应用胸脐皮瓣治疗前臂瘢痕

目的 :前臂瘢痕切除后 ,为创面修复提供简单、理想的治疗方法。方法 :8例前臂增生和疙瘩瘢痕患者 ,瘢痕切除后皮肤缺损面积最大 2 5cm× 13cm ,最小 16cm× 6cm。应用胸脐皮瓣转移或移植修复 (转移者 6周后断蒂 ) ,其中 3例采用转移 ,5例行移植。结果 :皮瓣全部成活 ,经随访 5～ 16个月 ,修复部位厚薄适中 ,与周边皮肤色泽相符 ,外观满意。结论 :该术式修复前臂瘢痕切除后遗留创面较为理想 ,操作简单 ,具有推广应用价值。

Current status of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is a rare primary liver cancer with a global increasing trend in recent years. Symptoms tend to be vague and insidious in development, often are diagnosed at an advanced stage when only palliative approaches can be used with a median survival rate of months. Comparing with HCC, ICC tends to spread to lymph nodes early, and is rarely limited to the regional lymph nodes, with a frequent postoperative recurrence. Surgery is the only choice of curative therapy for ICC, but recently no consensus has been established for operation. Thus, more data from multiple centers and more cases are needed. Generally speaking, current adjunctive therapy cannot clearly improve survival. Further research is needed to find more effective radio- and chemotherapeutic regimens.

OB glue paste technique for establishing nude mouse human gastric cancer orthotopic transplantation models

AIM： To establish nude mouse human gastric cancer orthotopic transplantation models using OB glue paste technique. METHODS： Using OB glue paste technique, orthtopic transplantation models were established by implanting SGC-7901 and NKN-45 human gastric cancer cell strains into the gastric wall of nude mice. Biological features, growth of the implanted tumors, the success rate of transplantation and the rate of auto-metastasis of the two models were observed. RESULTS： The success rates of orthotopic transplanration of the two models were 94.20% and 96%. The rates of hepatic metastasis, pulmonary metastasis, peritoneal metastasis, lymphocytic metastasis and splenic metastasis were 42.13% and 94.20%, 48.43% and 57.97%, 30.83% and 36.96%, 67.30% and 84.06%, and 59.75% and 10.53%, respectively. The occurrence of ascites was 47.80% and 36.96%. CONCLUSION： OB glue paste technique is easy to follow. The biological behaviors of the nude mouse human gastric cancer orthotopic transplantation models established with this technique are similar to the natural processes of growth and metastasis of human gastric cancer, and, therefore, can be used as an ideal model for experimental research of proliferative metastasis of tumors.

Clinical outcome after pulmonary metastasectomy from primary hepatocellular carcinoma:Analysis of prognostic factors

AIM： To review the surgical outcomes in terms of the surgical indications and relevant prognostic factors. METHODS： Sixteen patients underwent therapeutic lung surgery between March 1999 and May 2006. The observation period was terminated on May 31, 2007. The surgical outcomes and the clinicopathological factors were compared. RESULTS： There was no mortality or major morbidity encountered in this study. The mean follow-up period after metastasectomy was 26.7 ＋ 28.2 （range： 1-99 mo）, and the median survival time was 20 mo. The 1- and 5-year survival rates were 56% and 26%, respectively. At the end of the follow-up, 1 patient died from hepatic failure without recurrence, 6 died from hepatic failure with a recurrent hepatocellular carcinoma （HCC）, and 4 died from recurrent HCC with cachexia. Among several clinical factors, Kaplan Meier analysis revealed as a treatment for the that liver transplantation primary lesion, grade of cell differentiation, and negative evidence HBV infection were independent predictive factors. On Cox＇s proportional hazard model, there were no significant factors affecting survival after pulmonary metastasectomy in patients with HCC. CONCLUSION： A metastasectomy should be performed before other treatments in selected patients, Although not significant, patients with liver transplantation of a primary HCC survived longer, Liver transplantation might be the most beneficial modality that can offer patients better survival, A multi- institutional and collaborative study would be needed for identifying clinical prognostic factors predicting survival in patients with HCC and lung metastasis.

