Alexandre Balaphas

Robotic laparoendoscopy single site surgery: a transdisciplinary review

Recent developments in minimal invasive surgery have led to laparoendoscopic single site surgery (LESS). This new approach has great potential but remains technically challenging. In order to relieve these difficulties many authors have adapted robotic technology to single site surgery. Numerous approaches have been developed and there is no real consensus.

Xenotransplantation: back to the future?

The field of xenotransplantation has fluctuated between great optimism and doubts over the last 50 years. The initial clinical attempts were extremely ambitious but faced technical and ethical issues that prompted the research community to go back to preclinical studies. Important players left the field due to perceived xenozoonotic risks and the lack of progress in pig‐to‐nonhuman‐primate transplant models. Initial apparently unsurmountable issues appear now to be possible to overcome due to progress of genetic engineering, allowing the generation of multiple‐xenoantigen knockout pigs that express human transgenes and the genomewide inactivation of porcine endogenous retroviruses. These important steps forward were made possible by new genome editing technologies, such as CRISPR/Cas9, allowing researchers to precisely remove or insert genes anywhere in the genome. An additional emerging perspective is the possibility of growing humanized organs in pigs using blastocyst complementation. This article summarizes the current advances in xenotransplantation research in nonhuman primates, and it describes the newly developed genome editing technology tools and interspecific organ generation.

A Case of Ipilimumab-induced Anorectal Fistula.

Dear Sir, Ipilimumab (Yervoy®) is a human monoclonal antibody (anti-CTLA4) approved since 2011 by the FDA for the treatment of unresectable or metastatic melanoma. This drug is associated with autoimmune side effects affecting the gut, liver, skin, endocrine organs and nerves. Thirty-five percent of patients treated with ipilimumab will develop colitis, and 10% of these cases can evolve to a colonic perforation requiring surgical management.1,2 Ipilimumab-induced colitis shares immune and histological patterns with Crohn’s disease.3 Steroids are generally the first-line treatment to deal with this type of colitis, but anti-tumour necrosis factor α (TNFα) drugs have been used in …

Platelets Stimulate Liver Sinusoidal Endothelial Cells to Secrete Interleukin-6 During the Early Phase of Liver Regeneration in Mice

Background and Aims Platelets and liver sinusoidal endothelial cells (LSEC) are both known to independently regulate liver regeneration. Our aim was to investigate the role of interactions between platelets and LSEC in a model of liver regeneration. Methods Platelet and LSEC interactions were analyzed in vivo by intravital confocal microscopy in partially hepatectomized mice. Then, highly purified primary mouse LSEC were co-incubated with increasing concentrations of resting platelets, activated platelets, or platelet releasates, and secretion of growth factors was measured. The active fraction of platelet releasates was characterized and its effect on hepatocyte proliferation assessed. Finally, IL-6 serum concentrations were measured in mice with varying platelet counts after partial hepatectomy. Results Following partial hepatectomy, in vivo adhesion of platelets to LSEC was significantly increased, when compared to sham-operated mice. Co-incubation of increasing numbers of resting or activated platelets with LSEC resulted in significantly enhanced IL-6 secretion by LSEC. IL-6 release by LSEC was the highest after incubation with ADP-activated platelets. The effect of platelet releasates on LSEC was similar to that seen with intact, whole platelets. Further, the effect of platelets on LSEC was mediated by a platelet factor, whose action was synergistically enhanced by ADP. ADP-activated platelet releasates increased proliferation of hepatocytes co-cultured with LSEC. Decreased platelet counts resulted in decreased serum levels of IL-6 after partial hepatectomy in vivo. Conclusion We show that platelets modulate LSEC to constitutively secrete IL-6, a key player in liver regeneration. After partial hepatectomy, platelets adhere to LSEC and serum IL-6 levels depend on platelet concentration. Interactions between platelets and LSEC modulate IL-6 release by LSEC and increase hepatocyte proliferation. This effect is dependent on ADP.

Platelets in liver regeneration

Loss of liver tissue leading to impairment of liver function represents a major cause of mortality. Understanding the mechanism of liver regeneration and developing therapies to sustain liver regeneration are of high therapeutic relevance. In this regard, platelets are considered as potential candidates for stimulating liver regeneration.