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Substance P (SP) plays an important role in several types of cancer promotion and progression by binding to its preferential neurokinin 1 receptor (NK1R). However, the clinical significance and downstream mechanism of NK1R in esophageal squamous cell carcinoma (ESCC) have not been elucidated. The aim of this study was to investigate the role of SP/NK1R in the proliferation of ESCC and to screen related downstream molecules. In the current investigation, the expression of NK1R was detected via immunohistochemistry (IHC), western blot (WB) analysis and real-time reverse transcription-polymerase chain reaction (RT-qPCR) in ESCC tissues and cell lines. Thereafter, the optimal concentration of SP was determined in vitro. The proliferation ability of SP/NK1R was assessed by cell counting kit-8 (CCK-8) and colony formation assays and subcutaneous tumour formation in nude mice with EC109 cells. Moreover, the related downstream molecules were screened by performing isobaric tags for relative and absolute quantitation (iTRAQ) protein spectrum analysis. NK1R was upregulated in ESCC, and its overexpression correlated with larger tumour size, deeper tumour invasion, more perineural invasion and eventually caused poorer overall survival (OS). Both intrinsic and SP-activated NK1R upregulation could promote the proliferation and clonogenic capacity of ESCC cells. In nude mice, tumour growth was suppressed by EC109 cells of NK1R downregulation. Further experiments demonstrated that Hairy and Enhancer of Split 1 (Hes1) was markedly reduced upon NK1R downregulation in EC109 cell lines and could regulate cell proliferation in the downstream of SP/NK1R. The significant role of NK1R in mediating ESCC cell proliferation depended on the activation of SP and might be related to the downstream regulation of Hes1. • NK1R was overexpressed in ESCC tissues and predicts advanced stage and poorer OS. • SP/NK1R promotes cell proliferation both in vitro and in vivo. • SP/NK1R mediating ESCC cell proliferation via the downstream regulation of Hes1. [ABSTRACT FROM AUTHOR]

Background: Little is known about the clinicopathological features and prognosis in elderly gastric cancer (GC) patients aged 65-79 years. The aim of this study was to evaluate clinicopathological features and prognosis in elderly GC patients. Patients and methods: From May 2008 to December 2014, a total of 5,282 GC patients were enrolled in our present study. Patients were divided into elderly and middle-aged groups. The clinicopathological features and clinical outcomes were analyzed. Results: The proportion of dysphagia was significantly higher in elderly patients than that in middle-aged patients (P=0.002), whereas the proportion of abdominal pain and heartburn was significantly lower in elderly patients than that in middle-aged patients (P<0.001 vs P=0.038, respectively). The proportion of patients with carbohydrate antigen (CA) 19-9 was significantly higher in elderly patients than that in middle-aged patients (P=0.009). There was no significant difference in clinicopathological features between elderly and middle-aged patients with D2 gastrectomy (all P.0.05). Age, tumor size, histological type, tumor depth, lymph node metastasis, carcinoembryonic antigen, alpha fetoprotein, CA19-9, and CA125 were independent risk factors for the prognosis of GC patients in univariate and multivariate analyses. Overall survival in elderly patients was significantly reduced compared with middle-aged patients (P=0.001), especially in patients with tumor size .5 cm (P=0.002), poorly differentiated tumor (P<0.000), stage III tumor (P=0.002), or normal levels of carcinoembryonic antigen (P=0.009), alpha fetoprotein (P=0.002), CA19-9 (P=0.002), and CA125 (P=0.004). Conclusion: The clinicopathological features of elderly patients were different to those of middle-aged patients. The prognosis for elderly GC patients was significantly worse than for middle-aged patients. [ABSTRACT FROM AUTHOR]

