Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is rare and enhanced CT or MRI can be used for its diagnosis. Surgical procedure is the main treatment for HCC with BDTT. The authors introduce the experiences of recurrent patient with HCC and BDTT who was treated with targeted therapy plus immunotherapy, in order to provide reference for its clinical diagnosis and treatment.

【Objective】 To investigate the expression of pyruvate kinase M2 (PKM2) in intrahepatic cholangiocarcinoma (ICC) and the effect of PKM2 on the proliferation and epithelial-to-mesenchymal transition (EMT) of ICC cells. 【Methods】 PKM2 expression was evaluated in ICC tissues and cell lines by Real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR), and immunohistochemistry assays. In vitro, we knocked down PKM2 expression in ICC cell lines and investigated the biological function and the underlying mechanism of PKM2 in ICC. 【Results】 RT-PCR results showed that PKM2 was highly expressed in ICC (P<0.05). Moreover, PKM2 knockdown inhibited cell proliferation and the invasive capacities of ICC cells, and inhibited Wnt/ β-Catenin signaling, which subsequently regulated EMT signaling pathway in vitro. 【Conclusion】 PKM2 expression in cholangiocarcinoma is significantly higher than that in adjacent tissues. PKM2 can regulate EMT and invasion and metastasis of ICC via the Wnt/β-Catenin signal.

Objective:To analyse the clinical characteristics of mercury-toxic nephrotic syndrome and to find the risk factors.Methods:A total of 126 patients with mercury-toxic admitted to Beijing Chaoyang Hospital from January 2017 to January 2020 were selected as the research objectives. General data such as age, gender, mercury exposure history of all patients and laboratory data such as urine mercury and urine creatinine were collected. The clinical manifestations and pathological types of patients with mercury-toxic nephrotic syndrome were analyzed, and the risk factors of mercury-toxic nephrotic syndrome were found by univariate and multivariate logistic regression analysis.Results:Among the 24 patients with mercury-toxic nephrotic syndrome, 1 was poisoned by respiratory tract, 6 were poisoned by digestive tract, and 17 were poisoned by skin absorption. In addition to the manifestations of kidney injury, some of the patients also showed neurological symptoms such as dizziness, fatigue, hand tremor, and limb pain. The main pathological types were membranous nephropathy (9 cases) and micropathological nephropathy (10 cases) . The results of multivariate logistic regression analysis showed that the digestive tract and skin absorption pathways of mercury were risk factors for mercury-toxic nephrotic syndrome ( OR=21.099, 23.840, P<0.05) . Conclusion:The absorption pathway of mercury has an important influence on the pathogenesis of mercury-toxic nephrotic syndrome, especially in patients with mercury poisoning absorbed by the skin and digestive tract, the risk of complicating nephrotic syndrome is higher.

Objective:To analyse the clinical characteristics of mercury-toxic nephrotic syndrome and to find the risk factors.Methods:A total of 126 patients with mercury-toxic admitted to Beijing Chaoyang Hospital from January 2017 to January 2020 were selected as the research objectives. General data such as age, gender, mercury exposure history of all patients and laboratory data such as urine mercury and urine creatinine were collected. The clinical manifestations and pathological types of patients with mercury-toxic nephrotic syndrome were analyzed, and the risk factors of mercury-toxic nephrotic syndrome were found by univariate and multivariate logistic regression analysis.Results:Among the 24 patients with mercury-toxic nephrotic syndrome, 1 was poisoned by respiratory tract, 6 were poisoned by digestive tract, and 17 were poisoned by skin absorption. In addition to the manifestations of kidney injury, some of the patients also showed neurological symptoms such as dizziness, fatigue, hand tremor, and limb pain. The main pathological types were membranous nephropathy (9 cases) and micropathological nephropathy (10 cases) . The results of multivariate logistic regression analysis showed that the digestive tract and skin absorption pathways of mercury were risk factors for mercury-toxic nephrotic syndrome ( OR=21.099, 23.840, P<0.05) . Conclusion:The absorption pathway of mercury has an important influence on the pathogenesis of mercury-toxic nephrotic syndrome, especially in patients with mercury poisoning absorbed by the skin and digestive tract, the risk of complicating nephrotic syndrome is higher.

