Objective To investigate the clinical features and treatment of solid pseudopapillary neoplasm (SPN) of the pancreas.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 69 patients with SPN of the pancreas who were admitted to the Qilu Hospital of Shandong University from January 2012 to July 2017 were collected.Serum tumor markers detection,enhanced computed tomography (CT) and magnetic resonance imaging (MRI) of abdomen were carried out preoperatively for all the patients,and a part of the patients received endoscopic ultrasonography (EUS).Surgery plans were formulated after completion of examinations.Observation indicators:(1) clinical features;(2) treatment situation;(3) results of pathological examination;(4)follow-up.All the patients were followed up via outpatient examination and telephone interview to detect the survival and tumor recurrence and metastasis till July 2017.Measurement data with normal distribution were presented by (x)±s and were compared by Student's t test.Count data were compared by chi-square test.Results (1) Clinical features:① epidemiologic features:the ratio of male to female was 1∶5.9;patients were aged between 9 and 65 years,including 40 under 30 years and 29 above or equal to 30 years.The onset age was (34± 15)years for male patients and (28 ± 11)years for female patients,respectively,with no statistically significant difference (t=1.364,P＞0.05).Of 69 patients,SPN was located at pancreatic uncinate process in 25 patients,at neck of pancreas in 12 patients,body and tail of pancreas in 32 patients.② Medical history:history of acute or chronic pancreatitis and abdominal trauma were denied by all the 69 patients.③ Clinical manifestation:26 patients had no obvious symptoms and were detected by physical examination;31 patients had discomfort in upper abdomen,nausea and vomiting;other patients were admitted to the hospital because of upper abdominal mass (10 patients),jaundice (1 patient) or nausea,constipation (1 patient).④ Laboratory examination:the levels of preoperative carcinoembryonic antigen (CEA) and CA19-9 were normal.⑤ Imaging examination:plane scan of the CT examination showed round or round-like low-density shadows in the 69 patients,including 51 of cystic solid lesion,13 of solid lesion and 5 of cystic lesion.Complete capsules were observed in 64 patients,blurred boundary between pancreas and adjacent viscera in 5 patients,calcified foci in the pancreatic parenchyma and capsules in 14 patients.Ten patients received MRI examination,and the T1-weighted images showed equal or slightly lower signal,T2-weighted images showed slightly higher signal in the plane scan,and T1-weighted and T2-weighted images of the tumor capsule showed continuous or non-continuous ring-like signal.The results of enhanced scan showed slightly heterogeneous enhancement of the capsule and the parenchyma of the pancreas in the arterial phase,and progressive enhancement in the venous and delayed phase,while the enhancement degree was lower than that of the normal pancreas parenchyma.The parenchyma was cloud-,papillaor mural nodule-like enhanced.Obvious enhancement was observed in capsule while not in the cystic components.The boundaries of the tumors in 5 patients were clear under EUS.Hypo-,iso-and hyperechoic regions were found in the masses,and the masses were confirmed as cyst-solidary type.Obvious calcified foci were found in 1 patient.(2) Treatment outcome:twenty-seven patients received laparoscopic surgery,including tumor expiration in 13 patients,distal pancreatectomy with preservation of spleen in 8 patients,distal pancreatectomy combined with splenectomy in 2 patients,middle pancreatectomy in 2 patients,pancreaticoduodenectomy with preservation of pylorus in 1 patient,pancreatic head resection with preservation of duodenum under the assistance of laparoscopy in 1 patient.Forty-two patients received open surgery,including tumor expiration in 12 patients,distal pancreateetomy with preservation of spleen in 10 patients,distal pancreatectomy combined with spleneetomy in 6 patients,middle pancreatectomy in 5 patients,pancreaticoduodenectomy in 7 patients (with preservation of pylorus in 2 patients) and pancreatic head resection combined with preservation of duodenum in 1 patient.One patient with SPN + hepatic metastasis received distal pancreatectomy+ metastatic foci resection in the lesser omental bursa,and then followed by radiofrequency ablation in the hepatic metastatic foci.Postoperative complications:21 of 69patients had postoperative complications,including 17 intestinal fistulas,2 abdominal bleedings,1 incomplete obstruction,1 pleural effusion + atelectasis,and all of them were cured by symptomatic treatment.(3)Pathological examination:the resection margins of 69 patients were negative.The mean diameter of the tumor was (7±4) cm (21 patients with tumor diameter ＜ 5 cm,and 48 with tumor diameter ≥5 cm).The tumor diameters of 4 in 10 male patients were above or equal to 5 cm,and the number was 44 in 59 female patients,with statistically significant difference (x2 =4.828,P＜0.05).The tumor diameters of 32 in 40 patients who aged under 30 years were above or equal to 5 cm,and the number was 16 in 29 patients who were aged above or equal to 30 years,with statistically significant difference (x2=4.895,P＜0.05).Solid,pseudo-papillary and cystic regions in the SPN tissues were seen under the light microscope.Tumor cells were surrounded the blood vessels and were arranged in the nest or sheet shape in the solid region;blood vessels were surrounded by one or multiple layers of tumor cells in the axis or pseudopapillary shape in the pseudopapillary region;large amount of mucus and clusters of blood cells were seen in the cystic regions.The result of immunohistochemistry showed that the positive rates of α1-antitrypsin,vimentin,β-catenin,progesterone receptor,CD10,synaptophysin and chromogranin A were 100.0％ (39/39),96.6％ (28/29),95.7％ (45/47),94.4％ (51/54),92.5％ (49/53),72.9％ (35/48) and 5.6％ (3/54),respectively.(4) Follow-up:63 of 69 patients were followed up for 1-68 months,with median time of 29 months.No SPN recurrence or metastasis was detected.One patient died of lung cancer at postoperative month 35 and other patients survived well.Conclusions SPN of pancreas is mostly detected in young female patients,and it could be solid or cystic.Abdominal enhanced CT or MRI examination could clarify the diagnosis.EUS-fine needle aspiration examination could provide pathological evidence for definitive diagnosis.Typical cellular morphology and pseudopapillary regions may provide hints for the diagnosis of SPN,and the diagnosis could be clarified when combined with the detection of vimentin,α 1-antitrypsin or other indexes.Complete resection of SPN and ensure negative resection margin are fundamental principles of treatment.

