female patients with FAP can become pregnant. However, the current state of childbirth after surgery for FAP is unclear in Japan., Methods: The study investigated 303 patients (147 female) who had undergone surgery for FAP at the 23 institutions between 2000 and 2012., Results: Eighty female patients had information available on childbirth after surgery for FAP. Eight patients (10 %) gave birth after surgery. The mean age at surgery for FAP was 27 (range 20-41) years and 37 years in patients with and without childbirth after surgery, respectively (P = 0.044). The rate of childbirth after surgery was 17 % in women ≤30 years of age and 13 % in those ≤40 years of age. Although only one patient with invasive cancer (2.9 %) gave childbirth after surgery, seven patients without cancer (15.6 %) gave birth (P = 0.045)., Conclusions: This study clarified the current state of childbirth after surgery for FAP in Japan. It is important to use these data to determine the best therapeutic approach for female FAP patients.

Background and Objective: The aim of the study was to investigate the effects of ceramide-1-phosphate transfer protein (CPTP) on the intestinal epithelial tight junction proteins in patients with severe acute pancreatitis (SAP)., Methods: Fifty patients with SAP were classified into two groups according to the presence of bacterial translocation (BT) in the blood. Thirty healthy individuals were included in the control group. The presence of BT was analyzed by polymerase chain reaction. The expression of tight junction proteins and CPTP was determined using immunohistochemistry and western blotting., Results: Bacterial DNA was detected in the peripheral blood of 62.0% of the patients with SAP. The expression of CPTP and tight junction proteins in SAP patients was lower than that in healthy controls. Among the patients with SAP, those positive for BT(+) showed a lower level of CPTP and occluding (OC) and zonula occludens-1 (ZO-1) expression and a higher level of IVA cPLA2 expression than BT(-) patients. Moreover, the expression of CPTP was significantly associated with ZO-1 and showed a negative correlation with expression of IVA cPLA2 in SAP-BT(+) patients., Conclusions: CPTP affects the expression of tight junction proteins and may protects the intestinal epithelial barrier by downregulating the expression of IVA cPLA2., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

In this study, we identified CTCs using the previously reported CanPatrol CTC enrichment technique from peripheral blood samples of 126 patients with colorectal cancer (CRC) and found that CTCs could be classified into three subpopulations based on expression of epithelial cell adhesion molecule (EpCAM) (E-CTCs), the mesenchymal cell marker vimentin (M-CTCs), or both EpCAM and vimentin (biphenotypic E/M-CTCs). Circulating tumor microemboli (CTMs) were also identified in peripheral blood samples. Meanwhile, E-CTCs, M-CTCs, E/M-CTCs, and CTMs were detected in 76.98%, 42.06%, 56.35%, and 36.51% of the 126 patients, respectively. Interestingly, the presence of CTMs and each CTC subpopulation was significantly associated with blood lymphocyte counts and tumor-node-metastasis stage ( P < 0.001). Lymphocyte counts and the neutrophil-to-lymphocyte ratio (NLR) in patients lacking CTCs were significantly different from those in patients testing positive for CTMs and each CTC subpopulation ( P < 0.001). Our results indicate that tumor metastasis is more significantly associated with the presence of CTMs and M-CTCs than with other CTC subpopulations and suggest that EMT may be involved in CTC evasion of lymphocyte-mediated clearance.

Background: Data supporting the safety and feasibility of laparoscopic total proctocolectomy with ileal pouch-anal anastomosis (TPC-IPAA) and total colectomy with ileorectal anastomosis (TC-IRA) for patients with familial adenomatous polyposis (FAP) are limited. The aim of this study was to clarify the feasibility and morbidity of laparoscopic TPC-IPAA and TC-IRA for patients with FAP, using a large Japanese multicenter dataset., Methods: Data on 256 patients with FAP who underwent TPC-IPAA (n = 171) or TC-IRA (n = 85) at 23 institutions between the years 2000 and 2012 were collected. Short- and long-term clinical outcomes were compared between laparoscopic and open approaches for each procedure., Results: Among the 256 patients with FAP, a total of 126 patients underwent laparoscopic surgery, consisting of 74 laparoscopic TPC-IPAAs and 52 laparoscopic TC-IRAs. The proportion of the FAP patients who underwent laparoscopic surgery increased during the study period, reaching 79 % of all TPC-IPAAs and 82 % of all TC-IRAs in the final two years covered by the data. In both TPC-IPAA and TC-IRA, the laparoscopic approach was associated with a longer operative duration but a similarly low postoperative morbidity and comparably adequate anal function compared with the open approach. The overall survival and the incidence of desmoid tumor were also comparable between the laparoscopic and open approaches in both procedures., Conclusions: Laparoscopic TPC-IPAA and TC-IRA are both feasible options-with low rates of morbidity, good functional outcomes, and excellent overall survival rates-in patients with FAP. Since the data indicate that laparoscopic TPC-IPAA and TC-IRA are feasible, they also support the recent increase in laparoscopic surgery for patients with FAP in Japan.

Background: Oxaliplatin is a platinum compound that is widely used in the treatment of some solid tumours. Oxaliplatin-induced peripheral neuropathy (OIPN) in the upper and lower extremities is the major adverse side effect and represents the main dose-limiting factor of this drug. The aim of this single-arm study was to evaluate the feasibility and effects of laser acupuncture (LA) in the treatment of OIPN in patients with advanced gastrointestinal cancers., Methods: 17 gastrointestinal cancer survivors (14 colorectal and 3 gastric cancers), who had been treated with oxaliplatin-based chemotherapies, were recruited. Low-level laser stimulation (50 mW) bilaterally at PC6, PC7, PC8, P9, LU11, SP6, KI3, BL60, KI1, and KI2 was administered for 20 min/point for 12 sessions over 4 weeks. The pain quality assessment scale (PQAS), chemotherapy-induced neurotoxicity questionnaire (CINQ), oxaliplatin-specific neurotoxicity scale (OSNS), quantitative touch-detection threshold (using von Frey filaments), and cold-triggered pain withdrawal latency (using the cold-water immersion test) were measured before and after completion of the 12 treatment sessions., Results: PQAS, CINQ, and OSNS scores, as well as touch-detection threshold and cold-trigger pain withdrawal latency all improved significantly after LA in the cancer patients with OIPN (p<0.05). LA significantly relieved both oxaliplatin-induced cold and mechanical allodynia and also decreased the incidence and severity of neurotoxicity symptoms in the patients' upper and lower extremities and impact on their daily activities (all p<0.05)., Conclusions: Following treatment with LA, neurotoxicity symptoms were significantly improved in cancer patients with OIPN. Further randomised controlled trials are needed to evaluate the role of LA as a therapeutic option in the management of OIPN., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

This study was to investigate whether the time to the lowest postoperative CEA can predict cancer survival. We enrolled 155 rectal cancer patients in this retrospective and longitudinal cohort study. Deepness of response (DpR) of CEA refers to the relative change of the lowest postoperative CEA level from baseline, and time to DpR (TTDpR) refers to the time from surgery to the lowest postoperative CEA level. The median of TTDpR and DpR was 4.5 (range, 3.0-18.0) weeks and -67% (range, -99% to 114%) respectively. Patients with TTDpR 4.5 weeks. Using TTDpR as a continuous variable, the HR of DFS and OS was 1.13 (95% CI 1.06-1.22, P = 0.001) and 1.17 (95% CI 1.07-1.29, P = 0.001) respectively. On multivariate analysis, the predictive value of prolonged TTDpR remained [adjusted HRs: 1.12 (95% CI 1.03-1.21, P = 0.006) and 1.17 (95% CI 1.06-1.28, P = 0.001)]. These findings remained significant in patients with normal preoperative CEA. Our results showed prolonged TTDpR of CEA independently predicted unfavorable survival outcomes, regardless of whether preoperative CEA was elevated or not.

