Abstract:

Objective: To investigate the clinical value of preoperative serum levels of carbohydrate antigens (CA19-9, CA50, CA242, CA125) and carcino-embryonic antigen (CEA) in predicting resectability of pancreatic head cancer. Methods: The clinical data of 104 patients with cancer in the head of the pancreas admitted between January 2014 and December 2015 were analyzed retrospectively. The serum tumor markers associated with the resectability of pancreatic head cancer were picked up, and their predictive values for the resectability of pancreatic head cancer were determined by receiver operating characteristic curve (ROC) and the area under ROC curve (AUC). Results: All the 104 patients received surgical exploration, by which, the tumors in 54 cases were considered resectable (resectable group), and in 50 cases were unresectable (unresectable group). The preoperative serum CA50 and CEA levels showed significant difference between the two groups (both P>0.05), while the preoperative serum CA19-9, CA242 and CA125 levels in unresectable group were significantly higher than those in resectable group (317.99 kU/L vs. 152.98 kU/L; 67.81 kU/L vs. 39.36 kU/L; 71.53 kU/L vs. 29.22 kU/L, all P<0.05). ROC analysis showed that both CA19-9 and CA125 had predictive significance for the resectability of pancreatic head cancer, with the optimal cut-off value of 236.13 kU/L and 16.44 kU/L, and AUC of 0.667 and 0.678 respectively, while lone detection of CA242 had no predictive significance for the resectability of pancreatic head cancer (AUC=0.609, P=0.085). The sensitivity and specificity for predicting resectability of pancreatic head cancer were increased by combined detection of CA19-9 and CA125. Conclusion: Preoperative serum CA19-9 and CA125 levels can be used as auxiliary indicators for estimating the resectability of pancreatic head cancer, and their combined detection may increase the diagnostic sensitivity and specificity.

Abstract:Objective: To systematically evaluate the diagnostic value of circulating tumor cells (CTCs) in patients with pancreatic cancer through Meta-analysis. Methods: The studies regarding detection of CTCs in pancreatic cancer patients and non-pancreatic cancer subjects were collected through searching several national and international databases. The retrieval time was from inception of the database to 31 August 2016. After screening for inclusion criteria, data extraction and quality assessment, Meta-analysis was performed by the Metadisc 1.4 and Stata 12.0 software. Results: A total of 19 articles were selected, involving 693 pancreatic cancer patients and 406 non-pancreatic controls. Pooling the data using the random effect model showed that the pooled sensitivity and specificity of the CTCs for detection of pancreatic cancer was 0.67 (95% CI=0.63–0.60) and 0.94 (95% CI=0.91–0.96), the pooled diagnostic odds ratio was 50.47 (95% CI=20.13–126.55), and the pooled positive likelihood ratio and negative likelihood ratio was 11.15 (95% CI=5.42–22.95) and 0.36 (95% CI=0.28–0.45), respectively. The area under the curve of the summary receiver operating characteristic curve was 0.93 with a Q* value of 0.03. Diagnostic Test Deek’s funnel plot for diagnostic test demonstrated the presence of publication bias. Conclusion: CTCs detection is incompetent to be used dependently as an early diagnosis indicator for pancreatic cancer, while it may probably serve as a supplementary index for diagnosis of pancreatic cancer.

