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Background: The immune landscapes of gastrointestinal stromal tumors (GISTs) are still unclear. We aimed to explore the immune status of GISTs with different recurrence risks and sought potential immunotherapeutic targets. Methods: Immune cell infiltration and the expression of 93 tumor markers of 65 GISTs with different recurrence risks from public datasets were analyzed via bioinformatic methods. Infiltrating immune cell and OX40L expression of 417 patients from the Zhongshan cohort were analyzed by immunohistochemistry and immunofluorescence. The clinicopathological data of the patients were collected and the prognostic factors were analyzed by univariate and multivariate methods. Results: Macrophages, T cells and NK cells were the most abundant immune cells in tumor microenvironment. OX40L was the only differentially expressed marker in high- and low-risk patients, as well as in patients with primary and recurrent GIST. The positive rate of OX40L in GIST was 54%. OX40L was highly expressed in patients with no metastasis, low mitotic index and relapse risk. The amount of CD68 + macrophages was the independent factor of OX40L expression. The OX40L expression was positively correlated with M2 and resting mast cells. OX40L co-located with CD4 + T cells, M2 and activated mast cells. Patients with high OX40L levels experienced more prolonged relapse-free survival (RFS). Conclusions: We first reported that GIST cells could express OX40L, patients with high OX40L experienced longer RFS. The colocalization of OX40L with immune cells indicates that OX40L could be a promising potential target for immunotherapy in GIST. [ABSTRACT FROM AUTHOR]

The liver is the most common anatomical site for hematogenous metastases of colorectal cancer, and colorectal liver metastases is one of the most difficult and challenging points in the treatment of colorectal cancer. To improve the diagnosis and comprehensive treatment in China, the Guidelines have been edited and revised several times since 2008, including the overall evaluation, personalized treatment goals and comprehensive treatments, to prevent the occurrence of liver metastases, improve the resection rate of liver metastases and survival. The revised Guideline includes the diagnosis and follow-up, prevention, MDT effect, surgery and local ablative treatment, neoadjuvant and adjuvant therapy, and comprehensive treatment, and with advanced experience, latest results, detailed content, and strong operability. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is the third leading cause of death from cancer worldwide. Immature colon carcinoma transcript-1 (ICT1) has been reported to be correlated with lung cancer; however, whether ICT1 is a functional gene in CRC, as well as the molecular mechanism underlying ICT1 mediation of colorectal-tumor formation, remains unknown. Methods: The expression of ICT1 was firstly determined by using immunohistochemistry in 861 CRC specimens. The correlation of ICT1 expression with clinicopathological parameters and the survival rate was analyzed. Furthermore, we investigated the effect of ICT1 silencing on CRC cell proliferation and migration by MTT, colony formation, flow cytometry, and transwell in vitro. Results: ICT1 is highly expressed in a cohort of human CRCs, and that higher ICT1 expression may lead to reduced overall survival rate of CRC. Likewise, ICT1 silencing lowered the cell viability through cell-cycle arrest, inhibited cell migration, and induced apoptosis in CRC. We further revealed a novel mechanism in which ICT1 promoted CRC growth via the intracellular AMPK, SAPK/JNK, and PARP signaling pathways. Conclusions: Our data showed that ICT1 could be an important target for CRC diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated the clinical significance of polarized tumor-associated macrophages (TAMs) in gastric cancer whereas the cytokines orchestrating TAM polarization remain elusive. This study aims to evaluate the prognostic value of C-C motif ligand 2 (CCL2) expression in gastric cancer patients after surgery. We examined CCL2 expression in tumor tissues by immunohistochemical staining in retrospectively enrolled 414 gastric cancer patients receiving gastrectomy at Zhongshan Hospital during 2008. We used Kaplan-Meier analysis and Cox regression models to assess the prognostic value of CCL2 expression. We generated a predictive nomogram from integrating CCL2 expression with the TNM staging system to evaluate 3- and 5-year overall survival. High intratumor CCL2 expression associated with adverse clinical outcome. Intratumor CCL2 expression provided additional prognostic value in gastric cancer patients. CCL2 expression, as well as well-established TNM staging parameters, was identified as independent prognostic factor for overall survival. The generated nomogram corresponded well with the ideal model in predicting the 3- and 5-year overall survival of gastric cancer patients. CCL2, an identified potential independent adverse prognosticator, could be integrated with TNM staging system to improve the predictive accuracy for overall survival in gastric cancer patients especially with advanced stages. [ABSTRACT FROM AUTHOR]

