FXYD6: a novel therapeutic target toward hepatocellular carcinoma

FXYD6, FXYD domain containing ion transport regulator 6, has been reported to affect the activity of Na(+)/K(+)-ATPase and be associated with mental diseases. Here, we demonstrate that FXYD6 is up-regulated in hepatocellular carcinoma (HCC) and enhances the migration and proliferation of HCC cells. Up-regulation of FXYD6 not only positively correlates with the increase of Na(+)/K(+)-ATPase but also coordinates with the activation of its downstream Src-ERK signaling pathway. More importantly, blocking FXYD6 by its functional antibody significantly inhibits the growth potential of the xenografted HCC tumors in mice, indicating that FXYD6 represents a potential therapeutic target toward HCC. Altogether, our results establish a critical role of FXYD6 in HCC progression and suggest that the therapy targeting FXYD6 can benefit the clinical treatment toward HCC patients.

Application of Da Vinci surgical system in distal pancreatic tumor resection / 中国医师进修杂志

Objective To explore the clinical safety and validity of Da Vinci surgical system in distal pancreatic tumor resection.Methods The clinical data of 14 patients with distal pancreatic tumor underwent robotic surgeries by using Da Vinci surgical system from January 2009 to June 2012 were retrospectively analyzed.Results The average operation time was 343.93 (170-575) min,average blood loss was 192.5 (10-700) ml,without blood trahsfusion.Pathologic examination showed:pancreatic ductal adenocarcinoma in 7 patients,pancreatic cystadenoma in 1 patient,mucous cystadenoma in 1 patient,cystadenocarcinoma in 1 patient,high levels of pancreatic ductal intraepithelial neoplasia in 1 patient,insulinoma in 1 patient,solid pseudo-papillary tumor in 2 patients.Two patients with pancreatic leaks after operation and then relieved after conservative medical therapy.Others were discharged from hospital without complications.The average hospital stay was 10.64 d.Conclusions Da Vinci surgical system is safe and effective in treatment for patients with distal pancreatic rumor with minimally invasive advantage.Because lack of surgical experience and small sample,a large sample with long term follow-up of high-quality clinical research is required and then update the system to evaluate the efficacy and safety.

Expanded radical resection for gallbladder cancer at different portions / 中华普通外科杂志

ObjectiveTo explore the value of expanded radical resection for gallbladder cancer located respectively at body and bottom of the gallbladder and at the neck.MethodsIn this study,91 cases of gallbladder cancer were macropathologically divided into two groups, one with the lesion at the body and bottom of the gallbladder and the other at the neck, survival analysis was made accordingly. Three different kinds of resection were performed: the expanded radical resection, the standard radical resection and palliative operation.ResultsThe overall median survival rate of patients undergoing expanded radical operation was significantly longer than that of the cases doing other two procedures, that was 27. 1 ± 2. 4,10. 7 ±2. 2,4. 7 ±2.2 (months) respectively for body and bottom cancer, and 8.5 ±2. 1,6. 7 ± 1.9,3.1 ± 1.1 (months) respectively for neck cancer. For cancer at the body and bottom RO was achieved by expanded radical resection in 16/18(88％ ) cases and by standard radical resection in 7/12(58％ ) cases, while for cancer at the neck it was in 6/16(38％ ) cases, and in 3/13 (23％)cases only.ConclusionsThe median survival time is longer and RO resection rate is higher in patients with the cancer at the body and bottom than these at the neck of the gallbladder.

