Epidemiological characteristics, diagnosis, treatment and prognosis of gallbladder cancer in China: a report of 6 159 cases / 中华消化外科杂志

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

Standardized diagnosis and treatment process of gallbladder disease and technical details / 中华消化外科杂志

Based on current diagnosis and treatment of gallbladder disease, the occur-rence of incidental gallbladder cancer is partly caused by the irregular clinical diagnosis and treatment process of gallbladder disease, which leads to the failure to make the diagnosis of gallbladder cancer in time, carry out the correct preoperative and intraoperative staging, and cause R 1 or R 2 resection. The authors summarize standardized diagnosis and treatment process of gallbladder disease and technical details. In clinical practice, the concept of incidental gallbladder cancer should be discarded, and various gallbladder diseases should be taken as a whole. A more standardized diagnosis and treatment process should be established to improve the diagnostic accuracy of gallbladder cancer and achieve radical resection, which eventually improve survival of patients.

Comprehensive treatment based on oncology principles should also be emphasized for treating gallbladder cancer / 中华外科杂志

Gallbladder carcinoma(GBC) is one of the most malignant cancers of the digestive system with very poor prognosis due to its histopathological features of easy invasion to the liver, early lymph node metastasis and nerve infiltration, which result in low resection rate. It has been confirmed that radical surgery only makes sense to relatively early GBC in improving prognosis of patients. Therefore, based on recognition of biological characteristics of GBC and the theories of oncology, efforts should be focused on developing various adjuvant treatment methods for treating GBC including chemotherapy, radiotherapy, targeted therapy and immunotherapy.

Pilot study of the relationship between clinical classification of gallbladder cancer and prognosis: a retrospective multicenter clinical study / 中华外科杂志

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.

Viewpoint of systematic lymphadenectomy for intrahepatic cholangiocarcinoma patients / 中华外科杂志

Intrahepatic cholangiocarcinoma(ICC) is the second common primary liver cancer originated from epithelium of the sub-branches of intrahepatic bile ducts with extremely poor prognosis and lack of effective treatment.The prognosis of ICC is mostly affected by the origin,the type and the size of the tumor as well as the intrahepatic metastasis(satellite lesion) and lymph node metastasis etc.Surgical resection remains the first choice of treatment to patients with ICC.However, there are multiple issues in surgical treatment of ICC, which have not been reached a consensus.Among them, the value of systematic lymphadenectomy during hepatic resection for ICC patient remains one of the hot spot issues.Given the heterogeneity of ICC,we recommend planning the procedure of the radical resection and lymphadenectomy personally, according to the type and origin of the tumor, the number and locationof the lesion.The pre-operation imaging examination and the intra-operation lymph node tracing technique could provide valuable information to help the surgeon decide the range of systematic lymphadenectomy.Routine systematic lymphadenectomy is recommended in the surgical treatment of ICC patients by experienced surgeons even without evidence of lymph node metastasis.The resected lymph tissue should be labeled by the provenance for further study.

History, current situation and bottleneck of the diagnosis and treatment system of hepatic hilar cholangiocarcinoma in Japan / 中华外科杂志

Hilar cholangiocarcinoma is one of the most difficult malignant tumors to treat in the biliary system. In Japan, 5-year survival rate of the disease has increased from 32.5% to 67.1% during the past 30 years. The impressive progress reflects the solid efforts in preoperative endoscopic diagnosis, innovation in surgery such as PTPE as well as hepato-pancreatoduodenectomy and perioperative treatment including replacement of the bile and synbiotic treatment, which have finally formed a set of standardized diagnosis and treatment systems. The present review intends to report the history, current status and remaining bottlenecks of the diagnosis and treatment system of hilar cholangiocarcinoma in Japan as follows.

