Adhesion prevention after myomectomy by laparotomy: a prospective multicenter comparative randomized single-blind study with second-look laparoscopy to assess the effectiveness of PREVADH™.

OBJECTIVE: The objective of this multicenter, randomized study was to investigate the efficacy of the hydrophilic resorbable film PREVADH™ in preventing postoperative adhesions following myomectomy. STUDY DESIGN: Women scheduled for laparotomic myomectomy with intramural and/or subserous myomas of >60mm in diameter, and who wished to preserve fertility, were eligible. Patients were randomized immediately prior to abdominal wall closure to receive either hydrophilic resorbable film applied directly to the incisions (P-Group, n=33) or 500mL Ringer's lactate solution instilled into the pelvic cavity (R-Group, n=28). Incidence, severity, and extent of postoperative adhesions to the uterine incisions and adnexal and abdominopelvic adhesions were assessed during second-look laparoscopy 10-20 weeks after the initial surgery. Unedited videotapes of this second-look procedure were reviewed by two blinded independent surgeons. RESULTS: Fifty-four patients (P-Group, n=28; R-Group, n=26) underwent second-look laparoscopy. Significantly fewer P-Group patients developed adhesions to uterine incisions than R-Group patients (43% vs. 92%, P=0.001). Adhesions, which were confirmed by independent reviewers, were found in significantly fewer P-Group sites than R-Group sites (29% vs. 76%, P=0.001). No serious adverse events related to the barriers used or adhesion-related complications were reported in either group. CONCLUSION: The hydrophilic resorbable anti-adhesion film PREVADH™ significantly reduced adhesion incidence and severity after laparotomic myomectomy. CLINICAL TRIAL REGISTRATION: NCT01388907 (www.clinicaltrials.gov).

Impact of obesity on the results of fertility-sparing management for atypical hyperplasia and grade 1 endometrial cancer.

OBJECTIVES: The aim of the present study was to evaluate the impact of obesity on reproductive and oncologic outcomes on the success of fertility-sparing management. METHODS: This retrospective multicenter cohort study included women treated conservatively for atypical hyperplasia (AH) and endometrial cancer (EC) to preserve fertility. Five inclusion criteria were defined: (i) the presence of AH or grade 1 EC confirmed by two pathologists; (ii) adequate radiological examination before conservative management; (iii) available body mass index (BMI) at the beginning of treatment; and (iv) a minimum follow-up time of six months. RESULTS: Forty patients fulfilled the inclusion criteria (17 had EC, and 23 had AH), mean age and BMI were 33 years and 29kg/m(2) respectively. Among the 15 obese patients, after medical treatment, 10 patients responded (67%) and three relapsed, whereas in the 25 non-obese patients, 19 responded (76%) and three relapsed (p=0.72). The overall pregnancy rate and follow-up time were 35% and 35 months respectively. Among the 15 obese patients, after medical treatment, two patients became pregnant, whereas in the 25 non-obese patients, 12 became pregnant (p=0.04). CONCLUSION: Despite similar response and recurrence rates, our results suggest that fertility-sparing management for AH and EC is associated with a lower probability of pregnancy in obese patients.

Safety of transient abdominal ovariopexy in patients with severe endometriosis.

OBJECTIVE: To evaluate complications of transient ovariopexy performed to reduce adhesions in patients with severe endometriosis. METHODS: A bicentric retrospective study involved 193 consecutive patients who underwent laparoscopic surgery for severe endometriosis at 2 French university hospitals from 1997 to 2009. At the end of surgery, unilateral or bilateral transient ovariopexy was performed on 297 ovaries. Immediate (e.g. reproducibility, tolerance, and hospital stay) and long-term (evaluated via vaginal access to the ovaries, ovarian function, and ovarian vascularization) complications were assessed. RESULTS: The technique, which was easy and reproducible, did not increase hospital stay and was well tolerated. There were 2 (0.7%) immediate complications. There was no difference in ovarian accessibility before and after surgery (177/183 [96.7%] vs 176/183 [96.1%]). Potential vaginal oocyte retrieval for in vitro fertilization was possible for all patients. The antral follicle count and the pulsatility index of suspended ovaries were not different from those of contralateral unsuspended ovaries. Endometrioma excision did not modify these results. CONCLUSION: The short- and long-term safety results of transient ovariopexy for adnexal adhesions in patients with severe endometriosis were encouraging.

