Background Pancreatic cancer is a common malignant tumor of the digestive system.It is the fourth major cause of tumor-related death and its morbidity is increasing,and hence it is imperative to develop effective forms of therapy for pancreatic cancer.Peptide tyrosine-tyrosine (PYY) is an important gastrointestinal peptide hormone.According to previous literatures,PYY has been shown to inhibit tumor proliferation in cellular and animal models,but there has been limited research on the detailed mechanism of PYY in pancreatic cancer.This study was to observe the effects of PYY on pancreatic cancer cell and investigate the possible mechanism.Methods The expression of Y1,Y2,and Y5 receptors on pancreatic cancer cell lines were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR).The cytotoxicity of PYY toward the MiaPaCa-2 cell was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; the cell morphology and structure changes were observed under inverted microscope and transmission electron microscope respectively.Apoptosis and cell cycle were evaluated by flow cytometry.The activity of caspase-3 was determined by activity assay kits and Western blotting.The expression of survivin,vascular endothelial growth factor (VEGF),and cyclooxygenase-2 (COX-2) were determined by RT-qPCR and Western blotting.Results Expression of Y2 receptor is the most abundant PYY receptor on pancreatic cancer cell.PYY inhibited MiaPaCa-2 cell proliferation,blocked it in G0/G1 phase,increased the proportion of apoptosis cells and caspase-3 activity,and reduced the expression of survivin,VEGF,and COX-2.Conclusions PYY weakened the ability of the pancreatic MiaPaCa-2 cell viability through cell cycle blocking and apoptosis inducing.The inhibition effect of PYY may be mediated by the Y2 receptor.The increased caspase-3 activity and reduced expression of survivin,VEGF,and COX-2 may serve as a novel mechanism in PYY inhibition effect on MiaPaCa-2 cell.

Background Accumulating evidence indicates that systemic inflammation response is associated with the prognosis of various cancers.The aim of this study was to investigate the neutrophil-lymphocyte ratio (NLR),which is one of the systemic inflammation markers,in the prognosis of hepatocellular carcinoma (HCC) after treatment of transcatheter arterial chemoembolization (TACE).Methods The clinical data of 178 HCC patients who received TACE were retrospectively analyzed.The optimal NLR cutoff was determined according to the receiver operating characteristic (ROC) analysis.All patients were divided into NLR-normal group and NLR-elevated group according to the cutoff,and the clinical features of these two groups were comparatively analyzed.Meanwhile,the overall survival and disease free survival (DFS) were analyzed using the KaplanMeier method.The risk factors of postoperative survival were investigated using univariate and multivariate Cox regression analyses.Results The optimal NLR cutoff was defined at 1.85 and 42 (23.6％) patients had an elevated NLR (NLR＞1.85).The median survival time was 9.5 months (range 1-99 months).The clinical data between the two groups were comparable,except for α-fetoprotein.Follow-up results showed that the median survival of patients with normal NLR was 17.5 months (range:1-99 months) compared with 8 months (range:8-68 months) of patients with elevated NLR.The 1,3 and 5-year overall survival of patients in the NLR-normal group and NLR-elevated group were 57.3％,44.1％,and 27.2％ and 42.1％,19.6％,and 9.5％ respectively (x2=194.2,P ＜0.001).Similarly,the disease free survival also has a significant difference (x2=39.3,P ＜0.001).Multivariate Cox regression analysis showed that a high NLR was an independent factor affecting the survival rate of HCC after TACE (P=0.04).Conclusion Preoperative NLR was an important prognostic factor to predict the prognosis of patients with intermediate HCC treated with TACE.

Acute severe cholangitis is a serious disease with fast development and high mortality. The therapeutic options are stills limited. Once diagnosed, the key step of treatment is to timely reduce the high pressure of bile duct caused by biliary obstruction, and to block bacteria and toxins from entering the blood, which might trigger inflammation " cascade reaction" . The policy of " relieve obstruction, remove lesions, and bile duct drainage" raised by academician Huang Zhiqiang, is still the criterion for acute cholangitis treatment. Active biliary drainage, early continuous renal replacement therapy, and simultaneous antibacterial therapy and multi-organ function support can significantly improve the disease outcome and reduce mortality.

