Robotic transanal total mesorectal excision: Is the future now?

Total mesorectal excision (TME) is the standard surgical treatment for the curative radical resection of rectal cancers. Minimally invasive TME has been gaining ground favored by the continuous technological advancements. New procedures, such as transanal TME (TaTME), have been introduced to overcome some technical limitations, especially in low rectal tumors, obese patients, and/or narrow pelvis. The earliest TaTME reports showed promising results when compared with the conventional laparoscopic TME. However, recent publications raised concerns regarding the high rates of anastomotic leaks or local recurrences observed in national series. Robotic TaTME (R-TaTME) has been proposed as a novel technique incorporating the potential benefits of a perineal dissection together with precise control of the distal margins, and also offers all those advantages provided by the robotic technology in terms of improved precision and dexterity. Encouraging short-term results have been reported for R-TaTME, but further studies are needed to assess the real role of the new technique in the long-term oncological or functional outcomes. The present review aims to provide a general overview of R-TaTME by analyzing the body of the available literature, with a special focus on the potential benefits, harms, and future perspectives for this novel approach.     

Healthy by Association: The relationship between social participation and self-rated physical and psychological health

This paper investigates the relationship between social participation and subjective health. Using individual-level data from the British Household Panel Survey, we show that being an active member of a social or sport organisation increases self-rated physical and psychological health. For men, the benefits of social interaction work primarily via physical pathways, while women report a more psychosocial channel. We separate the main results by occupation and document some heterogeneity. Manual workers find more physical and psychological relief via social involvement, whereas non-manual workers are more likely to take relief from sport participation. Interestingly, as the number of associations in which the individual is active increases, the incremental increase in social benefits diminishes. Our findings point to the importance of promoting social and sport activities in health communication and policy making.     

Endothelial leukocyte adhesion molecule-1-dependent adhesion of colon carcinoma cells to vascular endothelium is inhibited by an antibody to Lewis fucosylated type I carbohydrate chain.

Endothelial leukocyte adhesion molecule-1 (ELAM-1) has been determined to be the mediator of adhesion of colon carcinoma cells to interleukin-1 (IL-1)-activated endothelial cells. To identify ELAM-1 ligand in colon carcinoma cells, we have screened a series of 11 monoclonal antibodies directed to these cells and found that only one MBr8 was able to inhibit the IL-1-induced increment in adhesion of HT29 and of SW948 colon carcinoma lines to endothelial cells. In contrast, MBr8 did not bind to polymorphonuclear cells, monocytes, and lymphocytes and did not inhibit polymorphonuclear adhesion to IL-1-activated endothelial cells. As expected, an ELAM-1 monoclonal antibody strongly inhibited IL-1 induced increment of adhesion of HT29, SW948, and polymorphonuclear cells. As negative control, MG63 osteosarcoma cells were used. These cells adhere more efficiently to IL-1 activated endothelial cells but MBr8 and ELAM-1 monoclonal antibodies did not affect their adhesion. The effect of MBr8 was also tested in an experimental system in vivo. As described previously, radiolabeled HT29 cell retention in the lung of nude mice was increased in animals given IL-1. MBr8 administration to nude mice or pretreatment of tumor cells with it inhibited this effect. These data suggest that cell adhesion to ELAM-1 might be mediated by different, cell type specific, sugar ligands.     

Ambroxol inhibits interleukin 1 and tumor necrosis factor production in human mononuclear cells

We have studied the effect of Ambroxol on the production of Interleukin-1 (IL-1) and Tumor Necrosis Factor (TNF) in human mononuclear cells (MNC). For this purpose MNC were cultured for 24 h in the presence of endotoxin and different doses of Ambroxol. The results indicate that Ambroxol markedly inhibited IL-1 and TNF production at doses of 10–100 g/ml, without any apparent toxicity.     