Abstract:Objective: To evaluate the surgical resection rates and clinical outcomes in patients with locally advanced pancreatic cancer (LAPC) after neoadjuvant treatment based on FOLFIRINOX regimen (5-fluorouracil, oxaliplatin, irinotecan, and leucovorin). Methods: The clinical studies regarding LAPC undergoing surgical resection after FOLFIRINOX-based treatment were collected by searching several national and international online databases. The retrieval time was from inception of the database to January 2016. Meta-analysis was performed on the enrolled studies by using STATA 12.0 software. Results: Fourteen studies involving 714 LAPC patients were included. Results of Meta-analysis showed that in LAPC patients receiving FOLFIRINOX-based treatment prior to surgical resection, the resection rate was 59% (95% CI=0.46–0.72, P=0.0001) in which the R0 rate was 70.0% (95% CI=0.51–0.88, P=0.001); the median overall survival was 20.63 months (95% CI=16.54–24.73, P=0.001) and median progression-free survival was 13.54 months (95% CI=10.54–16.54, P=0.0001); the incidence of adverse reactions was 8% (95% CI=0.05–0.11, P=0.0001). Conclusion: For LAPC, FOLFIRINOX-based neoadjuvant treatment can increase the resection rates and opportunity of R0 resection,and improve the overall survival of the patients, with low incidence of adverse reactions. So it is recommended as a preferred regimen.

Abstract:Objective: To identify the factors associated with the occurrence of pancreatic fistula after distal pancreatectomy. Methods: The clinical data of 100 patients who underwent distal pancreatectomy from February 2010 to May 2016 were reviewed. The relevant factors were analyzed by univariate and multivariate analyses. Results: Among the 100 patients, postoperative pancreatic fistula occurred in 32 cases (32%), with grade A pancreatic fistula (without clinical impact) in 18 cases (18%), and clinically significant pancreatic fistula in 14 cases (14%), compromising grade B pancreatic fistula in 8 cases and grade C pancreatic fistula in 6 cases. In univariate analysis, the high body mass index (≥25 kg/m2) was significantly associated with the occurrence of overall postoperative pancreatic fistula (χ2=4.128, P=0.042), but not with the occurrence of clinically significant postoperative pancreatic fistula (χ2=1.545, P=0.214), while soft pancreatic texture was significantly associated with the occurrence of both overall and clinically significant postoperative pancreatic fistula (χ2=4.569, P=0.033; χ2=11.374, P=0.001). Multivariate analysis showed that soft pancreatic texture was unique independent risk for the occurrence of overall or clinically significant postoperative pancreatic fistula (OR=2.476, P=0.043; OR=8.012, P=0.003). Conclusion: Pancreatic texture is an important influential factor for the occurrence of postoperative pancreatic fistula, and aggressive control measures should be adopted in those with soft pancreatic texture.

Abstract:Objective: To screen the differentially expressed genes in pancreatic carcinoma versus paired normal adjacent tissue by gene expression profile chip. Methods: The surgical specimens of pancreatic ductal cell carcinoma and adjacent normal pancreatic tissue from 10 patients from January 2014 to June 2016 in the Third Affiliated Hospital of Xinjiang Medical University were collected, and differentially expressed genes between them were screened by an Affymetrix gene expression profile chip containing 49 395 gene probes after total RNA extraction by TRIzol method, and then, GO and pathway analyses were performed. Finally, some differentially expressed genes were verified by real-time PCR. Results: The total RNA of samples passed the test, gene chip assessment yielded high-quality information and results of the test were reliable and highly repeatable; 38 079 genes were examined after denoising process of the chips, involving 512 differentially expressed genes that included 419 up-regulated genes and 93 down-regulated genes; there were 287 differentially expressed genes encoding proteins that were related to the three GO ontologies (biological process, molecular function and cellular component), and 29 signaling pathways were associated with significant differential gene expressions, involving 126 genes. The expressions of differentially expressed genes CPB1, CELA3B, CPA1, POSTN, PLA2G1B, CTRC and SPINK1 determined by real-time PCR were consistent with the results of gene chip analysis. Conclusion: There are a large number of differentially expressed genes between pancreatic ductal cell carcinoma and normal adjacent pancreatic tissue. These genes are mainly associated with biological processes, molecular functions and cellular components, and also involved in the regulation of multiple cellular signaling pathways.

