| Objective:To explore the clinicopathological features of biliary-pancreatic neuroendocrine neoplasms(BP-NENs)and the risk factors affecting the prognosis of patients.To explore the value of neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)in the prognosis of P-NENs patients,and the risk factors for P-NETs recurrence.At last,to explore the expression of INSM1 in biliary NENs.Methods:The clinicopathological data of 133 patients with BP-NENs admitted to the Affiliated Hospital of Qingdao University from Jan.2011 to Nov.2021 were retrospectively analyzed and patients were followed until death or closing date.Collecting pathological samples of B-NENs patients,and investigating the expression of INSM1 by immunohistochemical staining.Then,the relationship between its expression and clinical characteristics and prognosis was analyzed.Statistical analysis of all relevant data was performed using SPSS25.0.The measurement data were compared by two sample t-test or Mann-Whitney U test;enumeration data were compared by chi-square test or Fisher’s precise test.ROC analysis was used to determine cutoff values of NLR and PLR.Kaplan-Meier curves and multivariate Cox proportional models were used to calculate overall survival(OS),binary logistic analysis was used to calculate recurrence risk,P<0.05 was considered statistically significant.Results:1.(1)The male-to-female ratio of 104 P-NENs patients was 0.74:1,the age of onset ranged from 18 to 82 years old,and the median age was 58.5 years old.The median age of male patients was 61.5 years old,and the median age of female patients was 55.5 years old,there is a statistical difference between them.(2)The 104 P-NENs were divided into non-functional neoplasms(69 cases,66.3%)and functional neoplasms(35 cases,33.7%).The clinical symptoms of non-functional NENs were epigastric pain(40.6%),weight loss(20.3%),nausea and vomiting(7.2%),jaundice(7.2%),and 52.2% has no clinical symptoms.Among functional NENs,2 cases(5.7%)were VIP tumors,manifested as intractable diarrhea,hypokalemia,and 33 cases(94.3%)were insulinomas with neurological symptoms and autonomic symptoms,and 15.2% were misdiagnosed by other hospital.(3)There were 83(79.8%)solid tumors and 21(20.2%)non-solid tumors in P-NENs;The tumors were located in the pancreatic head/neck(41 cases,39.4%)and body/tail(63cases,60.6%).The maximum diameter of the tumor ranged from 0.70 cm to 13.80 cm,the mean was 3.50±0.22 cm.There was no correlation between tumor’s morphology,location and maximum tumor diameter.(4)Among the P-NENs,there were 10 cases of neuroendocrine carcinoma(NEC)and94 cases of neuroendocrine tumor(NET),including 42 cases of NET G1 grade,47 cases of G2 grade,and 5 cases of G3 grade.P-NENs with different pathological grades had statistical differences in tumor’s morphology,size,function,TNM stage,local invasion,lymph node metastasis,distant metastasis,and vascular tumor embolus.The tumors of patients in the G3 group(NETG3 and NEC)are more common in solid tumors,tumor diameter≥2cm,TNM stage III/IV,local invasion,vascular tumor embolus,lymph node metastasis and distant metastasis.the tumor diameter of G1 group was significantly smaller than that of G2/G3 group.(5)ROC curve analysis showed that the AUCs of the NLR,PLR were 0.701 and 0.785,and that the best cut-off values for the above parameters were 2.43、161.67,which were all statistically significant(P<0.01).High NLR or PLR was associated with TNM stage III/IV,G3 grade,lymph node metastasis,distant metastasis and poor prognosis(P<0.05).(6)All patients were followed up for 3-131 months,one patient was lost follow-up,and 18 patients were dead.The average survival time was(105±5.5)months,and the 1-year,3-year,and 5-year survival rates were 90.9%,86.1% and79.7%.Univariate analysis showed that age,NLR,PLR,tumor shape,size,grade,TNM stage,local invasion,lymph node metastasis,and distant metastasis affected the prognosis of patients.In multivariate analysis,pathologic grade,TNM stage,PLR were independent risk factors for prognosis of patients with P-NENs(P<0.05).The overall survival of patients with G3 grade,TNM stage III and IV,and PLR≥161.67 were decreased.