Role of different approaches to the abdominal retroperitoneum for aortic lymphadenectomy in patients with gynecological cancers.

BACKGROUND: Paraaortic lymphadenectomy (PALN) is a standard part of many interventions, but currently there are no established care protocols effective in preventing gastro-intestinal (GI) symptoms. The aim of our study was to retrospectively evaluate patients with gynecologic cancers submitted to PALN, in order to evaluate if different approaches to the retroperitoneum could influence the radicality of the procedure and the onset of GI complications. METHODS: We divided 121 patients with gynecologic tumors submitted to PALN into 3 groups according the used right, left or combined left-right approach to the retroperitoneum, comparing the groups according the main surgical-pathological parameters, such as the number of nodes removed and the incidence and severity of GI complications. RESULTS: The mean number of nodes removed did not significantly differ between the groups, while the mean number of positive nodes was significantly higher in combined approach. 39.8% of our patients experienced GI side effects, but those submitted to the combined approach had a significantly higher incidence of GI symptoms. CONCLUSIONS: Our data demonstrate that the choice of the retroperitoneal approach could be the most important feature for the appearance of post-operative GI side effects, even if there is no significant difference on the radicality of PALN performed retroperitoneal approach.

Robotic treatment of colorectal endometriosis: technique, feasibility and short-term results.

BACKGROUND: Deep infiltrating endometriosis (DIE) is a complex disease that impairs the quality of life and the fertility of women. Since a medical approach is often insufficient, a minimally invasive approach is considered the gold standard for complete disease excision. Robotic-assisted surgery is a revolutionary approach, with several advantages compared with traditional laparoscopic surgery. METHODS: From March 2010 to May 2011, we performed 22 consecutive robotic-assisted complete laparoscopic excisions of DIE endometriosis with colorectal involvement. All clinical data were collected by our team and all patients were interviewed preoperatively and 3 and 6 months post-operatively and yearly thereafter regarding endometriosis-related symptoms. Dysmenorrhoea, dyschezia, dyspareunia and dysuria were evaluated with a 10-point analog rating scale. RESULTS: There were 12 patients, with a median larger endometriotic nodule of 35 mm, who underwent segmental resection, and 10 patients, with a median larger endometriotic nodule of 30 mm, who underwent complete nodule debulking by colorectal wall-shaving technique. No laparotomic conversions were performed, nor was any blood transfusion necessary. No intra-operative complications were observed and, in particular, there were no inadvertent rectal perforations in any of the cases treated by the shaving technique. None of the patients had ileostomy or colostomy. No major post-operative complications were observed, except one small bowel occlusion 14 days post-surgery that was resolved in 3 days with medical treatment. Post-operatively, a statistically significant improvement of patient symptoms was shown for all the investigated parameters. CONCLUSIONS: To our knowledge, this is the first study reporting the feasibility and short-term results and complications of laparoscopic robotic-assisted treatment of DIE with colorectal involvement. We demonstrate that this approach is feasible and safe, without conversion to laparotomy.

Advances in surgical management of cervical cancer.

Cervical cancer (CC) remains an important health problem representing the second most frequent malignancy in women, with 470 000 new cases/year and 280 000 deaths, 80% of which occur in developing countries. In the last few years, new theoretical developments and advances in technology resulted in novel surgical approaches aimed at improving the therapeutic efficacy and/or reducing treatment related side effects. In particular, the authors focused their attention on the most relevant novelties related to the laparoscopic approach to CC treatment, and on the issue of modulation of surgical radicality. Moreover, the possible perspectives of sentinel lymph node concept and robotic surgery, as well as clinical issues related to conservative procedures including ''nerve sparing'' and ''fertility sparing'' strategies, have been evaluated.

Pathogenic role of anti-beta2-glycoprotein I antibodies on human placenta: functional effects related to implantation and roles of heparin.

Most of the clinical manifestations of the antiphospholipid syndrome (APS) can be related to thrombotic events; however, placental thrombosis cannot explain all of the pregnancy complications that occur in women with this syndrome. In this regard, it has been hypothesized that antiphospholipid (aPL) antibodies can directly attack trophoblasts, but it is still unclear what pathogenetic mechanisms play a role and which aPL antibodies subpopulations are involved. Although it has been assumed that aPL antibodies are directed against anionic phospholipids (PLs), current advances in the field suggest that antibodies to PL-binding plasma protein such as beta2-glycoprotein-I (beta2-GPI) are the clinically relevant aPL antibodies. It appears that following the attachment of beta2-GPI to PLs, both molecules undergo conformational changes that result in the exposure of cryptic epitopes within the structure of beta2-GPI allowing the subsequent binding of antibodies. aPL antibodies detected by anti-beta2-GPI assays are associated with fetal loss. However, there is still debate on how the antibodies might induce the obstetrical manifestations. The significantly improved outcome of pregnancies treated with heparin has stimulated interest in the drug's mechanisms of action. Several mechanisms could explain its beneficial effects, because in addition to a direct effect of heparin on the coagulation cascade, it might protect pregnancies by reducing the binding of aPL antibodies, reducing inflammation, facilitating implantation and/or inhibiting complement activation. Further investigations are needed to better understand how aPL antibodies induce obstetric complications and to better clarify the functional role of heparin in the human placenta leading to more successful therapeutic options.