Progestin treatment of atypical hyperplasia and well-differentiated adenocarcinoma of the endometrium to preserve fertility.

AIM: To evaluate the outcome of a cohort of young women treated with progestin for fertility-sparing management of endometrial atypical hyperplasia (AH) and endometrial carcinoma (EC). This retrospective multicentre cohort study included women under the age of 40 years treated conservatively for AH and EC to preserve fertility using progestin for at least 3 months. Four inclusion criteria were defined: (i) the presence of AH or grade 1 EC confirmed by two pathologists (including a reference pathologist); (ii) the use of conservative management for fertility sparing; (iii) adequate radiological examination before conservative management; and (iv) a minimal follow-up time of one year. RESULTS: Twenty-two patients fulfilled the inclusion criteria (8 had EC, and 14 had AH). After progestin treatment, 17 patients responded. Among the 17 patients who experienced remission, three also experienced disease relapse. One patient initially diagnosed with AH experienced progression of her disease to stage IIIA EC. Ten pregnancies were achieved in eight patients. CONCLUSION: Fertility-sparing management using progestin offers the opportunity to fulfil maternal desires in young patients diagnosed with AH and EC. However, progression of the disease is possible and close follow-up is needed.

[Fertility sparing management of endometrial adenocarcinoma and atypical hyperplasia: a literature review]. / Traitement conservateur du cancer et des hyperplasies atypiques de l'endomètre en vue de préserver la fertilité : revue de la littérature.

In endometrial carcinoma (EC) and atypical hyperplasia (AH) diagnosed in childbearing years, the principle of uterine sparing consists in prescription of antigonadotropic treatment to obtain the remission of the endometrial lesion and allow pregnancy, always with a close follow-up looking for progression or persistence of the tumour. Studies evaluating this strategy have suggested the safety of such an approach, but numerous questions remain unanswered, like those concerning the type and the duration of treatment, and the systematic use of Assisted Reproductive Technologies… We performed a critical literature review in order to analyse patients and tumoral characteristics, treatment management and the results of fertility sparing strategy. This review shows that fertility sparing management of AH and intramucous EC permits to obtain pregnancy in one third of candidates. Few disease-related deaths have been reported after this management. One-third of patients experienced progression lesion beyond the endometrium, but generally limited to the myometrium. Progestins have been widely evaluated in this indication and provide an overall remission rate of 80% with a recurrence risk of 25%.

Fertility-sparing management of grade 2 and 3 endometrial adenocarcinomas.

We report four cases of grade 2 and 3 endo-metrial adenocarcinomas managed conservatively in order to preserve fertility. In the literature, seven other cases have been reported. We discuss the management of these cases and compared the carcinologic and fertility outcomes with fertility-sparing management of grade 1 endometrial adenocarcinoma.

Infertile women with deep and intraperitoneal endometriosis: comparison of fertility outcome according to the extent of surgery.