Objective: To summarize the diagnosis and treatment of biliary pancreatic duct dilatation. Methods: The retrospective and descriptive study was conducted. The clinical data of 22 patients with biliary pancreatic duct dilatation who were admitted to Renji Hospital of Shanghai Jiaotong University School of Medicine between October 2013 to September 2017 were collected. There were 6 males and 16 females, aged from 33 to 82 years, with an average age of 66 years. Surgical exploration was decided according to clinical symptoms, results of laboratory test and imaging examinations. For patients with space occupying lesions, surgical procedure was selected based on results of pathological examination. Patients without surgical exploration or space occupying lesions were allocated into follow-up. Observation indicators: (1) surgical exploration; (2) relationship of clinical symptoms and preoperative examinations with surgical exploration positive for space occupying lesions; (3) surgical treatment; (4) follow-up. Follow-up using outpatient examination was performed on patients up to October 2018. Follow-up was performed on patients with positive surgical exploration to detect postoperative complications.For patients with positive results of imaging examinations, no jaundice, normal laboratory indicators or mild abnormality, liver function, tumor markers and B-ultrasound were re-examined each month, and computed tomography (CT) and magnetic resonance imaging (MRI) was performed once every 3 months. Surgical exploration was performed when total bilirubin (TBil) or tumor markers showed a progressive increase. Follow-up was performed on patients with negative results of imaging examination, jaundice, and mildly elevated CA19-9. TBil and CA19-9 were re-examined monthly, and if they were progressively elevated, patients were transferred to surgical exploration. For patients with negative results of imaging examination, no symptoms, and negative laboratory test, liver function, tumor markers, and B-ultrasound were re-examined once every 3 months, and enhanced CT and MRI were re-examined once every 6 months within one year. Follow-up was performed once every 6 months during the second year, and once a year after two years. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using the t test. Count data were descibed as absolute numbers, and they were analyzed using the chi-square test under R×C chart or Fisher exact probability. Results: (1) Surgical exploration: of 22 patients, 11 underwent surgical exploration, and 11 underwent follow-up. Of the 11 patients with surgical exploration, 4 were positive for space occupying lesions including 1 of false negative, and 7 were negative for space occupying lesions. (2) Relationship of clinical symptoms and preoperative examinations with surgical exploration positive for space occupying lesions. ① Relationship of clinical symptoms and laboratory test with surgical exploration positive for space occupying lesions: juandice was significantly associated with surgical exploration positive for space occupying lesions (P<0.05), and elevated TBil and DBil were significantly associated with surgical exploration positive for space occupying lesions (χ²=0, 0, P<0.05), with a sensitivity of 75.0% and specificity of 100.0%. ② Relationship between imaging examination and surgical exploration positive for space occupying lesions: results of CT, MRI, endoscopic retrograde cholangio-pancreatography, endoscopic ultrasonography, PET-CT, and combined imaging examinations had no significant association with surgical exploration positive for space occupying lesions (χ²=0, 0.77, 0, 0, 1.00, 0, 0, 0, 0, P>0.05). PET-CT had no significant association with surgical exploration positive for space occupying lesions (P>0.05). ③ Relationship of imaging examination and laboratory test with surgical exploration positive for space occupying lesions: positive imaging examination combined with elevated TBil and CA19-9 was significantly associated with surgical exploration positive for space occupying lesions (P<0.05), with a sensitivity of 50.0% and specificity of 100.0%. ④ Relationship of preoperative diameters of biliary ducts and pancreatic ducts with surgical exploration positive for space occupying lesions: of 22 patients, the diameters of biliary ducts and pancreatic ducts were (13.8±4.3)mm and (4.6±1.5)mm for patients with positive surgical exploration, (13.0±2.8)mm and (3.5±0.5)mm for patients with negative surgical exploration, (11.6±2.4)mm and (3.2±0.4)mm for patients with follow-up, respectively, showing no significant difference between them (t=0.22, 0.36, P>0.05). (3) Surgical treatment: 9 of 11 patients with surgical exploration followed the standard procedure. Of the 9 patients, 4 were found space-occupying lesions at the choledocho-pancreatico-duodenal junction (3 undergoing pancreaticoduodenectomy and 1 undergoing duodenal papilla partial resection), 5 with negative exploration underwent common bile duct incision and T-tube drainage (one patient was unable to pinch the T-tube one month after operation and detected obstruction at the lower end of the bile duct by radiography, and was confirmed pancreatic head cancer by reoperation 3 months after the first operation). Two patients didn′t follow the exploratory procedure, and underwent the child operation only based on the preoperative imaging findings, without intraoperative pathological examination. Postoperative pathological examination showed chronic ampulla and chronic pancreatitis, respectively. (4) Follow-up: 22 patients were followed up for 12-60 months, with a median follow-up time of 36 months. Two of 11 patients with surgical exploration had postoperative gastroplegia, 1 had bile leakage, 1 had incisional infection, and they were improved after symptomatic treatment. Four patients undergoing surgeries for positive exploration had no recurrence during follow-up. Of 5 patients with negative exploration undergoing common bile duct incision and T-tube drainage, 1 was confirmed pancreatic head cancer and underwent pancreaticoduodenectomy, 4 were removed T-tube after by T-tube cholangiography at 2 months after surgery. During the follow-up, no positive signs showed in laboratory test or imaging examination. No recurrence occurred in the two patients undergoing pancreaticoduodenectomy. Of 11 patients with follow-up, 10 had abdominal pain before surgery, including 3 with pain during follow-up and 7 with symptoms disappeared. There was no abnormalities in the laboratory test. Conclusions The positive imaging examinations combined with jaundice and elevated CA19-9 is an absolute indication for surgical exploration in patients with biliary duct dilatation. Those patients who do not meet this criteria should be distributed into the follow-up. If no positive pathological results were obtained during the operation, the surgery should be terminated and the patients should be transferred into follow-up. The reckless biliary anastomosis or biliary stents placement is opposed.

