Prognostic value of preoperative enhanced computed tomography as a quantitative imaging biomarker in pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with high mortality and short survival time. Computed tomography (CT) plays an important role in the diagnosis, staging and treatment of pancreatic tumour. Pancreatic cancer generally shows a low enhancement pattern compared with normal pancreatic tissue. AIM: To analyse whether preoperative enhanced CT could be used to predict postoperative overall survival in patients with PDAC. METHODS: Sixty-seven patients with PDAC undergoing pancreatic resection were enrolled retrospectively. All patients underwent preoperative unenhanced and enhanced CT examination, the CT values of which were measured. The ratio of the preoperative CT value increase from the nonenhancement phase to the portal venous phase between pancreatic tumour and normal pancreatic tissue was calculated. The cut-off value of ratios was obtained by the receiver operating characteristic (ROC) curve of the tumour relative enhancement ratio (TRER), according to which patients were divided into low- and high-enhancement groups. Univariate and multivariate analyses were performed using Cox regression based on TRER grouping. Finally, the correlation between TRER and clinicopathological characteristics was analysed. RESULTS: The area under the curve of the ROC curve was 0.768 (P < 0.05), and the cut-off value of the ROC curve was calculated as 0.7. TRER ≤ 0.7 was defined as the low-enhancement group, and TRER > 0.7 was defined as the high-enhancement group. According to the TRER grouping, the Kaplan-Meier survival curve analysis results showed that the median survival (10.0 mo) with TRER ≤ 0.7 was significantly shorter than that (22.0 mo) with TRER > 0.7 (P < 0.05). In the univariate and multivariate analyses, the prognosis of patients with TRER ≤ 0.7 was significantly worse than that of patients with TRER > 0.7 (P < 0.05). Our results demonstrated that patients in the low TRER group were more likely to have higher American Joint Committee on Cancer stage, tumour stage and lymph node stage (all P < 0.05), and TRER was significantly negatively correlated with tumour size (P < 0.05). CONCLUSION: TRER ≤ 0.7 in patients with PDAC may represent a tumour with higher clinical stage and result in a shorter overall survival.

Flurbiprofen axetil for postoperative analgesia in upper abdominal surgery: a randomized, parallel controlled, double-blind, multicenter clinical study.

PURPOSE: To investigate the efficacy and safety of flurbiprofen axetil in postoperative analgesia in upper abdominal surgery. METHODS: This was a multicenter, randomized, positive drug parallel controlled double-blind clinical study. Patients undergoing upper abdominal surgery were randomly divided to receive flurbiprofen axetil or tramadol. The VAS pain scores at rest and on coughing (pulmonary function training) were assessed immediately before drug usage (T1) to evaluate the efficacy of postoperative analgesia. Repeat assessment of the VAS was performed after T1. The timing of the recovery of the gastrointestinal function and the preoperative and postoperative IL-6, cortisol, and blood glucose levels were recorded as secondary endpoints. Vital signs and the occurrence of adverse reactions were evaluated for the assessment of safety. RESULTS: A total of 240 patients were enrolled in the current study; 119 used flurbiprofen axetil for postoperative analgesia. The VAS scores at rest and on coughing did not differ between the two groups to a statistically significant extent (P > 0.05). However, the reduction of the VAS score at rest in the flurbiprofen axetil group was greater than that in the tramadol group at 4-24 h after T1. The reduction of the VAS score on coughing at 8 h after T1 was greater in the flurbiprofen axetil group. The incidence of adverse reactions was significantly lower in the flurbiprofen axetil group, with only one adverse reaction recorded. In contrast, 18 adverse reactions were reported in the tramadol group. CONCLUSION: Flurbiprofen axetil showed superior efficacy to tramadol in early postoperative analgesia after upper abdominal surgery. Flurbiprofen axetil was associated with a significantly lower incidence of adverse reactions in comparison to tramadol.

A novel biopolymer device fabricated by 3D printing for simplifying procedures of pancreaticojejunostomy.