The coxsackie and adenovirus receptor (CAR) is considered a tumor suppressor and critical factor for the efficacy of therapeutic strategies that employ the adenovirus. However, data on CAR expression levels in colorectal cancer are conflicting and its clinical relevance remains to be elucidated. Immunohistochemistry was performed on tissue microarrays containing 251 pairs of colon cancer and adjacent normal tissue samples from Chinese Han patients to assess the expression levels of CAR. Compared with healthy mucosa, decreased CAR expression (40.6% vs. 95.6%; P<0.001) was observed in colorectal cancer samples. The CAR immunopositivity in tumor tissues was not significantly associated with gender, age, tumor size, differentiation, TNM stage, lymph node metastasis or distant metastasis in patients with colon cancer. However, expression of CAR is present in 83.3% of the tumor tissues from patient with colorectal liver metastasis, which was significantly higher than those without liver metastasis (39.6%; P=0.042). At the plasma membrane, CAR was observed in 29.5% normal mucosa samples, which was significantly higher than in colorectal cancer samples (4.0%; P<0.001). In addition, the survival analysis demonstrated that the expression level of CAR has no association with the prognosis of colorectal cancer. CAR expression was observed to be downregulated in colorectal cancer, and it exerts complex effects during colorectal carcinogenesis, potentially depending on the stage of the cancer development and progression. High CAR expression may promote liver metastasis. With regard to oncolytic therapy, CAR expression analysis should be performed prior to adenoviral oncolytic treatment to stratify Chinese Han patients for treatment.

Introduction: Left- and right-sided colon cancers were significantly different in epidemiologic, clinical and histological parameters. However, the impact of primary tumor location in metastatic colon cancer treated with front-line targeted triplet regimens is unclear, particularly in Asian populations., Methods: A total of 121 patients with KRAS exon 2 codon 12/13 wild-type metastatic colon cancer were enrolled between January 2007 and December 2013. All patients received one target agent, such as cetuximab or bevacizumab, as a front-line targeted triplet regimen. The impact of primary tumor location for cetuximab and bevacizumab groups was analyzed, respectively., Results: In cetuximab group, left-sided metastatic colon cancer was superior to right-sided metastatic colon cancer in objective response rate (70.1% vs 33.3%, P = 0.024), progression-free survival (15.0 vs 5.3 months, P < 0.001) and overall survival (35.8 vs 14.4 months, P = 0.031). Primary tumor location was an independent prognostic factor for progression-free survival (hazard ratio 0.240, 95% confidence interval 0.114-0.508, P < 0.001). However, in the bevacizumab group, there were no differences in outcomes for either side. Primary tumor location was insignificant for progression-free survival and overall survival in univariate analysis., Conclusion: Left-sided primary tumors were favored in cetuximab-based front-line targeted triplet regimen for metastatic colon cancer., (© 2016 John Wiley & Sons Australia, Ltd.)

Ethnopharmacological Relevance: Nelumbo nucifera Gaertn (Nymphaeaceae) has been recognized as a medicinal plant, which was distributed throughout the Asia. The aqueous extract of Nelumbo nucifera leaves extract (NLE) has various biologically active components such as polyphenols, flavonoids, oligomeric procyanidines. However, the role of NLE in breast cancer therapy is poorly understood., The Aim of This Study: The purpose of this study was to identify the hypothesis that NLE can suppress tumor angiogenesis and metastasis through CTGF (connective tissue growth factor), which has been implicated in tumor angiogenesis and progression in breast cancer MDA-MB-231 cells., Results: We examined the effects of NLE on angiogenesis in the chicken chorioallantoic membrane (CAM) model. The data showed that NLE could reduce the chorionic plexus at day 17 in CAM and the duration of this inhibition was dose-dependent. In Xenograft model, NLE treatment significantly reduced tumor weight and CD31 (capillary density) over control, respectively. We examined the role of angiogenesis involved restructuring of endothelium using human umbilical vein endothelial cell (HUVEC) in Matrigel angiogenesis model. The results indicated that vascular-like structure formation was further blocked by NLE treatment. Moreover, knockdown of CTGF expression markedly reduced the expression of MMP2 as well as VEGF, and attenuated PI3K-AKT-ERK activation, indication that these signaling pathways are crucial in mediating CTGF function., Conclusion: The present results suggest that NLE might be useful for treatment in therapy-resistance triple negative breast cancer., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To identify independent factors of sphincter preserving surgery, and to evaluated whether preoperative chemoradiotherapy (CRT) improves the sphincter preservation rate for lower rectal cancers. Methods: A total of 541 consecutive patients who underwent curative surgery for locally advanced rectal cancer (cT3-4Nx or cTxN+ ) within 6 cm of the anal verge with or without neoadjuvant CRT in Department of Colorectal Surgery, Union Hospital, Fujian Medical University between September 2000 and September 2013 were reviewed. Of these, 333 patients underwent surgery alone (Non-CRT group) and 208 patients also received preoperative chemoradiotherapy (CRT group). Clinical data were retrospectively reviewed to determine the factors influencing sphincter preservation, and to evaluate sphincter preservation rate according to tumor height over 1-cm intervals. The categorical variables were compared using χ 2 test and Fisher exact test. Continuous variables were compared using t test. Logistic regression was used to identify factors influencing sphincter preservation. A receiver operating characteristic (ROC) curve was constructed, and Youden's index was calculated to evaluate the predictive abilities of factors. Results: Multivariate analysis indicated that the independent factors influencing sphincter preservation were tumor height ( OR =5.867, 95% CI: 4.155 to 8.285, P =0.000), pathological T stage ( OR =0.688, 95% CI: 0.462 to 1.025, P =0.066), CRT ( OR =2.088, 95% CI: 0.971 to 4.492, P =0.060) and histopathological type ( OR =0.288, 95% CI: 0.136 to 0.611, P =0.001). The results of ROC analysis showed that the cut-off points for factors affecting sphincter preservation were as follows: (1) tumor height prior to CRT higher than 4.5 cm, (2) not mucinous or signet ring adenocarcinoma, (3) pathological T stage higher than T3, (4) had received preoperative CRT. In an analysis according to tumor height, the sphincter preservation rate was higher in CRT group only when tumor was located in 3.0 to 3.9 cm and 4.0 to 4.9 cm from the annal verge (3.0 to 3.9 cm, 59.4% vs . 2.8%, χ 2 =26.138, P =0.000; 4.0 to 4.9 cm, 76.9% vs. 37.9%, χ 2 =10.563, P =0.001). Conclusions: There is a large increased rate of sphincter preservation when patients meet the following conditions: (1) tumor height prior to CRT higher than 4.5 cm, (2) not mucinous or signet ring adenocarcinoma, (3)pathological T stage higher than T3, (4) had received preoperative CRT. Only when tumors are between 3 and 5 cm from the anal verge, CRT could increase the rate of anal sphincter preservation.

