The role of NADPH-derived reactive oxygen species production in the pathogenesis of endometriosis: a novel mechanistic approach.

Endometriosis is defined as endometriotic tissue growing outside the uterine cavity. It is a common gynecological disorder in women of reproductive age and is associated with chronic pelvic pain and infertility. Despite several studies and theories to explain its cause, the exact pathogenesis of endometriosis remains unclear. Retrograde menstruation is the most plausible theory, however, it is not exclusive. The disparity between the actual prevalence of retrograde menstruation and the prevalence of endometriosis suggests that other factors may determine the susceptibility to endometriosis development. Oxidative stress has been associated with endometriosis. This study aimed to explore the role of NADPH oxidase family in the production of reactive oxygen species (ROS) and to determine whether ROS induce the proliferation of endometriotic implants via mammalian target of rapamycin (mTOR) signaling. Anonymous endometriotic tissue samples were collected from women undergoing laparoscopy for endometriosis. The samples were stained with dihydroethidium and fluorescent images of the slides were taken to detect ROS production. After extraction of RNA from the samples and c-DNA generation, quantitative real-time PCR, protein extraction and Western blot were performed to study gene and protein expression of NADPH oxidase 1 (NOX 1), mTOR and fibronectin. The results showed an increase in ROS levels and NOX 1 gene and protein expression in the endometriotic tissues compared to the normal surrounding tissue control. Also, mTOR and fibronectin, gene expression was found to be increased. Up regulation of NOX at gene and protein level leads to increased production of ROS in the endometriotic tissue, which in turn causes proliferation of the ectopic tissue via alteration of the mTOR signaling pathway. Increased fibronectin gene expression points towards tissue injury in endometriosis as compared to the normal surrounding tissue. This manuscript adds a new insight into the pathogenesis of endometriosis and serves as a background for development of new treatments for the disease-associated pain and infertility.

Knee flexion contracture treated with botulinum toxin type A in patients with haemophilia (PWH).

INTRODUCTION: Knee flexion contracture (KFC) remains a common complication of haemoarthrosis in children and young adults with haemophilia. If the KFC is not treated properly it produces disability, postural and gait abnormalities. OBJECTIVE: Evaluate the effectiveness of conservative treatment of KFC with Botulinum toxin type A (BTX-A) in PWH. METHODS: Seventeen patients were treated, with 21 affected knees. Mean age was 26 years. The mean follow up was 12 months. We evaluated flexion and KFC pretreatment BTX-A and up to 12 months posttreatment. BTX-A application was in hamstring and calf muscles. To evaluate the function, a questionnaire about different activities was made, and it was checked 3, 6 and 12 months after BTX-A. According to the degree of KFC, knees were divided into 3 groups: Group 1: -10° to -30° (n = 10), Group 2: -31° to -45° (n = 6) Group 3: -46° or more (n = 5). RESULTS: The average KFC improved from -38° to -24°. The improvement was 14° (P < 0.001). The average KFC improvement was 9° in group 1, 17° in group 2, and 23° in group 3. There was a high correlation between the improvement in KFC and the total score of the questionnaire R = 0.77. CONCLUSIONS: Treatment of KFC with BTX-A improves knee-related functional activities, with the advantage of being a low-cost procedure and easy to apply.

Prevention of preterm delivery with vaginal progesterone in women with preterm labour (4P): randomised double-blind placebo-controlled trial.

OBJECTIVE: To evaluate the effectiveness of 200 mg of daily vaginal natural progesterone to prevent preterm birth in women with preterm labour. DESIGN: Multicentre, randomised, double-blind, placebo-controlled trial. SETTING: Twenty-nine centres in Switzerland and Argentina. POPULATION: A total of 385 women with preterm labour (24(0/7) to 33(6/7) weeks of gestation) treated with acute tocolysis. METHODS: Participants were randomly allocated to either 200 mg daily of self-administered vaginal progesterone or placebo within 48 hours of starting acute tocolysis. MAIN OUTCOME MEASURES: Primary outcome was delivery before 37 weeks of gestation. Secondary outcomes were delivery before 32 and 34 weeks, adverse effects, duration of tocolysis, re-admissions for preterm labour, length of hospital stay, and neonatal morbidity and mortality. The study was ended prematurely based on results of the intermediate analysis. RESULTS: Preterm birth occurred in 42.5% of women in the progesterone group versus 35.5% in the placebo group (relative risk [RR] 1.2; 95% confidence interval [95% CI] 0.93-1.5). Delivery at <32 and <34 weeks did not differ between the two groups (12.9 versus 9.7%; [RR 1.3; 95% CI 0.7-2.5] and 19.7 versus 12.9% [RR 1.5; 95% CI 0.9-2.4], respectively). The duration of tocolysis, hospitalisation, and recurrence of preterm labour were comparable between groups. Neonatal morbidity occurred in 44 (22.8%) cases on progesterone versus 35 (18.8%) cases on placebo (RR: 1.2; 95% CI 0.82-1.8), whereas there were 4 (2%) neonatal deaths in each study group. CONCLUSION: There is no evidence that the daily administration of 200 mg vaginal progesterone decreases preterm birth or improves neonatal outcome in women with preterm labour.

