Gastroenteropancreatic neuroencrine tumors (GEP-NETs) originate from the neuroendocrine cells of the digestive system.Over the past few years,the incidence has increased gradually.The clinical manifestations are diverse,and the related molecular mechanism is also more complex.Although there are more and more basic researches for GEP-NETs,the mechanism for carcinogenesis and metastasis has not been fully elucidated.This paper summarizes the latest progress on the development of GEP-NETs,and elaborates the new findings on tumor molecular mechanisms,mainly including the related receptors and its signaling pathways,gene mutations and epigenetic changes.

Objective To evaluate the relationship between angiogenesis and biological character of pancreatic carcinoma (PC). Methods Microvessel density (MVD) in 55 cases of PC were examined by use of immunohistochemical staining,and compared with the pathological features of PC. Results Mean MVD of PC was 54.8?18.6. MVD was positively correlated with tumor cell differentiation (P

Objectives To investigate the role of lymphangiogenesis in the perineural micrometastasis of pancreatic adenocarcinoma. Methods The clinical data of 30 pancreatic adenocarcinoma patients who were admitted from Sep. 2005 to Oct. 2006 for extended radical surgery were collected. The samples including pancreatic cancer, adjacent tissue, lower bile duct, pancreatic tail, the structure surrounding the SMA (peripancreatic nerve plexus) and lymph nodes were collected during operation. They were subjected to conventional pathological examination. The lymphatic capillaries weredetected by double immunohistochemical staining and the lymphatic vessel density ( LVD) was measured. Results Intra-pancreatic and/or peripancreatic neural invasion was observed in 25 patients (83. 3% ) , of which 20 were found to have both the peri-pancreatic and intra-pancreatic neural invasion. The other 5 only had the intrapancreatic neural fiber invasion and there was no single patient with peri-pancreatic neural fiber invasion only. Peri-neural invasion was not significantly associated with patients' age, gender, lymph node metastasis, tumor size and the location (P > 0.05) , but was obviously associated with JPS clinical staging ( P < 0. 05 ). The mean intratumoral LVD was (4.2 ±3.4) per field, which was significantly lower than (11.3 ±6.9) per field of adjacent tissue and (10.8 ±4.4)per field of normal pancreatic tissue(P<0.01). The mean intratumoral LVD between adjacent tissue and normal pancreatic tissue was not statistically different. Lymphatic vessel invasion was observed in non-malignant tissues in 18 patients, and there was a distribution correlation between lymphatic vessel invasion and extra-pancreatic neural plexus invasion (P<0.05). Conclusions The incidence of peri-neural invasion was high, peri-neural invasion was associated with JPS clinical staging and lymphatic vessel invasion, which suggested the possibility of the cancer spreading by peritumoral lymphangiogenesis route into the peri-SMA neural plexuses.

Objective To construct a human endostatin adenovirus vector and investigate its inhibitory effect on pancreatic carcinoma in nude mice.Methods Animal model of pancreatic carcinoma bearing nude mice was established by subcutaneous injection of SW1990 cells.All mice were randomized into Ad-hEnd group,Ad-LacZ group and control group with 8 mice in each group.The endostatin gene recombinant adenovirus were intratumorally injected every two days for 4 times.The rate of tumor growth was observed.lmmunohistochemical staining was employed to investigate the expression of vascular endothelial growth factor (VEGF) and micro-vessel density (MVD).TUNEL in situ was used to examine tumor cell apoptosis.Results The tumor formation rate was 100%.4 weeks later,the volumes of the tumors were (921.9±279.7 )mm3,(2804.4±553.5 )mm3 and ( 3040.6±487.6 ) mm3 in Ad-hEnd group,Ad-LacZ group and control group,respectively;the weights of the tumors were (1.19±0.18 ) g,( 2.38±0.42 ) g and ( 2.41±0.47 ) g,respectively;the VEGF positive rates were (36.3±7.1 )%,(81.2±6.6)% and (79.4±6.2)%,respectively;the levels of MVD were 12±4,27±5 and 25±6,respectively;the apoptotic rates were (31.2 ±5.4) %,( 9.4±4.9 ) % and ( 8.5±3.7 ) %,respectively.Compared with Ad-LacZ group and control group,the parameters in Ad-hEnd group were statistically different (P ＜0.01 ).The difference betweon Ad-LacZ group and control group was not statistically different.Conclusions Human endostatin gene mediated by recombinant adenovirus could inhibit tumor growth,angiogenesis and promote cell apoptosis of pancreatic carcinoma and could be used as geue therapy for pancreatic carcinoma.