Compared to gastric gastrointestinal stromal tumor (GIST), hepatic GIST is very rare in clinic. Reports on clinicopathological feature and prognosis of this rare disease are limited in literature. The purpose of this study was, therefore, to summarize clinical and pathological features as well as prognosis of the primary hepatic GIST. One case of primary hepatic GIST from our center and 22 cases reported in MEDLINE or China National Knowledge Infrastructure (CNKI) were enrolled into this study. Clinicopathological features as well as survival data of hepatic GIST were analyzed and compared with 297 gastric GISTs and 59 small intestinal GISTs from our center. Majority of the 22 cases (95.7%) of hepatic GIST was larger than 5 cm in size, and 75.0% of the tumors were over 5/50 HPF in mitotic index. Most of the hepatic GISTs (85.7%) displayed spindle cell shape in morphology. All of the hepatic GIST (100%) enrolled in this study were classified as high-risk category by the National Institute of Health (NIH) risk classification. The 5-year median disease-free survival (DFS) time was 24.0 months and 5-year disease-specific survival (DSS) rate was 33.3%, respectively. Distribution of clinicopathological features was significantly different among hepatic, gastric, and small intestinal GIST. The DFS and DSS of hepatic GIST were significantly lower than those of the other two groups. Majority of the hepatic GIST is large in size and highly malignant. Prognosis of the primary hepatic GIST is worse than that of gastric GIST and small intestinal GIST. [ABSTRACT FROM AUTHOR]

Background: It remains controversial whether prophylactic No.10 lymph node clearance is necessary for gastric cancer. Thus, the present study aims to investigate the impact of prophylactic No.10 lymph node clearance on the perioperative complications and prognosis of upper and middle third gastric cancer.Methods: A network meta-analysis to identify both direct and indirect evidence with respect to the comparison of gastrectomy alone (G-A), gastrectomy combination with splenectomy (G + S) and gastrectomy combination with spleen-preserving splenic hilar dissection (G + SPSHD) was conducted. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies published before September 2018. Perioperative complications and overall survival were analyzed. Hazard ratios (HR) were extracted from the publications on the basis of reported values or were extracted from survival curves by established methods.Results: Ten retrospective studies involving 2565 patients were included. In the direct comparison analyses, G-A showed comparable 5-year overall survival rate (HR: 1.1, 95%CI: 0.97-1.3) but lower total complication rate (OR: 0.37, 95%CI: 0.17-0.77) compared with G + S. Similarly, the 5-year overall survival rate between G + SPSHD and G + S was comparable (HR: 1.1, 95%CI: 0.92-1.4), while the total complication rate of G + SPSHD was lower than that of G + S (OR: 0.50, 95%CI: 0.28-0.88). In the indirect comparison analyses, both the 5-year overall survival rate (HR: 1.0, 95%CI: 0.78-1.3) and total complication rate (OR: 0.75, 95%CI: 0.29-1.9) were comparable between G-A and G + SPSHD.Conclusions: Prophylactic No.10 lymph node clearance was not recommended for treatment of upper and middle third gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Data about the clinicopathological features and prognosis of gastrointestinal stromal tumors (GISTs) located in jejunum and ileum are lacking. The present study aims to investigate the features and prognosis of jejunal and ileal GISTs based on the Surveillance, Epidemiology, and End Results (SEER) database. Patients and Methods: Cases of jejunal and ileal GISTs were extracted from SEER database. Clinicopathological characteristics and survival data of patients were recorded. The clinicopathological features and prognosis of patients were analyzed. Results: There were 399 male (56.8%) and 303 female (43.2%). The median age was 60 years (17–96). Four hundred and seventy-two tumors were located in the jejunum (67.2%) and 230 tumors in the ileum (32.8%). The median tumor size was 7.0 cm (0.5–90). The 5-, 10-, and 20-year disease specific survival (DSS) was 84.4, 71.2, and 54.2% respectively. Clinicopathological features were comparable between tumors located in the jejunum and ileum (all p > 0.05) except gender and tumor size (both p < 0.05). Jejunal GISTs, rather than ileal GISTs (p = 0.043), were commonly found in the males. The tumor size of jejunal GISTs was smaller than that of ileal GISTs (p = 0.010). The DSS of jejunal GISTs was comparable to that of ileal GISTs (p = 0.269). Conclusions: Jejunal GISTs were more common than ileal GISTs. The prognosis was comparable between jejunal and ileal GISTs. [ABSTRACT FROM AUTHOR]