Aim: Nodal stage is a strong prognostic factor of oncological outcome of rectal cancer. To compensate for the variation in total number of harvested nodes, calculation of the lymph node ratio (LNR) has been advocated. The aim of the study was to compare the impact, on the long-term oncological outcome, of the LNR with other predictive factors, including the quality of total mesorectal excision (TME) and the state of the circumferential resection margin., Method: Consecutive patients having elective surgery for nonmetastatic rectal cancer were extracted from a prospectively maintained database. Retrospective uni- and multivariate analyses were performed based on patient-, surgical- and tumour-related factors. The prognostic value of the LNR on overall survival (OS) and on overall recurrence-free survival (ORFS) was assessed and a cut-off value was determined., Results: From 1998 to 2013, out of 456 patients, 357 with nonmetastatic disease were operated on for rectal cancer. Neoadjuvant radiochemotherapy was administered to 66.7% of the patients. The mean number of lymph nodes retrieved was 12.8 ± 8.78 per surgical specimen. A lower lymph node yield was obtained in patients who received neoadjuvant chemoradiotherapy (11.8 vs 14.2; P = 0.014). The 5-year ORFS was 71.8% and the 5-year OS was 80.1%. Multivariate analysis confirmed LNR, the quality of TME and age to be independent prognostic factors of OS. LNR, age and perineural infiltration were independently associated with ORFS. Low- and high-risk patients could be discriminated using an LNR cut-off value of 0.2., Conclusion: LNR is an independent prognostic factor of OS and ORFS. In line with the principles of optimal surgical management, the quality of TME and lymph node yield are essential technical requirements., (Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.)

Objective: To explore the prognostic factors of postoperative incisional surgical site infections (I-SSI) for colorectal cancer. Methods: Clinical data of 2 385 colorectal cancer patients undergoing resection by the same surgical team in Department of Colon and Rectum Surgery, Fujian Medical University Union Hospital from January 2000 to February 2014 was analyzed retrospectively. There were 1 421 male and 964 female patients, with a mean age of (59±13) years. Univariate analysis and multivariate Logistic regression analysis were performed for independent prognostic factors of I-SSI. Results: The I-SSI occurred in 77 patients (3.23%). The results of univariate analysis showed that there were statistical differences in body mass index ( t =-3.356), operation time ( t =-3.609), length of incision ( t =-5.492), radical operation (χ 2 =8.963), laparoscopic surgery (χ 2 =25.884), combined evisceration (χ 2 =6.349) and intraoperative blood infusion (χ 2 =4.176) between two groups (all P <0.05) . The results of multivariate Logistic regression analysis showed that independent prognostic factors of I-SSI were identified to be body mass index ( OR =1.087, 95% CI: 1.023 to 1.155, P =0.007), operation time ( OR =1.007, 95% CI: 1.002 to 1.012, P =0.006), preoperative chemoradiotherapy ( OR =2.434, 95% CI: 1.099 to 5.393, P =0.028) and combined evisceration ( OR =2.596, 95% CI: 1.060 to 6.357, P =0.037). The independent protective prognostic factor of I-SSI was identified to be the laparoscopic surgery ( OR =0.386, 95% CI: 0.170 to 0.877, P =0.023). Conclusions: Body mass index, operation time, preoperative chemoradiotherapy and combined evisceration are identified to be independent prognostic factors for I-SSI. High-risk patients should receive individualized perioperative intervention. Nevertheless, the laparoscopic surgery can decrease the incidence of I-SSI.

A tobacco-specific component, 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK), is a major risk factor for many cancers. Recent reports have demonstrated that NNK exposure may be associated with tumor progression and chemoresistance in certain cancers. However, the underlying NNK-induced mechanism contributing to the aggressiveness of colorectal cancer (CRC) has not been thoroughly studied. In this study, we used HT29 cells treated with NNK to simulate the long-term exposure of cigarette smoke. A comparative analysis was performed to evaluate cell proliferation, migration, and invasion as well as epithelial-mesenchymal transition (EMT) markers and drug-resistance genes expression, cancer stem cell (CSC) properties, and anti-apoptotic activity. Signaling pathways related to chemoresistance were also investigated. As a result, NNK exposure dose-dependently stimulates cell proliferation, enhance abilities of migration and invasion, induce EMT phenomenon, and attenuate apoptosis. Furthermore, NNK exposure also promotes the capabilities of sphere formation, upregulation of Snail, and overexpression of CD133, Nanog, OCT4, and the drug-resistant genes. Knockdown of Snail results in upregulation of Raf kinase inhibitor protein (RKIP), increased apoptosis, reversal of EMT phenomenon, and reducation of expression of CSC markers, all of which contribute to a decrease of chemoresistance. Our study demonstrates a number of related mechanisms that mediate the effect of NNK exposure on increasing CRC therapeutic resistance via the Snail signaling pathway. Targeting Snail may provide a feasible strategy for the treatment of CRC., Competing Interests: The authors declared no conflicts of interest.

DDX3 plays a dual role in colorectal cancer; however, the role and underlying mechanism of DDX3 in colorectal tumorigenesis remains unclear. Here, we provide evidence that DDX3 enhances oncogenic KRAS transcription via an increase in SP1 binding to its promoter. Accelerating oncogenic KRAS expression by DDX3 promotes the invasion capability via the ERK/PTEN/AKT/β-catenin cascade. Moreover, the β-catenin/ZEB1 axis is responsible for DDX3-induced cell invasiveness and xenograft lung tumor nodule formation. The xenograft lung tumor nodules induced by DDX3-overexpressing T84 stable clone were nearly suppressed by the inhibitor of AKT (perifosine) or β-catenin (XAV939). Among patients, high KRAS, positive nuclear β-catenin expression and high ZEB1 were more commonly occurred in high-DDX3 tumors than in low-DDX3 tumors. High-DDX3, high-KRAS, positive nuclear β-catenin tumors, and high-ZEB1 exhibited worse overall survival (OS) and relapse free survival (RFS) than their counterparts. In conclusion, DDX3 may play an oncogenic role to promote tumor growth and invasion in colon cancer cells via the β-catenin/ZEB1 axis due to increasing KRAS transcription. We therefore suggest that AKT or β-catenin may potentially act as a therapeutic target to improve tumor regression and outcomes in colorectal cancer patients who harbored high-DDX3 tumors., Competing Interests: The authors declare no conflicts of interest.

Background: Several studies suggested that hypertension is positively related to cancer incidence and mortality. In this study, we investigated the association between perioperative blood pressure (BP) and long-term survival outcomes in patients with rectal cancer., Methods: This study included a cohort of 358 patients with stages I-III rectal cancer who underwent a curative resection between June 2007 and June 2011. Both pre- and postoperative BPs were measured, by which patients were grouped (low BP: <120/80 mmHg; high BP: ≥120/80 mmHg). The survival outcomes were compared between these two groups. The primary endpoints were disease-free survival (DFS) and cancer-specific survival (CSS)., Results: Univariate analysis showed that patients with high preoperative systolic BP had lower 3-year DFS (67.2% vs. 82.1%, P = 0.041) and CSS rates (81.9% vs. 94.8%, P = 0.003) than patients with low preoperative systolic BP, and the associations remained significant in the Cox multivariate analysis, with the adjusted hazard ratios equal to 1.97 [95% confidence interval (CI) = 1.08-3.60, P = 0.028] and 2.85 (95% CI = 1.00-8.25, P = 0.050), respectively. Similarly, in postoperative evaluation, patients with high systolic BP had significantly lower 3-year CSS rates than those with low systolic BP (78.3% vs. 88.9%, P = 0.032) in univariate analysis. Moreover, high pre- and/or postoperative systolic BP presented as risk factors for CSS in the subgroups of patients who did not have a history of hypertension, with and/or without perioperative administration of antihypertensive drugs., Conclusions: High preoperative systolic BP was an independent risk factor for both CSS and DFS rates, and high postoperative systolic BP was significantly associated with a low CSS rate in rectal cancer patients. Additionally, our results suggest that rectal cancer patients may get survival benefit from BP control in perioperative care. However, further studies should be conducted to determine the association between BP and CSS and targets of BP control.