Objective To improve the prognosis and radical resection of the extended pancreaticoduodenectomy for patients with pancreatic cancer in the ucinate process involving mesentery mot. Methods From Jan. 2004 to Dec. 2007, a total of 23 ( 14 male and 9 female, aged between 30 and 72 years old) patients with pancreatic cancer in the ucinate process involving mesentery root were treated in our department. Curative resection was performed for all patients by the extended pancreaticoduodenectomy with superior mesenteric artery (SMA) isolation and mesentery root resection. The surgical procedure, the safety and prognosis were analyzed retrospectively. Results 12 patients underwent the procedure, among them 11 also underwent combined SMV partial resection and reconstruction. The operation time was (4.2 ± 1.1 ) hours, and the blood loss was ( 1 635 ± 1 362) ml with the blood transfusion of ( 1 609 ± 1 462 ) ml. There was no operation related death in this case series, and mild to severe diarrhea occurred in 6 cases. The post-operative stay ranged 9 to 30 days. The pathological examination showed that the tumor size was (5.3 ± 1.4) cm. 13 patients (57%) had one or more lymph nodes metastasis. 20 patients (87%) had nerve involvement. Among 11 patients with SMV partial resection and reconstruction, 10 patients had endangium involvement. 22 patients had negative surgical margins for all specimens. Rapid intra-operative frozen pathological examination showed negative surgical margins in one patient, however, post-operative paraffin section pathological examination revealed nerve involvement between SMA and celiac trunk. After a follow-up of 5 to 42 months, liver metastasis occurred in 4 patients, and local recurrence occurred in 3 patients. The 1-year and 2-year accumulated survival rates were 77.2% and 42.5%, respectively. Conclusions Isolation SMA and the mesentery resection in extended pancreaticodudenectomy were safe and useful. Using this modified technique, Radical operation resection could be achieved in the treatment of pancreatic cancer in uncinate process.

Objective To investigate the clinical features, diagnosis and management of pancreatic lesions in patients with von Hippel-Lindau (VHL) disease, and improve the current understanding on pancreatic lesions in VHL disease.Methods The clinical data of three VHL disease patients with pancreatic lesions were analyzed retrospectively, including clinical features, laboratory findings, imaging, pathological features, operation method and follow-up.Results Two patients had a family history of hemangioblastoma in central neural system, and 1 patient had retinal multiple angioma and angioma in central neural system, who were diagnosed as VHL.One patient with pancreatic portal hypertension had splenectomy and biopsy of left renal tumor.During the surgery, pancreatic cystic lesions were observed and the transparent cysts were diffusively distributed on the surface.The other 2 patients were diagnosed as pancreatic multiple cysts and non functional pNETs, and pancreatic multiple cysts, respectively, based on the imaging.All the three patients had stable disease status, and followed up by outpatient visits.Conclusions VHL disease can manifest as simple pancreatic cyst, pancreatic serous cystadenoma and pNETs.The optimal individualized treatment should be determined by Multidisciplinary team (MDT) according to the general condition of patient.

Objective To investigate clinicopathological features、diagnosis and surgical treatment of duodenal stromal tumors. Methods A retrospective clinical analysis was made in 23 cases of duodenal stromal tumors admitted from 1995 to 2004. Results Melena and abdominal pain was the most common presenting symptom. Complete resection was achieved in all cases, including pancreatoduodenectomy in 13 cases, by pylorus-preserving pancreatoduodenectomy in 3 cases, and tumor enucleation in 7 cases. The mean size of the tumor was 6. 6 cm (2 - 21 cm) , among them 10 cm in 6. Pathologically tumors less than 5 cm were all of potential malignancy, whereas those larger than 5 cm were malignant. Follow-up of 2 months to 9 years found all cases alive and healthy except for one who died of liver metastasis one year postoperatively. Conclusion Duodenal stromal tumors were low malignancy tumors. Aggressive surgery is the choice of treatment. Favorable prognosis is expected after complete surgical excision.

