ADVANCE study is designed to explore the effects of intensive glucose control and routine blood pressure lowering measures on major macro-and micro-vascular complications in patients with type 2 diabetes.It reveals a series of risk factors of macrovascular disease,and analysis for risk factors will take effective actions to prevent or intervene macrovascular events.

Objective To investigate the epidemiological characteristics,clinical features,diagnosis,treatment and prognosis of benign tumor of the bile ducts.Methods The retrospective cross-sectional multicenter study was conducted.The clinical data of 136 patients with benign tumor of the bile ducts who were admitted to the eight hospitals between January 2007 and December 2016 were collected,including 70 in the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University,19 in the First Affiliated Hospital of Zhengzhou University,15 in the First Affiliated Hospital of Xi'an Jiaotong University,11 in the First Affiliated Hospital of Dalian Medical University,7 in the Affiliated Hospital of North Sichuan Medical College,6 in the Southwest Hospital of the Third Military Medical University,4 in the Cancer Center of Sun Yat-Sen University and 4 in the Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine.All the patients received laboratory and imaging examinations,and then underwent corresponding surgery when treatment planning was respectively determined by comprehensive hospitals according to clinical features and results of examinations.Surgical procedures were performed based on the results of intraoperative frozen section in rapid pathological diagnosis.Observation indicators:(1) epidemiological characteristics;(2) clinical features;(3) results of laboratory and imaging examinations;(4) treatment situations;(5) follow-up situations.Follow-up using outpatient examination and telephone interview was performed to detect the survival of patients up to March 2017.Measurement data with normal distribution were represented as-x±s.Results (1) Epidemiological characteristics:Of 136 patients,the male to female ratio was 1.78 ∶ 1.The incidence of whole bile duct tumors was from high to low,including 52 patients with duodenal papilla adenoma,32 with extrahepatic bile duct adenoma,24 with intrahepatic biliary cystadenoma,11 with intrahepatic papillary adenoma,9 with intrahepatic bile duct epithelial tumor,7 with epithelial tumor of duodenal papilla and 1 with neuroendocrine tumor of duodenal papilla.Among 136 patients,adenomas (including cystadenoma) was detected in 108 patients,papillomas in 11 patients,intraepithelial neoplasias in 16 patients,neuroendocrine tumor in 1 patient;intrahepatic bile duct benign tumors in 44 patients and extrahepatic bile duct (including duodenal papilla) benign tumors in 92 patients.(2) Clinical features:of 44 patients with intrahepatic bile duct benign tumors,29 had abdominal pain,fever and abdominal masses,4 had jaundice,11 had no obvious clinical symptoms and were diagnosed by physical examination.Among 92 patients with extrahepatic bile duct benign tumors,76 developed obstructive jaundice,68 were accompanied by abdominal pain or colicky pain,8 were combined with pancreatitis and 2 deveIoped hemobilia,some patients were combined with multiple clinical symptoms.(3) Results of laboratory and imaging examinations:82 patients received CA19-9 test,results of 22 patients were abnormal,with a level of (148-± 126)U/mL.Ninety-seven patients received carcinoembryonic antigen (CEA) test,with a level of test of (2.7±2.0) μg/L,and a level of CEA in 1 patient was slight abnormal,with a level of 11.2 pμg/L.One hundred and thirty-six patients underwent preoperative ultrasound examinations,showing unqualified hepatic and bile duct space occupying lesions and bile duct dilatation.Ninetyfive patients underwent preoperative computed tomography (CT),80 underwent preoperative magnetic resonance imaging (MRI) or magnetic resonanced cholangio-pancreatography (MRCP),and 13 underwent preoperative endoscopic ultrasonography (EUS).Twenty-nine patients were considered for intrahepatic bile duct benign tumors;76 were diagnosed with obstructive jaundice,with uncertain benign or malignant tumors;other patients had bile duct space occupying,considering bile duct tumor (including cancer).Twelve patients with bile duct obstruction underwent ERCP,showing obstruction site and morphology.