Objective:To examine the role of the number of lymph nodes examined(NLNE) on the prognosis of patients with curatively resected gallbladder carcinoma(GBC).Methods:The clinicopathological data and prognosis of 401 patients with GBC who underwent radical surgery from six institutions of China from January 2013 to December 2017 were analyzed retrospectively. There were 153 males(38.2%) and 248 females(61.8%), with age of (62.0±10.5) years (range: 30-88 years). Fifty-three patients(22.2%) were accompanied by jaundice. All patients underwent radical resection+regional lymphadenectomy.R0 or R1 resection was confirmed by postoperative pathological examination.The different cut-off values of NLNE were determined by the X-tile software, the optimal cut-off values were identified by analyzing the relationship between different cut-off values of NLNE with survival rate. Kaplan-Meier method was used for survival analysis. Univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.Results:Among the 401 patients enrolled, 135 cases (33.6%) had lymphatic metastasis, of which 98 cases were in N1 stage(24.4%) and 37 cases were in N2 stage(9.2%).A total of 2 794 NLNE were retrieved, with a median count of 6 (5).The median positive lymph nodes count was 0 (1), and the median positive lymph nodes ratio was 0 (IQR, 0-0.2). Since the 12 and 15 were determined as the cut-off values by X-tile, all patients were divided into three groups of 1-11, 12-15 and ≥16.The 3-year survival rate of the three groups was 45.2%, 74.5%, 12.0% respectively, with statistically significant difference between three groups (χ 2=10.94, P<0.01). The results of multivariate analysis showed that NLNE was an independent prognostic factor for overall survival ( P<0.05). Further analysis was performed specifically for subgroup of T stages. For T1b patients, the prognosis of the NLNE with 1-7 group was significantly better than that of the ≥8 group(χ 2=4.610, P<0.05). For T2 patients, the prognosis of the TLNE ≥7 group was significantly better than that of 1 -6 group (χ 2=4.287, P<0.05). For T3 and T4 patients, the prognosis of the TLNE with 12 - 15 group was significantly better than that of 1 -11 group (χ 2=5.007, P<0.01) and ≥16 group (χ 2=10.158, P<0.01). Conclusions:The NLNE is an independent factor affecting the prognosis of patients with GBC.For patients with stage T1b,8 lymph nodes should be retrieved; for patients with stage T2,extensive dissection of more than 6 lymph nodes can significantly improve the prognosis.For advanced patients (stages T3 and T4), extensive dissection with 12-15 lymph nodes is recommended. However, it fails to get more survival benefits by dissecting more than 16 lymph nodes.

Objective:To examine the role of the number of lymph nodes examined(NLNE) on the prognosis of patients with curatively resected gallbladder carcinoma(GBC).Methods:The clinicopathological data and prognosis of 401 patients with GBC who underwent radical surgery from six institutions of China from January 2013 to December 2017 were analyzed retrospectively. There were 153 males(38.2%) and 248 females(61.8%), with age of (62.0±10.5) years (range: 30-88 years). Fifty-three patients(22.2%) were accompanied by jaundice. All patients underwent radical resection+regional lymphadenectomy.R0 or R1 resection was confirmed by postoperative pathological examination.The different cut-off values of NLNE were determined by the X-tile software, the optimal cut-off values were identified by analyzing the relationship between different cut-off values of NLNE with survival rate. Kaplan-Meier method was used for survival analysis. Univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.Results:Among the 401 patients enrolled, 135 cases (33.6%) had lymphatic metastasis, of which 98 cases were in N1 stage(24.4%) and 37 cases were in N2 stage(9.2%).A total of 2 794 NLNE were retrieved, with a median count of 6 (5).The median positive lymph nodes count was 0 (1), and the median positive lymph nodes ratio was 0 (IQR, 0-0.2). Since the 12 and 15 were determined as the cut-off values by X-tile, all patients were divided into three groups of 1-11, 12-15 and ≥16.The 3-year survival rate of the three groups was 45.2%, 74.5%, 12.0% respectively, with statistically significant difference between three groups (χ 2=10.94, P<0.01). The results of multivariate analysis showed that NLNE was an independent prognostic factor for overall survival ( P<0.05). Further analysis was performed specifically for subgroup of T stages. For T1b patients, the prognosis of the NLNE with 1-7 group was significantly better than that of the ≥8 group(χ 2=4.610, P<0.05). For T2 patients, the prognosis of the TLNE ≥7 group was significantly better than that of 1 -6 group (χ 2=4.287, P<0.05). For T3 and T4 patients, the prognosis of the TLNE with 12 - 15 group was significantly better than that of 1 -11 group (χ 2=5.007, P<0.01) and ≥16 group (χ 2=10.158, P<0.01). Conclusions:The NLNE is an independent factor affecting the prognosis of patients with GBC.For patients with stage T1b,8 lymph nodes should be retrieved; for patients with stage T2,extensive dissection of more than 6 lymph nodes can significantly improve the prognosis.For advanced patients (stages T3 and T4), extensive dissection with 12-15 lymph nodes is recommended. However, it fails to get more survival benefits by dissecting more than 16 lymph nodes.

