Safety and Efficacy of IL-12 Plasmid DNA Transfection into Pig Skin: Supportive Data for Human Clinical Trials on Gene Therapy and Vaccination.

Gene electrotransfer (GET) of plasmids encoding interleukin 12 (IL-12) has already been used for the treatment of various types of tumors in human oncology and as an adjuvant in DNA vaccines. In recent years, we have developed a plasmid encoding human IL-12 (phIL12) that is currently in a phase I clinical study. The aim was to confirm the results of a non-clinical study in mice on pharmacokinetic characteristics and safety in a porcine model that better resembled human skin. The GET of phIL12 in the skin was performed on nine pigs using different concentrations of plasmid phIL12 and invasive (needle) or noninvasive (plate) types of electrodes. The results of our study demonstrate that the GET of phIL-12 with needle electrodes induced the highest expression of IL-12 at the protein level on day 7 after the procedure. The plasmid was distributed to all tested organs; however, its amount decreased over time and was at a minimum 28 days after GET. Based on plasmid copy number and expression results, together with blood analysis, we showed that IL-12 GET is safe in a porcine animal model. Furthermore, we demonstrated that pigs are a valuable model for human gene therapy safety studies.

Histologic changes of porcine portal vein anastomosis after electrochemotherapy with bleomycin.

Electrochemotherapy (ECT1) is used for treatment of unresectable abdominal malignancies. This study aims to show that ECT of porcine portal vein anastomosis is safe and feasible in order to extend the indications for margin attenuation after resection of locally advanced pancreatic carcinoma. No marked differences were found between the control group and ECT treated groups. Electroporation thus caused irreversible damage to the vascular smooth muscle cells in tunica media that could bedue to the narrow irreversible electroporation zone that may occur near the electrodes, or due to vasa vasorum thrombosis in the tunica externa. Based on the absence of vascular complications, and similar histological changes in lienal veinanastomosis, we can conclude that ECT of portal vein anastomosis is safe and feasible.

Residual disease in lymph nodes has no influence on survival in patients with incidental gallbladder cancer - institution experience with literature review.

BACKGROUND: A better appreciation of the course and factors that influence incidental gallbladder cancer (iGBC) is needed to develop treatment strategies aimed to improve outcomes. The purpose of the study was to determine the influence of residual disease in the liver and lymph nodes on overall survival in re-resected patients with iGBC. PATIENTS AND METHODS: Patients undergoing radical re-resection for iGBC from January 2012 to December 2018 were retrospectively identified. Patients with a 5-year follow-up and submitted to complete resection with stage I, II and III disease were analysed. The influence of residual disease (RD) in liver and lymph nodes on survival was assessed using the Kaplan-Meier curves. In addition, the rest of the group was assessed based on type of primary/secondary procedure, number of harvested lymph nodes and RD in liver and/or lymph nodes. RESULTS: In this retrospective study 48 out of 58 (83%) patients underwent re-resection. Among the group with a 5-year follow-up (re-operation between 2012-2014), 22 patients out of 28 (79%) were re-resected. Survival analysis showed that patients with no RD in the liver and lymph nodes had statistically significant better 5-year survival than those with RD. Comparing 5-year survival rate in patients with RD in the liver or lymph nodes against no RD group, patients with RD in the liver had statistically significantly worse 5-year survival, while lymph node metastases did not show any statistically significant different in 5-year survival. Besides, a statistically significant better prognosis was found in stage II disease compared to stage III, as expected. CONCLUSIONS: The most important predictors of a 5-year survival in our study were RD in liver and stage of the disease. Lymph node metastases did not have any impact on the overall 5-year survival rate.

Conservative management of abdominoperineal impalement trauma - A case report.

INTRODUCTION: Adult perineal impalement injuries are uncommon and notorious for their complex injury pattern and risk of massive pelvic bleeding. They present a challenge for the treating physician as there is no consensus about the optimal treatment in the existing literature. In most cases patients need operative intervention. CASE PRESENTATION: In this article the authors present a case report of a 63-year old man with an impalement injury in the left gluteus, who was managed conservatively. DISCUSSION: With the recent trends towards conservative management of abdominal penetrating trauma, increased morbidity and costs associated with nontherapeutic laparotomy, conservative management of impalement injuries in hemodynamically stable patients should be considered. Accurate determination of the impaling object trajectory path is vital for the decision and aids to answer two important questions: Did the impaling object enter the peritoneal, retroperitoneal or pelvic cavity? Is there an injury that will require an operation? CONCLUSION: Abdominoperineal impalement injuries have high mortality, but those patients, who manage to reach hospital alive, can sometimes be manages conservatively, as shown in our case report.