Abstract:

Objective: To investigate the expression and action of long non-coding RNA XIST in pancreatic cancer tissue. Methods: The XIST expressions in specimens of 56 paired pancreatic cancer and adjacent normal pancreatic tissues as well as in normal human pancreatic duct epithelial cells (HPDE) and 7 different pancreatic cancer cell lines (sPC-3, BxPC-3, Capan-1, CFPAC-1, Hs766T, Panc-1 and SW1990) were examined by real-time quantitative PCR. The relations of XIST expression with the clinicopathologic factors of pancreatic cancer patients were analyzed; in pancreatic cancer cells with high XIST expression after interference by XIST siRNA, the viability and proliferation were detected by MTT and BrdU assay, and protein expressions of Ki-67 and PCNA were determined by Western blot analysis. Results: The XIST expression in pancreatic cancer tissue was significantly higher than that in adjacent normal pancreatic tissues (2.452 vs. 0.9729, P<0.001), and high XIST expression was significantly associated with tumor stage (P=0.016) and lymph node metastasis (P=0.032) of the patients. The XIST expression levels in all 7 types of pancreatic cell lines were significantly higher than that in HPDE cells (all P<0.05), in which, XIST expression level was about 2.5-fold higher in SW1990 cells than that in HPDE cells. In SW1990 cells after XIST siRNA interference for 48 h compared with untreated SW1990 cells, the viability (0.812 vs. 1.215) and proliferation ability (0.708 vs. 1.007) were significantly reduced, and protein expressions of Ki-67 ((0.467 vs. 1.027) ) and PCNA (0.600 vs. 0.997) were significantly down-regulated (all P<0.05). Conclusion: XIST expression is increased in pancreatic cancer tissue and its overexpression can promote the growth of pancreatic cancer cells, and the mechanism may be associated with its regulating Ki-67 and PCNA expressions.

Abstract:Objective: To construct a stable pancreatic cancer cell line with high expression of the G-protein signaling modulator 2 (GPSM2), for investigating the relationship between GPSM2 and migration ability of human pancreatic cancer cells. Methods: The plasmids over-expressing GPSM2 gene (pCMV-Tag 3B-GPSM2) were constructed and then were identified. Human pancreatic cancer MIA-PaCa-2 cells were transfected with pCMV-Tag 3B-GPSM2 (GPSM2 transfection group) or empty pCMV-Tag 3B vectors (negative control group), with untreated MIA-PaCa-2 cells as blank control. In each group of cells, the GPSM2 mRNA expressions were measured by RT-PCR, the protein expressions of GPSM2 and β-catenin were determined by Western blot analysis, and the migration abilities were tested by Transwell assay, respectively. Results: The recombinant cell line with stable high GPSM2 expression was successfully constructed. In GPSM2 transfection group compared with blank control group, the GPSM2 mRNA expression was significantly up-regulated, with a 73.3-fold up-regulation, the protein expression levels of GPSM2 and β-catenin were significantly elevated, and the number of migrated cells was significantly increased (all P<0.05). In addition, a positive linear relationship existed between GPSM2 and β-catenin expressions in pancreatic cancer cells (P<0.05). There was no statistical difference in any of the indexes between negative control group and blank control group (all P>0.01). Conclusion: Up-regulating GPSM2 expression in pancreatic cancer cells can increase the migration ability of pancreatic cancer cells, which may be associated with increased β-catenin protein expression.

