Lomboaortic Lymphadenectomy in Gynecological Oncology: Laparotomy, Laparoscopy or Robot-Assisted Laparoscopy?

BACKGROUND: The outcomes of paraaortic lymphadenectomy were compared for the treatment of gynecological malignancies to identify the most appropriate surgical approach. METHODS: Our retrospective, multicentric study included 1304 patients who underwent paraaortic lymphadenectomy for gynecological malignancies. The patients were categorized into the following five groups based on treatment type: transperitoneal laparoscopy (group A, n = 198), extraperitoneal laparoscopy (group B, n = 681), robot-assisted transperitoneal laparoscopy (group C, n = 135), robot-assisted extraperitoneal laparoscopy (group D, n = 44), and laparotomy (group E, n = 246). RESULTS: The prevalence of cancer types differed according to the surgical approach: there were more ovarian cancers in group E and more cervical cancers in groups B and D (p < 0.001). Estimated blood loss was higher in group E (844.2 mL) than in groups treated with minimally invasive interventions (115.8-141.5 mL, p < 0.005). For infrarenal dissection, fewer nodes were removed in group C compared with the other approaches (16 vs. 21 nodes, respectively, p < 0.05). The average operative time ranged from 169 min for group A to 247 min for group E (p < 0.001). Length of hospital stay was 14 days for group E versus 3.5 days for minimally invasive procedures (p < 0.05). The early postoperative grade 3 and superior Dindo-Clavien complications occurred in 9-10% of the patients in groups B-D, 15% of the patients in group E, and only 3% and 4% for groups A and C, respectively. The most common complication was lymphocele. CONCLUSIONS: Laparotomy increases preoperative and postoperative morbidity. The robot-assisted transperitoneal approach demonstrated a poorer lymph node yield than laparotomy and extraperitoneal approaches.

The importance of jointly analyzing treatment administration and toxicity associated with targeted therapies: a case study of regorafenib in soft tissue sarcoma patients.

Background: Different methods have been proposed to analyze adverse events (AEs) associated with targeted therapies. While these AEs lead to dose adjustments for many patients, conventional reporting methods do not take drug administration into consideration. This paper underlines the importance of jointly reporting AEs and drug administration using prevalence, and proposes a complementary approach to reporting. Patients and methods: The prevalence method estimates the probability of progression-free patients being in a particular health state (state 1: AEs with full dose; state 2: AEs with reduced dose; state 3: no AEs with reduced dose) at different time points. To take into account the impact of dose adjustments on efficacy, the weighted prevalence method can be used by assigning utility weights to the different health states. The benefit of these methods was illustrated using data from a phase II trial of regorafenib. Results: Only 4.6% of progression-free patients developed mucositis/stomatitis (grade ≥2) at 3 months. The prevalence of patients not experiencing this AE but whose dose was reduced or treatment interrupted was 58.1%. The weighted prevalence of the regorafenib toxicity profile and dose reduction was higher in the control arm. Conclusion: This case study confirms the importance of jointly analyzing AEs and drug administration. The weighted prevalence approach is an average score that incorporates the dimension of drug administration into AE assessment. This can be helpful for regulatory agencies as well as for clinicians to evaluate the benefit-risk ratio of therapies in their treatment choice. Clinical trial: NCT01900743.

Scaling behavior in beta-wave amplitude modulation and its relationship to alertness.

We performed an experimental study of beta waves occurring in human electroencephalographic signals obtained from six healthy subjects that were monitored during the performance of a task requiring attention to auditory signals. We use wavelet analysis to study whether the fluctuations in the modulation of the beta-wave amplitude related to an indirect measurement of alertness. We found that these fluctuations exhibit a power-law behavior. When the level of alertness dropped, the associated exponent was found to increase, reflecting the fact that long-range correlations grow rapidly within the system. We also studied the fluctuations of amplitude modulation for alpha and theta waves, for which we did not find a power-law behavior.

Vibrational and theoretical study of the 2',6'-dimethoxyflavone cis-formic acid inclusion compound.