The epidemiology of life-threatening complications associated with reproductive process in public hospitals in Argentina.

OBJECTIVE: To analyse life-threatening obstetric complications that occurred in public hospitals in Argentina. DESIGN: Multicentre collaborative cross-sectional study. SETTING: Twenty-five hospitals included in the Perinatal Network of Buenos Aires Metropolitan Area. POPULATION: Women giving birth in participating hospitals during a 1-year period. METHODS: All cases of severe maternal morbidity (SMM) and maternal mortality (MM) during pregnancy (including miscarriage and induced abortion), labour and puerperium were included. Data were collected prospectively. MAIN OUTCOME MEASURES: Identification criteria, main causes and incidence of SMM; case-fatality rates, morbidity-mortality index and effective intervention's use rate. RESULTS: A total of 552 women with life-threatening conditions were identified: 518 with SMM, 34 with MM. Identification criteria for SMM were case-management (48.9%), organ dysfunction (15.2%) and mixed criteria (35.9%). Incidence of SMM was 0.8% (95% confidence interval [95% CI] 0.73-0.87%) and hospital maternal death ratio was 52.3 per 100 000 live births (95% CI 35.5-69.1). Main causes of MM were abortion complications and puerperal sepsis; main causes of SMM were postpartum haemorrhage and hypertension. Overall case-fatality rate was 6.2% (95% CI 4.4-8.6): the highest due to sepsis (14.8%) and abortion complications (13.3%). Morbidity-mortality index was 15:1 (95% CI 7.5-30.8). Use rate of known effective interventions to prevent or treat main causes of MM and SMM was 52.3% (95% CI 46.9-57.7). CONCLUSIONS: This study describes the importance of life-threatening obstetric complications that took place in public hospitals with comprehensive obstetric care and the low utilisation of known effective interventions that may decrease rates of SMM and MM. It also provides arguments that justify the need to develop a surveillance system for SMM.

Endometriosis and cancer: what do we know?

Endometriosis is the presence of endometriotic tissue outside of the uterus, composed of endometriotic glands and stroma. It affects between 10% to 12% of women in reproductive age. It presents with dysmenorrhea, dyspareunia, chronic pelvic pain, infertility, urinary or digestive symptoms. Diagnosis is based on clinical suspicion, clinical exam, pelvic ultrasound or pelvic magnetic resonance, and confirmed by laparoscopy with pathology studies. Its management is better understood nowadays. However, its association with neoplasia has been questioned for many years. It probably plays a role in the etiology of gynecological cancers, mainly ovarian neoplasia. In our review, we separately compared endometriosis and endometrioma to cancer, in terms of mutual causality, common risk factors, distinction based on histological findings, in addition to molecular and genetic pathways behind this association. This article reviews the English literature for studies on the association between endometriosis and gynecological cancers. Additional reports were collected by systematically reviewing all references from retrieved papers.

Systematic (complete) para-aortic lymphadenectomy: description of a novel surgical classification with technical and anatomical considerations.

The clinical indications for a complete para-aortic lymphadenectomy in the surgical management of gynaecological malignancies remain controversial. The debate on complete para-aortic node dissection is hindered by the absence of an identifiable and accepted definition for the procedure of systematic (complete) para-aortic node dissection. In this paper we propose a classification of para-aortic lymphadenectomy. We have identified and imaged the most common and rare para-aortic vascular anomalies that we have encountered. An understanding of the anatomical anomalies in this area also provides a useful reference for the surgical technique that is adopted in order to ensure the completeness of excision.

Video. Repeated transvaginal notes: is it possible?