Hepatocytes isolated from neoplastic liver-immunomagnetic purging as a new source for transplantation

AIM： To investigate whether hepatocytes isolated from macroscopically normal liver during hepatic resection for neoplasia could provide a novel source of healthy hepatocytes, including the development of reliable protocols for malignant cells removal from the hepatocyte preparation. METHODS： Hepatocytes were procured from resected liver of 18 patients with liver tumors using optimised digestion and cell-enrichment protocols. Suspensions of various known quantities of the HT-29 tumor cell line and patient hepatocytes were treated or not with Ep-CAM-antibody-coated immunomagnetic beads in order to investigate the efficacy of tumor-purging by immunomagnetic depletion, using a semi-quantitative RT-PCR method developed to detect tumor cells. Immunomagnetic bead-treated or bead-untreated tumor cell-hepatocyte suspensions were transplanted intra-peritoneally in Balb/C nude mice to assess the rates of tumor development. RESULTS： Mean viable hepatocyte yield was 9.3×10^6 cells per gram of digested liver with mean viability of 70.5%. Immunomagnetic depletion removed tumor cells to below the RT-PCR detection-threshold of 1 tumor cell in 10^6 hepatocytes, representing a maximum tumor purging efficacy of greater than 400000-fold. Transplanted, immunomagnetic bead-purged tumor cell-hepatocyte suspensions did not form peritoneal tumors in Balb/C nude mice. Co-transplantation of hepatocytes with tumor cells did not increase tumorigenesis of the tumor cells. CONCLUSION： Immunomagnetic depletion appears to be an effective method of purging contaminating tumor cells to below threshold for likely tumorigenesis. Along with improved techniques for isolation of large numbers of viable hepatocytes, normal liver resected for neoplasia has potential as another clinically useful source of hepatocytes for transplantation.

Early steroid withdrawal after liver transplantation for hepatocellular carcinoma

AIM: To evaluate the impact of early steroid withdrawal on the incidence of rejection, tumor recurrence and complications after liver transplantation for advanced- stage hepatocellular carcinoma. METHODS: Fifty-four patients underwent liver transplantation for advanced-stage hepatocellular carcinoma from April 2003 to June 2005. These cases were divided into a steroid-withdrawal group (group A, n = 28) and a steroid-maintenance group (group B, n = 26). In group A, steroid was withdrawn 3 mo after transplantation. In group B, steroid was continuously used postoperatively. The incidence of rejection, 6-mo and 1-year recurrence rate of carcinoma, 1-year survival rate, mean serum tacrolimus trough level, and liver and kidney function were compared between the two groups. RESULTS: In the two groups, no statistical difference was observed in the incidence of rejection (14.3 vs 11.5%, P > 0.05), mean serum tacrolimus trough levels (6.9 ± 1.4 vs 7.1 ± 1.1 μg/L, P > 0.05), liver and kidney function after 6 mo [alanine aminotransferase (ALT): 533 ± 183 vs 617 ± 217 nka/L, P > 0.05; creatinine: 66 ± 18 vs 71 ± 19 μmol/L, P > 0.05], 6-mo recurrence rate of carcinoma (25.0 vs 42.3%, P > 0.05), and 1-year survival rate (64.2 vs 46.1%, P > 0.05). The 1-year tumor recurrence rate (39.2 vs 69.2%, P < 0.05), serum cholesterol level (3.9 ± 1.8 vs 5.9 ± 2.6 mmol/L, P < 0.01) and fasting blood sugar (5.1 ± 2.1 vs 8.9 ± 3.6 mmol/L, P < 0.01) were signifi cantly different. These were lower in the steroid-withdrawal group than in the steroid- maintenance group. CONCLUSION: Early steroid withdrawal was safe after liver transplantation in patients with advanced-stage hepatocellular carcinoma. When steroids were withdrawn 3 mo post-operation, the incidence of rejection didnot increase, and there was no demand to maintain tacrolimus at a high level. In contrast, the tumor recurrence rate and the potential of adverse effects decreased signifi cantly. This may have led to an increase in long-term survival rate.