Objective To explore the diagnosis and treatment of Castleman's disease (CD) of the abdomen and pelvis.Methods The clinical data of 51 cases of abdomen and pelvis CD were analyzed retrospectively from Jan 2007 to Oct 2017 in the First Affiliated Hospital of Zhengzhou University.Patients were divided into two groups according to the different clinical classifications:Localized CD (n =42) and Multicentric CD (n =9).Results 32 cases of LCD were asymptomatic (76％),others accompanied by abdominal or waist pain,abdominal distention.The main pathological type was hyaline vascular (93％),which can be cured by surgical treatment (41/42).MCD always accompanied by multiple superficial and deep lymph node enlargement in the whole body.Most of them suffered from anemia,fever,weight loss and dyspnea.CRP increased,hypoproteinemia,globulin increased,neutropenia were found.The main pathological type was plasma cell type (56％).There were no progress in 3 cases,and 6 cases were on remission after operation.Conclusion The diagnosis of abdomen and pelvis CD depends on pathological examination.LCD clinical symptoms are mild and good prognosis after surgery.However,MCD clinical manifestations are complex,and relatively poor prognosis after comprehensive treatment.

Objectives: To propose a novel clinical classification system of gallbladder cancer, and to investigate the differences of clinicopathological characteristics and prognosis based on patients who underwent radical resection with different types of gallbladder cancer. Methods: The clinical data of 1 059 patients with gallbladder cancer underwent radical resection in 12 institutions in China from January 2013 to December 2017 were retrospectively collected and analyzed.There were 389 males and 670 females, aged (62.0±10.5)years(range:22-88 years).According to the location of tumor and the mode of invasion,the tumors were divided into peritoneal type, hepatic type, hepatic hilum type and mixed type, the surgical procedures were divided into regional radical resection and extended radical resection.The correlation between different types and T stage, N stage, vascular invasion, neural invasion, median survival time and surgical procedures were analyzed.Rates were compared by χ² test, survival analysis was carried by Kaplan-Meier and Log-rank test. Results: Regional radical resection was performed in 940 cases,including 81 cases in T1 stage,859 cases in T2-T4 stage,119 cases underwent extended radical resection;R0 resection was achieved in 990 cases(93.5%).The overall median survival time was 28 months.There were 81 patients in Tis-T1 stage and 978 patients in T2-T4 stage.The classification of gallbladder cancer in patients with T2-T4 stage: 345 cases(35.3%)of peritoneal type, 331 cases(33.8%) of hepatic type, 122 cases(12.5%) of hepatic hilum type and 180 cases(18.4%) of mixed type.T stage(χ²=288.60,P<0.01),N stage(χ²=68.10, P<0.01), vascular invasion(χ²=128.70, P<0.01)and neural invasion(χ²=54.30, P<0.01)were significantly correlated with the classification.The median survival time of peritoneal type,hepatic type,hepatic hilum type and mixed type was 48 months,21 months,16 months and 11 months,respectively(χ²=80.60,P<0.01).There was no significant difference in median survival time between regional radical resection and extended radical resection in the peritoneal type,hepatic type,hepatic hilum type and mixed type(all P>0.05). Conclusion With application of new clinical classification, different types of gallbladder cancer are proved to be correlated with TNM stage, malignant biological behavior and prognosis, which will facilitate us in preoperative evaluation,surgical planning and prognosis evaluation.