The research situation and progress in the invasion and metastasis mechanism of intrahepatic cholangiocarcinoma / 中华消化外科杂志

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy with an increasing incidence and mortality in recent years.Despite advanced improvements in its diagnosis and therapy,the prognosis for ICC patients remains poor.High heterogeneity and malignant biological behavior are the main factors determining the prognosis of ICC.An in-depth study of the mechanism of ICC invasion and metastasis is expected to help optimizing clinical decision-making.The application of advanced technologies such as next-generation sequencing has enhanced the researchers' understanding of heterogeneity of ICC and characteristics of invasion and metastasis.Studies have found that ICC gene expression abnormalities (gene mutations,fusion gene formation,and abnormalities in gene expression regulatory pathways) and microRNA expression disorders are closely related to ICC cell proliferation,invasion and metastasis.In addition,ICC is usually characterized by a dense desmoplastic stroma,in which cancer-associated myofibroblasts are the major cellular components and play an important role in inducing epithelial-mesenchymal transition,promoting malignant cell invasion and metastasis,and even accelerating ICC progression.

Surgical and comprehensive treatment for intrahepatic cholangiocarcinoma patients from the perspective of tumor heterogeneity / 中华外科杂志

Intrahepatic cholangiocarcinoma(ICC) is generally found late along with extremely poor prognosis and lack of effective and standardized treatment. Tremendous heterogeneities exist in onset factors, geographic distribution, clinical manifestation, and biological characteristics of ICC patients. However, the relevant causes and mechanisms have not been clearly illustrated. Recent studies indicate that the diverse celluar origins of ICC, including liver cells, bile duct epithelial cells, glandular cells around the duct, and liver stem cells, etc. Besides, the tumorigenesis, progression and metastasis of ICC are closed related to metabolism such as glucose, lipid metabolism. It can be inferred that the varieties of biological characteristics and clinical manifestation of ICC patients are possibly closely linked with heterogeneous cellular origins, multiple metabolic mechanisms or pathways. Therefore, it′s necessary to conduct research with regard to the connection between cellular origins, cell metabolism and clinical manifestation, biological characteristics, and make further classifications. Based on the accurate classification, surgeons can exert corresponding surgical and comprehensive treatment strategies on ICC patients, attaining the goal of individualized and standardized treatment, ultimately, improving prognosis and prolonging survival time.

Problems and reflections on the diagnosis and treatment of gallbladder cancer / 中华外科杂志

Although more and more attention has been paid on the diagnosis and treatment of gallbladder cancer, the patients′ survival were still unsatisfied.Increasing the early diagnosis rate, the raise of awareness and treatment of unexpected gallbladder cancer, performing radical surgery for early stage patients and utilizing comprehensive treatment with adjuvant therapy for aggressive T2 or higher stage cases were the key points to improve patients′ prognosis of gallbladder cancer.

Advances in biliary tract cancer research from the 30th annual meeting of the Japanese Society of Hepato-Biliary-Pancreatic Surgery / 中华消化外科杂志

The 30th annual meeting of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) was held in Yokohama,Japan between June 7 and 9,2018.The latest research trends and advances in biliary tract cancer from this meeting were summarized and shared in this paper.The main content includes:history of biliary cancer surgery for recent 30 years and the future of HBP surgery for malignancies,establish of worldwide prospective database of biliary cancer and identify the optimal treatment for early gallbladder cancer,clinical research of neoadjuvant / adjuvant therapy,and progress in basic research of biliary malignancies.

Clinicopathological features and lymph node metastases characteristics of intrahepatic cholangiocarcinoma: a multicenter retrospective study (A report of 1321 cases) / 中华消化外科杂志

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.