The FT-infrared and Raman microscopy spectra of the 2',6'-dimethoxyflavone and its 1:1 complex with formic acid in solid state have been recorded and analysed. Some vibrational components appear as specific to the cis-rotamer of formic acid in the crystalline sample, especially the CH group stretching vibration feature. The broad and intense infrared absorption observed in the range 3400-1900 cm(-1) and assigned to the hydrogen bonded OH group stretching vibration exhibits the characteristic ABC structure of strong hydrogen bonded complexes. This ABC pattern corroborates previous X-ray crystallographic data showing that cis-formic acid is strongly hydrogen bonded to the flavonic compound. The inclusion complex is quite unstable and the infrared spectrum clearly shows that formic acid disappears after a period of a few months. In order to get some information on the stability criterions of the intermolecular hydrogen bonded complex, semiempirical AM1 calculations have been investigated. The comparison of the calculated heats of complexation (deltacH) for chelates involving the cis- and trans-conformers of formic acid suggests that the reaction of hydrogen bonding complexation with the cis-rotamer is surely favoured.

Antioxidant properties of hydroxy-flavones.

The antioxidant properties of 24 hydroxy-flavones were evaluated. Results show that 2',3',4'-OH substitution on the B ring plays a crucial role in radical scavenger activity in the DPPH assay and in the inhibitory effect on pereoxydation of tissue lipids in the MDA test. The formation of stable radicals for this type of compounds has been studied by ESR. In addition, it has been found that 7-hydroxy-flavones are potent competitive inhibitors of xanthine oxidase. It is proposed that the C-7 OH of flavones may take the place of the C-2 or C-6 OH of xanthine in the active site of the enzyme. A C-4' OH or C-4' OMe substitution on the 7-hydroxy flavones is not favourable to a fit in the active site. The 2',3',4'-trihydroxy-flavones inhibited XO by another process, which remains to be determined. In summary, this study provides evidence that hydroxy-flavones exhibit interesting antioxidant properties expressed either by the capacity to scavenge free radicals (for 2',3',4'-trihydroxy-flavones) or to competitively inhibit xanthine oxidase (for 7-hydroxy-flavones). These compounds may be drug candidates for treating pathologies related to free radical oxidation.

Structural and conformational studies on bio-active flavonoids. Crystal and molecular structure of a complex formed between 2',6'-dimethoxyflavone and orthophosphoric acid: a model for flavone-nucleotide interactions.

In order to investigate mechanisms of action of flavones at the molecular level, we have prepared a complex between a flavone and orthophosphoric acid which can be considered as a simplest model of interaction between a flavone and a more complex biological phosphate such as nucleotide, coenzyme or DNA. With orthophosphoric acid, the title flavone forms crystals which have 1:2 stoichiometry (C17H14O4.2H3PO4). This compound was found to be the 1:1 salt co-crystallized with the unionized molecular acid C17H15O4+.H2PO4-.H3PO4. The symmetry is monoclinic, space group P2(1)/n and unit cell dimensions a = 15.571(2), b = 7.369(1), c = 17.837(2) A, beta = 100.84(1) degrees. One molecule of phosphoric acid is present as a solvate molecule of crystallization, but the other is ionized and protonates the carbonyl oxygen, introducing conformational and bond distance changes in the flavone. The dihedral angle between the benzopyrone and phenyl rings is 47 degrees. Complexes with phosphate groups involve strong hydrogen bonds and are expected to play important roles in biomolecular structures.

Scavenger and antioxidant properties of ten synthetic flavones.

To study the effect of the hydroxyl groups on biological activities of flavones, we synthesized 10 polyhydroxyflavones with varied substitution patterns. The abilities of the 10 compounds to act as radical scavengers were investigated using chemiluminescence in two biological models: the xanthine/xanthine oxidase system and the oxidative burst of rat alveolar macrophages. Stable radical formation was observed by electron spin resonance (ESR) spectroscopy. We found that the presence of the pyrogallol moiety in the B component of flavones gave rise to radical scavenger activity and that C-6 substituted hydroxyl group may also provide the basis for biological activity. Furthermore, compounds with a hydroxyl at C-7 position appeared to be xanthine oxidase inhibitors. One particular compound exhibited radical scavenger activity and xanthine oxidase inhibition. This type of compound should prove to be useful in the treatment of ischemia, for which both properties were required.