Objective: We investigated the necessity of preoperative bowel preparation for gynecological oncology surgery., Materials and Methods: We retrospectively reviewed the medical records of patients who underwent gynecological oncology surgery with simultaneous colon or rectal resection between April 2005 and September 2014 at the Tri-Service General Hospital, Taipei, Taiwan. Patients were divided into two groups based on whether preoperative mechanical bowel preparation (MBP) was performed. Patient characteristics, including duration of antibiotic treatment, surgical procedures, and occurrence of surgical and nonsurgical complications, were compared., Results: We enrolled 124 patients who underwent gynecological oncology surgery with simultaneous colon or rectal resection, of whom 76 received MBP and 48 did not receive mechanical bowel preparation. On comparison between the two groups, no significant differences were noted in the assessed patient characteristics, including mean age (p = 0.61), Federation of Gynecology and Obstetrics stage (p = 0.9), American Society of Anesthesiologists grade (p = 0.9), body mass index (p = 0.8), and residual tumor size (p = 0.86). Furthermore, duration of antibiotic treatment (p = 0.97), surgical procedures (p = 0.99), and total hospital days (p = 0.75), were not different between groups. The risk of surgical (p = 0.78) or nonsurgical (p = 1.0) complications was not significantly higher in the non-MBP group than in the MBP group., Conclusion: MBP provides no significant benefit during gynecological oncology surgery. Thus, preoperative MBP is not essential before gynecological oncology surgery and can be omitted., (Copyright © 2016. Published by Elsevier B.V.)

Objective: The upper gastrointestinal characteristics in Japanese familial adenomatous polyposis patients have not yet been clarified. The aim of the present study was to elucidate these characteristics in Japanese familial adenomatous polyposis patients., Methods: This study was conducted by the study group for familial adenomatous polyposis in the Japanese Society for Cancer of the Colon and Rectum. Familial adenomatous polyposis patients who underwent surgical resection from 2000 to 2012 were included in the study., Results: In total, 303 familial adenomatous polyposis patients were enrolled, with 265 cases of classical familial adenomatous polyposis (≥100 adenomas) and 38 cases of attenuated familial adenomatous polyposis (<100 adenomas). Fundic gland polyps were significantly more common in classical familial adenomatous polyposis than in attenuated familial adenomatous polyposis; however, gastric cancer was significantly less common in classical familial adenomatous polyposis than in attenuated familial adenomatous polyposis. Gastric cancer and duodenal adenoma were significantly more common in familial adenomatous polyposis patients with gastric adenoma than in those without gastric adenoma. Duodenal cancer was detected in 7 of 72 familial adenomatous polyposis patients with duodenal adenoma. The median tumour risk in 50-year-old familial adenomatous polyposis patients was 55.3, 21.8, 3.8, 39.2 and 7.7% for fundic gland polyp, gastric adenoma, gastric cancer, duodenal adenoma and duodenal cancer, respectively., Conclusions: Upper gastrointestinal tumours/polyps were frequently found in familial adenomatous polyposis patients, and their incidences were correlated; however, the frequency of gastric cancer in Japanese familial adenomatous polyposis patients was similar to that in the general population., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Unlabelled: Treatment failure followed by relapse and metastasis in patients with non-small cell lung cancer is often the result of acquired resistance to cisplatin-based chemotherapy. A cancer stem cell (CSC)-mediated anti-apoptotic phenomenon is responsible for the development of drug resistance. The underlying molecular mechanism related to cisplatin resistance is still controversial, and a new strategy is needed to counteract cisplatin resistance. We used a nonadhesive culture system to generate drug-resistant spheres (DRSPs) derived from cisplatin-resistant H23 lung cancer cells. The expressions of drug-resistance genes, properties of CSCs, and markers of anti-apoptotic proteins were compared between control cells and DRSPs. DRSPs exhibited upregulation of cisplatin resistance-related genes. Gradual morphological alterations showing epithelial-to-mesenchymal transition phenomenon and increased invasion and migration abilities were seen during induction of DRSPs. Compared with control cells, DRSPs displayed increased CSC and anti-apoptotic properties, greater resistance to cisplatin, and overexpression of p-Hsp27 via activation of p38 MAPK signaling. Knockdown of Hsp27 or p38 decreased cisplatin resistance and increased apoptosis in DRSPs. Clinical studies confirmed that the expression of p-Hsp27 was closely associated with prognosis. Overexpression of p-Hsp27 was usually detected in advanced-stage patients with lung cancer and indicated short survival., Summary: DRSPs were useful for investigating drug resistance and may provide a practical model for studying the crucial role of p-Hsp27 in the p38 MAPK-Hsp27 axis in CSC-mediated cisplatin resistance. Targeting this axis using siRNA Hsp27 may provide a treatment strategy to improve prognosis and prolong survival in lung cancer patients.

A transanal approach to rectal polyp and cancer excision is often an appropriate alternative to conventional rectal resection, and has a lower associated morbidity. There has been a steady evolution in the techniques of transanal surgery over the past 30 years. It started with traditional transanal excision and was revolutionized by introduction of transanal endoscopic microsurgery in early 1980s. Introduction of transanal minimally invasive surgery made it more accessible to surgeons around the world. Now robotic platforms are being tried in certain institutions. Concerns have been raised about recurrence rates of cancers with transanal approach and success of subsequent salvage operations.

Objective: To establish the classification of colorectal cancer recurrence patterns based on their relations to prognosis and recurrence., Methods: A total of 463 patients with recurrent rectal cancer (Stage I-III) following curative resection in our hospital from June 2002 to June 2012 were included consecutively. Recurrence status, time, location, survival time after relapse, curability, symptoms and CEA level were recorded. The correlation between each recurrent pattern and recurrent survival (RS) rate were analyzed retrospectively. The survival curve was drawn by Kaplan-Meier method. The Log-rank test was used to test the significance. Univariate analysis was performed by using Cox proportional hazard model., Results: Patients with recurrence within one year, multiple metastases, symptomatic disease, elevated CEA level and unresectable recurrence had significantly lower RS rate than patients with recurrence after one year, solitary metastasis, asymptomatic manifestation, normal CEA level and resectable recurrence respectively. The hazard ratio were 1.34 (95%CI 1.02-1.76, P= 0.033), 1.41 (95%CI 1.04-1.91, P= 0.026), 1.74 (95%CI 1.05-2.88, P= 0.032), 4.06 (95%CI 2.11-7.85, P<0.001) and 1.99 (95%CI 1.34-2.97, P= 0.001) respectively., Conclusion: Early recurrence (<12 months), multiple metastases, symptomatic, unresectable recurrence and elevated CEA indicate poor prognosis after relapse. This study provides a systematic basis for the classification of recurrence in colorectal cancer after radical resection.

Glioblastoma (GBM) is the most common and deadliest primary tumor in adults, with current treatments having limited specific and efficient delivery of therapeutic drugs to tumor sites or cells. Therefore, the development of alternative treatment options is urgently needed. Stem cells are considered as ideal cellular vehicles for gene therapy against glioblastoma. In this paper, we reviewed the recent studies investigating the use of different types of stem cells as cellular vehicles and the gene of interests against the glioblastoma, as well as the future directions of the application of cellular vehicles mediated therapy for glioblastoma.