Targeting gallbladder carcinoma: bone marrow-derived stem cells as therapeutic delivery vehicles of myxoma virus / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Gallbladder carcinoma (GBC) has a high mortality rate, requiring synergistic anti-tumor management for effective treatment. The myxoma virus (MYXV) exhibits a modest clinical value through its oncolytic potential and narrow host tropism.</p><p><b>METHODS</b>We performed viral replication assays, cell viability assays, migration assays, and xenograft tumor models to demonstrate that bone marrow-derived stem cells (BMSCs) may enhance efficiency of intravenous MYXV delivery.</p><p><b>RESULTS</b>We examined the permissiveness of various GBC cell lines towards MYXV infection and found two supported single and multiple rounds of MYXV replication, leading to an oncolytic effect. Furthermore, we found that BMSCs exhibited tropism for GBC cells within a Matrigel migration system. BMSCs failed to affect the growth of GBC cells, in terms of tumor volume and survival time. Finally, we demonstrated in vivo that intravenous injection of MYXV-infected BMSCs significantly improves the oncolytic effect of MYXV alone, almost to the same extent as intratumoral injection of MYXV.</p><p><b>CONCLUSION</b>This study indicates that BMSCs are a promising novel vehicle for MYXV to clinically address gallbladder tumors.</p>

Chimerism is required for neonatal transplantation tolerance / 中华微生物学和免疫学杂志

ObjectiveTo investigate the mechanisms of neonatal transplantation tolerance,especially the role of immature immune system and chimerism in tolerance.MethodsF1 ( or GFP-F1 ) mice were bred by crossing male C57BL/6 (or GPF transgenic C57BL/6) and female BALB/c mice. Within 24 h,newborn C57BL/6 mice were inoculated with different doses of splenocytes from F1 or GFP-F1 mice,irradiated spleen cells were used as control.Six weeks later,the mice were subjected to F1 skin grafting,and mixed-lymphocyte reaction was performed to determine their tolerance.Flow analysis was used to detect chimerism.ResultsLiving F1 spleen cells could induce chimerism and neonatal transplantation tolerance,but irradiated cells not.The chimerism in long-term tolerant mice is higher than that in chronic rejected mice,with 6.48％ ±4.02％ vs 1.57％ ±0.89％,the difference is significant in statistical analysis.The degree of neonatal transplantation tolerance is determined by the dosage of donor cells,the mice induced with 3 × 107 F1 spleen cells have 80％ long-term tolerance,but the dose of0.7×107 F1 spleen cells could only prolong allografts survival.ConclusionNeonatal transplantation tolerance is dependent on chimerism,the chimerism of donor cells leads to clonal deletion of alloreactive T cells.

Comprehensive management of gallbladder cancer / 中华消化外科杂志

Gallbladder cancer is the most common malignancy of biliary tract with a very poor prognosis. The therapeutic strategy of gallbladder cancer has been improved in some aspects. Identifying the accurate stage is the basis of surgical treatment. Radical resection is the only choice of treatment which provides patients long survival. For most patients in T1a stage, simple cholecystectomy is adequate, but dissection of hepatoduodenal ligament should be added when the lesions located in neck and duct of gallbladder. Patients in T1b stage often need radical cholecystectomy. Radical cholecystectomy with Ⅳb and Ⅴ segmentectomy and lymphadenectomy of N2 nodes should be performed to patients in T2 stage. Extended right lobe resection can improve the prognosis of selected T3 and T4 patients.The effect of chemotherapy for gallbladder cancer remains unsatisfactory, and current chemotherapeutic regimens were based on 5-FU, gemcitabine or S-1. The effect of a new chemotherapeutic sensitization scheme with continuous infusion of somatostatin,epirubicin 5-FU/CF and cisplatin is under research, and the preliminary results are promising. Radiation shows some benefits to patients with gallbladder cancer, but its effects are still uncertain.

Selection of range of regional lymphadenectomy for patients with T2 gallbladder cancer / 中华消化外科杂志

