Surgical treatment of ureteral obstruction from endometriosis: our experience with thirteen cases

Endometriosis is a biologically benign albeit aggressive pathology marked by high local recurrences. Ureteral involvement accounts for only a minority of cases (0.1–0.4%) with often non-specific symptoms at clinical presentation and difficult preoperative diagnosis. Thirteen cases of severe ureteral endometriosis (i.e. causing significant obstruction to the urinary flow) were observed and surgically treated, out of 17 ureteral units affected (three cases of bilateral involvement, one case of complete pyeloureteral duplicity). The initial symptomatology was acute and related to ureteral obstruction in eight cases, silent and non-specific in the other five; a presumptive diagnosis was made only for the seven patients (53.9%) with a positive medical history for pelvic (and in two cases also ureteral) endometriosis. Preoperative drainage of urine proved necessary for eight patients due to the complete functional exclusion of the excretory axis. One patient (7.7%) underwent nephrectomy due to renal atrophy. Segmental ureteral resection and termino-terminal anastomosis were performed in two patients, while seven patients underwent segmental ureterectomy and ureterocystoneostomy, with bladder psoas hitching in four cases and vesical flap according to Casati-Boari in one case. All three cases of bilateral involvement were treated by bilateral segmental ureterectomy and trans-uretero-uretero-cystoneostomy with bladder psoas hitching. Following histological examination, all patients were diagnosed with active ureteral endometriosis, which was found to be intrinsic in five cases (38.5%) and extrinsic in the other eight. One of the two patients that had undergone ureterectomy and termino-terminal anastomosis had to undergo ureteral resection and ureterocystoneostomy 22 months later due to relapsing endometriosis-induced stenosis. Conversely, no ureteral endometriosis relapses occurred in the remaining 12 patients within the mean follow-up time of 41.1 months (range 6–91). Ureteral endometriosis is marked by non-specific symptoms, making preoperative diagnosis often difficult. Therefore, an ultrasound or urographic examination of the urinary tract in case of pelvic endometriosis is absolutely essential. In our experience, terminal ureterectomy with ureterocystoneostomy has provided long-term favourable results as extended ureteral resection can be performed and continuity of the urinary tract can be restored without resorting to the distal pelvic ureter, which is often affected by the disease besides being more subject to relapses. Editorial Comment: The authors present an appropriate treatment option for a difficult problem. Frequently, endometriosis involving the urothelium, bladder or ureter is not responsive to medical management. This article further emphasizes the need to screen all patients who present with severe endometriosis for ureteral obstruction. A recent article (Yohannes P (2003) J Urol 170:20) discusses attempts at conservative therapy. However, close follow-up is required during attempts at conservative management. Those patients who have failed medical management and/or have extensive scarring with reduction in renal function will require surgery.     

Increase in motility and invasiveness of MCF7 cancer cells induced by nicotine is abolished by melatonin through inhibition of ERK phosphorylation

Through activation of the ERK pathway, nicotine, in both normal MCF‐10A and low‐malignant breast cancer cells (MCF7), promotes increased motility and invasiveness. Melatonin antagonizes both these effects by inhibiting almost completely ERK phosphorylation. As melatonin has no effect on nonstimulated cells, it is likely that melatonin can counteract ERK activation only downstream of nicotine‐induced activation. This finding suggests that melatonin hampers ERK phosphorylation presumably by targeting a still unknown intermediate factor that connects nicotine stimulation to ERK phosphorylation. Furthermore, downstream of ERK activation, melatonin significantly reduces fascin and calpain activation while restoring normal vinculin levels. Melatonin also counteracts nicotine effects by reshaping the overall cytoskeleton architecture and abolishing invasive membrane protrusion. In addition, melatonin decreases nicotine‐dependent ROCK1/ROCK2 activation, thus further inhibiting cell contractility and motility. Melatonin actions are most likely attributable to ERK inhibition, although melatonin could display other ERK‐independent effects, namely through a direct modulation of additional molecular and structural factors, including coronin, cofilin, and cytoskeleton components.     

A prospective study of pelvic floor dysfunctions related to delivery

Objective

To estimate the prevalence and impact on quality of life of urinary incontinence (UI) and anal incontinence (AI) three months after first delivery; to identify risk factors involved in UI or AI; to evaluate possible changes in sexual behaviour and anatomical modifications of pelvic floor after childbirth.

Study design

A multicenter prospective study, in six Italian Ob/Gyn departments, of nulliparous women who delivered at term (37-42 weeks of gestation) between April and September 2005. A structured questionnaire investigated several maternal and obstetric variables. UI and AI were assessed by administration of the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and according to Wexner's Continence Grading Scale, at 2-3 days post-partum and at 3 months after delivery. Changes in sexual behaviour, and pelvic floor condition after delivery, were also recorded. Statistical analysis included comparison of means (Mann-Whitney or Student's t-test) and proportions (Chi-square test). Multiple logistic regression analysis was performed including variables that were significant in univariate comparisons.