Background/objective: Inadvertent intraoperative hypothermia (core temperature <360 C) is a recognized risk in surgery and has adverse consequences. However, no data about this complication in China are available. Our study aimed to determine the incidence of inadvertent intraoperative hypothermia and its associated risk factors in a sample of Chinese patients., Methods: We conducted a regional cross-sectional survey in Beijing from August through December, 2013. Eight hundred thirty patients who underwent various operations under general anesthesia were randomly selected from 24 hospitals through a multistage probability sampling. Multivariate logistic regression analyses were applied to explore the risk factors of developing hypothermia., Results: The overall incidence of intraoperative hypothermia was high, 39.9%. All patients were warmed passively with surgical sheets or cotton blankets, whereas only 10.7% of patients received active warming with space heaters or electric blankets. Pre-warmed intravenous fluid were administered to 16.9% of patients, and 34.6% of patients had irrigation of wounds with pre-warmed fluid. Active warming (OR = 0.46, 95% CI 0.26-0.81), overweight or obesity (OR = 0.39, 95% CI 0.28-0.56), high baseline core temperature before anesthesia (OR = 0.08, 95% CI 0.04-0.13), and high ambient temperature (OR = 0.89, 95% CI 0.79-0.98) were significant protective factors for hypothermia. In contrast, major-plus operations (OR = 2.00, 95% CI 1.32-3.04), duration of anesthesia (1-2 h) (OR = 3.23, 95% CI 2.19-4.78) and >2 h (OR = 3.44, 95% CI 1.90-6.22,), and intravenous un-warmed fluid (OR = 2.45, 95% CI 1.45-4.12) significantly increased the risk of hypothermia., Conclusions: The incidence of inadvertent intraoperative hypothermia in Beijing is high, and the rate of active warming of patients during operation is low. Concern for the development of intraoperative hypothermia should be especially high in patients undergoing major operations, requiring long periods of anesthesia, and receiving un-warmed intravenous fluids.

Objective: To compare the therapeutic effect of arterial and lymphatic sparing microscopic retroperitoneal varicocelectomy (MRV) with that of microscopic subinguinal varicocelectomy (MSV) for treatment of varicocele in infertile men., Methods: We conducted a prospective and controlled study to evaluate the therapeutic efficacy of MRV and MSV for treatment of varicocele in infertile men. A total of 80 patients were randomly chosen to undergo MRV (n = 40) or MSV (n = 40) treatment. All patients were followed up at 3, 6, and 12 months after surgery. Semen parameters, pregnancy, recurrence, and complications were examined., Results: Mean operation time in the MRV group was significantly shorter than that in MSV group (38.92 ± 5.67 min vs 91.35 ± 15.08 min), and the number of observed spermatic veins in MRV group was significantly less than that in MSV group (3.59 ± 0.76 vs 18.22 ± 2.83). Sperm count and motility were significantly improved at 12 months follow-up in both groups compared with preoperative values, and the sperm count in the MRV group at 3 months was significantly higher than that in MSV group. Moreover, the incidence of scrotal edema was higher in the MSV group, although natural pregnancy rate was not significantly different between 2 groups at 1-year follow-up (42.1% vs 44.7%)., Conclusion: MRV with artery and lymphatic sparing is a simple and effective technique for treatment of varicocele in infertile men., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This study aimed to assess the association between postoperative body temperature and prognosis in patients with rectal cancer. Five hundred and seven patients with stage I to III rectal cancers were enrolled in the current study. Basal body temperature (BBT, measured at 6 am) and maximal body temperature (MBT) on each day after surgery were analyzed retrospectively. Patients were divided into two equal groups according to the median of BBT and MBT at each day. The primary end points were disease-free survival (DFS) and overall survival (OS). The univariate and multivariate analyses showed that patients with low D0-MBT (<37.4 °C) had lower 3-year DFS [adjusted hazard ratio (HR) 1.56 (95 % CI 1.08-2.24, P = 0.017)] as well as OS [adjusted HR 1.72 (95 % CI 1.05-2.82, P = 0.032)] rate as compared to those with high D0-MBT (>37.4 °C). In the subset of 318 patients with T3 stage tumor and the subgroup of 458 patients without blood transfusion as well, low D0-MBT continues to be an independent predictor of DFS/OS with an adjusted HR equal to 1.48 (95 % CI 1.02-2.24, P = 0.046)/1.68 (95 % CI 1.04-2.99, P = 0.048) and 1.45 (95 % CI 1.02-2.13, P = 0.048)/1.59 (95 % CI 1.01-2.74, P = 0.049), respectively. In addition, we found that patients have higher risk of 1-year recurrence if those were exhibiting low preoperative BBT (<36.6 °C) (17 vs. 10 %, P = 0.034). Low body temperature (D0-MBT < 37.4 °C) after surgery was an independent predictor of poor survival outcomes in patients with rectal cancer.

Introduction: Visible para-aortic lymph nodes of ≥2 mm in size are common metastatic patterns of colorectal cancer (CRC) seen on imaging. Their prognostic value, however, remains inconclusive. We aimed to assess the prognostic role of visible para-aortic lymph nodes (PALNs)., Methods: Patients with confirmed pathologic diagnosis of CRC were enrolled. Correlations among clinicopathologic variables were analyzed using the χ2 test. The Cox proportional hazards model was applied for univariate and multivariate analyses. Survival was estimated using the Kaplan-Meier method and log-rank test. A prognostic model for visible PALNs in CRC patients was established., Results: In total, 4527 newly diagnosed CRC patients were enrolled. Patients with visible PALNs had inferior overall survival compared to those without visible PALNs (5-year overall survival, 67% vs. 76%, P = 0.015). Lymphovascular invasion (LVI) (hazard ratio = 1.865, P = 0.015); nodal disease (pN+) status (hazard ratio = 2.099, P = 0.006); elevated preoperative serum carcinoembryonic antigen (CEA) levels (hazard ratio = 2.263, P < 0.001); and visible PALNs ≥10 mm (hazard ratio = 1.638, P = 0.031) were independent prognostic factors for patients with visible PALNs. If each prognostic factor scored one point, 5-year overall survival of lower- (prognostic score 0-1), intermediate- (prognostic score 2), and high- (prognostic score 3-4) risk groups were, 78%. 54%, and 25% respectively (P < 0.001)., Conclusions: The prognostic model, which included LVI, pN+ status, preoperative serum CEA level, and the size of visible PALNs, could effectively distinguish the outcome of patients with visible PALNs.

5-Fluorouracil (5-FU) is chemotherapeutic agent widely used for the treatment of colorectal cancer. Unfortunately, advanced colorectal cancer is often resistance to such chemotherapy and poor outcome. An adaptor protein paxillin (PXN) is phosphorylated at Y31/Y118 (pPXN-Y31/Y118) by Src contributes to cell mobility and Ser (S)272 of PXN in LD4 domain is important to the interaction between PXN and Bcl-2. We thus hypothesized that pPXN-Y31/Y118 may be required for Bcl-2 protein stability via PXN interacting with Bcl-2 to confer 5-FU resistance in colorectal cancer. Mechanistically, pPXN-S272 is phosphorylated through pPXN-Y31/Y118-mediated p21 protein-activated kinase 1 (PAK1) activation and pPXN-S272 is required for PXN to interact with Bcl-2. The interaction between PXN and Bcl-2 is essential for Bcl-2 protein stability through phosphorylation of Bcl-2 at S87 (pBcl-2-S87) by pPXN-Y31/Y118-mediated ERK activation. An increase in Bcl-2 expression by PXN is responsible for resistance to 5-FU. The resistance to 5-FU can be abolished by inhibitor of Src and PAK1 or Bcl-2 antagonist in cell and animal models. Among patients, Bcl-2 expression is positively correlated with expression of PXN and pPXN-S272, respectively. Patients with high PXN/high Bcl-2 or high pPXN-S272/high Bcl-2 tumors are commonly to have an unfavorable response to 5-FU-based chemotherapy, compared with patients who have high PXN, high pPXN-S272 or high Bcl-2 tumors alone. Therefore, we suggest that Src, PAK1 or Bcl-2 inhibitor may potentially overcome the resistance of 5-FU-based chemotherapy and consequently to improve outcomes in patients with PXN/Bcl-2 and pPXN-S272/Bcl-2-positive tumors.