Da Vinci surgical system-assisted hepatopancreatobiliary surgery:a report of 94 cases / 中华消化外科杂志

Objective To summarize the clinical experience in Da Vinci surgical system-assisted hepatopancreatobiliary surgery.Methods From January to December in 2009,94 patients with hepatopancreatobiliary diseases were treated at General Hospital of Second Artillery of PLA.The surgical procedure and postoperative recovery of patients were analysed.Results A total of 90 patients had successfully undergone robotic surgery,and 4 patients were converted to open surgery with the conversion rate of 4%(4/94).Sixteen patients received surgeries for hepatic diseases,and 1 patient with a giant hemangioma in the right posterior hepatic lobe was converted to open surgery,because a very close relationship between the hemangioma and inferior vena cava was observed;27 patients received surgeries for hilar diseases;19 patients underwent surgeries for pancreatic diseases,and 3 patients were converted to open surgery,including 2 with poor exposure of the giant pancreatic head carcinoma and 1 with tumors in the distal common bile duct:32 patients received other surgeries,including 6 with choledochojejunostomy and 11 with laparoscopic common bile duct exploration.Conclusions Almost all kinds of operations for hepatopanereatobiliary diseases could be performed by Da Vinci surgical system.Da Vinci surgical system expands the indications for laparoscopic surgery.

Challenges and inspirations brought by Da Vinci surgical system / 中华消化外科杂志

With almost 10 years of basic and clinical research,robotic surgery has entered the phase of commercial introduction and wide clinical application.Upon successful accomplishment of 100 cases of robotic assisted surgery,along with a systematic and retrospective study on Da Vinci surgical system-assisted complex hepatobiliary and pancreatic surgery,we summarized the main advantages of Da Vinci surgical system as follows:(1)the optimized three-dimensional and high-definition view provide surgeons with more stability and confidence during complex and delicate snrgical procedures;(2)the extremely agile multi-functional robotic arms have overcome the limitation of human hands,which makes complex surgery possible;(3)the totally new surgery modality helps to integrate various disciplines into a collaborative team,thus bringing revolutionary changes to minimally invasive surgery.Da Vinci surgical system marks a milestone in the development of minimally invasive surgery.

Selection of surgical approach for patients with reoperation using Da Vinci surgical system / 中华消化外科杂志

Objective To summarize the clinical experience of operations with Da Vinci surgical system in 27 patients with previous abdominal surgery.Methods The clinical data of 27 patients with previous abdominal surgery who had received reoperation using Da Vinci surgical system at General Hospital of Second Artillery of PLA from January to December 2009 were retrospectively analysed.The distribution of trocars was designed according to the surgical sites and previous surgical incision sites.The operation was divided into 2 steps:firstly,intraabdominal adhesion was dissected and the robotic arms were set up;secondly,the lesions were resected.Experience in trocars placement,surgical approach and management of complications were summarized.Results Six approaches were designed according to previous incision sites.Of all patients,22 were with severe intraabdominal and hepatic hilar band adhesion,and 5 with strip adhesion.One patient who underwent intraabdominal radiotherapy and chemotherapy abandoned robotic surgery because of the failure in trocar placement and pneumoperitoneum establishment.Twenty-six patients had successfully undergone robotic surgery and the success rate was 96%(26/27).Of the 26 patients,1 was complicated with enterorrhexis intraoperatively and received repairment.No postoperative complication was observed.Conclusions Previous abdominal surgery has little influence on robotic surgery with Da Vinci system. Pneumoperitoneum establishment,insertion point of the first trocar and dissection of the intraabdominal adhesions are key points for success of operation.

Comparison between Da Vinci surgical system-assisted and open surgery in pancreatoduodenectomy / 中华消化外科杂志

objective To summarize the clinical experience of pancreatoduodenectomy using Da Vinci surgical system,and to investigate the methods to improve its efficacy.Methods Sixteen patients who received pancreatoduodenectomy from January to December 2009 at the General Hospital of Second Artillery of PLA were divided into robotic group(n=8)and open group(n=8).Data on the surgical procedure,perioperative management and postoperative recovery between the 2 groups were retrospectively analysed using t test and chi-square test.Result The radical resection rates of robotic group and open group were 7/8 and 8/8,respectively,with no significant difference between the 2 groups(χ~2=1.067,P＞0.05).The operation time of robotic group was (718±186)minutes,which was significantly longer than(420±127)minutes of open group(t=3.714,P＜0.05＝.The blood loss of robotic group was(153±43)ml,which was significantly less than(210±53)ml of open group(t=2.318,P＜0.05＝.The postoperative ambulation time and length of hospital stay of robotic group were(28±7)hours and(16±4)days,which were significantly shorter than(96±18)hours and(24±7)days of open group(t=9.939,2.714,P＜0.05＝.The incidences of postoperative complications of robotic group and open group were 2/8 and 6/8,respectively,with significant difference between the 2 groups(χ~2=6.349,P＜0.05＝.The incidences of anastomotic leakage of robotic group and open group were 2/8 and 3/8,respectively,with no significant difference between the 2 groups(χ~2=0.291,P＞0.05).Conclusion Pancreatoduodenectomy performed by Da Vinci surgical system is feasible and safe,and with the advantages of less trauma and rapid recovery of patients.