An integrated biomarker response index for the mussel Mytilus edulis based on laboratory exposure to anthracene and field transplantation experiments

Organic pollution is a serious environmental problem in coastal areas and it is important to establish quantitative methods for monitoring this pollution. This study screened a series of sensitive biomarkers to construct an integrated biomarker response （IBR） index using Mytilus edulis. Mussels were exposed to the polycyclic aromatic hydrocarbon anthracene trader controlled laboratory conditions and the activities of components of the glutathione antioxidant system, and the concentrations of oxidative-damage markers, were measured in the gills and digestive glands. Anthracene exposure resulted in increased levels of malondialdehyde （MDA） and superoxide radicals （O2-·）, indicating that oxidative damage had occurred. Correspondingly, anthracene exposure induced increased activities of glutathione S-transferase （GST）, glutathione peroxidase （GPx） and reduced glutathione （GSH） in digestive glands, and GPx and glutathione reductase （GR） in gills, consistent with stimulation of the antioxidant system. A field experiment was set up, in which mussels from a relatively clean area were transplanted to a contaminated site. One month later, the activities of GST, GPx and GR had increased in several tissues, particularly in the digestive glands. Based on the laboratory experiment, an IBR, which showed a positive relationship with anthracene exposure, was constructed. The IBR is suggested to be a potentially useful tool for assessing anthracene pollution.

Solitary pulmonary metastasis arising thirteen years after liver transplantation for HBV-related hepatocellular carcinoma

We described a 59-year-old male patient who underwent liver transplantation in 1989 for hepatocellular carcinoma （HCC） complicating hepatitis B virus （HBV） cirrhosis. In 2001 （12 years after liver transplantation）, he developed a lung metastasis of HCC without intrahepatic recurrence and the resection was done. In July 2003, he was symptom free without any recurrence. HCC metastasis can develop even after a very long time of liver transplantation. Many HCCs grow slowly, and the growth rate of recurrent tumors in patients receiving immunosuppressive therapy is significantly greater than that of those who do not receive immunosuppressive therapy.

High efficiency DNA delivery into swine oocytes and embryos by electronic pulse delivery (EPD)

The production of transgenic swine for xenotransplantation has been proposed as an optimal option to overcome the chronic shortage of human organ donors. Generation of genetically engineered swine has been elusive due to the difficulties in gene transfer. In order to achieve effective gene delivery, a key step for the genetic modification, we applied electronic pulse delivery (EPD) technology to introduce HZKb-DC DNA construct into swine eggs. Using the developed EPD ProtocolsTM, we have achieved good viability of the EPD treated oocytes, satisfactory embryonic development of the EPD treated embryos, and stable DNA transfer into the swine embryos with high efficiency. Thus, application of the EPD technology promises to effectively facilitate the generation of large trangenic mammals.

EXPRESSION OF HUMAN α-GALACTOSIDASE AND α1,2-FUCOSYL-TRANSFERASE GENES MODIFIES THE CELL SURFACE GALα1,3GAL ANTIGEN AND CONFERS RESISTANCETO HUMAN SERUM-MEDIATED CYTOLYSIS

Objective To explore the strategies which reduce the amount of xenoantigen Galα1, 3 Gal. Methods Human α-galactosidase gene and α1,2-fucosyltransferase gene were transferred into cul-tured porcine vascular endothelial cells PEDSV.15 and human α-galactosidase transgenic mice were produced. The Galα1,3Gal on the cell surface and susceptibility of cells to human antibody-mediated lysis were analyzed. Results Human α-galactosidase gene alone reduced 78% of Galα1,3Gal on PEDSV.15 cell surface while human α-galactosidase combined with α1,2-fucosyltransferase genes removed Galα1,3Gal completely. Decrease of Galα1,3Gal could reduce susceptibility of cells to human antibody-mediated lysis, especially during co-expression of α-galactosidase gene and α1,2-fucosyltransferase gene. RT-PCR indicated positive human α-galactosidase gene expression in all organs of positive human α-galacto-sidase transgenic F1 mice including heart, liver, kidney, lung, and spleen, the amount of Galα1,3Gal antigens on which was reduced largely. 58% of spleen cells from F1 mice were destroyed by comp-lement-mediated lysis compared with 24% of those from normal mice. Conclusions Human α-galactosidase gene and α1,2-fucosyltransferase gene effectively reduce the expression of Galα1,3Gal antigens on endothelial cell surface and confers resistance to human serum-mediated cytolysis. The expression of human α-galactosidase in mice can also eliminate the Galα1,3Gal antigens in most tissues and decrease the susceptibility of spleen cells to human serum-mediated cytolysis.