Colorectal endoscopic submucosal dissection (ESD) has become common in recent years. Suitable lesions for endoscopic treatment include not only early colorectal carcinomas but also many types of precarcinomatous adenomas. It is important to establish practical guidelines in which the preoperative diagnosis of colorectal neoplasia and the selection of endoscopic treatment procedures are properly outlined, and to ensure that the actual endoscopic treatment is useful and safe in general hospitals when carried out in accordance with the guidelines. In cooperation with the Japanese Society for Cancer of the Colon and Rectum, the Japanese Society of Coloproctology, and the Japanese Society of Gastroenterology, the Japan Gastroenterological Endoscopy Society has recently compiled a set of colorectal ESD/endoscopic mucosal resection (EMR) guidelines using evidence-based methods. The guidelines focus on the diagnostic and therapeutic strategies and caveat before, during, and after ESD/EMR and, in this regard, exclude the specific procedures, types and proper use of instruments, devices, and drugs. Although eight areas, ranging from indication to pathology, were originally planned for inclusion in these guidelines, evidence was scarce in each area. Therefore, grades of recommendation were determined largely through expert consensus in these areas., (© 2015 The Authors. Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society.)

Stabilization of Bcl-2 protein by paxillin (PXN)-mediated ERK activation was recently reported to cause an unfavorable response to 5-Fluorouracil-based chemotherapy. Here, we present evidence from cell and animal models to demonstrate that stabilization of Bcl-2 protein by phosphorylation at Serine 87 (pBcl-2-S87) via PXN-mediated ERK activation is responsible for cancer cell invasiveness and occurs via upregulation of MMP2 expression. Immunostainings of 190 tumors resected from colorectal cancer patients indicated that PXN expression was positively correlated with Bcl-2, pBcl-2-S87, and MMP2 expression. A positive correlation of pBcl-2-S87 with Bcl-2 and MMP2 was also observed in this study population. Patients with high PXN, Bcl-2, pBcl-2-S87, and MMP2 had poor overall survival (OS) and shorter relapse free survival (RFS). In conclusion, PXN promotes Bcl-2 phosphorylation at Serine 87 via PXN-mediated ERK activation, and its stabilization associated with increased tumor formation efficacy in mice and poor patient outcome in colorectal cancer patients.

Aim: To assess the impact of Arpin protein and tight junction (TJ) proteins in the intestinal mucosa on bacterial translocation in patients with severe acute pancreatitis (SAP)., Methods: Fifty SAP patients were identified as study objects and then classified into two groups according to the presence of bacterial translocation (BT) in the blood [i.e., BT(+) and BT(-)]. Twenty healthy individuals were included in the control group. BT was analyzed by polymerase chain reaction, colonic mucosal tissue was obtained by endoscopy and the expression of TJ proteins and Arpin protein was determined using immunofluorescence and western blotting., Results: Bacterial DNA was detected in the peripheral blood of 62.0% of patients (31/50) with SAP. The expression of TJ proteins in SAP patients was lower than that in healthy controls. In contrast, Arpin protein expression in SAP patients was higher than in healthy controls (0.38 ± 0.19 vs 0.28 ± 0.16, P < 0.05). Among SAP patients, those positive for BT showed a higher level of claudin-2 expression (0.64 ± 0.27 vs 0.32 ± 0.21, P < 0.05) and a lower level of occludin (OC) (0.61 ± 0.28 vs 0.73 ± 0.32, P < 0.05) and zonula occludens-1 (0.42 ± 0.26 vs 0.58 ± 0.17, P = 0.038) expression in comparison with BT (-) patients. Moreover, the level of Arpin expression in BT (+) patients was higher than in BT (-) patients (0.61 ± 0.28 vs 0.31 ± 0.24, P < 0.05)., Conclusion: Arpin protein affects the expression of tight junction proteins and may have an impact on BT. These results contribute to a better understanding of the factors involved in bacterial translocation during acute pancreatitis.

Purpose: Beclin-1 is an autophagy gene. It promotes the formation of the autophagic vesicle as well as plays an essential role in guarding the cells against chromosomal instability. Overexpression of Beclin-1 has been reported to predict a favorable survival in various cancers. However, little is known about its prognostic significance in colorectal cancer., Methods and Materials: A total of three hundred and sixty-three (363) colorectal tissues from colorectal cancer (CRC) patients were collected. Tissue micro-arrays and immunohistochemistry were used to investigate the expression and prognostic significance of Beclin-1 in CRC. The associations among Beclin-1 expression, clinicopathological parameters and prognosis were evaluated., Results: Beclin-1 had a higher expression in CRC tissues than in normal tissues. A high expression of Beclin-1 was positively correlated with gender (P=0.027), histological grade (P=0.003), pM status (P=0.003) and clinical stage (P=0.024). Patients with a high Beclin-1 expression, when compared to those with a lower expression had both a better overall survival (OS, P=0.006) and disease-free survival (DFS, P=0.008). In the pT3 subgroup, Beclin-1 was also found to be a good prognostic indicator (P<0.05). Multivariate analysis showed a high expression of Beclin-1 was indeed a positive independent prognostic factor of OS and DFS for CRC patients (P<0.05)., Conclusion: Our results demonstrated that a high expression of Beclin-1 correlated with a better overall survival and disease-free survival, thus serving as a favorable independent prognostic marker in CRC., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Unlabelled: The nerve growth factor receptor (NGFR/p75) is a potential tumor suppressor, but its role in colorectal cancer is unknown. Here, the hypermethylation status, biologic function, and clinical relevance were determined for p75NGFR in colorectal cancer. The methylation status and expression of p75NGFR were assessed in colorectal cancer cell lines and clinical tissues by bisulfite genomic sequencing (BGS), qRT-PCR, and immunoblot assay. Methylation of p75NGFR was frequently found in colorectal cancer, leading to its silencing or downregulation, and it was effectively restored by a demethylation agent. The overexpression of p75NGFR in multiple colorectal cancer cell model systems significantly inhibited cell proliferation (concomitant with G1-phase arrest), invasion, and colony formation and induced cell apoptosis. In contrast, p75NGFR knockdown significantly promoted proliferative and invasive phenotypes. Importantly, p75NGFR methylation was observed in the majority of primary colorectal cancer specimens and was associated with histologic grade and preoperative serum CA19-9 levels. Multivariate analysis indicated that patients who lack p75NGFR have reduced overall survival (64% vs. 75%, P = 0.028) and disease-free survival (61% vs. 72%, P = 0.034) compared with p75NGFR-positive patients. In conclusion, p75NGFR is predominantly silenced or downregulated in colorectal cancer, and its biologic activities are consistent with it being a relevant tumor suppressor., Implications: p75NGFR is a candidate tumor suppressor and has independent prognostic potential in colorectal cancer., (©2014 American Association for Cancer Research.)