The prognosis for pancreatic ductal adenocarcinoma (PDAC) remains extremely poor. Recent studies have focused on the role of lymphocytes in the PDAC microenvironment. Using immunohistochemistry, our study explored the clinical significance of intratumoral or peritumoral CD4Foxp3 regulatory T cells (Tregs) and CD8 T cells in the tumor microenvironment and analyzed their relation to the prognosis of PDAC in a consecutive series of 92 patients after resection. CD8 T cells were more frequently seen within peritumoral sites, while CD4Foxp3 Tregs were more frequent within intratumoral areas. Neither exhibited any relationship with other clinicopathologic factors. Patients with low levels of intratumoral Tregs had longer disease-free survival than those with higher levels (DFS 22.2 vs. 11.2 months, p < 0.001), and patients with higher levels of peritumoral CD8 T cells had longer overall survival than those with lower levels (OS 31.0 vs. 14.2 months, p < 0.001). Multivariate analysis demonstrated that intratumoral Tregs (hazard ratio, HR 3.39, p = 0.010) and peritumoral CD8 T cells (HR 0.10, p < 0.001) are related to DFS and OS, respectively. These results indicate that intratumoral Tregs are a negative predictor of DFS, while peritumoral CD8 T cells are a positive predictor of OS for PDAC patients with pancreatectomy. [ABSTRACT FROM AUTHOR]

Objective: Enhanced recovery after surgery (ERAS) integrates evidence-based interventions to reduce surgical stress and accelerate rehabilitation. Our study was to compare the short-term quality of life (QOL) in patients undergoing open colonic surgery using ERAS program or conventional management.Methods: A prospective study of 57 patients using ERAS program and 60 patients using conventional management was conducted. The clinical characteristics of all patients were recorded. QOL was evaluated longitudinally using the questionnaires (EORTC QLQ-C30 and QLQ-CR29) pre- and postoperatively. Generalized estimating equation was used to do the analysis in order to determine the effective impact of correlative factors on the postoperative QOL, including age, sex, BMI, ASA grade, tumor location, tumor size, pTNM stage, recovery program and length of time after surgery.Results: The morbidity in ERAS and control group was 17.5 versus 26.7 % (p = 0.235). The patients in ERAS group had much faster rehabilitation and less hospital stay. In the primary statistical analysis, the scores of global QOL (on POD3, POD6, POD10, POD14, POD21), physical functioning (on POD3, POD6, POD10, POD14, POD21), role functioning (on POD6, POD10, POD14, POD21), emotional functioning (on POD3, POD6, POD10, POD14, POD21), cognitive functioning (on POD3, POD6) and social functioning (on POD3, POD6, POD10, POD14, POD21, POD28) were higher in ERAS group than in control group, which suggested that the patients in ERAS group had a better life status. However, the scores of pain (on POD10, POD14, POD21), appetite loss (on POD3, POD6), constipation (on POD3, POD6, POD10), diarrhea (on POD3, POD10), financial difficulties (on POD10, POD14, POD21), perspective of future health (on POD6, POD10, POD14), gastrointestinal tract problems (on POD3, POD6, POD10) and defecation problems (on POD6, POD10, POD14) were lower in ERAS group than in control group, which revealed that the patients in ERAS group suffered less symptoms. In the further generalized estimating equation analysis, the result showed that recovery program and length of time after surgery had independently positive impact on the patient's postoperative QOL.Conclusion: Short-term QOL in patients undergoing colonic cancer using ERAS program was better than that using conventional management. [ABSTRACT FROM AUTHOR]

Background: Inhibitors of nuclear factor (NF)-κB pathway have shown potential anti-tumor activities. However, it is not fully elucidated in gastric cancer.Methods: Firstly, we screened the inhibitory effect of pharmacologic NF-κB inhibitors on cell viability of human gastric cancer cells via CCK-8 assay. Next, cell apoptosis, cell cycle distribution, and mitochondrial membrane potential after BAY 11-7082 treatment were detected by annexin V staining, propidium iodide staining, TUNEL, and JC-1 assays in human gastric cancer HGC-27 cells. Expression of regulatory factors for apoptosis and cell cycle were measured by western blot. Finally, human gastric cancer xenograft model was established to verify the anti-tumor effects of BAY 11-7082 in vivo. Cellular apoptosis and growth inhibition in subcutaneous tumor section were detected by TUNEL and immunohistochemistry assays.Results: BAY 11-7082 exhibited rapid and potent anti-tumor effects on gastric cancer cells in vitro within a panel of NF-κB inhibitors. BAY 11-7082 induced rapid apoptosis in HGC-27 cells through activating the mitochondrial pathway, as well as down-regulation of Bcl-2 and up-regulation of Bax. BAY 11-7082 also induced S phase arrest through suppressing Cyclin A and CDK-2 expression. Xenograft model confirmed the anti-tumor effects of BAY 11-7082 on apoptosis induction and growth inhibition in vivo.Conclusions: Our results demonstrated that BAY 11-7082 presented the most rapid and potent anti-tumor effects within a panel of NF-κB inhibitors, and could induce cellular apoptosis and block cell cycle progression both in vitro and in vivo, thus providing basis for clinical application of BAY 11-7082 in gastric cancer cases. [ABSTRACT FROM AUTHOR]