PURPOSE: Transvaginal surgery has been performed by gynecologists for decades with abundant literature supporting its efficacy and safety. Recently, several groups reported on the NOTES transvaginal (TV) approach for extrapelvic disease. Nevertheless, repeated TV access for NOTES has never been reported to date. Two cases of "repeated" TV access for NOTES cholecystectomy after TV hybrid sleeve gastrectomy are described. METHODS: Two women, aged 57 and 32 years, developed symptomatic cholelithiasis respectively 6 and 8 months after TV sleeve gastrectomy for morbid obesity. Sleeve gastrectomy: a 2-cm posterior colpotomy was performed under laparoscopic control between the uterosacral ligaments. A double-channel endoscope and a 60-cm-long laparoscopic grasper were introduced transvaginally. Two abdominal ports were placed to allow the introduction of the stapling device and to assist during the procedure. An intragastric endoscope served to expose the stomach and to calibrate the gastric sleeve, which was performed in the standard fashion. Colpotomy was closed by separate 3/0 Vicryl stitches. At cholecystectomy, an exploratory laparoscopy ascertained the feasibility of a NOTES cholecystectomy. The posterior vaginal vault was carefully examined before regaining peritoneal access with the technique described above. Cholecystectomy was performed by using a double-channel endoscope introduced TV and a 5-mm transabdominal port. Follow-up consisted of 3 and 6 months pelvic examination and interview, which included sexual function assessment by sexual function questionnaire (SFQ31). RESULTS: Both operations were performed successfully with no intraoperative or postoperative complications. At cholecystectomy, minimal pelvic adhesions were found with no vaginal scarring at the colpotomy site. No bleeding, pain, or vaginal infection occurred after both procedures. Patients resumed sexual activity 5.2 weeks postoperatively with a consistently normal SFQ31. CONCLUSIONS: This report suggests that, in experienced hands, repeated TV access for extrapelvic surgery is possible and safe, putting forward the intriguing promises of less adhesions formation.

The appropriateness of enoxaparin use in Lebanese hospitals: a quality evaluation study.

BACKGROUND: Although, guidelines for the appropriate use of enoxaparin are published, yet the extent of their implementation in clinical practice is still questionable. Furthermore, the optimal dosing of enoxaparin in special populations such as renal insufficiency and obesity remains controversial. In the Middle East, there are insufficient data on the appropriateness of enoxaparin use in different indications. OBJECTIVE: (1) To assess the appropriateness of enoxaparin dosing and duration per indication in compliance with the recommended guidelines and their impact on safety and efficacy outcomes in Lebanese health care centers. (2) To evaluate the influence of the hospital type (teaching vs. non-teaching) on the extent of compliance with established guidelines. SETTING: Seventeen health care centers in Lebanon, including teaching and non-teaching hospitals. METHODS: An observational, cross-sectional, multicenter study was conducted in 17 Lebanese hospitals. Data on demographics, indication, dosing regimen and clinical outcomes were collected. The appropriateness of dosing practices was determined as per the ACCP guidelines and the FDA dosing recommendations. MAIN OUTCOME MEASURE: The appropriateness of enoxaparin dosing was compared across different hospital type and among special populations including severe renal insufficiency and very obese patients. RESULTS: Of the 463 patients who participated in the study, 40% received improper enoxaparin dosing, which was mostly observed in the VTE prophylaxis group (41.6%, P < 0.001). When comparing the overall dosing practices in Lebanese hospitals, there was no statistically significant difference in the correctness of enoxaparin dosing between teaching and non-teaching hospitals (61.6% vs. 58.2%, P = 0.449), respectively. Only 11.5% of renally impaired patients and 59.4% of obese patients received correct doses. CONCLUSION: This study highlighted the improper practice and thus the need of implementation of clinical practice guidelines for the dosing of enoxaparin, in Lebanese hospitals.

Management of deep endometriosis.

Deep endometriosis is still a challenging disease in terms of diagnosis and treatment. About 10-12% of women of reproductive age will have a form of endometriosis. This can affect pelvic as well as extra pelvic locations. Risk of malignant transformation has been studied over a long period of time. Medical and surgical treatments can be proposed to patients for endometriosis-associated pain depending on the severity of symptoms and location of the disease. Results and outcomes are different according to different publications. Understanding of the benefit of surgical treatment on fertility is increasing. The place of medical and surgical treatment in recurrent symptoms or disease is also of interest. Presented here is a review on the management of endometriosis in the light of recent data. Further investigations in many fields of endometriosis are still required.

Staging of gynaecological malignancies by natural orifice transluminal endoscopic surgery (N.O.T.E.S.).

