| Background:Pancreatic Neuroendocrine Neoplasms(pNENs)refer to the rare group of pancreatic neoplasms deriving from neuroendocrine cells,with heterogeneous characteristics of biological behavior,tumor function,clinical manifestation and long-term prognosis.Along with the development of diagnostic technique,the incidence of pNENs grew rapidly in recent decades,which has drawn the increased attention of the world nowadays.Notably,quite a number of cases emerge hepatic metastasis(HM)during the courses,bringing a series of difficulties to clinical practice.However,on account of limited evidence,there remains to be a range of controversies and unclear points currently with respect to management strategy for population of pNENs with HM.Objective:We aim to analyze the general feature,treatment effect and risk factors of such population,in order to improve the surgical decision system basing on reliable evidence,especially focusing on the implication of primary tumor resection for certain specific groups among them.Method:The study collected 228 cases of pNENs with HM from three high-volume medical centers(Peking Union Medical College,Shanghai Zhongshan Hospital Affiliated to Fudan University,and Peking University Third Hospital)in China.Important elements including general information,pathological examination,therapeutic data and long-term outcome were recorded in detail.Entire population,G1/2 grade pNENs with synchronous multiple HM(synchronous multiple G1/2-pNEN-HM)and G3 grade pNENs with synchronous HM(synchronous G3-pNEN-HM)were hierarchically analyzed in sequence.Potential prognostic factors were evaluated through univariate and multivariate survival analysis with Cox Regression Models.Overall survival(OS)of different groups were compared by Kaplan-Meier method.Standard propensity score matching(PSM)was performed when different groups with unequal baseline variables were supposed to be compared with each other parallelly.Result:The average age was 51.80±12.48 years old.There were 118 males(51.8%)and 110 females(48.2%).Overall 1-year,3-year and 5-year survival rate of this cohort were 87.2%,71.7%and 53.9%.Median and mean survival time were 72 months and 112.5 months,respectively.As for surgical management,86 cases(37.7%)didn’t undergo surgery,while 142 cases(62.3%)underwent operation of primary resection,including 67 cases(29.4%)of only primary resection(PR)and 75 cases(32.9%)of both primary and liver resection(PR+HR).Stratification analysis showed that:① As for the 110 cases of synchronous multiple G1/2-pNEN-HM,PR(HR 0.355,95%CI:0.139-0.903,p=0.03),PR+HR(HR 0.239,95%CI:0.085-0.674,p=0.007)were both prognostic protective factors.However,largest primary tumor size≥35mm(HR 2.346,95%CI:1.056-5.209,p=0.036)and extrahepatic metastasis(HR 3.815,95%CI:1.624-8.961,p--0.002)could be independent prognostic risk factors.After PSM revision,we used Kaplan-Meier method to compare long-term survival between cases of control group and operation group,showing that the median OS of operation group was significantly longer than control group(operation group vs control group,70 months vs 33 months,p=0.007).② As for the 40 cases of synchronous G3-pNEN-HM,there were 14 cases(35%)classified into pancreatic neuroendocrine tumors(G3-pNET-HM),while 26 cases(65%)of carcinoma(G3-pNEC-HM).The median OS of this whole group was 32 months.The median OS of synchronous G3-pNET-HM and G3-pNEC-HM were 69 months and 17 months,while their 1-year,3-year and 5-year survival rate were 90%,75%,75%versus 51.8%,26.9%and 0%,respectively,which implicated the significant difference of long-term survival between these two groups(p<0.001).Rather than single lesion,multiple HM accounts for the main part(92.5%)among these cases.Besides,40%people had extrahepatic metastasis.The result of multivariate survival analysis showed that classification of neuroendocrine carcinoma(HR 5.178,95%CI 1.066-25.163,p--0.041)and extrahepatic metastasis(HR 4.048,95%CI 1.226-13.361,p=0.022)were independent prognostic risk factors,while liver-directed local treatment(hepatic resection or radiofrequency ablation(RFA))(HR 0.095,95%CI 0.011-0.808,p=0.031)contributed to a better survival.Conclusion:With respect to synchronous multiple Gl/2-pNEN-HM,primary resection could have a favorable effect on long-term survival as a protective prognostic factor.Largest primary tumor size≥35mm and extrahepatic metastasis were prognostic risk factors.With regards to synchronous G3-pNEN-HM,the data showed that liver-directed local treatment benefited to long-term survival,since classification of neuroendocrine carcinoma and extrahepatic metastasis could be potential independent risk factors. |
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