Yangzi Tian

Substance P immunoreactive nerve fibres are related to gastric cancer differentiation status and could promote proliferation and migration of gastric cancer cells

Tachykinins such as SP (substance P) may be involved in the progression of gastric adenocarcinoma through binding to NK‐1 receptor. However, the existence and relationship between SP and gastric cancer progression and differentiation remained unknown. We have studied the NK‐1 receptor in human gastric cancer tissue and MKN45 cell line and found SP‐containing nerve fibres in human gastric cancer and found that the amounts of SP‐positive nerves were related to gastric cancer differentiation. SP could promote proliferation, adhesion, migration and invasion of MKN45 cells in vitro. In addition, the intracellular calcium level of MKN45 cells was elevated after SP stimulation, and administration of CRACs (calcium release‐activated calcium channels) inhibitor SKF‐96365 could partially abolish these effects induced by SP. These results demonstrated that NK‐1 receptor and SP‐containing nerves existed in human gastric cancer; SP positive nerves may play an important role in human gastric cancer progression, and calcium is critically significant among SP‐induced biological effects.

Clinicopathologic Features and Clinical Outcomes of Esophageal Gastrointestinal Stromal Tumor: Evaluation of a Pooled Case Series

AbstractClinicopathologic features and clinical outcomes of gastrointestinal stromal tumors (GISTs) in esophagus are limited, because of the relatively rare incidence of esophageal GISTs. Therefore, the aim of the current study was to investigate the clinicopathologic features and clinical outcomes of esophageal GISTs, and to investigate the potential factors that may predict prognosis.Esophageal GIST cases were obtained from our center and from case reports and clinical studies extracted from MEDLINE. Clinicopathologic features and survivals were analyzed and compared with gastric GISTs from our center.The most common location was lower esophagus (86.84%), followed by middle and upper esophagus (11.40% and 1.76%). The majority of esophageal GISTs were classified as high-risk category (70.83%). Mitotic index was correlated with histologic type, mutational status, and tumor size. The 5-year disease-free survival and disease-specific survival were 65.1% and 65.9%, respectively. Tumor size, mitotic index, and National Institutes of Health risk classification were associated with prognosis of esophageal GISTs. Only tumor size, however, was the independent risk factor for the prognosis of esophageal GISTs. In comparison to gastric GISTs, the distribution of tumor size, histologic type, and National Institutes of Health risk classification were significantly different between esophageal GISTs and gastric GISTs. The disease-free survival and disease-specific survival of esophageal GISTs were significantly lower than that of gastric GISTs.The most common location for esophageal GISTs was lower esophagus, and most of the esophageal GISTs are high-risk category. Tumor size was the independent risk factor for the prognosis of esophageal GISTs. Esophageal GISTs differ significantly from gastric GISTs in respect to clinicopathologic features. The prognosis of esophageal GISTs was worse than that of gastric GISTs.

Combination of PLR, MLR, MWR, and Tumor Size Could Significantly Increase the Prognostic Value for Gastrointestinal Stromal Tumors.

AbstractSystemic inflammation and immune response were associated with prognosis of tumors. However, data was limited due to the relatively low incidence of gastrointestinal stromal tumors (GISTs). The aim of the present study was to investigate the predictive value of preoperative peripheral blood cells in prognosis of GISTs.From September 2008 to July 2015, a total of 274 GIST patients in our department were enrolled in the present study. Clinicopathological features of GISTs were recorded. The association between preoperative peripheral blood cells and prognosis of GISTs were analyzed.Tumor location, tumor size, mitotic index, intratumoral necrosis, and National Institutes of Health (NIH) risk category were associated with prognosis of GISTs. High neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-white blood cell ratio (NWR), monocyte-to-white blood cell ratio (MWR) and low lymphocyte-to-white blood cell ratio (LWR) was associated with poor prognosis of GISTs (76.2% vs 83.7%, P = 0.010. 70.5% vs 98.7%, P = 0.000. 65.7% vs 96.4%, P = 0.004. 78.5% vs 82.5%, P = 0.044. 73.5% vs 97.8%, P = 0.004. 76.6% vs 83.6%, P = 0.012, respectively). However, tumor size was the only independent risk factor for prognosis according to multivariate analysis (P = 0.006). Tumor location, tumor size, mitotic index, and NIH risk category were significantly correlated with the above-mentioned parameters (all P < 0.05). The prognosis of GISTs with tumor size >5 cm, high MLR, high PLR, and high MWR was significantly lower than the remnant patients (P = 0.010).The peripheral blood routine test is convenient, reproducible, and inexpensive. High NLR, MLR, PLR, NWR, MWR, and low LWR were associated with poor prognosis of GISTs. The association between the above parameters and prognosis of GISTs may be attributed to their correlation with tumor size, mitotic index, and NIH risk category. The combination of tumor size, MLR, PLR, and MWR could further increase the predictive value of prognosis of GISTs.

