Ying Qiang Shi

Prognostic factors for extra‐abdominal and abdominal wall desmoids: A 20‐year experience at a single institution

Previous reports even large studies discussing the prognosis of desmoids have included tumors from intra‐ and extra‐abdominal sites as well as incomplete resection. The purpose of this study was to explore prognostic factors associated with the recurrence free survival (RFS) rate in surgically treated extra‐abdominal and abdominal wall desmoids.

The analysis of status and clinical implication of KIT and PDGFRA mutations in gastrointestinal stromal tumor (GIST)

to analyze the frequency and spectrum of KIT and platelet‐derived growth factor receptor‐alpha (PDGFRA) gene in a large series of study and to explore the clinical implication of mutations in the gastrointestinal stromal tumors (GISTs) in China.

Is there a role of surgery in patients with recurrent or metastatic gastrointestinal stromal tumours responding to imatinib: A prospective randomised trial in China

OBJECTIVES For advanced gastrointestinal stromal tumour (GIST) patients who are responding to imatinib mesylate, the role of surgery has not been formally demonstrated. This multicenter randomised controlled trial was designed to assess whether surgery to treat residual disease for patients with recurrent/metastatic GISTs responding to imatinib mesylate (IM) improved progression free survival (PFS) compared with IM treatment alone. METHODS Between 3 and 12months after starting IM for recurrent/metastatic GISTs, eligible patients were randomised to two arms: Arm A (surgery for residual disease) and Arm B (IM treatment alone). In Arm A (19pts), surgery was performed to remove residual macroscopic lesions as completely as possible, and IM treatment continued after surgery. In Arm B (22pts), IM was given alone at a dose of 400mg per day until disease progression. The primary end-point was PFS measured from the date IM started. This study was registered in the ChiCTR registry with the ID number ChiCTR-TRC-00000244. RESULTS This randomised trial was closed early due to poor accrual. Only 41 patients were enrolled as opposed to 210 patients planned. 2-year PFS was 88.4% in the surgery arm and 57.7% in the IM-alone arm (P=0.089). Median overall survival (mOS) was not reached in the surgery arm and 49months in patients with IM-alone arm (P=0.024). CONCLUSIONS While no significant differences were observed in the two arms, this study suggests that surgical removal of the metastatic lesion may improve the outcome of advanced GIST patients and should stimulate additional research on this topic.

Sox17 regulates proliferation and cell cycle during gastric cancer progression

Sox17, a transcription factor, was considered as an antagonist to inhibit canonical Wnt/β-catenin signaling in several malignant tumors. Extremely little is known about Sox17 in gastric cancer. Therefore, the aim of this study was to elucidate the vital role of Sox17 in the tumorigenesis and progression of gastric cancer. Real time PCR was used to detect the expression of Sox17 in gastric cancer tissue. Furthermore, a series of function assays, utilizing small interfering RNA (siRNA)-mediated knockdown of Sox17 expression in MKN45 gastric cancer cells, have been performed in this study, including proliferation assay, clonogenic assay, cell-cycle evaluation, apoptosis detection as well as western blot assay. Sox17 expression were low in gastric cancer tissues as compared to normal tissue (P=0.013). Knockdown of Sox17 by Sox17-siRNA markedly enhanced the proliferation ability of MKN45 cells when compared with negative siRNA-infected cells and mock group (P<0.05). Down-regulation of Sox17 contributed to increasing cloning efficiency and activating cell cycle of MKN45 cells (P<0.05). However, there was no significantly statistical difference in terms of apoptosis rate between Sox17-siRNA group and Negative or mock group. Western blot assay revealed that the expression of CyclinD1 observably increased while p27(Kip1) expression remarkably decreased in MKN45 cells with Sox17-siRNA transfection. Furthermore, apoptosis-related molecules, Caspase3 and Bcl-xl, have no dramatically discrepant expression when knockdown of Sox17 in MKN45 cells. Sox17 prominently contributes to gastric cancer progression through regulating proliferation and cell cycle, indicating a novel diagnosis and prognosis biomarker as well as a potential therapeutic target in gastric cancer.

Fibroblast growth factor receptor 4 regulates proliferation and antiapoptosis during gastric cancer progression

Fibroblast growth factor receptor 4 (FGFR4) belongs to the tyrosine kinase receptor family. Little is known about the effect of FGFR4 on gastric cancer (GC). Therefore, the objective of the current study was to elucidate the role of FGFR4 in the tumorigenesis and progression of GC.

Prognostic factors influencing event-free survival and treatments in desmoid-type fibromatosis: analysis from a large institution

BACKGROUND Prognostic factors and optimal management of desmoid tumors have been discussed for decades. The authors present the results of a large series of patients with desmoid tumors treated at a single institution to investigate the prognostic factors influencing event-free survival (EFS) and suitable treatments for these rare tumors. METHODS Two hundred fourteen patients with desmoid tumors admitted to the surgical department were included, of whom 20 were recommended for a policy of watchful waiting. The following clinical parameters were studied: admission status, age, sex, tumor site, tumor size, margin status, and therapeutic strategy. Univariate and multivariate analysis were performed for EFS. RESULTS Forty-two patients had local recurrence. One patient died of intra-abdominal disease. The 5-year and 10-year EFS rates were 78.8% and 77.9%, respectively. In univariate analysis, admission status, tumor site, tumor size, and group (R0 vs R1 and R0 vs R2) had significant impacts on EFS. EFS discrepancy was not significant between R1 and R2 or biopsy groups. In multivariate analysis, tumor size and admission status had independent value. The median delay to progression for patients undergoing watchful waiting was comparable with that for the surgical group. CONCLUSIONS This study demonstrates that tumor size and a history of recurrence are independent predictors of EFS. Surgery is warranted if it can be R0 and function sparing. Nonsurgical modalities or a policy of watchful waiting may be a better choice for unresectable disease.