Abstract:Objective: To investigate the effect of Qingyi II formula on intestinal immune injury secondary to severe acute pancreatitis in rats. Methods: Fifty-six SD rats were randomly divided into sham operation group, SAP model group (SAP group), SAP model plus Qingyi II formula treatment group (Qingyi II group), and SAP model plus positive drug control group (glutamine group), with 8 rats in sham operation group and 24 rats each in the other groups. SAP model was induced by retrograde injected 5% sodium taurocholate into the bile-pancreatic duct. After operation, rats in Qingyi II group and glutamine group were subjected to gavage administration of Qingyi II formula (10 mL/kg, once per 6 h) and glutamine (0.15 g/100 g, once per 6 h) respectively, while those in the other two groups were given the same volume of normal saline instead in the same fashion. The specimen samples, except in sham operation group that were harvested at 6 h after operation, were harvested at 6, 12 and 24 h after operation in all of the other groups, with 8 rats in each time point. Then, the pathological changes in pancreatic and ileal tissues were observed, the serum concentrations of IL-1 and IL-10 were determined by ELISA assay, the HMGB1 mRNA expressions in the ileal tissues were detected by RT-PCR, and the apoptosis of CD3+, CD4+ and CD8+T cell subsets in the Peyer’s patches of the ileum were measured by flow cytometry. Results: Except in sham operation group, obvious and gradually aggravated pathological changes were seen in the pancreatic and ileal tissues in all of the other groups, which were all milder in both treatment groups than those in SAP group at each postoperative time point. Compared with sham operation group, the serum concentrations of IL-1 and IL-10, and HMGB1 mRNA expressions in the ileal tissues were all significantly and increasingly elevated in the remaining groups (all P<0.05), but the increasing amplitudes of IL-1 and IL-10 in both treatment groups were milder than those in SAP group at each postoperative time point (all P<0.05); the apoptosis rates of CD3+, CD4+ and CD8+T lymphocytes in the ileal tissues were all significantly increased in the remaining groups (all P<0.05), which showed an ascending trend in SAP group while a descending trend in either treatment group,and further, the apoptosis rates of these T lymphocytes in either treatment group were significantly lower than those in SAP group at each time point (all P<0.05). The difference in all above parameters showed no statistical significance between the two treatment group at the same time points (all P>0.05). Conclusion: Qingyi II formula can lessen the intestinal immune injury secondary to SAP in rats, and the mechanism may be associated with its down-regulating of HMGB1 expression in the ileum and thereby decreasing the apoptosis of T lymphocytes.

Abstract:Objective: To investigate the reversal effect of neferine (Nef) on oxaliplatin (OXA)-resistance in human colon cancer cells and the mechanism. Methods: Human colon cancer HCT116 cells were cultured in a step-wised exposure to increasing concentrations of OXA (2, 4, 8, 12, 24 and 48 μmol/L) to induce and create the OXA-resistant cell line HCT116/OXA; the cytotoxic effect of Nef on HCT116/OXA cells was evaluated, and its optimal treatment concentration and time were determined; in HCT116/OXA cells after exposure to OXA (IC50 concentration) alone, Nef (optimal treatment concentration) alone or OXA (IC50 concentration) plus Nef (optimal treatment concentration), the proliferation and apoptosis as well as the expressions of apoptosis-associated proteins (Bcl-2, Bax, PARP and p-PARP) were analyzed and compared. Results: The resistance of HCT116/OXA cells to OXA was significantly increased compared with the parent HCT116 cells (IC50: 21.00 μmol/L vs. 112.00 μmol/L, P<0.05), with a resistance index of 5.33. Nef showed significant inhibitory effect on proliferation of HCT116/OXA cells in a concentration-dependent manner (P<0.05), and its optimal treatment concentration and time was 5 μmol/L and 24 h, respectively; compared with lone OXA treatment, the tolerance of HCT116/OXA cells to OXA plus Nef treatment was significantly reduced (IC50: 112.00 μmol/L vs. 45.47 μmol/L, P<0.05), and the reverse index was 2.46. Nef alone exerted no significant effect on apoptosis of HCT116/OXA cells (P>0.05), but the apoptosis inducing effect on HCT116/OXA cells by its combination with OXA was significantly greater than that by OXA alone treatment (P<0.05); compared with Nef or OXA alone treatment, the expression level of anti-apoptotic protein Bcl-2 was significantly decreased, and the expression levels of apoptotic protein Bax and p-PARP were significantly increased in HCT116/OXA cells after OXA plus Nef treatment (all P<0.05). Conclusion: Nef can reverse OXA-resistance in HCT116/OXA cells, and the mechanism may be associated with its regulating Bcl-2/Bax expression, and thereby, producing a synergistic effect with OXA.