Objective To investigate the application value of hepatectomy using Glissonean pedicle transection for hepatocellular carcinoma (HCC). Methods Clinical data of 54 patients with HCC undergoing radical hepatectomy in the First Affiliated Hospital of Medical College, Xi’an Jiaotong University from January 2002 to December 2012 were analyzed retrospectively. According to different surgical procedure, the patients were divided into hepatectomy with Glissonean pedicle transection group (Glisson group) and hepatectomy with Pringle maneuver (Pringle group) with 27 cases in each group. The informed consents of all patients were obtained and the ethical committee approval was received. In Glisson group, hepatectomy was performed after Glissonean pedicles were dissected and occluded. In Pringle group, hepatectomy was performed after the ifrst porta was occluded using Pringle maneuver. The intraoperative situation, the variation of liver function and incidence of complications after operation of two groups were observed. The patients received follow-up after operation and survival analysis was conducted. The comparison of measurement data between two groups was conducted using t test, the comparison of rates using Chi-square test or Fisher's exact probability test, and the survival analysis using Kaplan-Meier method and Log-rank test. Results The mean of intraoperative blood loss in Glisson group [(135±57) ml] was signiifcantly less than that in Pringle group[(248±87) ml] (t=-5.62, P<0.05). The total bilirubin (TB) level 1 d after operation in Glisson group [(23±5) μmol/L] was significantly lower than that in Pringle group [(34±5) μmol/L] (t=-8.08, P<0.05). In Glisson group, postoperative hemorrhage was observed in 2 cases and infection in 2 cases. In Pringle group, postoperative hemorrhage was observed in 3 cases, infection in 1 case, and bile leakage in 1 case. No signiifcant difference was observed in the incidence of postoperative complications between two groups (P>0.05). The 1-, 3-, 5-year cumulative survival rates were 89%, 50%, 39%in Glisson group and were 82%, 55%, 41%in Pringle group. The 1-, 3-, 5-year disease-free survival rates were 89%, 43%, 34%in Glisson group and were 82%, 47%, 41%in Pringle group. No signiifcant difference was observed in the cumulative survival rates and disease free survival rates between two groups (χ2=0.001, 0.011; P>0.05). Conclusion Hepatectomy using Glissonean pedicle transection is a safe, effective, and feasible surgical procedure for HCC with advantages of less blood loss, milder liver damage.

