Asparaginyl endopeptidase enhances pancreatic ductal adenocarcinoma cell invasion in an exosome-dependent manner and correlates with poor prognosis.

Pancreatic cancer is one of the most lethal types of cancer; owing to low early detection rates and high metastasis rates, it is associated with an extremely poor prognosis. Therefore, a better understanding of the molecular mechanisms that underlie its metastasis and the identification of potential prognostic biomarkers are urgently required. Although high expression levels of asparaginyl endopeptidase (AEP) have been detected in various types of solid tumor, the expression and functions of AEP in pancreatic carcinomas have yet to be determined. The present study aimed to examine the putative functions of AEP in pancreatic carcinoma. Immunohistochemical analysis revealed that AEP was highly expressed in pancreatic cancer tissues compared with adjacent normal tissues. Patients with high AEP expression exhibited a significantly shorter overall survival time. Results from multivariate Cox regression analysis revealed that AEP was an independent prognostic factor for overall survival. Gain- and loss-of-function experiments demonstrated that knockdown of AEP expression significantly reduced the invasive ability of pancreatic cancer cells, whereas overexpression of AEP increased the invasive ability. In addition, AEP was detected in exosomes that were derived from cultured pancreatic ductal adenocarcinoma cells (PDACs) and in the serum from patients with PDAC. The Matrigel-Transwell invasion assay revealed that exosomes enriched with AEP were able to enhance the invasive ability of PDAC cells, whereas exosomes lacking AEP decreased the invasive ability. Furthermore, results from the present study suggested that AEP may be crucial for activation of the phosphoinositide 3-kinase/RAC­α serine/threonine-protein kinase signaling pathway in PDAC cells. The present study data indicated that high AEP expression may be important for pancreatic carcinoma progression in an exosome-dependent manner, and that AEP may be an independent indicator of poor prognosis in patients with PDAC and may be a novel prognostic biomarker or therapeutic target in pancreatic carcinoma.

Laparoscopic Cholecystectomy in Patients With History of Gastrectomy.

BACKGROUND AND OBJECTIVES: Patients with previous gastrectomy have an increased incidence of gallstones and gallbladder morbidity requiring surgery. We investigated the possible risk factors that contribute to severe gallbladder disease in patients with previous gastrectomy and the role of laparoscopic cholecystectomy (LC) in the treatment of these patients. METHODS: In this retrospective study, we reviewed a database of patients who underwent LC in our hospital during the period January 1, 2010, through May 1, 2015. RESULTS: The average operation time in patients with previous gastrectomy was longer (P < .05), but the operation times of patients with a long interval (>5 years) between gastrectomy and LC showed no statistical difference from those of patients without a history of gastrectomy (P > .05). The conversion rate did not differ between the 2 groups (P > .05), but in patients with previous gastrectomy, the conversion rate was significantly reduced after we adopted a comprehensive preoperative evaluation procedure (P < .05). The frequency of cholecystitis attacks, rate of combination with gallbladder polyps, and rate of combination with pancreatitis were higher and gallstone formation time shorter, in the patients with malignant tumor, those undergoing Billroth II gastroenterostomy or esophagojejunostomy, and those with accompanying diabetes mellitus or hypercholesterolemia (P < .05). CONCLUSION: LC plays an important role in the treatment of benign gallbladder diseases in patients with a history of gastrectomy, and a comprehensive preoperative evaluation and accomplished surgical technique are necessary for successful outcomes. Previously identified clinical features may represent a risk factor for severe cholecystic morbidity in these patients.

Expression and Prognostic Role of FHIT, Fibronectin, and PTEN in Hepatocellular Carcinoma.