Objective To investigate the efficacy of regional lymphadenectomy for patients with T2 gallbladder cancer. Methods From January 1990 to December 2009, 48 patients with T2 gallbladder cancer received regional lymphadenectomy following radical surgery at the Xinhua Hospital of Shanghai Jiaotong University, and their clinical data were retrospectively analyzed. Patients were divided into two groups according to the range of lymphadenectomy. Standard group (23 patients): lymph nodes in the regions of bile duct, common bile duct and hepatoduodenal ligament were dissected; extended group (25 patients): lymph nodes in the regions of hepatoduodenal ligament, head of pancreas, duodenum, portal vein, common hepatic artery and celiac axis were dissected).The condition of patients in the two groups were compared after the treatment. The morbidity and survival rate were analyzed by using Fisher exact test and Kaplan-Meier method, respectively, and the survival rates between the two groups were compared by using Log-rank test. Results No perioperative death was found in the two groups. The morbidities was 17% (4/23) in the standard group and 24% (6/25) in the extended group, with no significant difference between the two groups ( P ＞ 0.05 ). The 5-year cumulative survival rate and median survival time were 40% and 29.8 months in the standard group, and 66% and 53.2 months in the extended group, with significant differences between the two groups ( x2 = 4. 687, P ＜ 0.05 ). Conclusion Extended regional lymphadenectomy should be performed on patients with T2 gallbladder cancer if the primary lesions can be dissected radically.

Role of laparoscopic staging in the resectability of gallbladder cancer / 中华普通外科杂志

Objective To evaluate the role of laparoscopic staging for the resectability of gallbladder cancer. Methods From Jan 2007 to Mar 2010,60 gallbladder cancer patients without of metastatic disease or main hepatic portal vessel invasion as assessed by preoperative imaging underwent staging laparoscopy for tumor resectability evaluation. Peritoneal and liver surface metastases were looked for and assessment of local spread was done if possible. Assessment was based on visual impression and biopsies were obtained routinely. T test and x2 test were used. Results At laparoscopy, 27 (45%) patients were found with disseminated disease on peritoneal cavity or the surface of liver, hence, senseless open surgery was avoided. The other 33 patients were converted to open laparotomy, among those 1 patient was found with disseminated metastasis in the liver and 12 patients with the invasion of main hepatic portal vessel,pancreatic head, duodenum did not undergo any further surgery. Finally 7 patients received surgical bypass procedure and 13 patients underwent radical resection. During the same period, 192 clinically diagnosed gallbladder cancer patients undergoing open laparotomy without laparoscopic pre-assessment served as control. Among those in control group 79 patients received radical or palliative resection. The resectability rate was significantly different between the two groups ( P ＜ 0. 05). Conclusion Staging laparoscopy in patients with gallbladder cancer is helpful in detecting liver and peritoneal metastases overlooked by preoperative imaging, avoiding unnecessary open explorations.

Value of different staging systems for gallbladder cancer / 中华消化外科杂志

Objective To discuss the value of different staging systems for gallbladder cancer.Methods The clinical data of 132 patients with gallbladder cancer who had been admitted to Xinhua Hospital from October 1992 to December 2006 were retrospectively analyzed.The clinical stage and postoperative survival of patients in each stage were analyzed by Nevin staging system,staging systems of AJCC 5th and 6th edition.The survivals of patients were analyzed by Kaplan-Meier method and the comparison between groups was analyzed by Log-rank test.Results According to the Nevin staging system,the accumulative survivals of patients with stages Ⅰ,Ⅱ,Ⅲ,Ⅳ or Ⅴ were 80.3%,75.6%,43.2%,16.2% and 6.5%,respectively.The accumulative survivals of patients with stages Ⅰ,Ⅱ or Ⅲ were significantly higherthan those with stages Ⅳ or Ⅴ(χ~2=7.239,6.152,3.992,12.354,13.171,15.084,P＜0.05).According to the AJCC 5th edition staging system,the accumulative survivals of patients with stagesⅠ,Ⅱ,Ⅲ or Ⅳ were 71.4%,40.9%,10.2% and 5.8%,respectively.The accumulative survivals of patients with stages Ⅰ or Ⅱ were significantly higher than those with stages Ⅲ or Ⅳ (χ~2=18.286,23.729,5.541,13.607,P＜0.05),and the survivals of patients with stage Ⅲ were significantly higher than those with stage Ⅳ (χ~2=7.758,P＜0.05).According to the AJCC 6th edition staging system,the accumulative survivals of patients with stages Ⅰ,Ⅱ,Ⅲ or Ⅳ were 51.1%,11.7%,8.2% and 6.5%,respectively.Patients with stages Ⅰ or Ⅱ had a comparatively low survival,while the survivals of patients with stage Ⅰ were significantly higher than those with stages Ⅱ,Ⅲ or Ⅳ(χ~2=15.300,21.956,31.397,P＜0.05).Patients with stage Ⅱ had a higher survival than those with stage Ⅳ(χ~2=8.789,P＜0.05).There was no significant difference in survival between patients with stage Ⅱ and Ⅲ,and between patients with stage Ⅲ and Ⅳ.Conclusions The AJCC 5th edition staging system is still the perfect staging system of gallbladder cancer.The Nevin staging system is not integrating enough,while AJCC 6th edition staging system is too strict.