STUDY OBJECTIVE: This study was undertaken to ascertain whether the incidence of spontaneous pregnancy is increased in infertile women with deep and intraperitoneal endometriosis undergoing extensive surgery compared with those undergoing only intraperitoneal surgery. DESIGN: Retrospective case control study (Canadian Task Force classification II-1). SETTING: University teaching hospital. PATIENTS: Infertile women under the age of 40 years with deep and intraperitoneal endometriosis and no other associated major infertility factors. Only patients with at least 1 year of postoperative follow-up were included. INTERVENTIONS: Intraperitoneal surgery only (group 1) or extensive surgery (group 2) according to a shared decision-making approach. MEASUREMENTS AND MAIN RESULTS: Among the 34 women in group 1, 6 became pregnant, compared with 8 of the 41 women who had extensive surgery (12-month cumulative probabilities, 24.8% and 11.4%, respectively, and 24-month cumulative probabilities, 24.8% and 23.2%, respectively; p = .82). Perioperative surgical complication rate was higher in group 2 (6/41 versus 0/34; p = .02). CONCLUSION: Extensive surgery for intraperitoneal and deep endometriosis in infertile women does not modify global fertility outcome but is associated with a higher complication rate.

Do patients manage to achieve pregnancy after a major complication of deeply infiltrating endometriosis resection?

OBJECTIVE: To evaluate the fertility status in women suffering from major postoperative complications following deep endometriosis surgery. STUDY DESIGN: A retrospective study in teaching and research hospitals (tertiary centers) including 23 women submitted to the surgical treatment for deep endometriosis and presenting a major postoperative complication. Postoperatively, women desiring pregnancy who conceived were compared to those who did not conceive using Mann-Whitney test and Fisher's exact test. Main outcome measure included the pregnancy rate among these women. RESULTS: The overall intrauterine pregnancy rate was 47.8% and the live birth rate was 30.4%. There were 10 spontaneous conceptions and 3 IVF conceptions among 11 patients. Women who did not conceive were older than those who conceived (33.9 vs. 29.3 years; p = 0.02). The pregnancy rate after intestinal complications was lower than after urinary complications (33.3% vs. 83.3%; p = 0.04). CONCLUSION: Fertility remains preserved among women experiencing a major complication after removal of deep endometriosis with a live birth rate of 30.4%. Women experiencing bowel complications have a reduced probability of conception compared with those who experience a urologic complication.

Efficacy of transient abdominal ovariopexy in patients with severe endometriosis.

OBJECTIVE: To assess adhesion formation and fertility outcome after transient abdominal ovariopexy performed in patients with severe endometriosis. STUDY DESIGN: Retrospective study including 218 patients who underwent surgery for severe endometriosis from 1997 to 2009. One hundred and thirty-nine (64%) patients were infertile. The initial ASRM stage was IV in 139 cases, III in 43 cases and II in 36 cases. Adnexal adhesions were scored by using the Operative Laparoscopy Study Group (OLSG) and modified AFS scoring systems. Unilateral or bilateral transient abdominal ovariopexy of 336 ovaries was performed to prevent adhesion formation or reformation for extensive surgery. In patients who underwent a second operation, adnexal adhesion scores were reported. Fertility outcome was evaluated by a questionnaire. RESULTS: Second-look surgery was performed after 11.7 ± 2.4 months in 24 patients (11%) who had undergone 38 ovariopexies. Transient abdominal ovariopexy significantly decreased adnexal adhesion scores (p<0.05). Regarding fertility outcome, the median follow up was 19.6 ± 1.5 months. Fifty-eight patients, out of 105 infertile women who actively tried to conceive after surgery, conceived, 21 (36%) spontaneously and 37 (64%) after ART. The median time interval for conception was 8.6 ± 1 months. CONCLUSION: In patients with severe endometriosis, transient abdominal ovariopexy is an effective technique in preventing postoperative adhesion formation and in improving fertility outcome. CONDENSATION: In 218 patients with severe endometriosis, transient abdominal ovariopexy was an effective technique in preventing adhesion formation and improving fertility outcome.

Pathologic response rate after concomitant neo-adjuvant radiotherapy and chemotherapy for adenocarcinoma of the uterine cervix: a retrospective multicentric study.

