Risk Predicting System And Relative Basic Research Based On 15-year Experience In The Management Of Pancreatic Cystic Neoplasms At A Single Institution

Objective To investigate the clinicopathological features and outcome of pancreatic cystic neoplasm (PCN) based on 15-year experience in the management of this rare neoplasms at a single institution and to improve the understanding of PCN.Method The clinical date of 695 patients with histologically confirmed PCN treated between January 2000 and October 2015 were studied retroprospectively, the date of demographic characteristics, clinical presentation, radiographic appearance, laboratory examination, surgical approach and long-term outcomes were analyzed, and investigate the risk factors of malignancy and prognosis of PCN.Results (1)Among 695 cases of PCN,177 males and 518 females, male-to-female ratio about 1:2.9, with a median age of 41.9±16.2 years (age range 9-82 years)> 41.3%(287) was solid pseudopapillary neoplasm (SPN),26.2%(182) was mucinous cystic neoplasm (MCN),22.2%(154) was serous cystic neoplasm (SCN) and 10.4%(72) was intraductal papillary mucinous neoplasm (IPMN).78.6%(546) patients were detected and received surgery after 2010.(2)PCN most affected the age group between 31 and 50 years old (41.2%,286). Male patients were significantly older than female (49.3±15.2 VS 39.5±15.9 year, P<0.001), the second highly rate of PCN in age group was 51-70 yeas old in male patients, however, for female was 11-30 years old. The mean age of SPN was youngest (30.4±12.6 year, P<0.001), and IPMN was highest (55.8±10.5 year, P<0.05).(3)52.1%(362/695) PCN were asymptomatic or accidentally detected on routine physical examination.333 patients presented obvious symptom, the most common presenting symptoms were abdominal pain or discomfort (n=237,71.2%), and jaundice was observed in 27 patients (8.1%).(4)Laboratory data were normal in most patients, tumor marker serum CA19-9 levels were elevated in 90 patients. Elevated CA19-9 in mucinous cystic neoplasm was significantly higher than SCNand SPN (χ2=107.845, P<0.001)(5)A variety of radiological examinations were performed preoperatively, the diagnostic accuracy of ultrasonography, enhanced CT, MRI was 53.2%,69.1%,81.0%. SCN and SPN had equal tumor location distribution, however, MCN was more frequently located at body and tail of pancreases, IPMN was head and neck of pancreases. Significant difference was shown when compared with each other. In terms of tumor size, the mean size of SPN was significantly larger (6.2±3.4cm) and that of IPMN was smaller (3.2±1.5cm) when compared with others tumor.(6)In imaging feature,51.3% SCN (79/154) appeared as olio/macrocystic,54.4% MCN (99/154)appeared as unilocular cyst or unilocular cyst with separations,59.9% SPN (172/287) appeared as heterogeneous mass with solid and cystic components, 50.0% IPMN (36/72) appeared as main pancreatic duct dilation. Only 58.0% PCN (403/695) appeared as typical radiographic appearance. SCN shared similar radiographic appearance with MCN, and SPN and IPMN showed special radiographic appearance.(7)94.5% PCN (657/695) received complete resection,47.8% PCN (332/695) underwent distal pancreatectomy and it was the major surgical approach in our study. 2 patients died during the perioperative period. Postoperative complications occurred in 41.6% patients (289/695), pancreatic fistulae was the main postoperative complications (32.2%,224/695).11 patients received reoperation during the perioperative period, and intra-abdominal hemorrhage occurred on the second to eleven days after surgery was the main reason of reoperation (9/11).(8)Based on the pathological examination,23.6% (60/254) mucinous neoplasms with invasive carcinoma and 194 patients with dysplasia. Among 287 case of SPN,74 had invasive behavior. All except one highly dysplasia case SCN was benign.(9)Elveated CA19-9 (OR=4.778, P<0.001), positive symptoms (OR=4.674, P=0.002), pancreatic duct dilation (OR=3.804, P=0.014) were independent risk factors of MCN with invasive carcinoma; age (OR=1.026, P=0.017), pancreatic duct dilation (OR=4.329, P=0.008) were independent risk factors of SPN with invasive behaviors, and tumor size (OR= 1.691, P=0.015), elevated CA19-9 (OR=10.999, P<0.001) independent risk factors of IPMN with invasive carcinoma.(11)70.8%(492/695) of PCNs were followed-up, the median follow-up time was 39.4±32.4 months.39 patients died during the follow-up period. The overall survival of PCNs at 1,3,5 years was 97.8%,93.0% and 91.4%, respectively; for SPN, was 98.4%,95.4%,94.5%, respectively; for MCNs, was 95.5%,87.3%,84.3%, respectively; for IPMN, was 96.9%,84.3%,80.5%, respectively. In overall survival, SCN and SPN had excellent prognosis, especially SCN. The long-term outcomes of MCN and IPMN was worse than that of SCN and SPN, however, MCN had better prognosis than IPMN.(12)Age>60 (HR-3.768,95%CI:1.461-9.718, P=0.006)and postoperative recurrence or metastasis (HR=6.193,95%CI:2.361-16.245, P<0.001) were independent prognostic factors for survival of MCN with invasive carcinoma; invasive behavior (HR=19.619,95%CI:2.454-59.856, P=0.005)and postoperative recurrence or metastases (HR=6.488,95%CI:1.832-22.968, P=0.004) were independent prognostic factors for survival of survival; lymphatic metastasis (X2=4.089, P=0.043) was important prognostic factors for survival of IPMN with invasive carcinoma.Conclusions (1)PCN are mainly affected middle-age females and no specific clinical symptoms and laboratory examination, different type of PCN have different demographic characteristics, tumor size, location, radiographic appearance and biological behavior.