Current status and challenges of accurate preoperative assessment of pancreatic cancer / 中华外科杂志

Pancreatic cancer is a malignant tumor with very poor prognosis. In the past decade, the surgical technique has made significant progress, but it has not brought desired effect in improving the survival outcome of pancreatic cancer patients. With the development of the concept of cancer treatment and the emergence of precision medicine, the surgical centered multidisciplinary treatment and collaborative diagnosis and treatment mode has gradually become the mainstream. Accurate preoperative assessment of pancreatic cancer has become a breakthrough for further improving the prognosis of patients with pancreatic cancer. From the perspective of precise assessment, this paper mainly summarized the status and progress on the following four aspects: the preoperative diagnosis and staging, the resectability evaluation, the neoadjuvant therapy strategy and efficacy evaluation of neoadjuvant therapy in pancreatic cancer, and also discussed the shortcomings and challenges in the field of precise assessment, finally in order to make the preoperative assessment of pancreatic cancer more precise and standard, and to provide useful reference for future research work.

Synthesis of colon-specific prodrug of indomethacin and its inhibitory effect on liver metastasis from colon cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To develop a colon-specific prodrug of Indomethacin microbially triggered, carry out in vitro/in vivo evaluation of drug release, and appraise its inhibitory effect on liver metastasis from colon cancer.</p><p><b>METHODS</b>Indomethacin prodrugs were synthesized and characterized by FTIR and NMR, and dissolution test simulating gastrointestinal tract was employed to screen the colon-specific prodrug. Then, the pharmacokinetic profile of portal vein and peripheral blood in Sprague-Dawley rats was studied. Lastly, the inhibitory effect on liver metastasis from colon cancer in nude mice was observed.</p><p><b>RESULTS</b>The chemical structure characterized by FTIR and NMR demonstrated that six kinds of indomethacin-block-amylose with different drug loading (IDM-AM-1-6) were synthesized, among which IDM-AM-3 was degraded 1.3%, 9.3% and 95.3%, respectively, in simulated gastric fluid for 4 h, small intestine for 6 h, and colon for 36 h. The pharmacokinetic test of IDM-AM-3 showed that absorption was delayed significantly (P < 0.01), peak time [(11.35 + or - 2.45) h], elimination half-life [(16.74 + or - 4.04) h] and mean residence time [(22.27 + or - 0.52) h] were significantly prolonged (P < 0.01), as well as peak serum concentrations [(9.69 + or - 2.40) mg/L] and AUC(0-t) [(236.7 + or - 13.1) mg x L(-1) x h] were decreased markedly (P < 0.01) as compared with those of IDM regarding to portal vein. Additionally, its AUC(0-t) in peripheral blood was remarkably lower than that in Portal vein (P < 0.01). The tumor suppression observation showed that it could remarkably reduce the number of liver metastases in contrast to IDM (P < 0.05).</p><p><b>CONCLUSION</b>Colon-specific IDM-AM-3 possesses advantage of sustained release in portal vein providing some experimental basis for colon-specific delivery system applied to sustained release in the portal vein.</p>

Preparation and antitumor effects of nanovaccines with MAGE-3 peptides in transplanted gastric cancer in mice / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>As a prospective vaccine carrier, nanoparticles can protect antigens from degradation and enhance immune response. This study prepared nanovaccines with MAGE-3-derived CD4+-CD8+T cell epitope peptides, and investigated its character and antitumor effects on transplanted gastric cancer in mice.</p><p><b>METHODS</b>We adopted the self-assembly method to prepare peptide/chitosan conjugated with deoxycholic acid (chitosan-deoxycholic acid) nanoparticles. We observed the appearance of the chitosan-deoxycholic acidnanoparticles through a transmission electron microscope (TEM) and analyzed the peptide content and its release pattern by fluorescence spectrophotometry. We observed tumor-suppression efficacy in vivo through animal experiments.</p><p><b>RESULTS</b>We successfully prepared nanoparticles with MAGE-3 peptide antigen, and its encapsulation efficiency and loading level were about 37% and 17.0%, respectively. These nanoparticles presented a delayed release pattern in phosphate buffered saline (PBS) at pH 7.4, and the full release time was about 48 h. In 2 mg/mL lysozyme, the nanoparticles showed a sudden release, and the full release time was about 24 h. ELISPOT and cytotoxic experiments showed that the MAGE-3 peptide loaded nanoparticles could stimulate immune response in vivo and could generate MAGE-3-targeted cytotoxic T lymphocytes (CTLs), and kill MAGE-3-specific tumor cells. Tumor suppression experiments showed that the regression ratio of the peptide-loaded nanoparticles group was 37.81%.</p><p><b>CONCLUSIONS</b>MAGE-3 peptide/chitosan-deoxycholic acidvaccine-loaded nanoparticles can stimulate antitumor immune response in vivo and can regress the growth of mouse forestomach carcinoma cell line MFC.</p>