Preliminary studying on dendritic cell culture and its killing effect on gastric carcinoma cell line MKN 45 / 国际肿瘤学杂志

Objective To explore the cultivated methods of dendritic cells (DC) and the killing effect of DC stimulated by CpG ODN1826 on gastritic cancer cells MKN45 in vitro. Methods DC was induced from peripheral blood monocytes stimulated by A group ( GM- CSF + IL-4 ), B group ( GM- CSF + IL-4 + TNF- α), C group(nonCpG ODN) and D group( CpG ODN 1826). The surface markers of DC was analyzed via flow cytometry, and the abilities to stimulate proliferation of allogenic lymphocyte by DC and antitumor experiment were detected by MTT assay. Results On day 10, a majority of cells showed typical morphology of DC in D group and B group with visible branching-like and pseudopod-like structures under microscope. The results of flow cytometry showed that there are significantly high expressed co-stimulated molecules such as CD40, CD1a,CD80, CD86 and MHC- Ⅱ in D group compared to other experimental groups ( P ＜ 0.05 ), which dramatically stimulate the proliferation of allogenic lymphocytes and enhance the killing activity of DC on gastric cancer cells. Conclusion This method can acquire relatively high purified DC, and CpG ODN can significantly induce the differentiation and maturation of DC isolated from peripheral blood and enhance the killing activity of DC on MKN45 by stimulating PBMC in vitro.

Research progress on the antitumor immuoregulation of CpG ODN induced dendritic cell / 肿瘤研究与临床

Oligodeoxynucleotides containing CpG motifs have shown powerful immunoregulation effects, which are able to activate a variety of immune cells such as natural killer (NK) cells, monocytes,macrophages, dendritic cells(DC), B and T lymphocytes. CpG oligodeoxynucleotides (CpG ODN) can not only induce and enhance nonspecific and specific immune responses, but also regulate the type of immune responses through inducing Th1-type immune response and suppressing Th2-type immune response. DC are known to be the most powerful special antigen-presenting cells (APC) at present. It plays an important role in antigen recognition,antigen processing presenting, and T cell activation, and can kill various kinds of tumor cells. Recently, the immunotherapy based on tumor vaccines of dendritic cell has become more and more important. The research progress on dendritic cells for cancer treatment is reviewed in this article.

Effect of the differences in clinical classification and operational method of gallbladder carcinoma on the prognosis after resection / 中国综合临床

Objective To investigate the effect of clinical classification and operational methods of gallblad-der carcinoma on the prognosis.Methods Clinical data of 88 patients with gallbladder carcinoma treated surgically from January 1994 to December 2004 were retrospectively analyzed.Results 8 cases were in class Ⅰ and Ⅱ , 14 in class Ⅲ ,28 in class Ⅳ,38 in class Ⅴ.The mean survival of these 4 classifications was 36.5,9.3,4.6,3.9 months respectively.There was a remarkable difference(P <0.01,P<0.05) in survival among these 4 classifications ex-cept between class Ⅳ and class Ⅴ (P0.05).The mean survival of radical resection and palliative resection in class Ⅳ and Ⅴ was 4.2 and 3.8 months.There was no remarkable difference( P0.05 ) between them.Conclusion The key to increase the therapeutic effect gallbladder carcinoma is early diagnosis and radical resection.