Objectives: The purpose of our study was to report the results of the implementation of computed tomography colonography in a university hospital setting serving a Brazilian population at high risk of colorectal cancer., Methods: After creating a computed tomography colonography service in our institution, 85 patients at high risk of colorectal cancer underwent computed tomography colonography followed by a same-day optical colonoscopy from September 2010 to May 2012. The overall accuracy of computed tomography colonography in the detection of lesions ≥6 mm was compared to that of optical colonoscopy (direct comparison). All colonic segments were evaluated using quality imaging (amount of liquid and solid residual feces and luminal distension). To assess patient acceptance and preference, a questionnaire was completed before and after the computed tomography colonography and optical colonoscopy. Fisher's exact test was used to measure the correlations between colonic distension, discomfort during the exam, exam preference and interpretation confidence., Results: Thirteen carcinomas and twenty-two lesions ≥6 mm were characterized. The sensitivity, specificity and accuracy of computed tomography colonography were 100%, 98.2% and 98.6%, respectively. Computed tomography colonography was the preferred method of investigation for 85% of patients. The preparation was reported to cause only mild discomfort for 97.6% of patients. According to the questionnaires, there was no significant relationship between colonic distension and discomfort (p>0.05). Most patients (89%) achieved excellent bowel preparation. There was a statistically significant correlation between the confidence perceived in reading the computed tomography colonography and the quality of the preparation in each colonic segment (p≤0.001). The average effective radiation dose per exam was 7.8 mSv., Conclusion: It was possible to institute an efficient computed tomography colonography service at a university hospital that primarily assists patients from the public health system, with high accuracy, good acceptance and effective radiation doses. Our results seem to be comparable to other centers of excellence and fall within acceptable published guidelines, showing that a successful computed tomography colonography program can be reproduced in a South American population screened in a university hospital.

Background: A disintegrin and metalloprotease 8 (ADAM8) has been reported to be associated with various malignancies. However, no studies have examined ADAM8 association in colorectal cancer (CRC). The aim of this study was to investigate the expression and function of ADAM8 in CRC., Methods: Expression level of ADAM8 in CRC was evaluated by quantitative RT-PCR, western blot and immunohistochemical staining analysis. The role of ADAM8 in colorectal carcinogenesis was evaluated by in vitro assays. The correlations between ADAM8 status and clinicopathological features including survival were analyzed., Results: ADAM8 was highly expressed in CRC tissues compared with adjacent normal tissues. Knockdown of ADAM8 in two CRC cell lines resulted in reduced cellular growth and proliferation, and increased apoptosis. Immunohistochemistry analysis showed no significant correlations of ADAM8 protein expression with clinicopathologic features. Survival analysis indicated that patients with ADAM8-positive tumors had worse 5-year overall survival (OS, p = 0.037) and 5-year disease free survival (DFS, p = 0.014) compared with those with ADAM8-negative tumors. Multivariate analysis indicated ADAM8 expression was an independent prognostic factor for both OS and DFS (both p< 0.001). Subgroup analysis showed that 5-year OS of colon cancer, T3-T4 stage and N0 stage was worse for patients with ADAM8-positive tumors than those with ADAM8-negative tumors (p < 0.05). The 5-year DFS in colon cancer, T3-T4 stage, N0 stage, TNM stage II, adenocarcinoma, moderate differentiation and male patient subgroups was also worse for patients with ADAM8-positive tumors than those with ADAM8-negative tumors (p < 0.05)., Conclusions: Our results show that ADAM8 is overexpressed in CRC, promotes cell growth and correlates with worse OS and DFS, and thus could serve as a biomarker for individual CRC patient therapy.

Background: Quality of publications is considered a subjective measurement, and more weight is placed on prospective studies, especially randomized clinical trials and meta-analyses., Objective: This study describes the type of publications and evaluates the quality of randomized clinical trials and review articles using an objective measurement., Data Sources: Medline (PubMed) is the data source for this work., Study Selection: We used the terms "rectal neoplasms/surgery" and the filters "10 years," "humans," and "English.", Main Outcome Measures: We measured compliance with checklist items. Randomized clinical trials were reviewed using the Consolidates Standards of Reporting Trials statement; systematic reviews/meta-analyses were reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement., Results: A total of 3603 articles were identified: 20.8% were case report/series, 20.5% were retrospective cohorts, 14.0% were reviews or meta-analyses, 16.4% were prospective cohorts, 14.0% were other types of articles (comments, letters, or editorials), 5.5% were clinical trials (phase I/II), 4.2% were randomized clinical trials, and 4.4% were cross-sectional studies. We reviewed 108 randomized clinical trials; the maximum score possible was 74.0, the average score was 44.6 (range, 20.0-64.0), 4 (3.7%) were graded as "excellent," 21 (19.4%) were "good," 44 (40.7%) were "deficient," and 39 (36.1%) were graded as "fail." The predictors of higher scores for randomized clinical trials were year of publication after 2007 (p = 0.00), higher impact factor (p = 0.03), and declared funding (p = 0.01). Twenty-nine meta-analyses were reviewed; the average score was 19.64 (range, 12.0-25.0); 5 articles (17.2%) were graded as "excellent," 12 (41.4%) were "good," 10 (34.5%) were "deficient," and 2 (6.9%) were "fail.", Limitations: Only 1 electronic database was used, so we lacked a validated score. In addition, the search terms did not include "colorectal.", Conclusions: A total of 20.8% of the articles published were case reports and 25.0% of the articles were prospective or clinical trials. Although randomized clinical trials and systematic reviews provide the highest level of evidence, publications with missing data limit replication of the study and affect the generalizability of results to other populations. To improve the quality of our publications, authors, reviewers, and journal editors should consider the endorsement of standardize checklists.

Objective: To evaluate the clinical efficacy and safety of tissue-selecting therapy (TST) in treatment of mixed hemorrhoids., Methods: A single-blind randomized study was carried out. A total of 120 patients with mixed hemorrhoids from January to December 2012 were prospectively enrolled in the study and equally divided into two groups, TST group and procedure for prolapse and hemorrhoids(PPH) group. Surgical data, efficacy and postoperative complications were compared between the two groups., Results: As compared to PPH group, patients in TST group had shorter operation time [(15.9±5.18) min vs. (22.6±7.1) min, P<0.05], lower scores of rectal urgency (0.5±0.2 vs. 1.5±1.4, P<0.05), and shorter hospital stay [(11.2±3.7) d vs. (14.8±3.7) d, P<0.05]. No anastomotic stricture case was found in TST group, while 11 cases(18.3%) developed anastomotic stricture in PPH group. There were no significant differences in effective rate and pain score of first defecation between the two groups., Conclusion: TST is reliable and safe for mixed hemorrhoids with the advantage of simple, rapid recovery and less complications.

Background: Parikartika resembles fissure-in-ano which is very common among all ano-rectal disorders. In Ayurvedic texts, Parikartika is described as a complication of Vamana and Virechana as well as complication of Atisara. Ksharasutra was proved successful in the management of fistula-in-ano, piles, and there is a need to try its efficacy in fissure-in-ano., Aim: To evaluate the role of Ksharasutra suturing (KSS) in fissure bed in chronic fissure-in-ano., Materials and Methods: Total 100 patients of chronic fissure-in-ano were selected and randomly divided into two groups (50 in each group). In group-A, patients were undergone by KSS; while in patients of Group-B Lord's anal dilatation followed by KSS was done under spinal anesthesia. The KSS was done once and after slough out of Ksharasutra, the wound was treated for 4 weeks and assessment of the result was done on the basis of gradation adopted., Results: The pain relief on 14(th) day in Group-A was 86% while in Group-B 100% was observed. As on 7(th) day in Group-A, oozing was stopped in 68% patients, while in Group-B, oozing was stopped in 82% patients. On 21(st) day, Group-B showed more healing (85%) as compared to Group-A (69%). In this study 68% of patients were cured., Conclusion: In Group-B (KSS with Lord's anal dilatation) patients were cured early as compared to patients of Group-A (KSS alone).