(4) Treatment situations:among 136 patients,65 underwent pancreaticoduodenectomy,17 underwent right hemihepatectomy + cholecystectomy,16 underwent cholecystectomy + hepatic left lateral lobectomy,11 underwent left hemihepatectomy + cholecystectomy,11 underwent duodenal papillary local excision+papilla reconstruction,11 underwent Roux-en-Y choledochojejunostomy anastomosis,4 underwent cholecystectomy + extrahepatic bile duct local excision + end-to-end bile duct anastomosis and 1 underwent endoscopic mucosal resection of duodenal papillary adenomna.Of 136 patients with postoperative complications,25 were complicated with pancreatic leakage,11 with bile leakage,2 with postoperative hemorrhage and 1 with hepatic failure.Two patients with pancreatic leakage died of massive hemorrhage caused by abdominal infection,1 died of hepatic failure and other patients were discharged from hospital after symptomatic treatment.(5) Follow-up situations:47 of 136 patients were followed up for 3-123 months,with a follow-up rate of 34.6％.During follow-up,2 patients undergoing duodenal papillary local excision + papilla reconstruction had canceration,and other patients had good survival.Conclusions There is a low clinical incidence of benign tumor of the bile ducts,which is more common in male than in female,and in adenomas (including cystadenoma) and papillomas.The preoperative imaging examinations or ERCP biopsy pathological examination can increase an accuracy of preoperative diagnosis.Benign tumors with high canceration rates need positive surgical treatment.

Objective To analyze the clinicopathological features and lymph node metastases characteristics of intrahepatic cholangiocarcinoma (ICC).Methods The retrospective case-control study was conducted.The clinicopathological data of 1 321 ICC patients who were admitted to 12 hospitals from April 2007 to November 2017 were collected,including 182 in the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University,173 in the First Affiliated Hospital of Xi'an Jiaotong University,156 in the First Hospital Affiliated to Army Medical University (Third Military Medical University),139 in the Cancer Center of Sun Yatsen University,128 in the Zhongshan Hospital of Fudan University,113 in the Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine,109 in the First Affiliated Hospital of Dalian Medical University,84 in the Tianjin Medical University Cancer Institute and Hospital,65 in the First Affiliated Hospital of Zhengzhou University,62 in the Affiliated Hospital of North Sichuan Medical College,58 in the Affiliated Drum Tower Hospital of Nanjing University Medical School and 52 in the Second Affiliated Hospital of Zhejiang University School of Medicine.Treatment planning was respectively determined by comprehensive hospitals according to clinical features and results of related examinations.Surgical procedures were performed based on the results of intraoperative examinations and patients' conditions.Observation indicators:(1) laboratory examination and treatment situations;(2) relationship between clinicopathological features and primary tumor location and diameter;(3) diagnosis of lymph node dissection and metastases;(4) relationship between clinicopathological features and lymph node metastases.Measurement data with normal distribution were represented as x±s,and comparison between groups was done by the t test.Measurement data with skewed distribution were described as M (range).Comparison of count data were analyzed using the chi-square test.Results (1) Laboratory examination and treatment situations:of 1 321 patients,cases and percentages of positive hepatitis B virus (HBV),positive serum alpha-fetoprotein (AFP) (＞ 20 μg/L),positive serum carcinoembryonic antigen (CEA) (＞ 5 μg/L),positive serum alanine transaminase (ALT) (＞75 U/L),positive serum CA19-9 (＞37 U/mL) and positive serum total bilirubin (TBil) (＞20 μmol/L) were respectively 202,80,329,207,590,300 and 15.586％ (202/1 296),7.339％(80/1 090),26.299％ (329/1 251),16.587％ (207/1 248),49.789％(590/1 185),24.000％ (300/1 250).Of 1 321 patients,1 206 underwent surgery,including 904 with hepatectomy,193 with transcatheter arterial chemoembolization (TACE),72 with percutaneous transhepatic biliary drainage (PTBD),3 with endoscopic retrograde cholangiopancreatography (ERCP),3 with PTBD + ERCP and 31 with other treatments;115 had missing registration of surgical procedures.