Pathogenic role of anti-beta 2-glycoprotein I antibodies in antiphospholipid associated fetal loss: characterisation of beta 2-glycoprotein I binding to trophoblast cells and functional effects of anti-beta 2-glycoprotein I antibodies in vitro.

BACKGROUND: Antiphospholipid antibodies reacting with beta2-glycoprotein I (beta 2GPI) have been associated with recurrent fetal loss and pregnancy complications. OBJECTIVE: To investigate whether specific mutations in the phospholipid binding site of beta 2GPI might affect its binding to trophoblast and in turn the anti-beta 2GPI antibody induced functional effects. METHODS: beta 2GPI adhesion to trophoblast was evaluated as human monoclonal IgM or polyclonal IgG anti-beta 2GPI antibody binding to trophoblast monolayers cultured (1) in complete medium; (2) in serum-free medium; (3) after serum starvation in the presence of purified human beta 2GPI; or (4) in the presence of beta 2GPI with single or multiple mutations in the amino acid loop Cys(281)-Lys-Asn-Lys-Glu-Lys-Lys-Cys(288). The effect of anti-beta 2GPI binding to trophoblast was evaluated as chorionic gonadotropin (hCG) mRNA expression, and protein release by RT-PCR and radioimmunoassay, respectively. RESULTS: beta 2GPI adhesion to trophoblast and its consequent recognition by the specific antibodies were inversely proportional to the mutation number in the phospholipid binding site. Anti-beta 2GPI antibodies reduced gonadotropin release, hormone dependent hCG mRNA expression, and protein synthesis in the presence of beta 2GPI, while the addition of the mutants or the absence of beta 2GPI had no effect. CONCLUSIONS: beta 2GPI binds to trophoblast in vitro through its fifth domain, as reported for endothelial cells, and can be recognised by anti-beta 2GPI antibodies; the antibody binding downregulates trophoblast hCG synthesis and secretion. Such a mechanism might contribute to defective placentation in women with fetal loss associated with the antiphospholipid syndrome.

Antiphospholipid antibodies as cause of pregnancy loss.

Antiphospholipid antibodies detected by lupus anticoagulant, anticardiolipin or anti-beta2 glycoprotein I assays were associated with fetal loss. Rather than being diagnostic tools only, antiphospholipid antibodies are thought to be pathogenic. The strongest demonstration of their pathogenic role lies in the ability to induce fetal resorptions--the experimental equivalents of the human fetal losses--when passively infused in pregnant naive animals. However, still debated is how the antibodies might induce the obstetrical manifestations. Thrombotic events at the placental levels might be related to endothelial cell activation, inhibition of protein C/S system and fibrinolysis as well as to Annexin V displacement. However, the thrombophilic state apparently cannot explain all the miscarriages and a direct antibody-mediated damage on the trophoblast has been suggested. During differentiation to syncytium, trophoblasts express cell membrane anionic phospholipids that can bind beta2 glycoprotein I, the main cationic phospholipid binding protein recognized by the antiphospholipid antibodies. Adhered beta2-glycoprotein I might be recognized by the antibodies that, once bound, strongly interfere with in vitro trophoblast cell maturation so resulting in a defective placentation. These mechanisms have been suggested to play a role in early fetal loss, while thrombotic events would be responsible for miscarriages late in the pregnancy.

Effect of folic acid on homocysteine-induced trophoblast apoptosis.

In trophoblast cells exposed to homocysteine (Hcy) we observed cellular apoptosis and the inhibition of trophoblast functions. Because folate and Hcy, linked in the same metabolic pathway, are inversely related, we investigated the role of folic acid in reversing the Hcy effect in human placenta. In primary trophoblast cells we examined the cytosolic release of cytochrome c, both M30 and terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling (TUNEL) and DNA laddering. Hcy (20 micromol/l) treatment resulted in cytochrome c release from mitochondria to the cytosol, and an increased number of M30-positive trophoblast cells and TUNEL positive nuclei. Furthermore, DNA cleavage in agarose gel and the determination of histone-associated DNA fragments have been investigated. Homocysteine induced DNA fragmentation and significantly reduced hCG secretion. The addition of folic acid (20 nmol/l) resulted in inhibition of the effects of Hcy on human trophoblast. These results suggest a protective role of folic acid in the prevention of trophoblast apoptosis linked to Hcy.