Analysis Of Clinical Features And Risk Factors For Postoperative Survival Outcomes In Gastrointestinal Neuroendocrine Tumors

Objective:Neuroendocrine neoplasms(NEN)are a group of epithelial tumors with neuroendocrine differentiation morphology and immunohistochemical features,and are highly heterogeneous tumors originating from neuroendocrine tumor cells or peptidergic neurons throughout the body.The aim of this study was to analyze the clinical characteristics and risk factors for long-term postoperative survival outcome of patients with gastrointestinal neuroendocrine tumors in our hospital,hoping to draw clinicians’ attention to gastrointestinal neuroendocrine tumors.Method:Retrospective analysis was performed on patients who visited the Sino-Japanese Friendship Hospital of Jilin University from June 2012 to July 2022 and were pathologically diagnosed with GI-NEN.Clinical history data including clinical features,CT,MRI,endoscopic and ultrasound endoscopic findings,and clinicopathological data and prognostic information of patients with GI-NEN were collected for analysis.Results:1.190 patients who met the criteria were included in this study,including 117 males and73 females,with a male-to-female ratio of 1.60:1.00.The age of onset ranged from 22-85 years,with a median age of 53 years.2.The rectum(73.7%)was the most common among the 190 patients with GI-NEN,followed by the stomach(15.8%),duodenum(5.3%),colon(3.2%),and appendix(2.1%).3.Among the 190 patients included in this study,non-functional GI-NEN accounted for95.8%(182/190)and functional GI-NEN(with clinical manifestations of carcinoid syndrome,such as diarrhea and flushing)accounted for 4.2%(8/190).4.Among the 190 patients included in this study,abdominal pain(33.3%)was the most common clinical manifestation in patients with an incidence in the stomach,abdominal pain and abdominal distension(50.0%)in patients with an incidence in the duodenum,abdominal pain(75.0%)in patients with an incidence in the appendix,and eczema(33.3%)in patients with an incidence in the colon.The most common clinical manifestation was blood(33.3%)in patients with colonic disease,and the most common clinical manifestation was change in bowel habit(34.3%)in patients with rectal disease.5.The preoperative CT detection rate of GI-NEN patients was 31.9%,and the ultrasound endoscopic detection rate was 93.0%.6.Of the 190 patients with GI-NEN included in this study,57.9% had a maximum tumor diameter <1 cm,while only 23.2% had a maximum tumor diameter ≥2 cm.7.Postoperative pathological returns of the patients included in this study: only 12 cases showed both vascular and nerve infiltration and lymph node metastasis,accounting for14.6% of surgical treatment;12 cases showed both vascular infiltration and lymph node metastasis,accounting for 14.6% of surgical treatment;2 cases showed both nerve infiltration and lymph node metastasis,accounting for 2.4% of surgical treatment.In 7cases,only lymph node metastasis without vascular and nerve infiltration;in 1 case,only nerve infiltration without vascular infiltration and lymph node metastasis;and in 4 cases,vascular infiltration without nerve infiltration and lymph node metastasis.8.Of the 190 patients included in this study,1 had distant metastases that had developed preoperatively.During the follow-up of the remaining patients,a total of 20 patients developed distant metastases,including liver metastases in 8 cases,lung metastases in7 cases,small bowel mesenteric metastases in 4 cases,and total abdominal metastases in 1 case.9.Of the 190 patients included in this study,70.5%(134/190)were stage I patients,12.6%(24/190)were stage II patients,16.3%(31/190)were stage III patients,and 0.5%(1/190)were stage IV patients.10.78.9% of Cg A positivity,95.8% of Syn positivity,82.6% of CD56 positivity,93.2% of CK positivity,and 80.0% of Vimentin positivity in this study.11.The