Objective: To investigate the associated factors for postoperative ileus following radical resection for colorectal cancer., Methods: Clinical data of 1366 colorectal cancer patients undergoing radical resection by the same surgical team in our hospital from January 2000 to September 2011 were analyzed retrospectively. Univariate analysis and multivariate logistic regression analysis were used to identify the associated factors of postoperative ileus., Results: A total of 70 patients(5.1%) developed postoperative ileus. Univariate and multivariate analyses showed that N2(OR=1.893, 95%CI:1.083-3.306), history of colorectal cancer resection(OR=4.899, 95%CI:1.490-16.110), preoperative obstruction (OR=2.616, 95%CI:1.297-5.280), right hemicolectomy(OR=2.024, 95%CI:1.052-3.894) and left hemicolectomy(OR=3.030, 95%CI:1.401-6.550) were risk factors for postoperative ileus following radical resection for colorectal cancer, while laparoscopic operation(OR=0.520, 95%CI:0.319-0.849) was protective., Conclusions: Postoperative ileus following radical resection for colorectal cancer is associated with surgical procedures. Laparoscopic colorectal resection can reduce the incidence of postoperative ileus.

Goals and Background: There is increasing evidence that bacterial translocation (BT) might contribute to the occurrence and development of cancer cachexia, but the detailed mechanism remains unknown. Thus, we undertook further investigations into the association of BT with cancer cachexia and the possible pathway., Study: The colon cancer patients enrolled in this study were divided into cachectic and noncachectic. BT was analyzed by polymerase chain reaction and bacterial culture. Intestinal epithelial T-cell subsets and NK cells were evaluated using flow cytometry. Western blotting and immunofluorescence were used to check tight junction (TJ) proteins in intestinal epithelium. Fluorescence in situ hybridization and immunohistochemistry were used to detect the translocated bacteria and endotoxin., Results: Compared with noncachectic patients, cachectic patients had a significantly higher BT ratio (P<0.001). We observed the translocated bacteria in the intestinal mucus layer associated with lower levels of T-cell subsets and NK cells in the intestinal epithelium in BT-positive patients (P<0.05). Endotoxin was detected within the small intestinal wall and the concentration of endotoxin decreased from the mucosal side to serosal side gradually in these patients. These were associated with an altered composition of TJs., Conclusions: This study suggests that BT may contribute to colon cancer in cachectic patients, and TJ could be the gateway to the possible pathway of BT.

Introduction: Appendiceal diverticulosis is a rare entity, with a global incidence between 0.004% and 2.1% of all appendectomies. It has been related with an elevated risk of perforation in comparison to acute appendicitis, as well as an increased risk for synchronic appendicular cancer in 48% of the cases, and colonic cancer in 43%. The incidence of chronic appendicitis has been reported in 1.5% of all appendicitis cases., Presentation of Case: We present a 73-year-old female, with no relevant familial history, who presented due to a four-month-long oppressive, moderate pain in the lower right abdominal quadrant without irradiation or any other accompanying symptoms., Discussion: The documented incidence of appendiceal diverticula and chronic appendicitis by themselves is low; therefore the presence of both entities at the same time is extremely rare., Conclusion: We present a case in which both diagnoses concurred in the same patient. The relevance of this case relies on the importance of the adequate knowledge of these pathologies, so we can approach them correctly. Although it does not represent an absolute surgical emergency, appendectomy represents the first therapeutic option., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Perioperative anticancer therapy that does not impair wound healing is needed to counter the persistent proangiogenic plasma compositional changes that occur after colorectal resection. Polyphenon E (PolyE), a green tea derivative (main component EGCG), and Siliphos (main component silibinin), from the milk thistle plant, both have antitumor effects. This study assessed the impact of PolyE/Siliphos (PES) on wound healing and the growth of CT-26 colon cancer in several murine models., Methods: One wound healing and three tumor studies were performed. Tumor Study (TS)1 assessed the impact of PES on subcutaneous tumor growth, whereas TS2 assessed PES's impact on subcutaneous growth when given pre- and post-CO(2) pneumoperitoneum (pneumo), sham laparotomy, or anesthesia alone. TS3 determined the ability of PES to limit hepatic metastases (mets) after portal venous injection of tumor cells. In the final study, laparotomy and gastrotomy wound healing were assessed several ways. BALB/c mice were used for all studies. The drugs were given via drinking water (PolyE) and gavage (Siliphos), daily, for 7-9 days preprocedure and for 7-21 days postoperatively. Tumor mass, number/size of hepatic mets, and proliferation and apoptosis rates were assessed. The abdominal breaking strength and energy to failure were measured postmortem as was gastric bursting pressures., Results: PES significantly inhibited subcutaneous growth in the nonoperative setting. PES also significantly decreased the number/size of liver mets when given perioperatively. Abdominal wound breaking strength, energy to wound failure, and collagen content were not altered by PES; gastrotomy bursting strength also was not affected by PES. Neither drug alone had a significant impact on tumor growth., Conclusions: The PES combination inhibited subcutaneous and hepatic tumor growth yet did not impair wound healing. PES holds promise as a perioperative anticancer therapy.

Background and Aims: Thrombocytosis is frequently observed in patients with malignancy. We undertook this study to determine the prognostic value of thrombocytosis in patients with rectal cancer., Methods: We performed a retrospective study of patients undergoing low anterior resection for rectal cancer between January 2000 and March 2007. Preoperative platelet count was measured before surgery. Postoperative platelets were determined 1 month after surgery. Two-tailed p values <0.05 were considered statistically significant., Results: One hundred sixty three patients with rectal cancer were included in the study. Preoperative platelet count >350,000 was found in 8% of patients. Postoperative platelet count >350,000 was found in 6% of patients. Distant metastases were found in 17 patients (10.4%). Significant variables in the multivariate analyses were preoperative platelets >350,000 (p = 0.001), postoperative platelets >350,000 (p = 0.002), carcinoembryonic antigen >13 ng/dL (p = 0.003). Patients with preoperative platelet count <350,000 showed a 5-year survival rate of 81%, whereas patients with platelet count >350,000 had a 25-month survival [95% confidence interval (CI): 20-26]; p <0.001. Patients with postoperative platelets <350,000 showed a 5-year survival rate of 80%, whereas patients with platelets >350,000 showed a 3-year survival rate of 37.5% (p <0.05)., Conclusions: Pre- or postoperative platelet count >350,000 is associated with poor survival in patients with rectal cancer. The measurement of platelets is a clinical marker useful to define the prognosis for patients with rectal cancer., (Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the differences in long-term outcomes between laparoscopic and open complete mesocolic excision(CME) for colon cancer., Methods: A total of 273 patients with colon cancer who underwent CME at the Fujian Medical University Union Hospital from September 2000 to December 2008 were divided into laparoscopic(LP, n=147) and open(OP, n=126) groups in a non-random manner. The oncologic and long-term outcomes were compared., Results: No significant differences were seen in the length of distal and proximal margin, and number of lymph nodes(all P>0.05). Median postoperative follow up was 50 months. Local regional recurrence rates (LP 6.1% vs. OP 7.9%) and distal metastasis rates(LP 23.8% vs. OP 16.7%) were similar between the two groups(all P>0.05). The 5-year overall survival rates (LP 69.4% vs. OP 74.0%, P=0.840) and 5-year disease-free survival rates(LP 68.5% vs. OP 70.9%, P=0.668) between the two groups were not statistically different., Conclusions: Laparoscopic CME has the same oncologic clearance effects compared with open CME for colon cancer. It might become a new standardized surgery for colon cancer.