INTRODUCTION: Exclusive chemoradiotherapy (including brachytherapy) is the current standard of care for locoregionally advanced cervical cancer. The aim of the present study was to evaluate the responsiveness and to identify factors predicting the response to concomitant chemoradiotherapy before surgery in cervical adenocarcinoma. METHODS: A multicentric retrospective study was done in 9 French centers. A total of 54 women with cervical adenocarcinoma stage IB2 to IIIB who had undergone concurrent chemoradiation therapy followed by surgical treatment were included. The patients were stratified by histopathologic response after concomitant chemoradiotherapy (lesions smaller than 1 cm or larger). RESULTS: The median (SD) age at diagnosis was 44.2 (12.4) years (range, 19.3-77 years). The median (SD) follow-up duration was 30.9 (36.5) months (range, 4.1-17 years). After clinical evaluation, the mean (SD) tumor size was 5 (1.2) cm (range, 2-7 cm).The patients achieved a clinical complete response after concurrent chemoradiation in 18 cases (33.5%). Pathologic residual tumor was noted in 36 cases (67%); tumors smaller than 1 cm were found in 18 cases (33.5%), and lesions greater than 1 cm were observed in 18 cases (33.5%). Factors being associated with a significant decreased sensitivity to neoadjuvant chemoradiotherapy were the following: menopause (P = 0.012), parametrial invasion (P < 0.001), lymphovascular space invasion (P = 0.003), and mucinous subtype (P = 0.001). CONCLUSIONS: Identification of predictive markers associated with incomplete response to neoadjuvant chemoradiotherapy in cervical adenocarcinoma may prove clinically useful and implement an individualized treatment plan.

Conservative management of low-grade endometrial stromal sarcoma followed by pregnancy and severe recurrence.

BACKGROUND: Since low-grade endometrial stromal sarcoma (LGESS) has the most favourable prognosis in comparison to other sarcomas, fertility-sparing surgery in young women has been reported in rare cases. However, such tumours almost always show positive sex steroid receptors and their evolution in the hormonal milieu of pregnancy remains unpredictable. CASE REPORT: We report the case of a 34-year-old woman treated conservatively for LGESS who conceived rapidly after hysteroscopic resection of the tumour. In the post partum period, pelvic pain motivated a laparoscopic exploration which revealed severe peritoneal recurrence. CONCLUSION: This case report highlights the possible dramatic evolution of LGESS after pregnancy and suggests that definitive surgery should not be postponed but performed as soon as the diagnosis of ESS has been made.

Hysterectomy for benign uterine pathology among women without previous vaginal delivery.

OBJECTIVE: To evaluate the feasibility and the complication rate of vaginal hysterectomy in benign uterine pathology (except for uterine prolapse) among patients without previous vaginal delivery. METHODS: A review of the medical records in patients without previous vaginal delivery who underwent hysterectomies between January 1995 and June 2004 was carried out. Patients were divided into two different groups: group 1 included patients with first-intention abdominal hysterectomy; group 2 included patients with vaginal approach further stratified into 2a without and 2b with laparoscopic assistance. RESULTS: Three hundred patients without previous vaginal delivery underwent hysterectomy during this period. Vaginal hysterectomy was planned in 75.7% of cases. Success rate for planned vaginal hysterectomies was 92.1%. The mean weight of uteri extracted by vaginal and abdominal approaches were 326 g and 1,047 g, respectively (P<.001). The mean operative time was significantly longer in the laparoscopic-assisted approach (160 minutes) than in the abdominal approach (120 minutes), and significantly shorter in exclusively vaginal (75 minutes) than in other procedures (P<.001). The use of the laparoscopic assistance in hysterectomy decreased significantly over the period of the study (P<.001). The mean duration of hospital stay was significantly shorter in group 2 than in group 1 (3.8 days compared with 6.2 days, P<.001), but no differences were noted between subgroups 2a and 2b. CONCLUSION: Vaginal hysterectomy should not be contraindicated in patients lacking previous vaginal delivery. In these particular patients, most of the procedures can be performed by vaginal approach, with the benefit of limiting the costs and the duration of hospital stay.

Impact of infertility drugs after treatment of borderline ovarian tumors: results of a retrospective multicenter study.