Diagnostic progress in molecular biology of biliary tract malignant tumours / 国际外科学杂志

Biliary tract malignant tumours do not have any special symptom or physical sign in early stages.It is easy to be delayed for diagnosis and it is often very serious when the disease was diagnosised.With the development of technology of molecular biology,the biliary tract malignant tumours' diagnosis in molecular biology has been made some progresses,and it is expected to be possible to diagnose and treat the diseases in early stages.

The effect and safety of new chemotherapy regimen for advanced gallbladder carcinoma: an open multicenter randomized controled trial / 中华肝胆外科杂志

Comprehensive therapy is the leading method to improve the overall survival for patients with advanced gallbladder cancer, especially the study of new chemotherapy regimen are on demand.From 2010 to 2011, a phase Ⅲ study of new chemotherapy regimen in the treatment of advanced gallbladder carcinoma would be undertaken nationwide to assess the clinical outcome and safety, in 31 clinical centers led by the department of General Surgery of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, and a total of 260 patients would be accrued for this study.Chemotherapy consists of 2 regimes, conventional regime(cisplatin, epirubicin, and 5-fluorouracil, leucovorin)and new regime(conventional regime plus somatostatin).At present, the study has been approved by Clinical Trial Registration Platform of National Institutes of Health in U.S.A., and more than 30 patients are rolling in the study.The clinical trial could provide the high-quality evidence of EBM(evdence based medicine)for the chemotherapy of advanced gallbladder caner, and it will be one of the important components in the large-scale clinical study of chemotherapy for the advanced gallbladder cancer in China and worldwide.

Clinical value of detecting serum tumor markers in postoperative breast cancer patients / 中华内分泌外科杂志

Objective To investigate the relationship between serum levels of CA15-3, CA-125 and CEA in postoperative breast cancer patients and clinicopathological parameters and pathogenetic condition turnover. Methods From January 2004 to December 2007, 219 breast disease cases with integrity clinical information, admitted to general surgery and oncology department of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, were collected. The serum concentrations of CA15-3, CA-125 and CEA were determined by chemiluminescent immunoassay(CLIA). Wilcoxon Kruskal Wallis analysis, crosstable analysis and spearman correlation analysis were used to investigate the association between the serum concentration and clinical parameters and pathogenetic condition turnover. Results The serum concentrations of CA15-3,CA-125 and CEA in metastatic breast cancer group were significantly higher than those in nonmetastatic group(P=0.000). The sensitivity of the 3 tumor markers in combination was 64.1% in metastatic breast cancer diagnosis. CA15-3 and CA-125 at the time of initial metastasis were correlated with estrogen receptor state(PCA15-3=0.039, PCA-125=0.049). The level of 3 tumor markers in multiorgan metastatic group were significantly higher than those in single organ metastastic patients(P=0.000). There were significant differences between the levels of CA15-3 and CEA in distant metastatic group and those in local metastatic group (PCA15-3=0.001,PCEA=0.022). Conclusion The high serum concentrations of CA15-3,CEA and CA-125 were useful in monitoring the metastasis. The high serum levels of CA15-3 and/or CA-125 may indicate that the patients will be more sensitive to endocrine therapy.