Objective To evaluate the prognosis and management of recurrent primary clear cell carcinoma of liver (PCCCL).Methods 214 patients with PCCCL treated by curative resection from January 1996 to March 2006 were retrospectively studied.Tumour recurrences were classified into early (≤1 year) and late (＞1 year) recurrences.Results Of 99 patients who developed recurrences,28 developed early recurrence while 71 developed late recurrence.The patients with recurrences were treated with re-resection (n=33),percutaneous ethanol injection (PEI,n=7),radiofrequency ablation (RFA,n=10),transcatheter arterial chemoembolization (TACE,n =27),systemic chemotherapy (n=1),Chinese medicine (n=1),and conservative management (n=20).The re-resection rate was higher in the late than in the early recurrence group (P=0.04).In this study,reresection,PEI,and RFA were considered as curative therapies.There was no significant difference in the overall survival (OS) for patients who received these different curative therapeutic procedures (P=0.68).The 1,3-,and 5-year OS of patients with recurrences who were treated with curative treatment were comparable to those patients who did not develop recurrences (100％,86.0％,63.5％ vs 85.2％,72.2％,64.3％,P=0.71).The 1-,3-,and 5-year OS of patients who received TACE for recurrences were 100％,66.7％,and 44.4％ respectively.The results were poorer than patients who received curative treatment for recurrences (P=0.03),but were better than those who received conservative management after recurrences (80.0 ％,25.0 ％,and 10.0 ％,P＜ 0.01).Conclusions Reresection,PEI and RFA are optimal curative methods for recurrent PCCCL.TACE plays an important role in the management of patients with recurrent PCCCL who cannot be treated with curative methods.

ObjectiveTo study the role and mechanism of low-dose aspirin with IFN-α in inhibiting growth and metastasis of hepatocellular carcinoma (HCC).MethodsMHCC97L cells were cultured and a metastatic model of human HCC was established by orthotopic implantation of histologically intact human HCC tissue into the liver of nude (nu/nu) mice.After administration of different doses of Aspirin and IFN-α for 40 days,the mice bearing xenografts in liver were killed,and the tumor volume and lung metastasis were evaluated.Cell proliferation and MMP-2 activity were measured by MTT and gelatin zymography,respectively.The expressions of VEGF and MMP-2 were measured by western blot and ELISA.ResultsCompared to the control group,there were no significant differences in the high-dose Aspirin [45 mg/(kg · d)] treated group regarding tumor volume [(1.89 ±0.88) cm3 vs (3.12±0.85) cm3,P＞0.05] and incidence of lung metastases (58.3％ vs 66.7％,P＞0.05),but the tumor volume and incidence of lung metastasis were significantly inhibited in the highdose IFN-α group [1.5 × 107/(kg · d)],the high-dose IFN-α combined with high-dose Aspirin group,and the low-dose IFN-α [7.5 × 106 / (kg · d) ] combined with low-dose Aspirin [15 mg/(kg · d] group (P＜0.05).2 mmol/L Aspirin did not inhibit the proliferation of MHCC97 cells (P＞0.05),but inhibited the activities and expressions of MMP-2 and VEGF.Low-dose IFN-α combined with low-dose Aspirin significantly decreased the expressions of MMP-2 and VEGF in nude mice (P＜0.05).ConclusionLow-dose Aspirin combined with low-dose IFN-α significantly inhibited the growth and metastasis of HCC through suppressing the expressions of MMP-2 and VEGF.