patients included in this study were divided into 3 groups according to the 2010 neuroendocrine tumor grading criteria of <3%,3-20%,and >20%,and each group accounted for 66.8%(127/190),12.6%(24/190),and 20.5%(39/190),respectively.12.All 190 patients included in this study reported information on the grading of the tumor.Among them,G1 accounted for 67.4%(128/190),G2 accounted for 12.6%(24/190),G3 accounted for 13.7%(26/190),and mixed neuroendocrine and non-neuroendocrine(Mi NEN)tumors accounted for 6.3%(12/190).Patients with GI-NEN of different WHO pathologic classification had different age of onset,tumor site,embryonic origin,maximum tumor diameter,T-stage,and T-stage,vascular invasion,nerve invasion,lymph node metastasis,AJCC staging,CK positivity on the differences were statistically significant.13.The treatment of 190 patients included in this study was counted,82 patients were treated surgically,57 of them underwent open or laparoscopic surgery,25 patients underwent transanorectal mass resection,and the remaining 108 patients were treated endoscopically.Nine patients underwent chemotherapy,and all of them were treated with postoperative chemotherapy,and only three patients underwent postoperative radiation therapy.Open or lumpectomy was performed in 80.8% of GI-NEN patients with a maximum tumor diameter of ≥2 cm,while 73.3% of GI-NEN patients with a maximum tumor diameter of <1 cm underwent transanal mass resection and 79.6% of GI-NEN patients with a maximum tumor diameter of <1 cm underwent endoscopic treatment.The difference in GI-NEN patients with different tumor diameter sizes treated by different treatment modalities(X2=139.829,P=0.000)was statistically significant.14.190 patients were followed up to 180 cases and 10 cases were missed,with a followup rate of 94.7%.The follow-up time ranged from 4 to 124 months,with a median followup time of 20.5 months.Among the 180 patients followed up,18 patients died,17 of whom died due to systemic metastasis of the tumor and 1 patient died of underlying disease.The overall survival rate was 90.0%,and the Log Rank(Mantel-Cox)analysis yielded a statistically significant difference between the postoperative survival of GI-NEN patients with pathological grade G1 and GI-NEN patients with pathological grade G2,G3 and Mi NEN.The postoperative survival of GI-NEN patients with pathology grade G2 was statistically different from that of GI-NEN patients with pathology grade Mi NEN.Postoperative disease-free survival of GI-NEN patients with pathology grade G1 was statistically different from that of GI-NEN patients with pathology grade G3 and Mi NEN.The disease-free postoperative survival of GI-NEN patients with pathology grade G2 was statistically different from that of GI-NEN patients with pathology grade Mi NEN.Log Rank(Mantel-Cox)analysis yielded a statistically significant difference in postoperative survival of GI-NEN patients treated surgically versus those treated endoscopically.15.G1 showed significantly better overall survival(OS)compared to G2,G3 and Mi NEN(P = 0.008,P = 0.000 and P = 0.000,respectively),while there was no significant difference between G2 and G3(P = 0.078).Compared with Mi NEN,G2 showed significantly better OS(P = 0.002).And there was no significant difference between G3 and Mi NEN(P=0.380).G1 showed significantly better DFS compared to G2,G3 and Mi NEN(P = 0.016,P = 0.000 and P = 0.000,respectively),while there was no significant difference between G2 and G3(P = 0.059).G2 showed significantly better disease-free survival(DFS)compared to Mi NEN(P = 0.003).And there was no significant difference between G3 and Mi NEN(P=0.419).16.There were statistical differences in postoperative survival of GI-NEN patients with different primary tumor sites.The 5-year survival rates were 19.0%,82.0%,100.0%,50.0%,and 80.0% for gastric,duodenal,appendiceal,colonic,and rectal NEN,respectively.When