ObjectiveTo investigate the association between tumor size and prognosis of patients with hepatocellular carcinoma (HCC) after hepatectomy.MethodsClinical data of 172 patients undergoing radical hepatectomy and diagnosed as HCC by pathological examination in the First Afifliated Hospital of Xi'an Jiaotong University between December 2002 and December 2011 were retrospectively studied. The informed consents of all patients were obtained and the local ethical committee approval had been received. Among the 172 patients, 139 were males and 33 were females; 98 were with age≤55 years old and 74 were with age >55 years old. The receiver operating characteristic (ROC) curve of the relationship between postoperative survival time and tumor size was drawn, and the cut-off value for tumor size was determined at 5.75 cm. According to the best cut-off value, the patients were divided into the small HCC group (tumor size < 5.75 cm,n=85) and huge HCC group (tumor size≥5.75 cm,n=87). The relationship between tumor size and clinicopathologic parameters was analyzed, and the median survival time, cumulative survival rate and disease free survival rate of two groups were compared. The clinicopathologic parameters were included as the factors inlfuencing the survival and prognosis of patients, and independent risk factor analysis was performed. The relationship between tumor size and clinicopathologic parameters was analyzed using Chi-square test. Kaplan-Meier method and Log-rank test were used for survival and prognosis analysis. Cox proportional hazard model was used for univariate analysis and multivariate analysis.ResultsTumor size was associated with the preoperative AFP, number of tumors and TNM staging (χ2=13.272, 9.378, 7.311;P<0.05). The median survival time and the median recurrence time for the huge HCC group were 24 months and 9 months respectively and were 39 months and 37 months for the small HCC group. The 1-, 3-, 5-year cumulative survival rate for the huge HCC group were 65.5%, 36.0%, 22.9% respectively and were 89.5%, 76.3%, 72.5% respectively for the small HCC group. The overall survival of the huge HCC group was lower than that of small HCC group (χ2=33.644,P<0.05). The 1-, 3-, 5-year disease free survival rate for the huge HCC group were 44.7%, 25.5%, 21.9% respectively and were 84.8%, 67.8%, 66.3% respectively for the small HCC group. The disease free survival rate of huge HCC group was lower than that of small HCC group (χ2=38.908,P<0.05). Preoperative platelets count (Plt)≥155×109/L, tumor size > 5.75 cm and advanced stage of TNM were the independent risk factors inlfuencing the postoperative prognosis of HCC patients (HR=1.588, 3.066, 2.029;P<0.05).ConclusionsTumor size is the independent risk factor inlfuencing the prognosis of HCC patients after hepatectomy. The prognosis of patients with tumor size > 5.75 cm is poor.

BACKGROUNDPancreatic cancer is a common malignant tumor of the digestive system. It is the fourth major cause of tumor-related death and its morbidity is increasing, and hence it is imperative to develop effective forms of therapy for pancreatic cancer. Peptide tyrosine-tyrosine (PYY) is an important gastrointestinal peptide hormone. According to previous literatures, PYY has been shown to inhibit tumor proliferation in cellular and animal models, but there has been limited research on the detailed mechanism of PYY in pancreatic cancer. This study was to observe the effects of PYY on pancreatic cancer cell and investigate the possible mechanism.