BACKGROUND: Fragile histidine triad (FHIT), fibronectin (FN), and phosphatase and tensin homology deleted on chromosome ten (PTEN) are widely reported as having abnormal expression in malignant tumors. The role of FHIT, fibronectin, PTEN expression in patients with hepatocellular carcinoma (HCC) has not been characterized. Our study aims to investigate the expression of FHIT, fibronectin, and PTEN in human HCC and their relationship with clinicopathological features and prognosis of HCC. METHODS: Immunohistochemistry was used to detect expression of FHIT, FN, and PTEN in tumor tissues from 138 HCC patients. The correlation between their expression and clinicopathological features and prognosis were analyzed. RESULTS: FHIT, fibronectin, and PTEN proteins have different expressions between HCC and adjacent nontumor tissue (χ2 = 5.968, 7.380, 4.962; p < 0.05), which are expressed differently in the groups of different tumor stage, grade, tumor size, tumor number, lymph node metastasis, HBV infection, and cirrhosis in the background of nontumor sections (p < 0.05). In the FHIT and fibronectin positive expression group, the cumulative survival times were shorter than those in the negative expression groups (χ2 = 4.443, 9.867; p < 0.05), and in the PTEN positive expression group the cumulative survival times were longer than in the negative expression group (χ2 = 4.199; p < 0.05). CONCLUSIONS: FHIT, fibronectin, and PTEN were abnormally expressed in HCC cells, which have stimulative or suppressive effects on HCC carcinogenesis and progression. FHIT and fibronectin can be used as negative makers for prognosis and PTEN as a positive one.

Optimal cut-off values for CYFRA 21-1 expression in NSCLC patients depend on the presence of benign pulmonary diseases.

BACKGROUND: Serum cytokeratin fragment 21-1 (CYFRA 21-1) expression levels are reported to be useful in the diagnosis of lung cancer, especially non-small cell lung cancer (NSCLC). However, the clinical value of CYFRA 21-1 as a tumor marker remains unclear, and no optimal cut-off value has been determined thus far. The purpose of this study was to establish a potential clinical cut-off value for serum CYFRA 21-1 as a diagnostic marker in patients with NSCLC. METHODS: A total of 90 patients with NSCLC, 237 patients with benign pulmonary disease (BPD), and 1296 healthy controls were enrolled in this study. Among BPD there are 84 with chronic obstructive pulmonary disease (COPD), 81 with pneumonia, 38 with tuberculosis and 34 with chronic bronchitis. CYFRA 21-1 was measured in sera with an electrochemiluminescence (ECL) E170 analyzer. Comparisons were conducted using the chi-squared test and the Mann-Whitney test (two-sided). A receiver operating characteristic (ROC) curve was constructed to investigate the diagnostic power of CYFRA 21-1 expression, and the recommended cut-off value was chosen to calculate its sensitivity and specificity. RESULTS: The cut-off values of CYFRA 21-1 in NSCLC by the ROC curve were 4.70 ng/mL when compared with COPD, which was obviously greater than that found with pneumonia (2.79 ng/mL) (P<0.05), tuberculosis (2.66 ng/mL) (P<0.05), and chronic bronchitis (3.94 ng/mL) (P<0.05) patients. Therefore, a cut-off value of 4.24 ng/mL in NSCLC was suggested. CONCLUSIONS: The presence of various BPDs may be one of the main reasons that no optimal cut-off value for CYFRA 21-1 expression in NSCLC has been determined previously.

Analysis of Possible Clinical Risk Factors Contributing to Postsurgical Gastroparesis Syndrom (PGS) after Subtotal Gastrectomy.

BACKGROUND/AIMS: To investigate the possible clinical risk factors contributing to PGS after subtotal gastrectomy. METHODOLOGY: The clinical data of 422 patients administering subtotal gastrectomy in our hospital were reviewed retrospectively from Jan, 1, 2005 to May, 1, 2012. RESULTS: The higher morbility of PGS were found in the patients whose age were over 65 years, combining with anxiety disorder or diabetes mellitus, with low-albuminemia in perioperative period or having pyloric obstruction in preoperative period, administering Billroth II gastroenterostomy, whose operation time over 4 hours, using patient-controlled analgesia, injecting liquid per day over 3500 ml. CONCLUSION: The clinical factors referred previously maybe the identified risk factors of PGS after subtotal gastrectomy, avoiding these clinical factors in perioperative period would reduce the occurrences of PGS after subtotal gastrectomy.

[Risk factors analysis of postsurgical gastroparesis syndrome and its impact on the survival of gastric cancer after subtotal gastrectomy].