Gynaecological malignancies are most often diagnosed and staged by surgery. With the expanding evidence of efficacy and benefit of neoadjuvant treatments, such tumor confirmation and assessment should be ideally done with the least associated morbidity. Thus sentinel node biopsy has already been proposed for selected indications so that the morbidity associated with formal lymphadenectomy could be avoided in those patients without nodal metastases. The era of natural orifice transluminal endoscopic surgery (N.O.T.E.S.) heralds an operative methodology of 'least invasiveness' that could be useful in gynaecological cancer. In this article, we present an overview of the staging of gynaecological malignancies with a focus on the potential applications and benefits that N.O.T.E.S. may provide in this field. In particular, we believe that performing sentinel lymph node dissection with N.O.T.E.S. could associate the low morbidity rate of the former technique with the minimal invasiveness of the latter one and therefore consolidate the potential of this technique.

[Synchronous sigmoid colon and breast cancers in man]. / Association synchrone d'un cancer du sigmoïde chez l'homme et d'un cancer du sein.

We report the case of 72-year-old man with sigmoid colon cancer associated with synchronous right breast cancer. However, in the present case, we found breast cancer insidiously at physical exam. The patient died after six months after the dissemination of the breast cancer.

Successful salvage of a relapsed high risk gestational trophoblastic neoplasia patient using capecitabine.

BACKGROUND: Although most patients at high risk of Gestational Trophoblastic Neoplasia (GTN) respond to standard treatments, there is a group of patients that will die because of it. The use of new single or combination drugs in this population has become a priority. CASE REPORT: We present the case of a relapsed high risk choriocarcinoma patient who did not respond to several chemotherapy treatments nor to PET guided salvage surgery. Because of treatment toxicity, the patient was started on Capecitabine, with which she achieved total remission, still present after 15 months of starting treatment. CONCLUSIONS: The use of Capecitabine and the multidisciplinary management of this population should be taken into account for patients at high risk of relapsing to EP/EMA because of its efficacy and little toxicity.

Long-term survival of the T-28 versus the TR-28 cemented total hip arthroplasties.

Between 1974 and 1980, 550 total hip arthroplasties (THAs) (479 patients) were performed using T-28 and TR-28 cemented prostheses (TR-28 is shot-blast chrome and T-28 is polished stainless steel). There were 379 cemented THAs in 321 patients in the T-28 group and 171 cemented THAs in 158 patients in the TR-28 group. Average follow-up of the patients still alive at the end of the study was 20.96 years in the T-28 group and 17.54 years in the TR-28 group. When considering failure as revision of the hip for aseptic acetabular loosening, there were 36 (9.5%) failures in the T-28 group and 12 (7%) failures in the TR-28 group. This difference was statistically significant (P = .0132). When considering failure as radiographic acetabular loosening with or without radiographic femoral loosening, there were 52 failed acetabula (13.7%) in the T-28 group and 18 failed acetabula (10.5%) in the TR-28 group. These differences were not statistically significant. When considering failure as revision for aseptic femoral loosening with or without acetabular component loosening, there were 42 failures (11.1%) in the T-28 group and 22 failures (12.8%) in the TR-28 group. This difference was not statistically significant. When considering failure as radiographic femoral loosening with or without acetabular component loosening, there were 42 failures (11.1%) in the T-28 group and 27 failures (15.8%) in the TR-28 group. This difference was statistically significant for log-rank test (P = .0318) and Wilcoxon's test (P = .0083). Surface finish may be an important contributor to the survival of cemented femoral stems.

The effect of intraoperative intravenous fixed-dose heparin during total joint arthroplasty on the incidence of fatal pulmonary emboli.

All patients who underwent primary total knee arthroplasty (TKA), revision TKA, primary total hip arthroplasty (THA), and revision THA between January 1, 1990, and December 31, 1996, were retrospectively reviewed to determine the incidence of fatal pulmonary emboli. All TKA patients received 1,000 U of intravenous heparin sodium before the tourniquet was inflated and an additional 500 U of intravenous heparin sodium before the inflation of the second tourniquet during bilateral TKA. All THA patients received 1,000 U of intravenous heparin sodium at the time of the skin incision and 500 U of intravenous heparin sodium before preparation of the femoral canal. The overall incidence of fatal pulmonary emboli was extremely low (TKA, 0.096%; THA, 0.16%). With this regimen of intravenous intraoperative heparin, postoperative aspirin, thromboembolic disease hose, and early ambulation, there is no risk of postoperative bleeding, it is inexpensive, and there is no concern on how long to keep the patients on this regimen postoperatively. We recommend this regimen for the prevention of fatal pulmonary emboli after total joint arthroplasty.