Clinicopathological feature and prognosis of primary hepatic gastrointestinal stromal tumor

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.

Postoperative fever predicts poor prognosis of gastric cancer

Data about prognostic value of postoperative fever in gastric cancer was lacking. Thus, the present study aims to investigate the prognostic value of postoperative fever in gastric cancer. From September 2008 to March 2015, 2938 gastric cancer patients were enrolled in the present study. Clinicopathological features were recoded. The association between postoperative fever and prognosis of gastric cancer were analyzed. There were 2294 male (78.1%) and 644 female (21.9%). Seven hundred and fifty-six patients suffered from fever. Among them, the duration of fever less than 48h occurred in 508 cases, and duration of fever over 48h occurred in 248 cases. Univariate and multivariate analysis showed that postoperative fever was an independent risk factor for prognosis of gastric cancer (P < 0.001). For the entire cohort, duration of fever over 48h was significantly associated with decreased survival (P < 0.001). In subgroup analysis, duration of fever over 48h was significantly associated with poor prognosis of stage I and II gastric cancer (both P < 0.001). However, postoperative fever was not associated with the prognosis of stage III gastric cancer (P = 0.334). Considering the type of gastrectomy, postoperative fever was not associated with the prognosis of patients with proximal (P = 0.318) and distal gastrectomy (P = 0.806), but duration of fever over 48h was significantly associated with poor prognosis of patients with total gastrectomy (P = 0.004). In conclusion, postoperative fever was associated with poor prognosis of gastric cancer.Data about prognostic value of postoperative fever in gastric cancer was lacking. Thus, the present study aims to investigate the prognostic value of postoperative fever in gastric cancer. From September 2008 to March 2015, 2938 gastric cancer patients were enrolled in the present study. Clinicopathological features were recoded. The association between postoperative fever and prognosis of gastric cancer were analyzed. There were 2294 male (78.1%) and 644 female (21.9%). Seven hundred and fifty-six patients suffered from fever. Among them, the duration of fever less than 48h occurred in 508 cases, and duration of fever over 48h occurred in 248 cases. Univariate and multivariate analysis showed that postoperative fever was an independent risk factor for prognosis of gastric cancer (P < 0.001). For the entire cohort, duration of fever over 48h was significantly associated with decreased survival (P < 0.001). In subgroup analysis, duration of fever over 48h was significantly associated with poor prognosis of stage I and II gastric cancer (both P < 0.001). However, postoperative fever was not associated with the prognosis of stage III gastric cancer (P = 0.334). Considering the type of gastrectomy, postoperative fever was not associated with the prognosis of patients with proximal (P = 0.318) and distal gastrectomy (P = 0.806), but duration of fever over 48h was significantly associated with poor prognosis of patients with total gastrectomy (P = 0.004). In conclusion, postoperative fever was associated with poor prognosis of gastric cancer.

Pancreatic Gastrointestinal Stromal Tumor: Clinicopathologic Features and Prognosis.

Goals: The present study aimed to investigate the clinicopathologic features and prognosis of pancreatic gastrointestinal stromal tumor (GIST). Background: Reports on clinicopathologic features and prognosis of pancreatic GIST are limited due to the extremely rare incidence. Study: One case of pancreatic GIST from our center and 44 cases reported in MEDLINE were enrolled in this study. Clinicopathologic features and prognosis of pancreatic GISTs were analyzed and compared with 297 gastric GISTs from our center. Results: The most common location was head of pancreas (38.5%). The majority of pancreatic GISTs exceeded 5 cm (74.4%), displayed cystic or mixed imaging features (56.4%), and were high risk (85.7%). The 5-year disease-free survival (DFS) and disease-specific survival rates were 66.1% and 95.8%, respectively. Mitotic index was the only risk factor for DFS of pancreatic GISTs. The distribution of tumor size, histologic type and National Institutes of Health risk category were significantly different between pancreatic and gastric GISTs. The 5-year DFS rate of pancreatic GISTs was significantly lower than that of gastric GISTs. Multivariate analysis showed that location was an independent prognostic factor for DFS between pancreatic and gastric GISTs. Conclusions: The most common location was head of pancreas. The majority of pancreatic GISTs were large and highly malignant. Pancreatic GISTs differed significantly from gastric GISTs in respect to clinicopathologic features. The DFS of pancreatic GISTs was worse than that of gastric GISTs.