Background: Up to date, investigation of the prognostic value of differentiation status mainly focused on signet ring cell and mucinous gastric cancer. Thus, the present study aims to investigate the clinicopathological features and prognosis of gastric cancer patients with well, moderately and poorly differentiation status.Methods: From September 2008 to March 2015, a total of 3090 gastric cancer patients treated with radical D2 gastrectomy were enrolled in the present study. Clinicopathological characteristics and prognosis of gastric cancer patients with well, moderately and poorly differentiation status were analyzed.Results: There were 2422 male (78.4%) and 668 female (21.6%). The median age was 58 (20-90) years. There were 370 (12.0%) well differentiated tumors, 836 (27.0%) moderately differentiated tumors and 1884 (61.0%) poorly differentiated tumors. Well and moderately differentiation status were associated with older age, male gender, smaller tumor, shallower invasion, less lymph node involvement and earlier tumor stage (all p < 0.001). Inversely, poorly differentiation status was associated with younger age, female gender, larger tumor, deeper invasion, more lymph node involvement and later tumor stage (all p < 0.001). With respect to prognosis, well differentiation status was associated with favorable overall survival and poorly differentiation status was associated with unfavorable overall survival (p < 0.001). However, after matching with age, tumor size, T and N stage, there was no significant difference among the overall survival of the three groups (p = 0.415).Conclusions: Well, moderately and poorly differentiation status was significantly associated with clinicopathological features of gastric cancer patients. However, it was not associated with the prognosis of gastric cancer patients. [ABSTRACT FROM AUTHOR]

Background: The relatively low incidence of duodenal gastrointestinal stromal tumors (GISTs) and the unique anatomy make the surgical management and outcomes of this kind of tumor still under debate. Thus, this study aimed to explore the optimal surgical strategy and prognosis of duodenal GISTs.Methods: A total of 300 cases of duodenal GISTs were obtained from our center (37 cases) and from case reports or series (263 cases) extracted from MEDLINE. Clinicopathological features, type of resections and survivals of duodenal GISTs were analyzed.Results: The most common location of duodenal GISTs was descending portion (137/266, 51.5%). The median tumor size was 4 cm (0.1-28). Most patients (66.3%) received limited resection (LR). Pancreaticoduodenectomy (PD) was mainly performed for GISTs with larger tumor size or arose from descending portion (both P < 0.05). For both the entire cohort and tumors located in the descending portion, PD was not an independent risk factor for disease-free survival (DFS) and disease-specific survival (DSS) (both P > 0.05). Duodenal GISTs were significantly different from gastric GISTs with respect to tumor size, mitotic index and NIH risk category (all P < 0.05). The DFS and DSS of duodenal GISTs was significantly worse than that of gastric GISTs (both P < 0.05).Conclusions: LR was a more prevalent surgical procedure and PD was mainly performed for tumors with larger diameter or located in descending portion. Type of resection was not an independent risk factor for the prognosis of duodenal GISTs. Prognosis of duodenal GISTs was significantly worse than that of gastric GISTs. [ABSTRACT FROM AUTHOR]

Background: Data on the safety and feasibility of laparoscopic versus open resection for gastric gastrointestinal stromal tumors (GISTs) larger than 5 cm are limited. Therefore, the aim of this meta-analysis was to compared laparoscopic and open resection for gastric GISTs larger than 5 cm.Methods: We perform a literature search on PubMed, the Cochrane Library, and Embase. Review Manage version 5.1 (RevMan 5.1) was used for data analysis. The GRADE profiler software (version 3.6) was used to estimate the level of evidence.Results: A total of 6 observational studies and one unpublished retrospective cohort study met the inclusion criteria for the meta-analysis: 203 patients in LAP and 214 patients in OPEN group. The pooled result revealed that laparoscopic resection was associated with a same operative time (WMD = -0.87 min; 95% CI: -47.50 to 47.75; P = 0.97), intraoperative blood loss (WMD = -34.38 ml; 95% CI: -79.60 to 10.84; P = 0.14), overall complications (RR = 0.65; 95% CI: 0.38 to 1.12; P = 0.12), better 5-year disease-free survival (HR = 0.40; 95% CI: 0.17 to 0.91; P = 0.03) and overall survival (HR = 0.09; 95% CI: 0.02 to 0.40; P = 0.002) compared with open resection.Conclusion: Laparoscopic resection is a technically and oncologically safe and feasible approach for large-sized gastric GISTs (≥ 5 cm) compared to open resection. [ABSTRACT FROM AUTHOR]