Abstract:Objective: To investigate the influence of Tg737 gene overexpression on cell cycle and apoptosis in human hepatocellular carcinoma cell lines and the possible mechanism. Methods: Human hepatocellular carcinoma HepG2 and MHCC97-H cells were transfected with pcDNA3.1-Tg737 plasmid (Tg737 overexpression group) or empty pcDNA3.1 vector (empty vector group) mediated by liposome delivery, or cultured with liposomes alone (liposome group), respectively, with corresponding untreated cells as blank controls. Forty-eight hours later, the cell cycle status and apoptosis were analyzed by flow cytometry, nuclear morphological changes were examined by Hoechst 33342 assay, and the expression levels of cyclin A, Bax and Bcl-2 were detected by Western blot analysis. Results: Compared with corresponding blank controls, in Tg737 overexpression group of either HepG2 or MHCC97-H cells, the number of cells in the S stage and apoptosis rate were significantly increased (all P<0.05), and presented with the typical nuclear morphological changes of apoptosis, with significant upregulation of cyclin A and Bax and downregulation of Bcl-2 (all P<0.05); both HepG2 or MHCC97-H cells in empty vector group or liposome group showed no evident morphological changes of apoptosis, and the difference in all above indexes showed no statistical significance (all P>0.05). Conclusion: Tg737 gene overexpression can inhibit the cell-cycle progression and promote apoptosis of hepatocellular carcinoma cells, and the mechanism may be associated with the participation of Tg737 in regulating the signaling pathways involving cyclin A, Bax and Bcl-2.

Abstract:

Objective: To investigate the factors for Budd-Chiari syndrome (BCS) with complicated portal vein thrombosis (PVT) . Methods: The clinical data of 28 patients diagnosed as BCS with complicated PVT (PVT group) in the First Affiliated Hospital of Zhengzhou University from January in 2010 to December 2015, and 40 patients diagnosed as BCS without PVT (non-PVT group) in the same period by random pick were retrospectively analyzed. The risk factors for BCS with complicated PVT were screened by univariate analysis and unconditional Logistic regression model. The diagnostic efficiency of each risk factor was analyzed by receiver operating characteristic curve (ROC) and the area under ROC curve (AUC), and their optimal cut-off values were also determined. Results: Univariate analysis showed that the velocity of the portal vein blood flow and the hemoglobin level were significantly lower and the D-dimer (DD) level and splenic thickness were significantly higher in PVT group than those in non-PVT group (all P<0.05); the results of unconditional Logistic regression model analysis identified that DD level, velocity of the portal vein blood flow and splenic thickness were independent risk factors for BCS with complicated PVT (OR=31.67, 0.61 and 1.23, all P<0.05). ROC curve demonstrated that the velocity of the portal vein blood flow had no diagnostic value for BCS with complicated PVT (AUC<0.5), while the AUC of DD level and splenic thickness for prediction of BCS with complicated PVT was 0.724 and 0.673 with the optimal cut-off value of 0.283 μg/L and 49.5 mm, respectively. Conclusion: Serum DD level, velocity of the portal vein blood flow, and splenic thickness are independent risk factors for BCS with complicated PVT, and the possibility of PVT is increased especially in BCS patients with DD level higher than 0.283 μg/L or splenic thickness greater than 49.5 mm.

Abstract:Objective: To investigate the indications and the surgical techniques for excision of substernal goiter via cervical approach. Methods: The clinical data and surgical results of 57 patients with substernal goiters undergoing surgical excision through cervical approach from January 2013 to September 2016 were retrospectively analyzed. Results: Of the 57 patients (including 2 cases of ectopic goiters), 22 cases had no obvious clinical symptoms and the other 35 cases presented with compression symptoms such as dyspnea, dysphagia and hoarseness; the lesions were classified according to Randolph’s criteria as type I in 34 cases, type IIA in 16 cases, type IIB in 5 cases and type III in 2 cases, and based on CT classification as grade 1 in 30 cases, grade 2 in 18 cases and grade 3 in 9 cases, respectively. Cervical approach thyroidectomy was performed in all these patients, including repeat thyroid surgery in 6 cases (10.5%). There were benign diseases in 49 patients and differentiated thyroid cancers in 8 patients as evidenced by pathological findings. Postoperative complications included temporary vocal cord paralysis in one case (1.8%) and temporary hypocalcemia in 5 cases (8.8%). Conclusion: The majority of substernal goiters can be safely excised through cervical approach after thorough preoperative assessment. Excellent surgical skills, operation by experienced surgeons and readily accessible thoracotomy set are the premises and critical to surgical success.