(2)It is difficult to diagnosis and differential diagnosis of PCN through radiographic features, especially for SCN and MCN, because similar radiographic appearance can be appeared in different type of PCN. In mucinous cystic tumor, elevated CA19-9 is associated with malignancy.(3)Surgery is the main therapeutic modality for PCN. Good prognosis can be received by radical resection. Mucinous cystic tumor have high malignant potential, poor prognosis is expected when tumor have malignancy transformation.(4)Different type of PCN have different and yet similar risk factors of malignancy and prognosis, understanding of related risk factors is useful for preoperative diagnosis and surgical strategy.Objective To establish a sensitive risk predicting system for the pre-operative evaluation of malignant pancreatic cystic neoplasms based on analysis of the clinical date, and investigate the value of 18F-FDG PET/CT imaging in the management of pancreatic cystic neoplasms.Method Retroprospectively analyzed the clinical date of 695 patients with histologically confirmed PCN treated between January 2000 and October 2014, established risk predicting system of PCN with malignancy. A group of 109 PCNs were then included and validate the sensitivity and specificity of the predicting system. Analyzed the imaging features of PET/CT in 71 patients with PC A, and investigate the value of 18F-FDG PET/CT in the diagnosis and differential diagnosis of PCN.Results (1)Elevated CA19-9, tumor size, main pancreatic duct dilation, mural nodules, and age were independent risk factors for PCN with malignance base on the Logistic multivariate analysis. Among them, elevated CA19-9 had the highest prediction efficiency, however, the area under the receiver operating curve (ROC) was only 0.744 (95%CI:0.644-0.844)(2)A risk predicting system was established by those five independent indexes: X= Exp(-6.5a8*i.aS4(elMte<lCa1■8)+0.207 (tumorsiza)+1.128 (mainpancnatkductovation;+1.201 (muttnodutea}+0.047 (age)) 1+Exp(-e.S88+1.B54(elevated Ca19-9)+0.2O7 (tumorsin)+1.128 (mam pancreatic duct dUbon)+1.201 (mural nodules)+0.047 (age)) the area under the receiver operating curve (ROC) was 95%CI:0.863-0.956). The optimal cut-off was 0.229 in reference to the Youden index.(3)109 patients with PCN in prospective validation group were include to risk predicting system, and achieved fitted ROC, the area of fitted ROC was 0.837 (95%CI:0.740-0.933), no significant difference was seen compared with ROC of model group (z=l.338,P=0.181). the sensitivity and specificity of predicting system was 81.3%,92.5%.(4)The median of SUVmax in PCNs with benign or dysplasia was significant higher than that of patients with malignancy (1.9 VS 3.6,P<0.001). Analyzed the early SUVmax value of 71 patients underwent F-FDG PET/CT examanition and calculited the optimal cut-off value. When the early SUVmax was 3.65, the sensitivity and specificity of predicting system was 82.3%,94.6%.(5)Combined with serum CA19-9, the sensitivity, specificity, and diagnostic accuracy of 18F-FDG PET/CT was 87.5%,91.5%,91.5%, and that of predicting system was 83.3%,89.5%,87.3%. Both methods had good diagnostic efficiency and diagnostic accuracy, however, 18F-FDG PET/CT with serum CA19-9 had better diagnostic accuracy than predicting system.Conclusions (1) Elevated CA19-9, tumor size, main pancreatic duct dilation, mural nodules, and age are significantly associated with malignant PCN, single index have poor prediction efficiency, combined multi indexes can improve prediction efficiency.(2)Our risk predicting system of PCN with malignance has good prediction accuracy, which can provide important reference for the management of PCN.(3)18F-FDG PET/CT on PCN diagnosis with higher sensitivity, specificity and accuracy, which have important role in the management of PCN.Objective To investigate the expression of GRP78 and GRP94 in invasive solid-pseudopapillary neoplasm of the pancreas (SPN) and its relationship with clinicopathological features and prognosis.Method The expression of GRP78, GRP94 was detected by immunohistochemistry in 87 SPN and normal pancreatic specimens. Reverse transcription-polymerse chain reaction (RT-PCR) and western bolt was applied to detect the expression of mRNA and protein of GRP78, GRP94 in tissue. The correlations among expression of proteins and clinicopathological features and prognosis were analyzed using univariate and multivariate analyses.Results (1)The overexpression of GRP78 and GRP94 was detected in the cytoplasms of the tumor cell. The positive rate of protein expression in invasive SPN was higher than those in the non-invasive and normal pancreatic tissues. The positive rate of GRP78 expression was higher than those of GRP94 (66.7% VS 52.6%), however, the difference was not statistically significant (χ2=2.332, P=0.127) and no correlation was found between them(Spearman rank correlation coefficient=0.113, P=0.295).(2) RT-PCR and Western was applied to detect the expression of mRNA and protein of GRP78 and GRP94 in fresh tissues, the results were quite consistent with immunohistochemistry date. Univariate analysis showed the positive GRP78 expression was associated with invasive behavior(χ2=5.718, P=0.017). and tumor size>5cm(χ2=3.930, P=0.047). Survival analysis demonstrated the expression of GRP78 was associate with poor outcome(χ2=2.172, P=0.140), and was important risk factors of invasive SPN. However, no correlation of those results was found in GRP94 expression.Conclusions (1) GRP78 and GRP94 both have overexpression in SPN especially in tumor with invasive behavior, its may have relationship with the regulation of transcription and tumorigenesis and progression.(2)GRP78 can be used as prognostic factor of invasive SPN, the expression of GRP78 protein in invasive SPN indicate higher possibility of recurrence or metastasis, close follow-up is recommended for those people.