Background: The clinicopathological features and prognosis of gastric cancer in young patients are both limited and controversial. Therefore, the aim of this study was to define the clinicopathological features and prognosis of gastric cancer in young patients after curative resection.Methods: From May 2008 to December 2014, 198 young patients (age ≤ 40 years) and 1096 middle-aged patients (55 ≤ age ≤ 64 years) were enrolled in this study. The clinicopathological features and prognosis of gastric cancer in these patients were analyzed.Results: Compared with middle-aged patients, the proportion of females, lower third tumors, tumor size less than 5 cm, poorly differentiated tumors and T1 tumors were significantly higher in young patients (all P < 0.05). The proportions of comorbidity, upper third tumors, well and moderately differentiated tumors, T4 tumors, and positive carcinoembryonic antigen (CEA), alpha fetoprotein (AFP) and carbohydrate antigen (CA) 19-9 were significantly lower in young patients (all P < 0.05). The distributions of N status and CA125 were comparable between young and middle-aged patients (all P > 0.05). The five-year overall survival rates were comparable between young patients and middle-aged patients (62.8 vs 54.7 %, P = 0.307). The tumor location, T status, N status and CA125 were independent predictors of prognosis in young patients. The overall survival of patients with tumors located in the upper or middle third was significantly lower than for those located in the lower third (60.8 vs 50.6 % vs 68.4 %, P = 0.016). The overall survival of CA125-positive patients was significantly lower than CA125-negative patients (49.0 vs 64.4 %, P = 0.001).Conclusion: The clinicopathological features were significantly different between young and middle-aged patients. The prognosis of gastric cancer in young patients was equivalent to that of middle-aged patients. Tumor location, T status, N status and CA125 were independent risk factors for prognosis in young patients. [ABSTRACT FROM AUTHOR]

Background: The optimal length of proximal margin for Siewert type II/III adenocarcinoma of the esophagogastric junction (AEJ) is still need to be clarified. The aim of the present study was to investigate the appropriate length of proximal margin for Siewert type II/III AEJ through transhiatal approach. Methods: From September 2009 to December 2014, a total of 693 consecutive patients with Siewert type II/III AEJ were retrospectively analyzed. All patients received transhiatal R0 resection. The proximal margin length was measured immediately after resection. The prognostic value of proximal margin length on Siewert type II/III AEJ with transhiatal approach was analyzed. Results: There were 404 cases of Siewert type II AEJ (58.3 %) and 289 cases of Siewert type III AEJ (41.7 %). Total gastrectomy was performed in 526 patients (75.9 %), and proximal gastrectomy was performed in 167 patients (24.1 %). The median length of the gross proximal margin was 2.4 (range 0.1-5.0) cm. Lymph node metastasis was the only independent prognostic predictor for Siewert type II AEJ. Tumor size and lymph node metastasis were independent prognostic predictors for Siewert type III AEJ. Conclusions: For Siewert type II/III AEJ with esophageal invasion of 3 cm or less, proximal margin length does not influence the prognosis of patients after transhiatal curative gastrectomy. [ABSTRACT FROM AUTHOR]