Objective To investigate the application value of choledochoscopy and imaging examination in the diagnosis and treatment of residual bile duct stones.Methods The retrospective descriptive study was conducted.The clinical data of 618 patients who underwent choledochoscopy and imaging examination after operation of hepatolithiasis in the First Affiliated Hospital of Zhengzhou University between April 2014 and September 2018 were collected,including 300 males and 318 females,aged from 19 to 89 years,with an average age of (58 ± 12)years.Observation indicators:(1) situations of residual bile duct stones diagnosed by choledochoscopy and imaging examination;(2) stone extraction situations of patients with hepatolithiasis.Measurement data with normal distribution were represented as Mean±SD,and measurement data with skewed distribution were described as M (range).Count data were represented as absolute number or percentage,and analyzed using the chi-square test or Fisher exact propability.Results (1) Situations of residual bile duct stones diagnosed by choledochoscopy and imaging examination:all the 618 patients underwent choledochoscopy,and 505 of them underwent the imaging examination before choledochoscopy.① Of patients undergoing single imaging examination,72 received ultrasonography,with false-negative rate of 29.17％ (21/72);37 received CT examination,with false-negative rate of 10.81％(4/37);33 received T-tube cholangiography,with false-negative rate of 39.39％ (13/33).② Of patients undergoing combined two imaging examinations,61 received ultrasonography + CT,with false-negative rate of 8.20％ (5/61);129 received ultrasonography + T-tube cholangiography,with false-negative rate of 12.40％ (16/129);52 received CT + T-tube cholangiography,with false-negative rate of 5.77％(3/52).③ There were 121 receiving ultrasound+CT+T-tube cholangiography,with false-negative rate of 7.44％ (9/121).There were statistically significant differences in the false-negative rates of combined two or three examinations of ultrasound + CT+ T-tube cholangiography and single imaging examination (x2=40.83,P＜0.05).The further analysis showed a statistically significant difference among the single imaging examination (x2=7.70,P＜0.05).There was no statistically significant difference among the combined two of imaging examinations (x2=2.10,P＞0.05).There were statistically significant differences in the combined three examinations of ultrasound +CT+T-tube cholangiography and ultrasound and T-tube cholangiography examination respectively (x2=16.23,21.62,P＜0.05).There was no statistically significant difference in the combined three of imaging examinations and CT examination and combination of CT+T-tube cholangiography respectively (P＞ 0.05).There was no statistically significant difference in the combined three of imaging examinations and combination of ultrasound+CT examinations and combination of ultrasound+T-tube cholangiography (x2=0.33,1.71,P＞0.05).Seventy-one patients without residual bile duct stone by preoperative imaging examination were detected residual bile duct stones by intraoperative choledochoscopy,and residual bile duct stones of 36,31 and 4 patients are respectively distributed around the distal common bile duct,small intrahepatic bile duct,left and right hepatic ducts,common hepatic duct and remaining common bile duct.(2) Stone extraction situations of patients with hepatolithiasis:of 618 patients,cases with 1,2,3,4,5,6,7,8,9 and 10 times of residual bile duct stones clearance were respectively 392,116,48,39,9,6,3,2,2 and 1.Residual bile duct stones clearance frequency of patients was an average of 1.73 times.There were 63.43％(392/618) and 96.28％(595/618) of patients had stone clearance with once and ≤ 4 times of stone extraction,respectively.Conclusion The negative results of preoperative imaging examinations cannot be as standards of bile duct stone clearance before choledochoscopy,and the best choice is to detect whether there are residual bile duct stones and remove the stones combined with choledochoscopy.