The objectives of this study were to assess the toxicity and immunological response induced by the intra-dermal (i.d.) administration of MUC1-peptide-pulsed dendritic cells (DCs) in advanced pancreatic cancer patients. Patients with recurrent lesions or metastasis after surgery, and immunohistochemistry positive for MUC1 were treated in cohorts that received 3-6 × 10 DCs i.d. for three or four vaccines. Each vaccine was composed of autologus DCs pulsed with MUC1-peptide. Peripheral blood mononuclear cells (PBMCs) that harvested 2 weeks after the second immunization were compared with PBMCs obtained before treatment for immunological response. Serial ELISPOT assays of PBMCs for antitumor reactivity were performed. Three patients received all four vaccines, and four patients received three vaccines. These patients were evaluable for toxicity and immunological monitoring. There were no grade 3 or 4 toxicities associated with the vaccines or major evidence of autoimmunity. Interferon-γ and granzyme B ELISPOT assay reactivity increased significantly in 2 of 7 patients ( P < 0.05). The administration of MUC1-peptide-pulsed DCs is non-toxic and capable of inducing immunological response to tumor antigen MUC1 in advanced pancreatic cancer patients. Additional studies are necessary to improve tumor rejection responses. [ABSTRACT FROM AUTHOR]

Background: The aim of this trial was to compare the Enhanced Recovery After Surgery (ERAS) program with conventional perioperative management in patients who underwent radical resection for colorectal cancer. Methods: A combination of evidence-based and consensus methodology was used to develop the ERAS protocol. Five hundred ninety-seven consecutive patients who underwent elective colorectal resection were randomized to either the ERAS ( n = 299) or the control group ( n = 298). Outcomes relating to nutrition and metabolism index, stress index, and recovery index were measured and recorded. Results: Demographic and operative data were similar between the two groups. Patients in the ERAS group showed improved nutritional status when compared with those of the control group. On postoperative day (POD) 1, the HOMA-IR (insulin resistance index) of the ERAS group was lower than that of the control group ( p < 0.001). The cortisol level of the control group was elevated on both POD 1 ( p = 0.007) and POD 5 ( p = 0.002) compared to the preoperative level. However, the cortisol level of the ERAS group was not increased until POD 5 ( p = 0.001). Reduced levels of TNF-α, IL-1β, IL-6, and IFN-γ in the ERAS group indicated less postoperative stress responses. In addition, ERAS was associated with accelerated recovery of gastrointestinal function. The postoperative length of stay ( p < 0.001) and expense ( p < 0.001) for the ERAS group were reduced in comparison to the controls. Twenty-eight cases in the control group and twenty-nine in the ERAS group suffered complications, which was not significantly different. Conclusion: The ERAS protocol attenuates the surgical stress response and accelerates postoperative recovery without compromising patient safety. [ABSTRACT FROM AUTHOR]

The natural history and clinical manifestation of resected intraductal papillary mucinous neoplasm (IPMN) of the pancreas were elucidated, and based on this, a retrospective pancreatic database was reviewed to identify patients with IPMN who were surgically managed in our department from 1999 to June 2006. Pathologic rereview of each case was performed, and the clinico-pathologic features were examined. Student’s T test and χ2 analysis were used to identify factors associated with malignancy. Fifty-one patients were identified. There were 33 males and 18 females. One patient’s pancreas was unresectable, two patients underwent a total pancreatectomy, 42 patients had a pancreatecoduodenectomy and five patients had distal pancreatectomy. Main-duct type carcinoma was identified in 24 patients; branch-duct type in 15 patients, and mixed type in 12 patients. Invasive carcinoma was present in 35 patients. Weight loss and jaundice occurred more commonly in the invasive group. The average serum CA19-9 level was significantly higher in the invasive group (1542μ vs 94.5μ). The average diameter of the pancreatic duct was also wider in the invasive group (8.7 mm vs 4.3 mm). Significant predictors of malignant IPMNs included weight loss, jaundice, a high level of serum CA19-9, a large pancreatic duct and main-duct type carcinoma. [ABSTRACT FROM AUTHOR]

Since first described in 1982, intraductal papillary mucinous neoplasm (IPMN) has been the preferred term to describe the proliferation of the pancreatic ductal epithelium. It is totally different from pancreatic carcinoma in epidemiology, histology, pathology and prognosis. According to the site of involvement, IPMNs are classified into three categories, i.e. main duct type, branch duct type, and combined type. Most branch duct IPMNs are benign, whereas the other two types are often malignant. A large branch duct IPMN and marked dilation of the main pancreatic duct indicate the presence of adenoma at least. The additional existence of large mural nodules increases the possibility of malignancy in all types. The prognosis is more favorable after complete resection of benign and non-invasive malignant IPMNs. Malignant IPMNs that become more aggressive after parenchymal invasion necessitate adequate lymph node dissection. On the other hand, asymptomatic branch duct IPMNs without mural nodules can be observed without the need for resection for a considerable period of time. Our review addresses available data, current understanding, controversy, and future directions about IPMNs. [ABSTRACT FROM AUTHOR]