Robot-assisted pancreatoduodenectomy / 中华消化外科杂志

Pancreatoduodenectomy (PD) is considered as a complex and difficult surgical procedure even to the experi-enced surgeons, and it is thought to be the last frontier for mini-really invasive surgeons. Laparoscopic PD, despite the initial enthusiasm towards it, discourages laparoscopic surgeons by its long operating time and procedure-related fatigue resulting from technical difficulties associated with laparoscopic instruments and unstable camera platform. Although robotic surgical system with its known advantages has successfully overcome the limita-tions of traditional laparoscopic surgery, and completed the com-plex and advanced surgical procedures required in PD, reports on robot-assisted (laparobotic) PD remain few. Furthermore, there has not yet been a single report detailing PD techniques modified to take advantage of the Da Vinci platform. In this report, laparobotic PD was successfully performed on 7 patients. Five patients underwent pyloric preserving PD and 2 had stand-ard PD. All the 7 patients have been followed up till January 2009. The overall mean operative time was 326 minutes (290-400 minutes) and the mean length of postoperative stay was 10.2 days (5-30 days). There was no mortality. Five patients had perioperative complications but went on well after manage-ment. The stepwise cando-cranial approach PD is a unique approach, which is ideal for robotic platform. Although it has been shown to be feasible, safe, efficient, and reproducible in this small series, a larger scale multi-institutional study is needed to validate its efficacy.

Surgical treatment of iatrogenic biliary strictures / 中华消化外科杂志

Objective To assess the surgical treatment of iatrogenic biliary strictures. Methods The clinical data of 235 patients with iatrogenic biliary injuries and strictures who had been admitted to our hospital from January 1989 to December 2006 were reviewed retrospectively. Cholangio-jejunal Roux-en-Y anastomosis (n=182), surgical repair with pediele flap of autogenous tissues (n=34), end-to-end choledocho-choledo-chostomy (n= 12), common bile duct incision and figuration +T-tube drainage ( n =6) and liver transplanta-tion ( n = 1 ) were applied to the patients. Results A total of 189 patients were followed up for 1 to 10 years. The total excellent and good rate was 94.7% (179/189). The recurrence rate of the biliary stricture was 5.3% (10/189), and the main cause of which were biliary cirrhosis, selerosing cholangitis and calculus. One patient with severe biliary cirrhosis and portal hypertension died of liver failure postoperatively. Conclusions The cholangio-jejunal Roux-en-Y anastomosis is a reliable and effective method. Surgical repair of the bile duet with pedicle flap of autogenous tissues could preserve the function of the sphincter of Oddi, but the long-term effect needs further investigation. Biliary stent is not usually necessary to install. Liver transplantation is efficient for the patients with end stage of biliary diseases caused by biliary stricture.

Prevention of Hepatitis B Virus Reinfection after Liver Transplantation / 中华医院感染学杂志

OBJECTIVE To discuss the preventive methods of hepatitis B virus reinfection after liver transplantation. METHODS Eighty eight liver transplantation recipients with HBV-related end-stage liver diseases including chronic fulminant hepatitis B,end-stage liver cirrhosis and liver carcinoma were analyzed retrospectively,and were given lamivudine pre-transplantation to prevent hepatitis B virus reinfection.Post-transplantation medicines of lamivudine were administered in 3 cases;lamivudine and hepatitis B immunoglobulin(HBIg) in 85 cases.The follow-up criteria included serum HBV,HBV-DNA,liver biopsy,immunohistochemical study of liver biopsy specimens and clinical manifestations.All of patients were followed-up 6 months at least.RESULTS Two of the three cases who taken lamivudine developed reinfection,the little time is 6 months following liver transplantation.There were three of eighty five cases taken lamicudine and HBIg(small dosage) developed reinfection.CONCLUSIONS Liver transplantation is an effective treatment for HBV-related end-stage liver diseases.Given lamivudine at the pre-transplantation could reduce the levels of the HBV virus copies.Lamivudine and HBIg post-transplantation offer effective prevention against hepatitis B virus reinfection.