Low forced vital capacity predicts poor prognosis in gastric cancer patients

Preoperative pulmonary function assessment is used to select surgical candidates and predict the occurrence of postoperative complications. The present study enrolled 1210 gastric cancer patients (949 males and 261 females). Forced vital capacity (FVC) and maximal voluntary ventilation (MVV) were measured as a percent of predicted values. We then analyzed associations between patient pulmonary function and both prognosis and postoperative complications. Patient 1-, 3- and 5-year overall survival rates were 88.8%, 65.7% and 53.0%, respectively. FVC and MVV optimal cutoff values were 87.0 (P=0.003) and 83.6 (P=0.026), respectively. Low FVC and low MVV were associated with higher rates of postoperative fever (23.8% vs. 13.9%, P<0.001; 17.8% vs. 13.3%, P=0.049, respectively) and poor patient prognosis (5-year overall survival: 43.5% vs. 57.6%, P=0.003; 51.8% vs. 54.3%, P=0.026, respectively). Only low FVC was an independent prognostic predictor for gastric cancer (P=0.012). In subgroup analyses, FVC was not associated with stage I or II gastric cancer patient prognoses (P>0.05), but low FVC was an independent risk factor for poor prognosis in stage III gastric cancer cases (P=0.004). These findings indicate that low FVC is predictive of poorer prognosis and higher risk of postoperative fever in gastric cancer patients.

Suggested cutoff tumor size for small gastric gastrointestinal stromal tumors

Background: To investigate if there is an appropriate cutoff tumor size for small gastric gastrointestinal stromal tumors (GISTs) or not, and whether the cutoff size could be used to predict the tumor progression for small gastric GISTs during follow-up. Methods: From May 2010 to March 2014, 97 patients were enrolled in the present study, including 90 small gastric GIST patients underwent resection, and 7 endoscopic ultrasound (EUS) suspected small gastric GIST patients. The cutoff tumor size of small gastric GISTs was calculated based on mitotic index using receiver operating characteristic (ROC) analysis. Results: Of the 90 patients, mitotic index of 18 small gastric GISTs (20%) exceeded 5/50 HPF. Using ROC analysis, we found that 1.4 cm may be considered as an appropriate cutoff tumor size. The ratio of CT enhancement, tumor ulceration, mitotic index exceeds 5/50 HPF and low risk category was significantly higher in tumors between 1.4 and 2.0 cm than that of tumors less than 1.4 cm (all P<0.05). EUS suspected small gastric GISTs between 1.4 and 2.0 cm showed significant tumor progression during follow-up (median 11.8 months, range from 10.1 to 24.5 months). Conclusions: The 1.4-cm may be considered as a more reasonable cutoff tumor size for small gastric GISTs. We recommended that all small gastric GISTs should be resected once diagnosed, at least for tumors between 1.4 and 2.0 cm.

OP9‐DL1 cell co‐culture enhances anti‐tumour immunity of mouse bone marrow‐derived dendritic cells

DCs (dendritic cells) are the strongest professional APCs (antigen‐presenting cells) to initiate immune responses against pathogens, but they are usually incompetent in initiating efficient immune responses in the progress of solid tumours. We have shown that Notch signalling plays a pivotal role in DC‐dependent anti‐tumour immunity. Compared with the control DCs, OP9‐DL1 (Delta‐like1) cell co‐cultured DCs gained increased tumour suppression activity when inoculated together with tumour cells. This was probably due to the activation of Notch signalling in DCs enhancing their ability to evoke anti‐tumour immune responses in solid tumours. Indeed, the OP9‐DL1 cell co‐cultured DCs expressed higher levels of MHC I, MHC II, CXCR4 (CXC chemokine receptor 4), CCR7 (CC chemokine receptor 7), IL‐6 (interleukin 6), IL‐12 and TNFα (tumour necrosis factor α), and a lower level of IL‐10 than control DCs, resulting in more efficient DC migration and T‐cell activation in vivo and in vitro. T‐cells stimulated by OP9‐DL1 cells co‐cultured DCs more efficiently; and were cytotoxic against tumour cells, in contrast with control DCs. These results indicated that up‐regulation of Notch signalling in DCs by co‐culturing with OP9‐DL1 cells enhances DC‐dependent anti‐tumour immune reactions, making the Notch signalling pathway a target for the establishment of the DC‐based anti‐tumour immunotherapies.