Therapeutic clinical effect of radiofrequency ablation for small hepatocellular carcinoma in cirrhotic patients: a meta-analysis / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the value of radiofrequency ablation in the treatment of small hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>MEDLINE (1966 - 2008), EMBASE (1966 - 2008), CBMdisc (1978 - 2008) were searched. The Cochrane Library, Evidence Base Medicine Reviews (Ovid Edition), Cancerlit (1993 - 2008) and so on, date of last search: 30 January 2008. There were no restrictions in language. Randomized controlled trials (RCTs) and non-RCTs were both included in this study, and the quality of each included study was assessed. Meta-analysis was performed by RevMan 4.2 software.</p><p><b>RESULTS</b>Four prospective controlled studies and two retrospective studies met the inclusion criteria. The results of meta-analysis showed that 1-, 3-, 4-year survival rates and 1-year tumor-free survival rate had not statistically significant difference in RFA group compared with surgical resection group (P > 0.05), but surgical resection was more effective to improve 3-year tumor-free survival rate than RFA (P < 0.05).</p><p><b>CONCLUSIONS</b>The effect of RFA therapy on small HCC is similar to resection, RFA could be considered as the first-line treatment of choice for surgical candidates with small HCC in cirrhotic patients.</p>

Study of the anti-tumor effect of anti-vascular endothelial growth factor McAb 5-fluorouracil loaded polylactic acid nanoparticles / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the anti-tumor efficacy of anti- vascular endothelial growth factor (VEGF) McAb 5-fluorouracil (5-FU) loaded polylactic acid (PLA) nanoparticles (NPS) in human gastric carcinoma xenografts of nude mice.</p><p><b>METHODS</b>Anti-VEGF McAb 5-FU loaded PLA NPS were made by ultrasound emulsification. Nude mice model of human gastric carcinoma xenografts was established. Therapeutic effects of drugs on human gastric carcinoma xenografts and side effects concerned were observed.</p><p><b>RESULTS</b>The tumor inhibition rates of control group, nanosphere without 5-FU group, 5-FU (20 mg/kg) group, anti-VEGF McAb nanosphere without 5-FU group, anti-VEGF McAb group, nanosphere with 5-FU group, 5-FU (20 mg/kg) combined with anti-VEGF McAb group, anti-VEGF McAb 5-FU loaded nanosphere group was 0, 6.61%, 24.26%, 27.94%, 35.29%, 37.50%, 39.71% and 52.21% respectively, and there were no significant differences between anti-VEGF McAb 5-FU loaded nanosphere group and nanosphere group without 5-FU in WBC count, serum alanine transferase level or creatinine level. Compared with control group and anti-VEGF McAb 5-FU loaded nanosphere group, the 5-FU group decreased by 34.43% and 37.38% respectively in WBC count (P< 0.05), and increased by 93.17% and 66.56% respectively in alanine transferase. There were significant differences between experimental groups and control group in apoptosis index, especially between anti-VEGF McAb 5-FU loaded nanosphere group and control group (P< 0.05). The microvessel density (MVD) of experimental groups containing anti-VEGF McAb was significantly lower than that of control group or groups containing 5-FU (P< 0.05).</p><p><b>CONCLUSION</b>Anti-VEGF McAb 5-FU loaded nanosphere can increase the tumor inhibitory rate of 5-FU, induce apoptosis by inhibiting tumor angiogenesis with less side effect, and then enhance therapeutic effect, which indicate its potential as a novel, safe nano-tumor-targeting drug.</p>