Objective To investigate the role and mechanism of low-dose aspirin concurrent with IFN-a in inducing hepatocellular carcinoma apoptosis in BEL-7402 cells. Methods BEL-7402 cells were cultured and treated with IFN-α,or low dose aspirin or both.MTT and flow cytometry were used to measure the cell proliferation and apoptosis after treatment with a singular drug or the combined regiment.The expressions of the apoptosis-related proteins were detected by Western blot.Results MTT assay revealed after IFN α administration alone or combined with aspirin treatment for 48 h,the proliferation ratio of the IFN-α or aspirin group were 82.45％ ± 1.71％ and 83.22％ ±2.26 ％,compared with the control group.The group which received the combined therapy had a proliferation ratio of 69.84 ％ ±1.18 ％,which was significantly lower than the single groups (P＜0.05).The flow cytometry revealed that the apoptosis ratio in IFN-α group and aspirin group were 14.78 ％ ±1.93％ and 14.00％±0.61％,respectively,while the IFN-α + aspirin group was 21.68％±1.28％,which was also significantly higher than that of the single groups (P＜0.05).Western blot detected that IFN-α and aspirin (1 mmol/L) could promote caspase-3 and caspase-9 protein expressions,and when the two drugs were combined,caspase-3 and caspase-9 were also significantly activated.IFN-α alone or combined with aspirin can promote the expression of pro-apoptotic protein Bax (P＜0.05),while the anti-apoptotic proteins expression of Bcl-2 and Bcl-xl did not change significantly (P＞0.05).Conclusions Low-dose aspirin can cooperate with IFN-α in inhibiting the BEL-7402 cell growth and inducing the cell apoptosis by activating and increasing caspase-3 and caspase-9 levels,which may be related to the increased expression of pro-apoptotic protein Bax.

Objective To investigate the clinicopathological characteristics and prognostic factors of hepatolithiasis associated with intrahepatic cholangiocarcinoma (HLAIHCC).Method A ret rospective study was conducted on 36 patients who suffered from histopathologically confirmed HLAIHCC.These patients received surgical resection of the tumor from June 2006 to September 2009.Results The overall 1,3,5 year survival rates for patients with HLAIHCC were not significantly better than those patients with ICC (63.6％,36.4％,and 30.3i％ vs.65.4％,34.3％,and 28.6％,P=0.57).For the patients who received curative resection,the 1-,3-,and 5-year survival rates (81.4 ％,61.7 ％,and 58.6 ％) were significantly better than those who received palliative resections (x2 =20.426,P＜0.001).The white blood cell count was significantly higher in the HLAIHCC group than in the ICC group (x2 =19.70,P＜0.001) and tumor size was significantly smaller in the ICC group than in the HLAIHCC group (P=0.04).Serum CA19-9 level (P=0.049) and resection margin (P=0.019) were independent risk factors of prognosis.Conclusions This study showed HLAIHCC to have different clinicopathological characteristics from ICC.Curative resection was the optimal surgical treatment for HLAIHCC.Serum CA19-9 level and resection margin were independent risk factors of prognosis.

Objective To investigate the mechanism of pseudomonasaeruginosa mannose sensitive hamemagglutination vaccine (PA-MSHA) in inducing apoptosis in hepatocellular carcinoma (HCC).MethodsA metastatic model of human hepatocellular carcinoma (HCC) was established by orthotopic implantation of histologically intact human HCC tissue into the liver of nude mice.Mice bearing xenografts in liver were randomly divided into three groups:control group,PA-MSHA intraperitoneal administration group,and PA-MSHA subcutaneous administration group.The agent was administered every day after the third day post-tumor implantation.At the end of the sixth week,the mice were killed.Serum levels of TNF-α,IL-4,IL-6 and IFN-γ were measured by ELISA and the activities of caspase 3,caspase 8 and caspase 9 in the tumor samples were tested by spectrophotometric method.Fas/FasL expressions were evaluated by Western blotting.ResultsSerum TNF-α levels in the control group,PA-MSHA subcutaneous administration group and PA-MSHA intraperitoneal administration group were 25.24±3.22 pg/ml,25.50±4.55 pg/ml(P＞0.05) and 34.22±2.42 pg/ml (P＜0.01),respectively,while there were no significant differences in serum IL-4,IL-6 and IFN-γ among these three groups(P＞0.01).Compared with the control group,the activities of caspase 3,caspase 8 and caspase 9 in tumors in the intraperitoneal administration group increased by 4.1,2.3 and 1.9 fold(P＜0.01),respectively,and Fas/FasL expressions were significantly elevated in the intraperitoneal administration group and subcutaneous administration group.ConclusionWhen given intraperitoneally,PA-MSHA can induce apoptosis in HCC by promoting the secretion of TNF-α and expression of Fas/FasL,thereby inhibiting HCC growth and metastasis.