The purpose of our research was to verify the feasibility and effectiveness of a novel three-dimensional printed biopolymer device (3DP-BPD) for duct-to-mucosa pancreaticojejunostomy (PJ) in minipigs. Polylactic acid (PLA) was selected as the raw materials for 3DP-BPD. Three components of a 3DP-BPD were designed and manufactured: hollow stent, supporting disk, and nut. A pancreatic duct dilation model was developed in six minipigs. After 4 weeks, minipigs underwent operations with duct-to-mucosa PJ using 3DP-BPD. The operation time and postoperative complications were analyzed. The anastomotic sites were evaluated grossly 4 weeks and 24 weeks after PJ, and the histological evaluation of anastomotic sites was performed 24 weeks after PJ. The operation time of six stitches duct-to-mucosa PJ was 9.1 ±â€¯1.7 min. All minipigs survived without any adverse events like postoperative pancreatic fistula (POPF). Serum C reactive protein (CRP) and procalcitonin (PCT) levels were normal, and the anastomotic sites were connected tightly on gross observation and touch at 4 weeks and 24 weeks. Histological examinations indicated that the tissues were continuous between the pancreas and the jejunum. The use of 3DP-BPD did not increase the risk of severe local inflammation and POPF. 3DP-BPD used for duct-to-mucosa PJ is more convenient and clinically feasible for pancreatoenteric reconstruction.

Bone marrow-derived mesenchymal stem cells alleviates renal injury in severe acute pancreatitis via RhoA/Rho kinase.

Acute pancreatitis (AP) is a common acute abdominal disease, 10%-20% of which can evolve into severe acute pancreatitis (SAP). SAP causes significant morbidity and mortality. RhoA/Rho kinase is activated in SAP. Bone marrow-derived mesenchymal stem cells (BMSCs) have been demonstrated to be a therapeutic role in SAP, but the underlying molecular mechanism is still unclear. This study was designed to determine whether RhoA/Rho kinase involved in APS, and the specific mechanism of BMSCs in APS. We validated that BMSCs could promote renal repair, reduce the ratio of wet to dry kidney weight, renal EB concentration, pancreatic edema and serum amylase, Cr, BUN and systemic TNF-α, IL-6 levels. BMSCs also reduce ROCK I and increase ZO-1 protein levels in APS, but the effects are inhibited by RhoA/Rho promoter CNF1. These results indicated that BMSCs can alleviate SAP rat kidney injury by inhibiting the RhoA/Rho kinase signaling pathways, increase the ZO-1 expression, reduce capillary permeability, blood capillary leakage and improve renal function.

The influence of functional polymorphisms in matrix metalloproteinase 9 on survival of breast cancer patients in a Chinese population.

Matrix metalloproteinase 9 (MMP9) plays a critical role in cancer aggression, and its overexpression is associated with a poor prognosis in breast cancer. Because common genetic variants can alter the expression or function of MMPs, we hypothesized that potentially functional single-nucleotide polymorphisms (SNPs) in the MMP9 gene may be associated with the survival of patients with invasive breast cancer. In this case-cohort follow-up study, a total of 245 breast cancer patients in southeast China were investigated, and five haplotype tagging SNPs (htSNPs) in the MMP9 gene were genotyped by using matrix-assisted laser desorption/ionization mass spectrometry and polymerase chain reaction-restriction fragment length polymorphism methods. Disease-free survival (DFS) and distance disease-free survival (DDFS) analyses were used to identify the SNPs associated with prognosis and determine their interdependence with the recognized prognostic factors. We found that the MMP9 rs3787268 GA+AA genotypes were significantly associated with poor DFS and DDFS of patients with breast cancer (log-rank p-values 0.045 and 0.028, respectively), especially in some subgroups of patients. Multivariate Cox regression and stepwise COX regression analyses suggested that rs3787268 may be a candidate independent biomarker to predict breast cancer survival in this population. Further, among estrogen receptor (ER)+/epidermal growth receptor 2 (HER-2)- patients, the rs3787268 GA+AA genotypes and rs17577 GG genotype showed a locus-dosage effect between combined the genotypes and decreased survival (adjusted HR 2.59, 95% confidence interval [CI] 1.29-5.19 and adjusted HR 3.25, 95% CI 1.39-7.58, respectively, for DFS and DDFS). Our results suggest that the polymorphisms in the MMP9 gene may be genetic modifiers for breast cancer prognosis in this Chinese population.

[Effects of cucurmosin on the cell proliferation and apoptosis in human pancreatic PANC-1 cells].