A 26-year clinical observation of splenic auto-transplantation and oesophageal transection anastomosis: a new treatment strategy in patients with portal hypertension / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Surgical treatment options for patients with cirrhosis and portal hypertension are complicated. In this study, we evaluated the effectiveness of a new treatment strategy, splenic auto-transplantation and oesophageal transection anastomosis. We report results from clinical observations, splenic immune function and portal dynamics in 274 patients.</p><p><b>METHODS</b>From 1979 to 2005, 274 cirrhosis patients with portal hypertension underwent the new treatment strategy, and were followed up to compare results with those patients who underwent traditional surgical treatment. From 1999 to 2002, a randomized controlled trial (RCT) was performed on 40 patients to compare their post-operative immune function. From 1994 to 2006, another RCT enrolled 28 patients to compare portal dynamics using three-dimensional dynamic contrast-enhanced magnetic resonance angiography (3D DEC MRA) investigation post operation.</p><p><b>RESULTS</b>Among 274 patients (mean age 41.8 years), the emergency operative mortality (4.4%), selective operative mortality (2.2%), complication rate (17.9%), prevalence of hepatic encephalopathy (< 1%), rate of portal hypertension gastritis (PHG) bleeding (9.1%), and morbidity of hepatic carcinoma (8%) were similar to those patients undergoing traditional operation; the spleen immunology function (Tuftsin, IgM) decreased in both groups 2 months post operation, but this decrease did not reach statistical significance. Through 3D DCE MRA, the cross sectional area and the velocity and volume of blood flow of the main portal vein decreased significantly after operation in both groups. The velocity and volume of blood flow in the auto-transplantation group was significantly lower than that in the control group.</p><p><b>CONCLUSIONS</b>Splenic auto-transplantation and esophageal transection anastomosis is a safe, effective, and reasonable treatment strategy for patients with portal hypertension with varicial bleeding. It not only can correct hypersplenism, but may also achieve complete hemostasis. Spleens auto-transplanted into the retroperitoneal space can preserve immune function and establish broad collateral circulation.</p>

Human normal biliary epithelial cells transformation and tumor development induced by hepatitis C virus core protein / 中华外科杂志

<p><b>OBJECTIVE</b>To study the effect of hepatitis C virus core protein (HCV-C) on human normal biliary epithelial cells (BEC) transformation and tumor development.</p><p><b>METHODS</b>BEC cells were transfected with plasmid pcDNA HCV-C (expressing HCV-C) by lipofectamine and selected in G418. The expression of HCV-C gene and protein was determined by PCR and immunohistochemical staining, respectively. Biological effect of transfected cells was observed through cell proliferation assay, anchor independent growth, and tumor development in nude mice. The expression of HCV-C protein in the induced tumor was evaluated by immunohistochemistry.</p><p><b>RESULTS</b>HCV-C was strongly expressed in BEC cells transfected with plasmid pcDNA HCV-C and the positive signal was located in cytoplasm. The HCV-C expression protein in the induced cytoplasm. Cell proliferation assay showed that the population doubling time in the pcDNA HCV-C transfected cells was much shorter than that in the pcDNA3 and non-transfected cells (14 h, 28 h, 30 h respectively). The cloning efficiencies of transfected cells with pcDNA HCV-C, pcDNA3 and non-transfected cells were 36%, 2.5% and 1.5%, respectively (P < 0.01). Tumor developed in nude mice inoculated with pcDNA HCV-C transfected cells after the inoculation. HE staining showed bile duct carcinoma character and immunohistochemistry confirmed HCV-C expression in the tumor tissue. The positive control group also showed tumor development, while no tumor mass obtained in the nude mice inoculated with pcDNA3 and non-transfected cells even 36 days after the injection.</p><p><b>CONCLUSION</b>HCV-C protein showed human normal biliary epithelial cells transformation and tumorigenic features.</p>