(7)Among 82 P-NETs patients who had radical surgery,10 patients found tumor recurrence,the disease-free survival was ranged from13 months to 94 months.The most common recurrence location was the liver(5 cases,50%),followed by lymph nodes and residual pancreas(2 cases each,25%),adrenal glands(10%).The recurrence rate was12.2%,which was related to the TNM stage,WHO classification,Ki-67 index,tumor size,local invasion,lymph node metastasis,neurovascular invasion,and multivariate analysis showed that Ki-67 index and TNM stage were independent recurrence risk factors in PNETs patients with radical surgery(P<0.05).2.(1)Among the 29 patients with biliary NENs,the male to female ratio was1.23:1,the age ranged from 34 to 78 years,and the median age was 60 years.Tumors were located in gallbladder in 14 cases,extrahepatic bile duct in 9 cases,and hepatopancreatic ampulla in 6 cases.The maximum diameter of the tumor ranged from 0.8cm to 5.0cm,with a median of 2.35 cm.The clinical symptoms of gallbladder tumors are not obvious,and bile duct and ampulla tumors are mostly manifested as jaundice and abdominal pain.(2)CA19-9 was abnormal in 10 cases(10/25,40%),CEA was abnormal in 13 cases(13/27,48%).For NE makers,the positive rates of CD56,Syn and CgA were 96.2%,89.7%and 75.0%.(3)1 case of neuroendocrine tumors was grade G1,3 cases were grade G2,2 cases were grade G3,14 cases were neuroendocrine carcinomas,and 10 cases were mixed neuroendocrine-non-neuroendocrine tumors.TNM staging showed 5 cases of stage I,9cases of stage II,11 cases of stage III,and 4 cases of stage IV.Lymph nodes and liver are the most common sites of metastases.(3)28 patients underwent surgical treatment,1 patient underwent medical treatment,25 patients underwent radical surgery,1 patient underwent simple cholecystectomy,2patients underwent palliative surgery,and 15 patients underwent postoperative drug adjuvant therapy.The follow-up results showed that the cumulative survival rates of 1 and2 years were 75.5% and 45.0%,and the median survival time was 19 months.(4)Immunohistochemical staining of INSM1 was performed on tumor specimens from 25 patients,24(96%)were positive,including 8 weakly positive(+),15 positive(++),and strongly positive(+++)1 case.Log-rank univariate analysis showed that the expression of INSM1 was associated with overall survival,and the survival time of the high expression group(++,+++)was shorter than that of the low expression group(–,+).Conclusions:1.The incidence of P-NENs in men and women is similar,and the age of onset in women is earlier than that in men;functional NENs are the most common type of insulinoma,and their special clinical manifestations are easy to be missed or misdiagnosed as other diseases;non-functional NENs have atypical clinical symptoms and should be paid attention to Physical examination.2.The pathological grading of P-NENs patients was different in terms of age of onset,tumor shape,function,TNM stage,local invasion,lymph node metastasis,distant metastasis,and vascular tumor thrombus.3.Tumor grade and stage were independent risk factors for the prognosis of patients with P-NENs.Ki-67 index and TNM stage were independent risk factors for recurrence after radical resection of P-NETs.4.NLR and PLR may affect the prognosis of patients with P-NENs,and PLR is an independent risk factor for the prognosis of patients with P-NENs.5.B-NENs have different clinical manifestations based on different locations.The pathological types of B-NENs are mainly NEC and Mi NEN.The metastasis rate of lymph node and liver is high,and the prognosis is poor.Combined with the literature,age,tumor size,pathological classification,whether surgery,and disease recurrence may be risk factors affecting prognosis.6.The detection rate of INSM1 was higher than the rates of CgA and Syn,INSM1 is an effective marker for the diagnosis of B-NENSs,and its expression is related to prognosis.High expression of INSM1 indicates a shortened survival period. |
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