OBJECTIVE: To observe the effects of cucurmosin (CUS) on the cell proliferation and apoptosis in pancreatic PANC-1 cells. METHODS: The inhibition of CUS on the PANC-1 cell growth was observed using MTT assay. The inhibition ratio of CUS on the pancreatic orthotopic transplantation was in vivo observed in the NOD/SCID mouse model. The changes of microstructure of the apoptosis-inducing effect of CUS on PANC-1 was observed under electron microscope. The cell cycle and apoptosis after CUS intervention was detected using flow cytometry. The Caspase-3 activity after CUS treatment was detected using enzyme linked immunospecific assay (ELISA). RESULTS: Treatment with CUS at the dose of 0.125, 0.25, and 0.5 mg/kg inhibited the growth of pancreatic carcinoma PANC-1 xenografs with the ratio of 45.2%, 50.0%, and 59.7%, respectively (P < 0.05). After exposure to 10 microg/mL CUS for 24 h, most cells presented typical morphologic changes of apoptosis such as chromatin condensation and shrunken nucleus. The apoptotic cells increased. Some nuclear shrinkage and fragmentation, as well as the apoptotic body were observed when cells were exposed to CUS for 72 h. Being exposed to 0, 2.5, 10.0, and 40.0 microg/mL of the CUS for 72 h, the percentage of G0/G1 phase cells was 46.56% +/- 5.08%, 53.33% +/- 5.05%, 67.50% +/- 6.50%, and 77.00% +/- 6.73%, respectively (P < 0.05). The apoptosis ratio was 2.50% +/- 0.13%, 8.30% +/- 1.23%, 23.40% +/- 2.45%, and 48.50% +/- 3.65% shown by Annexin V/PI (P < 0.05). The Caspase-3 activity (unit) was 0.009 +/- 0.002, 0.011 +/- 0.003, 0.035 +/- 0.009, and 0.065 +/- 0.009, respectively (P < 0.05). These data showed that CUS induced the apoptosis of PANC-1 cells in a dose-dependent maner. Being exposed to 40.0 microg/mL of the CUS for 24, 48, and 72 h, the percentage of G0/ G1 phase cells was 56.60% +/- 6.65%, 67.83% +/- 6.76%, and 77.00% +/- 6.73%, respectively (P < 0.05), the apoptosis ratio was 16.51% +/- 2.97%, 38.51% +/- 2.38%, and 48.50% +/- 3.65% shown by Annexin V/PI (P < 0.05). These data showed that CUS induced apoptosis of PANC-1 cells in the G0/G1 phase of the cell cycle in a time-dependent maner. CONCLUSION: CUS significantly inhibited the growth of PANC-1 cells possibly through the G0/G1 cell cycle arrest and apoptosis.

Adjuvant imatinib treatment after R0 resection for patients with high-risk gastrointestinal stromal tumors: a median follow-up of 44 months.

BACKGROUND: The optimal duration of Imatinib adjuvant treatment for patients with high-risk gastrointestinal stromal tumors (GISTs) is uncertain. PATIENTS AND METHODS: A total of 90 patients with high-risk GISTs after curative resection were recruited into this non-randomized case-control study, including 35 having Imatinib adjuvant therapy and 55 having follow-up alone. The recurrence-free survival (RFS) was compared. RESULTS: After a median follow-up of 44.0 months, a significantly reduced recurrence rate was observed in the treatment group than the control group (17.1% vs. 78.2%, P = 0.000). One-year, 2-year, and 3-year RFS rates were 100% vs. 70.9%, 88.0% vs. 37.8%, and 88.0% vs. 27.5%, respectively; with a significant advantage for Imatinib adjuvant therapy versus the surgery only (P = 0.000, HR 0.122, 95% CI 0.041-0.363). Continuation Imatinib treatment further improved RFS by comparison with the interruption treatment (both 2-year and 3-year RFS were 95.8% vs. 63.6%, P = 0.011, HR 0.103, 95% CI 0.012-0.883). There were no serious adverse events in the adjuvant therapy group. CONCLUSIONS: Imatinib Adjuvant therapy could significantly prolong the RFS of patients with high-risk GISTs. Extended Imatinib adjuvant treatment strategy may further reduce the risk of relapse with a low drug resistance rate and toxicity profile.

Outcome of palliative total gastrectomy for stage IV proximal gastric cancer.