Objective To investigate the role and mechanism of TMPRSS4 in radiation induced metastasis of hepatocellular carcinoma (HCC).Methods Metastatic model of human HCC was established by orthotopic implantation of histologically intact human HCC tissue into the liver of nude mice.Mice bearing xenografts in liver were killed after radiation and the residual tumors were resected and reimplanted into the liver of normal nude mice.At the end of sixth week,the mice were killed and the histopathological features,tumor volume,intrahepatic and lung metastasis were evaluated.Expression of epithelial-mesenchymal transition (EMT) related genes including N-cadherin,Vimentin,SIP1 and TMPRSS4 were measured by Western blotting and RT-PCR.Results The tumor volume and frequency of lung metastasis of control group was 2.25±0.52 cm3 and 66.7％,respectively.Compared to control group,tumor diameter (1.61±0.51 cm3,P＜0.05) and lung metastasis (12.5％,P＜0.05) were significantly inhibited 2 days after radiation.Whereas,30 days after radiation,tumor growth recovered (2.60±0.61 cm3,P＞0.05) and lung metastasis was enhanced (100％,P＜0.05).There were no intrahepatic metastasis in the control group and in the group of reimplantation of HCC 2 days after radiation,while the tumors from those 30 days after radiation showed enhanced intrahepatic metastasis (18 ± 8.05,P＜ 0.01 ),with overexpression of SIP1,N-cadherin,Vimentin and TMPRSS4,and reduced expression of E-cadherin.Conclusion The metastasis potential of residual HCC after radiation was first inhibited and then promoted.Overexpression of TMPRSS4 plays a critical role in radiation induced long-term metastasis of HCC by facilitating EMT.

Objective To investigate the effect of antisense oligodeoxynueleotide targeting sur-vivin (survivin ASODN) on hilar cholangioearcinoma cell line FRH-0201 depressing the expression of survivin. Methods Survivin ASODN was transfected into hilar eholangiocarcinoma cell line FRH-0201by liposome. Morphologieal changes were observed by inverted phase contrast microscope. RT-PCR and Western blot methods were performed to detect the expressions of survivin mRNA and protein re-spectively. The changes in cell apoptosis were detected by flow cytometry. Results The expression of survivin mRNA and protein was significantly decreased in survivin ASODN group than that in the con-trol group(mRNA: 0.51-t-0. 03 vs 0. 82-t-0.02,P%0. 05～protein: 1.82-t-0.16 vs 3. 08--t-_0. 27, P-Q 0.05). The morphologieal apoptotic changes were observed and the apoptosis rate was increased (11.50+1.49% vs 0.39-+-0.08～, P%0.05). Conclusion Survivin AS()DN can induce hilar cholan-gioeareinoma cell line FRH-0201 into apoptosis by decreasing the expression of survivin.

0.05). Conclusion:The excessive expression of Survivin in gallbladder cancer indicates that Survivin could be not only correlated with the occurrence of carcinoma but an early and common event in gallbladder carcinogenesis. Surviv in will promisingly become a novel tumor marker and can be applied in the clinic al practice for helping the early diagnosis as well as targeting gene therapy fo r gallbladder cancer.

Objective:To explore the general pattern of lymph node metastasis and its effect on prognosis in early gastric cancer.Methods:The clinicopathological and follow-up data of early gastric cancer cases from 1990.6~2000.6 were retrospectively analyzed.Results:The tumor size and depth of invasion were related to lymph node metastasis in early gastric cancer.The 5-year survival rate of patients with node-positive early gastric cancer was significantly lower than those of patients with node-negative,72.4% and 92.5% respectively.The 5-year survival rate of patients with ≥4 metastatic lymph nodes was significantly lower than those of patients with 1~3 metastatic lymph nodes,50.0% and 84.2% respectively.Conclusion:Lymph node metastasis is the independent prognostic factor.Postoperative therapy should be recommended for the patients with ≥4 metastatic lymph nodes.