TGF-?_1-mediated apoptosis of murine hepatocytes / 医学研究生学报

Objective:The aim of this study was to determine the relationships between the effect of TGF-? 1 and apoptosis in normal and cirrhotic murine hepatocytes. Methods: Liver cirrhosis was induced by means of injection with 50% carbon tetrachloride in BALB/c mice. Hepatocytes were isolated an in situ perfusion method with collagenase solution with minor modification. Normal hepatocytes treated with TGF-? 1(5 ng/ml) were stained with fluorescent DNA-binding dyes Hoechst 33342. The apoptosis of hepatocytes was determined by electrophoresis on 1.5% agarose gel to observe DNA ladder. Results:The viability of hepatocytes isolated from mice by in situ two step collagenase digestion was 95.2%. Internucleosomal fragmented DNA ladder was observed using a 1.5% agarose gel in normal hepatocytes treated with TGF-? 1.obvious DNA ladder from cirrhotic hepatocytes was not observed. The percentage of apoptotic rate in TGF-? 1 treated normal hepatocytes were much higher than that of hepatocytes untreated with TGF-? 1. Conclusion: It was revealed that cirrhotic hepatocytes have poor response to apoptosis induced by TGF-? 1.

The expression and significance of oncogene C-erbB-2,p16,nm23H1 in exhepatic bile duct cancer / 中国普通外科杂志

Objective This study was to investigate correlations between the expression of oncogene c erbB 2 , p16 and nm23H1 and the development of the carcinoma. Methods Immunohistochemical S P method was used to examine the expression of oncogenes in 46 cholangiocarcinoma cases and 13 cases of benign bile duct lesions. The relationship between the expression and clinical pathology was analyzed. Results The positive rate of C erbB 2 in cholangiocarcinoma increased significantly ( P

Study on the mechanism of apoptotic signal transduction of hepatocytes induced by TGF-?1 in liver cirrhosis mice / 中国普通外科杂志

Objective To determine the relationships between apoptosis induced by transforming growth factor-beta 1(TGF-?1 )and caspase-3 as well as caspase-8 in liver cirrhosis mice. Methods In BALB/C mice,liver cirrhosis was induced by means of injection with 50% carbon tetrachloride for 8 weeks. Hepatocytes were isolated from normal and cirrhotic mice by means of a modified in situ collagenase solution perfusion method. The effects of caspase-3 and caspases-8 on TGF-?1-induced apoptosis were detected and compared . Results The viability of hepatocytes(isolated) from the mice by in situ two step collagenase digestion method was 95.2%. Internucleosomal(fragmented) DNA ladder was observed in TGF-?1 treated normal hepatocytes,but no obvious DNA ladder in(cirrhotic) hepatocytes was observed. The apoptotic rate in TGF-?1 treated normal hepatocytes (58.76%) was much higher than that of hepatocytes not treated with TGF-?1 (18.03%) .The apoptosis could be blocked by(Z-IETD-FMK) and(DEVD-CHO). Conclusions This study reveals that cirrhotic hepatocytes have poor response to(apoptosis) induced by TGF-?1,which indicates that inhibitory regulation of cell growth is impaired in cirrhotic hepatocytes. TGF-?1 can(induce) apoptosis of mice hepatocytes via caspase-8 and caspase-3-transducted signal(pathway).