Abstract:Objective: To assess the importance of multidisciplinary collaboration mode in diagnosis and treatment of severe acute pancreatitis (SAP). Methods: A multidisciplinary discussion was held for two patients, who died of SAP, the relevant literature was reviewed, and the experiences and lessons from their diagnosis and treatment were summarized. Results: SAP patients should be given organ function support in ICU during the acute stage, and minimally invasive "step-up" approach was recommended for the occurrence of infectious necrosis. Conclusion: Multidisciplinary collaborations can improve the treatment outcomes of SAP.

Abstract:Intraductal papillary mucinous neoplasms (IPMNs) are a rare type of pancreatic cystic tumor, with risk of transforming to pancreatic ductal adenocarcinoma and once it occurs may confer a poor prognosis. Currently, studies on IPMNs are still scarce at home and abroad. Therefore, better understanding the molecular pathological mechanism responsible for IPMNs may have great importance in diagnosis and treatment as well as improving the prognosis of IPMNs. A great amount of oncogenes, tumor suppressor and signaling molecules have been found involving the process of occurrence and development of IPMNs as well as the malignant transformation. In this paper, the authors mainly address the research progress on molecular pathology of IPMNs.

Abstract:Most pancreatic pseudocysts (PPCs) are local complications after acute or chronic pancreatitis or pancreatic trauma, and are collections of leaked pancreatic fluids and enzymes gathering in the adjacent pancreatic space and enclosed by a wall of fibrous and granulation tissue with no epithelium lining. Although the sterile, asymptomatic and small (<6 cm) PPCs usually can be treated conservatively by diet control, nutritional support and medication, surgical treatments are still the main solution. With the development and wide application of the high resolution imaging devices as well as the interventional procedures guided by the former, the diagnostic accuracy of pancreatic pseudocysts has been improved, the treatment methods have evolved from open surgery to diversification strategies, and the treatment efficacy and safety have been raised in recent years. In this paper, the authors address the research progress of PPCs based on recent literature review.

Abstract:Pancreaticobiliary maljunction (PBM) is a rare congenital malformation defined as a union of the pancreatic duct and the bile duct outside the duodenal wall. PBM has become eye-catching due to its frequent association with the occurrence of a variety of biliary and pancreatic diseases. Here, the authors address the progress in terms of classification, pathological and pathophysiological process, as well as early diagnosis and treatment of PBM.

Abstract:Colorectal cancer is one of the common gastrointestinal tumors, for which surgery is the main treatment. However, patients with locally advanced colorectal cancer have lower tolerance to surgery, with high risk for surgery and high possibility of recurrence, and are generally treated by chemotherapy. Preoperative chemoradiotherapy can effectively reduce the tumor size and kill metastatic cells early, thereby providing favorable conditions for further treatment, so it is now widely used in clinical practice. Nevertheless, preoperative chemoradiotherapy is not suitable for all patients with advanced colorectal cancer, and its clinical application should be analyzed individually according to patients’ specific condition, and the sensitivity of the patients to this treatment should be ascertained. Here, the authors address the recent progress in research of application of preoperative chemoradiotherapy in patients with locally advanced rectal cancer and its sensitivity prediction, and discuss the existing problems in the relevant studies in China and abroad as well as new treatment concepts in recent years, so as to provide a reference for its clinical application.