OBJECTIVE: To investigate the risk factors of postsurgical gastroparesis syndrome (PGS) after subtotal gastrectomy in gastric cancer and the impact of PGS on prognosis. METHODS: Clinical data of 422 patients who underwent subtotal gastrectomy for gastric cancer in the Central Hospital of Huzhou Sity from January 2004 to May 2010 were analyzed retrospectively. Risk factors of PGS were indentified and the recurrence-free survival was compared between the patients with and without PGS. RESULTS: PGS occurred in 42 patients (9.5%). Univariate analysis showed that: age over 65, combination of anxiety disorder, low-albuminemia in perioperative period, pyloric obstruction in preoperative period, high serume glucose level (≥ 11.2 mmol/L) in postoperative period, Billroth II (gastroenterostomy, operation time over 4 hours, using patient-controlled analgesia, or intravenous fluid over 3500 ml/d (all P<0.05) were prone to develop PGS. These might be potential clinical risk factors associated to PGS. Correlation analysis showed the number of clinical risk factors was positively correlated with the incidence of PGS (r=0.967, P<0.05). A total of 215 cases (50.9%) were followed up for 3-60 months. The mean recurrence-free survival time of patients with PGS was 26.1 months, which was shorter than that of those without PGS (33.4 months, P=0.029). CONCLUSIONS: Gastric cancer patients with the clinical risk factors mentioned above are prone to develop PGS after subtotal gastrectomy. PGS is associated with poor prognosis.

Efficacy of postoperative antiviral combined transcatheter arterial chemoembolization therapy in prevention of hepatitis B-related hepatocellular carcinoma recurrence.

BACKGROUND: Recurrence of hepatitis B-related hepatocellular carcinoma (HCC) after curative resection is the leading factor influencing the prognosis of the disease. Therefore, further improvement of long-term survival may depend on the prevention and treatment of the recurrent tumor. The aim of this research was to investigate the role of antiviral therapy and postoperative transcatheter arterial chemoembolization (TACE) in the prevention and treatment of hepatitis B-related HCC recurrence. METHODS: One hundred and twenty patients who underwent curative resection of hepatitis B-related HCC between January 2005 and June 2008 at our hospital were enrolled. Patients were divided into four groups according to the post-operative adjuvant therapy they received, i.e., control, antiviral therapy group, TACE group, and combined group. The disease-free survival (DFS) and the 12-, 24-, 36-month cumulative recurrence rates were studied. RESULTS: There was no significant difference between isolated postoperative antiviral therapy group and control in terms of disease-free survival (P = 0.283), while it was significantly higher in the TACE group compared to control (P = 0.019). In all patients, however, viral prophylactic therapy combined with/without TACE brought a favorable result compared to those only with/without TACE (P < 0.001). Similarly, no matter combined with or without antiviral treatment, postoperative TACE prolonged DFS (P = 0.015). Naturally, a combination of viral prophylactic therapy on the baseline TACE significantly benefited patients' postoperative DFS (P = 0.047) and vice verse (P = 0.002). The 24-month cumulative recurrence rates of combined group were significantly lower than that of isolated control group and antiviral therapy (P < 0.001 and P = 0.011 respectively). However, 36-month recurrence rate was significantly different in the control group compared to the TACE group and combined group (P = 0.040 and 0.002 respectively); same as the antiviral group compared to the combined group (P = 0.034). CONCLUSIONS: Post-operative TACE prevents early recurrence while antiviral therapy prevents late recurrence of HCC. Combination of antiviral therapy and TACE are suggested for prevention in HCC patients with high risk of recurrence.

[Effects of combined enteral nutrition support on hemorrheologic parameters and the level of inflammatory factors in rabbits with severe acute pancreatitis].