Effects of 6-hydroxydopamine on pre- and post-junctional 5-HT1-like receptor-mediated responses in dog saphenous vein

Summary To investigate whether 5-HT₁-like receptor-mediated inhibition of adenosine 3 : 5-cyclic monophosphate (cyclic AMP) accumulation occurs in nerves or smooth muscle of saphenous vein, infusions of 6-hydroxydopamine (6-OHDA) were administered to dogs with the aim of inducing sympathetic nerve damage. The effects of 6-OHDA on other 5-HT₁-like receptor-mediated responses at the pre- and post-junctional level were investigated for comparison by studying 5-hydroxytryptamine (5-HT)-induced inhibition of ³H-noradrenaline release and contraction of smooth muscle respectively.Disruption of nerve function by 6-OHDA was revealed by the lack of catecholaminergic fluorescence and neurogenic contractile responses in saphenous veins from dogs treated with 6-OHDA. In addition, severe impairment of neuronal uptake mechanisms were apparent since basal efflux of ³H-noradrenaline, electrically-evoked release of ³H-noradrenaline and remaining ³H-noradrenaline content were considerably reduced. Some ³H-noradrenaline was taken up and released in 6-OHDA treated tissues which is consistent with the existence of nerve varicosities resistant to the present dosing regime of 6-OHDA, an observation substantiated by electron microscopy studies showing inconsistent lesions of nerve terminals.6-OHDA pre-treatment potentiated the smooth muscle contractile responses mediated by 5-HT₁-like receptors as well as potentiating 5-HT-evoked inhibition of prostaglandin E₂-stimulated cyclic AMP accumulation. It did not, however, affect 5-HT-induced inhibition of ³H-noradrenaline release. The present results suggest that inhibition of cyclic AMP accumulation by 5-HT occurs predominantly in smooth muscle. Correspondence to A. J. Kaumann at the above address     

In vitro and in vivo effects of cisplatin on the generation of lymphokine-activated killer cells

Pretreatment of human peripheral blood lymphocytes (PBL) with cisplatin (CDDP) before in vitro culture with interleukin-2 (IL-2) inhibited the generation of lymphokine-activated killer (LAK) cells and strongly inhibited proliferation. This inhibition was dose dependent, was significant only at concentrations greater than 6 microM, and it required exposure to the drug for more than 1 hour. This period of IL-2 unresponsiveness was maximum at 6 hours, but was spontaneously recovered within 24-48 hours and was more rapidly restored by increasing dosages of IL-2. Because inhibition of the generation of LAK cells by CDDP was observed only at relatively high levels of exposure to the drug (greater than 6 microM for greater than 1 hr), it was important that we explore the in vivo significance of these findings. The peripheral blood lymphocytes from patients bearing ovarian adenocarcinoma collected 1 hour after an iv infusion of 50 mg of CDDP/m2 were not inhibited, compared with those collected immediately before therapy. Relatively high levels of exposure to CDDP are required for inhibition of the generation of new cytotoxic effectors, most likely because of its antiproliferative effect. These results may bear relevance to approaches involving the combined use of CDDP and IL-2-LAK.     

Chemokine production by human vascular smooth muscle cells: modulation by IL-13

1. The production of chemokines by vascular smooth muscle cells (SMC) is implicated in the pathogenesis of atherosclerosis, although the factors regulating chemokine production by these cells are incompletely characterized.
2. We describe the differential stimulation of interleukin-(IL)-8, monocyte chemoattractant protein (MCP)-1 and regulated on activation normal T-cell expressed and secreted (RANTES) synthesis following treatment of human vascular SMC with IL-1α or tumour necrosis factor α (TNFα). Under basal conditions, cultured SMC release very low amounts of IL-8, MCP-1 and RANTES as assessed by specific ELISA. Concentration-response studies with IL-1α or TNFα revealed that each stimulus induced a similar amount of MCP-1. In contrast approximately three fold more IL-8 was induced by IL-1α than by TNFα whereas significant RANTES production was induced only by TNFα. These findings point to a divergence in the regulation of synthesis of the different chemokines in response to IL-1α or TNFα stimulation.
3. The T-cell derived cytokines IL-10 and IL-13 were also found to have differential effects on chemokine production by SMC. IL-13, but not IL-10, significantly enhanced IL-8 and MCP-1 release in response to IL-1α or TNFα. This increase in chemokine release appeared to be accounted for by increased mRNA expression.
4. These findings provide support for the concept that smooth muscle cells can have an active role in a local immune response via the production of chemokines which can be selectively modulated by T-cell derived cytokines.