Prognostic analysis of familial gastric cancer in Chinese population.

The aim of this study was firstly to elucidate the prognosis of familial gastric cancer (FGC) in Chinese population.

Combination of the FGFR4 inhibitor PD173074 and 5-fluorouracil reduces proliferation and promotes apoptosis in gastric cancer.

Our previous findings revealed that FGFR4 may be a novel therapeutic target for gastric cancer. The aim of the present study was to explore the effects of a combination of PD173074 (PD) and 5-fluorouracil (5-Fu) on the biological behavior of gastric cancer cell lines and the relevant mechanisms involved. MKN45, a gastric cancer cell line, was treated with each single agent alone or a combination of FGF19, PD and 5-Fu. Then, a series of functional assays were performed using CCK-8 assay and flow cytometry. Western blot analysis was used to determine the expression of signaling pathway and downstream-related molecules in the MKN45 cells following the different treatments. As the concentration of PD and 5-Fu increased, the cell viability gradually decreased; the viability of the combination group was less than the viability following single administration. Western blot analysis showed that FGFR4 expression was weak in the 5-Fu-treated groups when compared with the control. PD markedly increased the apoptosis rate of MKN45 cells when compared to the control; the apoptosis rate in the cells treated with the combination of PD and 5-Fu was higher than that in the cells following single treatment. Furthermore, PD reduced the expression of p-ERK and Bcl-xl and increased caspase-3 expression. Inhibition of the activity of FGFR4 may be the main mechanisms of PD effect while 5-Fu reduced FGFR4 expression. Furthermore, the effects of the combination of 5-Fu and PD in inhibiting proliferation, increasing apoptosis and arresting cell cycle were superior to these effects following the single agent treatments, suggesting that the two drugs applied in combination may contribute to the effective treatment of gastric cancer.

Impact of lymphatic and/or blood vessel invasion in stage II gastric cancer

AIM To determine the prognostic value of lymphatic and/or blood vessel invasion (LBVI) in patients with stage II gastric cancer. METHODS From January 2001 to December 2006, 487 patients with histologically confirmed primary gastric adenocarcinoma were diagnosed with stage II gastric cancer according to the new 7th edition American Joint Committee on Cancer stage classification at the Department of Gastric Cancer and Soft Tissue Surgery, Fudan University Shanghai Cancer Center. All patients underwent curative gastrectomy with standard lymph node (LN) dissection. Fifty-one patients who died in the postoperative period, due to various complications or other conditions, were excluded. Clinicopathological findings and clinical outcomes were analyzed. Patients were subdivided into four groups according to the status of LBVI and LN metastases. These four patient groups were characterized with regard to age, sex, tumor site, pT category, tumor grading and surgical procedure (subtotal resection vs total resection), and compared for 5-year overall survival by univariate and multivariate analysis. RESULTS The study was composed of 320 men and 116 women aged 58.9 ± 11.5 years (range: 23-88 years). The 5-year overall survival rates were 50.7% and the median survival time was 62 mo. Stage IIa cancer was observed in 334 patients, including 268 T3N0, 63 T2N1, and three T1N2, and stage IIb was observed in 102 patients, including 49 patients T3N1, 51 T2N2, one T1N3, and one T4aN0. The incidence of LBVI was 28.0% in stage II gastric cancer with 19.0% (51/269) and 42.5% (71/167) in LN-negative and LN-positive patients, respectively. In 218 patients (50.0%), there was neither a histopathologically detectable LBVI nor LN metastases (LBVI(-)/LN(-), group I); in 51 patients (11.7%), LBVI with no evidence of LN metastases was detected (LBVI(+)/LN(-), group II). In 167 patients (38.3%), LN metastases were found. Among those patients, LBVI was not determined in 96 patients (22.0%) (LBVI(-)/LN(+), group III), and was determined in 71 patients (16.3%) (LBVI(+)/LN(+), group IV). Correlation analysis showed that N category and the number of positive LNs were significantly associated with the presence of LBVI (P < 0.001). The overall 5-year survival was significantly longer in LN-negative patients compared with LN-positive patients (56.1% vs 42.3%, P = 0.015). There was a significant difference in the overall 5-year survival between LBVI-positive and LBVI-negative tumors (39.6% vs 54.8%, P = 0.006). Overall 5-year survival rates in each group were 58.8% (I), 45.8% (II), 45.7% (III) and 36.9% (IV), and there was a significant difference in overall survival between the four groups (P = 0.009). Multivariate analysis in stage II gastric cancer patients revealed that LBVI independently affected patient prognosis in LN-negative patients (P = 0.018) but not in LN-positive patients (P = 0.508). CONCLUSION In LN-negative stage II gastric cancer patients, LBVI is an additional independent prognostic marker, and may provide useful information to identify patients with poorer prognosis.

Poor prognostic factors in patients with stage I gastric cancer according to the seventh edition TNM classification: A comparative analysis of three subgroups

The purpose of this study was to investigate the prognosis of stage I gastric cancer and to compare clinicopathologic characteristics by subgroup.