OBJECTIVE: To explore the effects of combined enteral nutrition (CEN) on the hemorheologic parameters and the changing levels of inflammatory factors in an animal model of severe acute pancreatitis (SAP). METHODS: The experimental animals were divided randomly into 3 groups, i.e. early enteral nutrition (EEN) group, CEN group and parenteral nutrition(PN)group (n = 20 each). Enteral nutrition was administered to the EEN and CEN group animals at 24 h and 72 h post-modeling respectively. The PN group animals were supported by parenteral nutrition all time. Hemorrheologic indices of all experimental animals were examined on Days 1, 3 and 7 post-modeling. And the inflammatory factors were examined on Days 1 and 7. RESULTS: Compared with the EEN and PN groups, some hemorrheologic indices of the CEN group decreased significantly (P < 0.05) on Day 7 post-modeling. They included blood sedimentation, hematocrit (HCT), whole blood high-cut reduction viscosity and whole blood low-cut reduction viscosity. As compared within the CEN group, each hemorrheologic index was lower on Day 7 than that on Day 1 (P < 0.05). Except for whole blood high-cut reduction viscosity and erythrocyte aggregation index in the EEN group after a 7-day nutrition support, there was no significant change for all hemorrheologic indices in the PN group. As to the level of inflammatory factors, the values of interleukin 8 (IL-8) and tumor necrosis factor-α (TNF-α) in the CEN group were lower than those in the PN group on Day 7 post-modeling (P < 0.05). The values of IL-8 and IL-6 in the CEN group were lower than those in the EEN group on the same day (P < 0.05). As compared within the CEN group, the values of IL-6 and TNF-α were lower on Day 7 than those on Day 1 post-modeling (P < 0.05). CONCLUSION: The modulatory mechanism of EN over SAP should be achieved by correcting hemorrheologic index change and lowering the level of inflammatory factors. A proper timing of EN is probably the most optimal nutrition support mode of SAP therapy.

Treatment of abdominal compartment syndrome in severe acute pancreatitis patients with traditional Chinese medicine.

AIM: To investigate the therapeutic effect of traditional Chinese traditional medicines Da Cheng Qi Decoction (Timely-Purging and Yin-Preserving Decoction) and Glauber's salt combined with conservative measures on abdominal compartment syndrome (ACS) in severe acute pancreatitis (SAP) patients. METHODS: Eighty consecutive SAP patients, admitted for routine non-operative conservative treatment, were randomly divided into study group and control group (40 patients in each group). Patients in the study group received Da Cheng Qi Decoction enema for 2 h and external use of Glauber's salt, once a day for 7 d. Patients in the control group received normal saline (NS) enema. Routine non-operative conservative treatments included non-per os nutrition (NPON), gastrointestinal decompression, life support, total parenteral nutrition (TPN), continuous peripancreatic vascular pharmaceutical infusion and drug therapy. Intra-cystic pressure (ICP) of the two groups was measured during treatment. The effectiveness and outcomes of treatment were observed and APACHE II scores were applied in analysis. RESULTS: On days 4 and 5 of treatment, the ICP was lower in the study group than in the control group (P < 0.05). On days 3-5 of treatment, acute physiology and chronic health evaluation II (APACHE II) scores for the study and control groups were significantly different (P < 0.05). Both the effectiveness and outcome of the treatment with Da Cheng Qi Decoction on abdominalgia, burbulence relief time, ascites quantity, cyst formation rate and hospitalization time were quite different between the two groups (P < 0.05). The mortality rate for the two groups had no significant difference. CONCLUSION: Da Cheng Qi Decoction enema and external use of Glauber's salt combined with routine non-operative conservative treatment can decrease the intra-abdominal pressure (IAP) of SAP patients and have preventive and therapeutic effects on abdominal compartment syndrome of SAP.

[Evaluation of lymph node dissection in the central neck area in managing thyroid microcarcinoma].

OBJECTIVE: To evaluate lymph node dissection in the central neck area to treat micro-sized thyroid carcinoma. METHODS: The clinical data of 65 surgically treated thyroid microcarcinoma patients in our hospital were retrospectively reviewed. RESULTS: In this series, the positive metastasis rate of cervical lymph node was 40%. A total of 62 patients had been followed up until the data were reviewed. None was found to be dead nor having distant metastasis. Five patients were re-operated due to countralateral lobe meatstasis 3 years after initial operation, 2 of them had developed para-tracheal lymph node metastasis; another 2 cases underwent functional neck lymph node dissection due to lymph node metastasis on the operated side 2 years later. CONCLUSION: Thyroidectomy with lymph node dissection of the central neck area is more effective than the thyroidectomy alone for managing thyroid microcarcinoma. It can improve the quality of life and survival through reducing cervical lymph node metastasis.