(2) Relationship between clinicopathological features and primary tumor location and diameter:① Relationship between clinicopathological features and primary tumor location:cases with CA19-9 level ≤ 37 U/mL,38-200 U/mL and ＞ 200 U/mL were respectively 227,91,146 with primary tumor located in left liver and 282,134,137 with primary tumor located in right liver.Cases combined with hepatitis and intrahepatic bile duct stone were respectively 67,73 with primary tumor in left liver and 111,47 with primary tumor in right liver,with statistically significant differences in above indictors (x2 =6.710,5.656,12.534,P＜0.05).The results of further analysis showed that incidence age of ICC was (63± 10)years old in patients with hepatitis and (59± 10) years old in patients without hepatitis,with statistically significant differences (t =4.840,P＜0.05).② Relationship between clinicopathological features and primary tumor diameter:cases with primary tumor diameter ≤ 3 cm,with 3 cm ＜ primary tumor diameter ≤ 5 cm and with primary tumor diameter ＞ 5 cm were respectively 159,250,229 with CEA level ≤ 5 pg/L and 40,65,95 with CEA level ＞ 5 μg/L and 165,258,286 with ALT level ≤ 75 U/L and 34,57,36 with ALT level ＞ 75 U/L and 148,242,281 with TBil level ≤ 20 μmol/L and 51,73,43 with TBil level ＞ 20 μmol/L,and 37,70 and 131 patients had satellite loci of tumor,with statistically significant differences in above indictors (x2=8.669,6.637,15.129,34.746,P＜0.05).(3) Diagnosis of lymph node dissection and metastases:of 904 patients with hepatectomy,346 received lymph node dissection,total number,number in each patient and median number of lymph node dissected were respectively 1 894.0,5.5 and 4.0 (range,1.0-26.0);157 had lymph node metastases,with a rate of lymph node metastasis of 45.376％ (157/346),number and number in each patient of positive lymph node were respectively 393.0 and 2.5.Of 346 patients with lymph node dissection,114 had lymph node metastasis by preoperative imaging examination,postoperative pathological examinations confirmed 64 with lymph node metastasis and 50 without lymph node metastasis;232 didn't have lymph node metastasis by preoperative imaging examination,postoperative pathological examinations confirmed 93 with lymph node metastasis and 139 without lymph node metastasis.The sensitivity,specificity and diagnostic accuracy by imaging examination were respectively 40.8％,73.5％ and 58.7％.(4) Relationship between clinicopathological characteristics and lymph node metastases:lymph node metastasis rate was respectively 51.397％ (92/179) in patients with primary tumor located in left liver,39.103％ (61/156) in patients with primary tumor located in right liver,34.615％(18/52) in patients with primary tumor diameter ≤ 3 cm,42.500％(51/120) in patients with 3 cm ＜ primary tumor diameter ≤ 5 cm,52.980％(80/151) in patients with primary tumor diameter ＞ 5 cm,48.790％(121/248) in patients with CEA ≤ 5 μg/L,59.302％ (51/86) in patients with CEA ＞ 5 μg/L,40.234％ (103/256) in patients with TBil ≤ 20 μmol/L,35.106％ (33/94) in patients with TBil ＞ 20 μmol/L,with statistically significant differences in above indictors (x2 =5.078,6.262,9.456,5.156,P ＜ 0.05).Conclusions The related etiological factors may be different due to different primary location of ICC.Primary tumor in left liver is significantly associated with intrahepatic bile duct stone of left liver,and primary tumor in right liver is associated with combined hepatitis,while combined hepatitis could lead early occurrence of ICC.At present,there is a low rate of lymph node dissection in ICC patients and a high lymph node metastasis rate in patients receiving lymph node dissection.Lymph node metastasis is associated with primary tumor location and diameter,levels of CEA and TBil.Lymph node metastasis rate in left liver is higher than that in right liver,and is getting higher with increased primary tumor diameter.