Results

Of 960 enrolled women, 744 were evaluated 3 months after delivery and included in final analysis. The prevalences of UI and AI at that time were 21.6% and 16.3%, respectively. Onset of incontinence during pregnancy was an independent predictor for persistent UI (Odds Ratio (OR) 4.6, Confidence Interval (CI) 3.1-6.8, p < 0.001) and AI (OR 3.6, CI 2.2-6.1, p < 0.001). Family history of urinary or anal incontinence were respectively associated with UI (OR 2.6, CI 1.6-4.0, p < 0.001) and AI (OR 2.4, CI 1.4-4.0, p < 0.001) 3 months after delivery. Among obstetric factors, vaginal delivery was a strong risk factor for UI (OR 3.3, CI 2.0-5.3, p < 0.001). The sexual score improved 3 months after delivery in 72.4% of women. Urogynaecological evaluation showed a significant association between grade 1-2 anterior prolapse, urethral hypermobility and UI.

Conclusion

New onset of UI or AI during pregnancy, positive family history and vaginal delivery are independent risk factors for the persistence of symptoms of UI and AI in the early postpartum period. Adequate counselling and the implementation of targeted strategies to prevent or early identify these conditions are therefore mandatory to improve the patient's quality of life.     

Transpulmonary thermodilution during extracorporeal organ support (ECOS): is it worth it?A brief commentary on the effects of the extracorporeal circuit on TPTD-derived parameters

Journal of Clinical Monitoring and Computing -     

Relation between heart rate variability and training load in middle-distance runners

PURPOSE: Monitoring physical performance is of major importance in competitive sports. Indices commonly used, like resting heart rate, VO2max, and hormones, cannot be easily used because of difficulties in routine use, of variations too small to be reliable, or of technical challenges in acquiring the data. METHODS: We chose to assess autonomic nervous system activity using heart rate variability in seven middle-distance runners, aged 24.6 +/- 4.8 yr, during their usual training cycle composed of 3 wk of heavy training periods, followed by a relative resting week. The electrocardiogram was recorded overnight twice a week and temporal and frequency indices of heart rate variability, using Fourier and Wavelet transforms, were calculated. Daily training loads and fatigue sensations were estimated with a questionnaire. Similar recordings were performed in a sedentary control group. RESULTS: The results demonstrated a significant and progressive decrease in parasympathetic indices of up to -41% (P < 0.05) during the 3 wk of heavy training, followed by a significant increase during the relative resting week of up to +46% (P < 0.05). The indices of sympathetic activity followed the opposite trend, first up to +31% and then -24% (P < 0.05), respectively. The percentage increasing mean nocturnal heart rate variation remained below 12% (P < 0.05). There was no significant variation in the control group. CONCLUSION: This study confirmed that heavy training shifted the cardiac autonomic balance toward a predominance of the sympathetic over the parasympathetic drive. When recorded during the night, heart rate variability appeared to be a better tool than resting heart rate to evaluate cumulated physical fatigue, as it magnified the induced changes in autonomic nervous system activity. These results could be of interest for optimizing individual training profiles.     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

A practical method to statistically classify devices according to their relative accuracy

Mathematical methods to statistically compare the relative accuracy of physiological monitoring devices to reference measurements are scarce. We developed such a method to compare any number of devices to each other as well as to reference values. This new statistical comparative procedure uses a combination of different known mathematical processes. The method allows the separation of the error of the devices into two components, the first, being systematic, can be easily amended, while the second, inherent to the technical limitations of the measuring device as well as to the physical properties of the explored phenomenon, cannot be corrected and will thus be used as the comparative criterion for statistics. That method, which is easy to implement should ease comparisons of the accuracy of any number of devices as well as comparison of other sets of physiological values, by giving an easy access to statistical results.     

An Escalation for Bivariate Binary Endpoints Controlling the Risk of Overtoxicity (EBE-CRO): Managing Efficacy and Toxicity in Early Oncology Clinical Trials

For about a decade, early clinical development in oncology is facing new challenges. This is due to two main reasons. The first one is linked to the developed molecular targeted agents (MTA) themselves for which the maximum tolerated dose (MTD) is no longer the only dose of interest. The second reason is related to the fact that costs and attrition rates are huge. When selecting a dose, evidence of early activity signal becomes required for future engagements. This implies the need to handle both toxicity and activity endpoints in the analysis and also in the dose escalation design of early-phase trials. We propose a model-based design taking into account both safety and activity for dose escalation. The proposed model involves a bivariate Gaussian latent variable depending on a monotonic toxicity curve and a quadratic activity curve. This model is fitted under the Bayesian framework that allows the incorporation of prior information. The predictive distributions of dose-response curves are used to lead the dose recommendation. Uncertainty in the dose–response relationship is taken into account to calculate the probability of being an over-toxic or a target dose. The proposed design is compared to two other widely used methods.