Laparoscopic liver resection: Report of 16 cases / 中国微创外科杂志

Objective To evaluate the anatomical basis and techniques in laparoscopic liver resections. Methods Entered the study there were 16 patients with both their lesions located at liver margin, or the surface of the right liver, or left liver and their liver functions classified as Child B or above, including 8 cases of primary liver cancer, 3 cases of liver hemangioma, 1 case of cholangiocarcinama, 1 case of hepatic adenoma, 1 case of focal nodular hyperplasia, 1 case of liver abscess and 1 case of infected liver cyst. The procedures were performed, via 4～6 epigastric ports, by using electriccautery, ultracision or endo-cutter for transecting liver and by titanic clip or medical albumin glue for dealing with the cut surface. Results Laparoscopic liver resection was completed under pneumoperitoneum in 16 cases (18 lesions), including 8 cases of local liver resection and 8 cases of anatomical left liver resection. The operation time was (206?75) min and the blood loss was (354?282) ml. An intraoperative blood transfusion of 800 ml was required in 2 cases because of a blood loss of 1000 ml. The abdominal drains were left for (2～4) days and no bile leakage, bleeding or other complications happened. The postoperative hospital stay was (5.8?1.6) days. Conclusions Proper dealing with hepatic portal vessels is the key to the laparoscopic liver resection. In order to effectively control the bleeding during the partial hepatectomy or left hemihepatectomy, it is crucial to fully dissect the sub-grade hepatic portal vessels.

Diagnosis and management of regional portal hypertension / 中华消化杂志

Objective To summarize the experience of diagnosis and management of regional portal hypertension. Methods The clinical manifestations, diagnostic methods and therapeutic modalities of 16 cases of regional portal hypertension were analyzed retrospectively. Results Among 16 patients with ~regional portal hypertension, 12 cases resulted from pancreatic diseases, and 4 cases were complicated with non-pancreatic diseases. The main clinical findings were splenomegaly in 16(100%), abdominal pain ~in 10(63%) , gastrointestinal bleeding in 7(44%) and abdominal masses in 3(19%). All had normal liver function test. The main diagnostic methods were ultrasonography(US), computerized tomography (CT) and endoscopy. Splenic vein thrombosis could be detected by color Doppler ultrasonography (7/7). ~Enhanced CT could demonstrate enlarged and tortuous short gastric veins, gastroepiploic veins, and ~coll- ~ateral vessels around splenic hilum(16/16). Isolated gastric varices (4/5) were revealed mainly by ~gastro- ~scopy . Splenectomy was effective for controlling gastrointestinal bleeding, and its complication of portal vein thrombosis occurred in 1 case. Conclusions It is not difficult to diagnose regional portal ~hyper- ~tension based on findings of US and CT, together with special clinical characteristics. Therapeutic options should be ~individualized according to underlying diseases, however, splenectomy should be performed in the ~patients with gastrointestinal bleeding.

Interventional drainage through sinus tracts for the treatment of postoperative abdominal abscess / 解放军医学杂志

Objective To explore a new way to drain a postoperative abdominal abscess. Method Drainage catheter and sinography were employed to locate the site of the abscess, and a 10.2F~16F catheter with single or double lumen was inserted into the abscess by interventional technique. Result A 100% success was obtained for the 15 patients with 18 abscesses by inserting the drainage catheters, and all the abscesses were cured 7~65 days after drainage. Conclusions Compared with the surgical or percutaneous drainage, the present method is less traumatic, safer, more economical and effective, and it could be applies to all kinds of postoperative intraperitoneal abscesses which could not been drained adequately or with formation of sinus because of displacement of drainage tube.

A STUDY ON RELATIONSHIP BETWEEN HEPATOCYTE GROWTH FACTOR AND EXPRESSION OF ITS C-MET RECEPTOR AND POSTOPERATIVE RECURRENCE OF SMALL HEPATOCELLULAR CARCINOMA / 解放军医学杂志

Objective To investigate the possible relationship between the changes in the serum level of hepatocyte growth factor (HGF) and the tumor c-Met expression in postoperative patients with small primary hepatocellular carcinoma (SHCC) and the recurrence of the cancer. Methods We examinated the HGF concentration in serum by ELISA within 1 day before and 3 days after operative removal of the tumor, and also determined the expression of c-Met protein in the tumor and non-tumor tissue by Western and Northern blotting in situ. Results The serum HGF concentration 1-day before or 3-days after operation was 0.64?0.15ng/ml and 1.41?0.28ng/ml, respectively. There was statistically significant difference between them (P