Objective To analyze the pathological results and current treatment situation of patients with unexpected gallbladder carcinoma from multi-centers in China,and explore the diagnosis and treatment of unexpected gallbladder carcinoma.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 223 patients with unexpected gallbladder carcinoma who were admitted to the 8 clinical centers from January 2010 to December 2016 were collected,including 86 in the First Affiliated Hospital of Xi'an Jiaotong University,41 in the First Affiliated Hospital of Zhengzhou University,30 in the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University,27 in the Xinhua Hospital of Shanghai Jiaotong University,13 in the First Affiliated Hospital of Dalian Medical University,11 in the Tianjin Medical University Cancer Institute & Hospital,9 in the First Affiliated Hospital of Army Medical University (Third Military Medical University) and 6 in the Affiliated Hospital of North Sichuan Medical College.Treatment of patients with unexpected gallbladder carcinoma who were diagnosed by intraoperative frozen section biopsy and postoperative pathological examination followed guideline for the diagnosis and treatment of gallbladder carcinoma (2015 edition).According to tumor staging and patients' decision,postoperative adjuvant treatment was selectively performed.Observation indicators:(1) diagnosis and treatment of unexpected gallbladder carcinoma;(2) followup and survival.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to June 2017.Measurement data with normal distribution were represented as (x)±s.Measurement data with skewed distribution were described as M (range).The survival time was calculated using the Kaplan-Meier method.Results (1) Diagnosis and treatment of unexpected gallbladder carcinoma:of 223 patients with unexpected gallbladder carcinoma,80 were initially diagnosed using intraoperative frozen section biopsy [20 received T stage results (intraoperative T stage of 14 patients had not matched postoperative results),and 60 didn't receive T stage results],and 143 were initially diagnosed using postoperative pathological examination (13 were initially diagnosed with gallbladder benign disease by intraoperative frozen section biopsy and 130 didn't intraoperatively receive frozen section biopsy).Of 223 patients,209,10,3 and 1 were respectively confirmed as adenocarcinoma,adenoma canceration,neuroendocrine tumor and squamous cell carcinoma;6,16,32,73,75,12 and 9 were respectively detected in Tis,T1a,T1b,T2,T3 and T4 stages and undefined stage;140 underwent reoperations,including 106 with radical resection of gallbladder carcinoma and 34 with extended radical resection of gallbladder carcinoma;operation of 126 patients reached the standard and operation of 97 patients didn't reach the standard.Of 27 patients with postoperative complications,12 with postoperative hemorrhage received successful hemostasis by reoperations (7 with cystic artery hemorrhage and 5 with blood oozing from gallbladder bed);8 with suppurative cholangitis received endoscopic retrograde cholangiopancreatography and choledochotomy with drainage,including 2 deaths and 6 with improvement;2 with common bile duct injury were improved by reoperation of choledochojejunostomy + T tube drainage;2 were complicated with bile leakage induced to peritonitis and underwent bile duct repair with drainage,including 1 death and 1 with improvement;2 with hepatic failure died of treatment failure;1 with colonic injury was improved by reoperation of anastomosis.Of 223 patients,207 didn't receive postoperative adjuvant treatment and 16 received postoperative adjuvant treatment,including 8 with chemotherapy,4 with radiotherapy,2 with immunologic therapy and 2 with Chinese medicine treatment.(2) Follow-up and survival:of 223 patients,193 were followed up for 6-90 months,with a median time of 33 months.Of 193 patients with follow-up:① The operation of 2 patients in stage Tis reached the standard,including 1 with cholecystectomy and 1 with radical resection of gallbladder carcinoma,and the postoperative survival time of them were respectively 28 months and 52 months.② The operation of 14 patients in stage T1a reached the standard,including 8 with cholecystectomy and 6 with radical resection of gallbladder carcinoma,and the postoperative survival time of them were respectively (74±5)months and (79±6)months.③ Of 26 patients in stage T1b,13 and 13 received respectively cholecystectomy and radical resection of gallbladder carcinoma (reaching the standard),and postoperative survival time of them were respectively (66±4)months and (76±8)months.④ Of 68 patients in stage T2,25,37,4 and 2 patients received respectively cholecystectomy,radical resection of gallbladder carcinoma (reaching the standard),extended radical resection of gallbladder carcinoma (reaching the standard) and palliative resection,and postoperative survival time of them were respectively (42±7) months,(66±6) months,(42±3) months and (26±3) months.⑤ Of 71 patients in stage T3,20,48 and 3 patients received respectively cholecystectomy,radical resection of gallbladder carcinoma (reaching the standard) and extended radical resection of gallbladder carcinoma (reaching the standard),and postoperative survival time of them were respectively (39±8) months,(48± 11) months and (10±6) months.⑥ Of 12 patients in stage T4,3,1,5 and 3 patients received respectively cholecystectomy,radical resection of gallbladder carcinoma (reaching the standard),extended radical resection of gallbladder carcinoma (reaching the standard) and palliative resection,and postoperative survival time of them were respectively (10±4) months,12 months,(9± 5) months and (11±3) months.Conclusions The intraoperative frozen section biopsy and pathological results are the key points for diagnosis and treatment of unexpected gallbladder carcinoma.Patients in stage Tis and T1a should undergo cholecystectomy,while patients in stage T1b and above should undergo radical resection of gallbladder carcinoma or extended radical resection of gallbladder carcinoma.