Human breast carcinoma xenografts in nude mice

OBJECTIVE: To investigate spontaneous metastasis, micrometastasis and genetic stability in human breast carcinoma xenografts in nude mice. METHODS: Intact tissue from surgical specimens from breast carcinoma patients was xenografted into nude mice and transplanted from generation to generation. Cells from the xenografts were cultured in vitro and retransplanted into nude mice. Microsatellite DNA in the genome of human breast carcinomas, xenotransplanted tumors and metastases in nude mice were analyzed at three microsatellite loci. RESULTS: The tumorigenicity of orthotopic xenotransplantation was 88.6% (31/35), with a metastatic rate of 41.9% (13/31). Cells from xenotransplants were successfully cultured in vitro. The taking rate of retransplantation into nude mice and the spontaneous lung metastasis rate were both 100% (10/10). Microsatellite DNA sequences in the genome of xenotransplanted tumors and metastases in nude mice were identical with that of the original human breast carcinoma at three microsatellite loci. CONCLUSIONS: Tumorigenicity and metastatic potential can be improved in human breast carcinoma xenografts using intact fresh tumor tissue and orthotopic grafts. Xenotransplanted tumors and tumors after serial passage maintained the genetic stability. The detection of microsatellite DNA may identify micrometastases in a nude mouse model.

Cancer metastases: challenges and opportunities

Cancer metastasis is the major cause of cancer morbidity and mortality, and accounts for about 90% of cancer deaths. Although cancer survival rate has been signi fi cantly improved over the years, the improvement is primarily due to early diagnosis and cancer growth inhibition. Limited progress has been made in the treatment of cancer metastasis due to various factors. Current treatments for cancer metastasis are mainly chemotherapy and radiotherapy, though the new generation anti-cancer drugs(predominantly neutralizing antibodies for growth factors and small molecule kinase inhibitors) do have the effects on cancer metastasis in addition to their effects on cancer growth. Cancer metastasis begins with detachment of metastatic cells from the primary tumor, travel of the cells to different sites through blood/lymphatic vessels, settlement and growth of the cells at a distal site. During the process, metastatic cells go through detachment, migration, invasion and adhesion. These four essential, metastatic steps are inter-related and affected by multi-biochemical events and parameters. Additionally, it is known that tumor microenvironment(such as extracellular matrix structure,growth factors, chemokines, matrix metalloproteinases) plays a signi fi cant role in cancer metastasis. The biochemical events and parameters involved in the metastatic process and tumor microenvironment have been targeted or can be potential targets for metastasis prevention and inhibition. This review provides an overview of these metastasis essential steps, related biochemical factors, and targets for intervention.

The presence and outcome of biliary sphincter disorders in liver-transplant recipients according to the Rome IV classification

Background Biliary sphincter disorders after liver transplantation(LT)are poorly described.We aim to describe the presence and outcome of patients with papillary stenosis(PS)and functional biliary sphincter disorders(FBSDs)after LT according to the updated Rome IV criteria.Methods We reviewed all endoscopic retrograde cholangiopancreatographies(ERCPs)performed in LT recipients between January 2003 and December 2019.Information on clinical and endoscopic findings was obtained from electronic health records and endoscopy databases.Laboratory and clinical findings were collected at the time of ERCP and 1 month after ERCP.Results Among the 1,307 LT recipients,336 underwent 849 ERCPs.Thirteen(1.0%)patients met the updated Rome IV criteria for PS[former sphincter of Oddi dysfunction(SOD)type I]and 14 patients(1.0%)met the Rome IV criteria for FBSD(former SOD type II).Biliary sphincterotomy was performed in 13 PS and 10 FBSD cases.One month after sphincterotomy,bilirubin,gamma-glutamyl transferase and alkaline phosphatase levels decreased in 85%,61%,and 92%of those in the PS group(P¼0.019,0.087,and 0.003,respectively)and in 50%,70%,and 80%of those in the FBSD group(P¼0.721,0.013,and 0.093,respectively).All the 14 patients initially suspected of having a FBSD turned out to have a different diagnosis during the follow-up.Conclusions PS after LT is uncommon and occurs in only 1%of LT recipients.Our data do not support the presence of an FBSD after LT.Sphincterotomy is a safe and effective procedure in LT recipients with PS.