BACKGROUND: A few studies have investigated the outcome of palliative total gastrectomy (PTG) in stage IV proximal gastric cancer. In this study, we tried to summarize the outcome of PTG in stage IV proximal gastric cancer. METHODS: Between January 1991 and January 2005, complete clinical data of 197 patients with stage IV proximal gastric cancer undergoing PTG, 642 patients undergoing curative total gastrectomy (CTG), 152 nonsurgical patients, 102 patients undergoing explorative laparotomy, and 78 patients undergoing jejunostomy were enrolled in this study. Survival rates, median survival, complication rates, and mortality were analyzed. RESULTS: The 1-year, 3-year, and 5-year survival rates were 61.3%, 8.9%, and 6.4% in the PTG group, respectively, and 92.3%, 58.5%, and 48.9% in the CTG group, respectively (P < .05). The median survival periods in the PTG, no surgery, laparotomy, and jejunostomy groups were 16.4, 5.5, 4.7, and 5.8 months, respectively. The median survival in the PTG group was significantly longer than that in the other 3 groups (P < .05). The postoperative complication rate and mortality rate were, respectively, 24.3% and 3.0% in the PTG group and 13.5% and 2.3% in the CTG group (P > .05). CONCLUSIONS: PTG for stage IV proximal gastric cancer when compared with no surgery, laparotomy, and jejunostomy is associated with prolonged survival time and improved quality of life. However, despite the feasibility and safety of PTG, patients with stage IV proximal gastric cancer who are suitable for this treatment should be selected, and thoughtful preparation should be made in the perioperative period.

[The study of the relationship between interleukin gene polymorphism and the morbidity of patients with acute pancreatitis].

OBJECTIVE: To explore interleukin-1 beta (IL-1 beta) and IL-6 gene polymorphism, and investigate the relationship between their gene polymorphism and the morbid state of patients with acute pancreatitis (AP). METHODS: The polymorphism of IL-1 beta gene 511C/T and IL-6 gene 634C/G site was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in patients (74 patients) with AP, including mild acute pancreatitis (MAP, 36 patients) and severe acute pancreatitis (SAP, 38 patients), and also a group of normal control (78 patients). The plasma concentrations of IL-1 beta and IL-6 were measured by enzyme linked immunosorbent assay (ELISA). The patients with SAP were divided into groups on the basis of different genotypes, and the clinical data were compared among different groups. RESULTS: The plasma levels of IL-1 beta and IL-6 in patients with AP were significantly higher than normal control group [IL-1 beta: (13.16+/-2.82) ng/L vs. (6.21+/-1.57) ng/L; IL-6: (84.86+/-32.92) ng/L vs. (9.95+/-2.49) ng/L, both P<0.05]. There was no statistical significance between IL-1 beta gene 511 site and IL-6 gene 634 site genotype or allele frequency between the patients with AP and the normal control. In patients with SAP, IL-1 beta gene 511 site T/T genotype and T allele frequency were significantly higher than that of MAP group (both P<0.05). There was no statistically significant difference in plasma levels of IL-1 beta between C/C group and C/T+T/T group, and the plasma levels of IL-6 in patients with IL-6 gene 634 site C/G were significantly higher than C/C group [(97.23+/-35.49) ng/L vs. (72.14+/-24.55) ng/L, P<0.05]. In patients with SAP, the scores of clinical evaluation in IL-1 beta gene 511 site C/T+T/T group and IL-6 gene 634 site C/G group were significantly higher than that in IL-1 beta gene 511 site C/C group and IL-6 gene 634 site C/C group (all P<0.05). CONCLUSION: IL-1 beta gene 511 site C/T and IL-6 gene 634 site C/G polymorphism may be genetic susceptibility factors for exacerbation of AP.

[Observation of the short term therapeutic effectiveness of body gamma-knife in 48 patients with advanced pancreatic carcinoma].

OBJECTIVE: To investigate the short-term therapeutic effectiveness of body gamma-knife in patients with advanced pancreatic carcinoma. METHODS: Forty-eight patients with advanced pancreatic carcinoma were treated by body gamma-knife therapy. The dosage distribution and other radiotherapeutic plans were established on the basis of the carcinoma position, clinical target volume, and patient health condition. The isodose curve was 50%-60% and covered about 95% of the target volume. The single dose was 350-450cGy. The radiation was performed once every one or two days for 10-12 times. RESULTS: There were 33 patients with back pain. 63.6% of the patients got completely controlled, 30.3% pain remitted, and 6.1% ineffective after 2 to 18 months of therapy. The analgesic effective rate was 93.9%. Among 28 patients with obstructive jaundice, 21 patients (75.0%) recovered. Among 42 patients who received CT, tumor disappeared in 5 patients (11.9%), tumor size decreased in 30 patients (71.4%), remained unchanged in 5 patients (11.9%), and enlarged in 2 patients (4.8%). The 6-month, 12-month, and 18-month overall survival rates were 77.1%, 37.5%, and 10.4%, respectively. The whole process was tolerable for all patients and no severe side-effect was observed. CONCLUSIONS: Body gamma-knife can achieve a high local control rate and survival rate. Its short-term therapeutic effectiveness is satisfactory. Body gamma-knife is a safe and reliable treatment option for patients with locally advanced pancreatic carcinoma.