comparing the OS of GI-NEN patients with recurrent different primary tumor sites,the difference between primary tumor sites was not statistically significant.the difference in DFS between the five primary tumor sites was statistically significant(P=0.000).The 5-year DFS rates were 23.0%,82.0%,100.0%,50.0%,and 80.0% for gastric,duodenal,appendiceal,colonic,and rectal NEN,respectively.The recurrence rate was 50.0% for gastric NEN,10.0% for duodenal NEN,0% for appendiceal NEN,33.3% for colonic NEN,and 1.5% for rectal NEN.17.the OS and DFS of GI-NEN patients were compared across all different AJCC stages.the OS of the stage I patient subgroup was better than that of stage II,III,and IV patients(stage I vs.stage II,P = 0.002;stage I vs.stage III,P = 0.000;stage I vs.stage IV,P =0.000).OS was better in the stage II patient subgroup than in the stage III and IV patients(stage II vs.stage III,P = 0.010;stage II vs.stage IV,P = 0.000).OS was better in the stage III patient subgroup than in the stage IV patients(stage III vs stage IV,P = 0.000).DFS was better in the subgroup of stage I patients than in stage II,III and IV patients(stage I vs stage II,P = 0.001;stage I vs stage III,P = 0.000;stage I vs stage IV,P =0.000).The subgroup of patients with stage II had better DFS than patients with stage III and IV(stage II vs.stage III,P = 0.013;stage II vs.stage IV,P = 0.000).The subgroup of patients with stage III had better DFS than patients with stage IV(stage III vs.stage IV,P= 0.000).18.Univariate analysis showed that age(>53 years)(p=0.009),embryonic origin(mid/hindgut)(p=0.000),preoperative Hb(≥139)(p=0.014),PLR(≥90.19)(p=0.030),lymph node metastasis(p=0.000),maximum tumor diameter(≥2 cm)(p=0.000),WHO tumor pathological grading(G3,Mi NEN)(P=0.000),T-stage(T3,T4)(P=0.000),AJCC stage(III,IV)(P=0.000),Ki67(>20%)(P=0.000),CK(+)(P=0.002),nerve infiltration(P=0.000),vascular infiltration(P=0.000),endoscopic treatment(p=0.002),and postoperative recurrence(p=0.000)were associated with long-term survival outcomes after GI-NEN(p<0.05).Using a forward stepwise(likelihood ratio)approach,these factors were included in multivariate analysis,and preoperative Hb(≥139)(p=0.043),CK(+)(p=0.034),nerve infiltration(p=0.045)and postoperative recurrence(p=0.015)were independent factors affecting postoperative survival outcome in patients with GI-NEN.Conclusion:1.The differences in age at presentation,tumor site,embryonic origin,maximum tumor diameter,T-stage,vascular invasion,nerve invasion,lymph node metastasis,AJCC stage,and CK positivity rate were statistically significant among patients with GI-NEN of different WHO pathological classifications.2.G1 showed significantly better OS and DFS compared with G2,G3 and MiNEN,while there was no significant difference between G2 and G3.G2 showed significantly better OS and DFS compared to Mi NEN,while there was no significant difference between G3 and Mi NEN.OS and DFS of GI-NEN patients were compared across all AJCC stages. stage I patient subgroup showed better OS and DFS than stage II,III and IV patients.The OS and DFS of the stage II patient subgroup were better than those of stage III and IV patients.The OS and DFS of the stage III patient subgroup were better than those of the stage IV patients.3.Long-term survival outcome after GI-NEN was associated with age(>53 years),embryonic origin(mid/posterior intestine),preoperative Hb(≥139),PLR(≥90.19),lymph node metastasis,maximum tumor diameter(≥2 cm),WHO tumor pathology classification(G3,Mi NEN),T-stage(T3,T4),AJCC stage(III,IV),Ki67(>20%)),CK(+),nerve infiltration,vascular infiltration,endoscopic treatment,and postoperative recurrence were associated with long-term survival outcome after GI-NEN,and preoperative Hb(≥139),CK(+),nerve infiltration,and postoperative recurrence were independent factors affecting the postoperative survival outcome of GI-NEN patients.