Background: Existing data about the prognostic value of absolute count of blood cells in gastric cancer was limited. Thus, the present study aims to investigate the prognostic value of absolute count of white blood cell (WBC), neutrophil, lymphocyte, monocyte and platelet in gastric cancer patients.Methods: From September 2008 to March 2015, 3243 patients treated with radical gastrectomy were enrolled in the present study. Clinicopathological characteristics were recorded. The prognostic value of blood test in gastric cancer patients were analyzed.Results: There were 2538 male and 705 female. The median age was 58 years (range 20-90). The median follow-up time was 24.9 months (range 1-75). The 1-, 3- and 5-year overall survival rate was 88.9%, 65.8% and 57.2%, respectively. The optimal cut off value was 6.19 × 109/L for WBC (P = 0.146), 4.19 × 109/L for neutrophil (P = 0.004), 1.72 × 109/L for lymphocyte (P = 0.000), 0.51 × 109/L for monocyte (P = 0.019) and 260.0 × 109/L for platelet (P = 0.002), respectively. Neutrophil, lymphocyte, monocyte and platelet were risk factors for the prognosis of gastric cancer (all P < 0.05). However, only lymphocyte and monocyte were independent risk factors (both P < 0.05). Combination of lymphocyte and monocyte could increase the prognostic value for gastric cancer patients, especially in stage II/III gastric cancer patients.Conclusions: High absolute count of neutrophil, monocyte and platelet, and low absolute count of lymphocyte were associated with poor prognosis of gastric cancer. However, only lymphocyte and monocyte count were independent prognostic predictors. Combination of lymphocyte and monocyte count could further increase the predictive value for gastric cancer. [ABSTRACT FROM AUTHOR]

Background: The diagnostic and prognostic significance of carcinoembryonic antigen (CEA), carbohydrate associated antigen 19-9 (CA19-9), alpha-fetoprotein (AFP) and cancer antigen 125 (CA125) in early gastric cancer have not been investigated yet. Thus, the present study aimed to explore the diagnostic and prognostic significance of the four tumor markers for early gastric cancer.Methods: From September 2008 to March 2015, 587 early gastric cancer patients were given radical gastrectomy in our center. The clinicopathological characteristics were recorded. The association between levels of CEA and CA19-9 and clinicopathological characteristics and prognosis of patients were analyzed.Results: There were 444 men (75.6%) and 143 women (24.4%). The median age was 57 years (ranged 21-85). The 1-, 3- and 5-year overall survival rate was 99.1%, 96.8% and 93.1%, respectively. The positive rate of CEA, CA19-9, AFP and CA125 was 4.3%, 4.8%, 1.5% and 1.9%, respectively. The positive rate of all markers combined was 10.4%. The associations between the clinicopathological features and levels of CEA and CA19-9 were analyzed. No significant association was found between CEA level and clinicopathological features. However, elevated CA19-9 level was correlated with female gender and presence of lymph node metastasis. Age > 60 years old, presence of lymph node metastasis and elevation of CEA level were independent risk factors for poor prognosis of early gastric cancer.Conclusions: The positive rates of CEA, CA19-9, APF and CA125 were relatively low for early gastric cancer. Elevation of CA19-9 level was associated with female gender and presence of lymph node metastasis. Elevation of CEA level was an independent risk factor for the poor prognosis of early gastric cancer. [ABSTRACT FROM AUTHOR]

Perineural invasion (PNI) has been recognized as a poor prognostic factor in several malignancies, but the definition and pathogenesis of PNI in esophageal squamous cell carcinoma (ESCC) remains to be defined. PNI was evaluated by H&E staining and S100 immunohistochemistry. The predictive value of PNI in the prognosis of ESCC patients was analyzed. PNI was evaluated in vitro and in vivo. A total of 54 specimens (17.88%) were defined as PNI-a and 99 specimens (32.78%) as PNI-b. S100 staining was superior to H&E staining for PNI detection (50.66% vs 27.15%, P < 0.001, κ = 0.506). Tumor depth (P = 0.001), tumor stage (P = 0.010), and vascular invasion (P < 0.001) were significantly associated with PNI. PIN-a and PNI-b had significant lower disease free survival (DFS) and disease specific survival (DSS) than PNI-0 patients, and the prognosis of PNI-b patients was significantly worse than PNI-a patients for DFS (P = 0.009). PNI was an independent predictor for DFS and DSS in ESCC as evaluated by univariate and multivariate analyses. ESCC cells could metastasize along the nerve in vitro and in vivo, and PNI was a dynamic process. S100 staining significantly improved the accuracy of PNI detection. PNI was associated with local recurrence and poor prognosis of ESCC patients. [ABSTRACT FROM AUTHOR]