METHODSThe expression of Y1, Y2, and Y5 receptors on pancreatic cancer cell lines were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The cytotoxicity of PYY toward the MiaPaCa-2 cell was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; the cell morphology and structure changes were observed under inverted microscope and transmission electron microscope respectively. Apoptosis and cell cycle were evaluated by flow cytometry. The activity of caspase-3 was determined by activity assay kits and Western blotting. The expression of survivin, vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) were determined by RT-qPCR and Western blotting.

RESULTSExpression of Y2 receptor is the most abundant PYY receptor on pancreatic cancer cell. PYY inhibited MiaPaCa-2 cell proliferation, blocked it in G0/G1 phase, increased the proportion of apoptosis cells and caspase-3 activity, and reduced the expression of survivin, VEGF, and COX-2.

CONCLUSIONSPYY weakened the ability of the pancreatic MiaPaCa-2 cell viability through cell cycle blocking and apoptosis inducing. The inhibition effect of PYY may be mediated by the Y2 receptor. The increased caspase-3 activity and reduced expression of survivin, VEGF, and COX-2 may serve as a novel mechanism in PYY inhibition effect on MiaPaCa-2 cell.

Blotting, Western ; Caspase 3 ; genetics ; metabolism ; Cell Cycle ; drug effects ; genetics ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclooxygenase 2 ; genetics ; metabolism ; Dipeptides ; pharmacology ; Humans ; Inhibitor of Apoptosis Proteins ; genetics ; metabolism ; Pancreatic Neoplasms ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

BACKGROUNDAccumulating evidence indicates that systemic inflammation response is associated with the prognosis of various cancers. The aim of this study was to investigate the neutrophil-lymphocyte ratio (NLR), which is one of the systemic inflammation markers, in the prognosis of hepatocellular carcinoma (HCC) after treatment of transcatheter arterial chemoembolization (TACE).

METHODSThe clinical data of 178 HCC patients who received TACE were retrospectively analyzed. The optimal NLR cutoff was determined according to the receiver operating characteristic (ROC) analysis. All patients were divided into NLR-normal group and NLR-elevated group according to the cutoff, and the clinical features of these two groups were comparatively analyzed. Meanwhile, the overall survival and disease free survival (DFS) were analyzed using the Kaplan-Meier method. The risk factors of postoperative survival were investigated using univariate and multivariate Cox regression analyses.

RESULTSThe optimal NLR cutoff was defined at 1.85 and 42 (23.6%) patients had an elevated NLR (NLR>1.85). The median survival time was 9.5 months (range 1-99 months). The clinical data between the two groups were comparable, except for a-fetoprotein. Follow-up results showed that the median survival of patients with normal NLR was 17.5 months (range: 1-99 months) compared with 8 months (range: 8-68 months) of patients with elevated NLR. The 1, 3 and 5-year overall survival of patients in the NLR-normal group and NLR-elevated group were 57.3%, 44.1%, and 27.2% and 42.1%, 19.6%, and 9.5% respectively (χ(2) = 194.2, P < 0.001). Similarly, the disease free survival also has a significant difference (χ(2) = 39.3, P < 0.001). Multivariate Cox regression analysis showed that a high NLR was an independent factor affecting the survival rate of HCC after TACE (P = 0.04).

CONCLUSIONPreoperative NLR was an important prognostic factor to predict the prognosis of patients with intermediate HCC treated with TACE.

Adult ; Aged ; Carcinoma, Hepatocellular ; pathology ; therapy ; Chemoembolization, Therapeutic ; Female ; Humans ; Liver Neoplasms ; pathology ; therapy ; Lymphocytes ; metabolism ; physiology ; Male ; Middle Aged ; Neutrophils ; metabolism ; physiology