Objective To analyse the clinical characterization of intraductal papillary mucinous neoplasm of pancreas (IPMNs) and to improve the understanding of IPMNs.Methods Three hundred and sixty-one patients with IPMN at Shanghai Changhai Hospital between 1993 and 2012 were retrospectively analyzed.Results Among 361 cases of IPMNs,241 were men and 120 were female,with a female to male ratio of 2.6∶1.Mean age of the patients was 62 years old (16 ～ 87 years old).The duct type included the main duct in 102 patients (28.3％),a branch duct in 109 (30.2％),and mixed ducts in 150 (41.6％).The most common symptom at presentation is pancreatitis,which occur in 167 patients (46.3％).The sensitivity for the detection of IPMN was 80.2％ by ERCP,76.9％ by MRCP,63.9％ by CT,and 50.5％ by EUS.One hundred and twenty-nine patients (35.7％) were operated and diagnosed with 87 (67.2％) IPMA,21 (16.4％) IPMB,10(8.2％) IPMC(CIS) and 10 (8.2％) had invasive carcinomas.The 5-year survival rates of IPMA,IPMB,IPMC,and invasive carcinomas were 100％,100％,66.5％,and 44.7％,respectively.Conclusions IPMNs were fregrently occured is 60 years old,half of patients had acute pancreatitis history and the frequtly attack,mixed type is most anatomy type,and the outcome after surgery is good.

Hilar cholangiocarcinoma (HCCA) is the most common type of cholangiocarcinoma, with in sidious onset and a high degree of malignancy, and there are often lymph node metastasis and vascular invasion. R 0 resection by surgery is still the main treatment for cure. This article reviews the hot issues and their related advances in surgical treatment of hilar cholangiocarcinoma, including preoperative evaluation, surgical treatment and systematic treatment.

Pancreatic cancer is a common malignancy with the worst prognosis.Radical surgery has been the only curative treatment for pancreatic cancer.With the advancement of surgical techniques and the implementation of the concept of comprehensive treatment for cancer in recent years,neoadjuvant therapy for pancreatic cancer has received more attention.There are continuing controversies in the hotspots and difficulties,with opportunities and challenges coexisting.Four famous experts and their teams in pancreatic surgery discussed selection strategy of neoadjuvant therapy for pancreatic cancer based on clinical experiences.Professor Wang Chunyou proposed that surgery was prior for patients with a higher likelihood of achieving R0 resection for pancreatic cancer to avoid the possibility of tumor progression and loss the opportanity of radical resection during neoadjuvant therapy.For patients with less chance of radical resection for pancreatic cancer and unresectable pancreatic cancer,neoadjuvant therapy is worthy of a positive attempt.Professor Jin Gang and his team believed that neoadjuvant therapy played an important role in improving the survival time of patients with pancreatic head cancer,especially with borderline resectable pancreatic head cancer.After neoadjuvant therapy,pancreatic surgeons should pay attention to improvement of surgery safety and R0 resection rate.Professor Dai Menghua and his team suggested that patients with resectable pancreatic cancer and borderline resectable pancreatic cancer could benefit from neoadjuvant therapy,which required proof from clinical trials.Surgeons should choose the appropriate treatment strategy based on guidelines and individual conditions for patients with pancreatic cancer.Professor Shao Cheghao and his team suggested that surgical treatment after neoadjuvant therapy or translational therapy for locally advanced pancreatic head cancer is safe,effective and feasible,especially for pancreaticoduodenectomy with combined revascularization.For the treatment of patients with pancreatic head cancer after neoadjuvant chemotherapy,the choice of next treatment options,evaluation indicators,timing of surgery and surgical methods need to be further studied.