OBJECTIVE: To evaluate safety and fertility outcome after the use of infertility drugs in patients who were treated conservatively for a borderline ovarian tumor (BOT). DESIGN: A retrospective multicenter study. SETTING: Centers participating in the French National Register on In Vitro Fertilization registry. PATIENT(S): Thirty patients who were treated for BOT who underwent ovarian induction (OI). INTERVENTION(S): Ovarian induction was performed in 25 patients for infertility after conservative surgery and before surgery for recurrent disease in 5 patients with a single ovary (emergency cases). MAIN OUTCOMES MEASURE(S): Fertility and recurrences rates. RESULT(S): The mean number of cycles of OI per patient was 2.6 (range, 1-10 cycles). The median follow-up time after treatment of the BOT was 93 months (range, 26-276 months). After a median follow-up time of 42 months after OI, 4 recurrences were observed (initial management was simple cystectomy in 3 of them). All recurrences were borderline tumors on a remaining ovary that had been treated by surgery alone. All patients are currently disease-free. Thirteen pregnancies were observed (10 pregnancies (40%) in the group of 25 patients who were treated for infertility). CONCLUSION(S): These results suggest that infertility drugs could be used safely in patients who experience infertility after conservative management of an early-stage BOT.

Latzko operation for vault vesicovaginal fistula.

BACKGROUND: Various surgical procedures are currently performed for the treatment of posthysterectomy vesicovaginal fistula. Most of them are carried out via an abdominal incision. OBJECTIVE: Report of our experience with Latzko's operation, a simple purely transvaginal procedure. METHODS: Retrospective study of vesicovaginal fistulas treated by a Latzko procedure between June 1991 and June 2005. RESULTS: Eleven patients were operated on. Two (18%) had a prior failed attempt of vesicovaginal fistula repair. Mean size of the fistulas was 12+/-11 mm (range: 2-40 mm). Mean operative duration was 62+/-33 min (range: 20-110 min). All fistulas healed. No intraoperative complications were observed. There was only one postoperative complication, a lower urinary tract infection in one patient. Mean hospital stay was 6+/-4 days (range: 2-12 days). CONCLUSIONS: The Latzko procedure is an efficient, safe, and simple technique for the management of vault vesicovaginal fistulas, and can therefore be proposed as the first-line surgical treatment.

Expression of BRCA1, HER-1 (EGFR) and HER-2 in sporadic breast cancer and relationships to other clinicopathological prognostic features.

BACKGROUND: The BRCA1 caretaker gene is associated with poor prognostic features in hereditary breast cancer and may also play a role in sporadic breast cancer (SBC). HER-1 and HER-2 overexpression is associated with adverse prognosis in SBC. We studied whether BRCA1 expression was associated with HER1, HER2 and other prognostic features in SBC. PATIENTS AND METHODS: Fifty newly-diagnosed SBC patients were studied for prognostic features and immunohistochemical expressions of BRCA1, HER-1 and HER-2. RESULTS: Tumors were positive for BRCA1 in 26%, HER-1 in 32% and HER-2 in 20% of cases. Lack of BRCA1 expression was associated with node metastases and decreased estrogen receptor. HER-2 expression was associated with young age, HER-1, Ki67 and decreased hormone receptors. No correlation was observed between BRCA1 and HER-1 or HER-2. CONCLUSION: In SBC, the lack of BRCA1 expression was associated with poor prognostic features, but unrelated to HER-1 and HER-2. HER2 and HER-1 were, however, highly correlated.

Paradoxic activation of the renin-angiotensin system in twin-twin transfusion syndrome: an explanation for cardiovascular disturbances in the recipient.

Despite advances in treatment, twin-to-twin transfusion syndrome (TTTS) still carries a high risk for perinatal mortality and morbidity. Simple blood transfer from the donor to the recipient twin cannot explain all of the features of this disease, in particular the recipient's hypertensive cardiomyopathy. We report a case in which TTTS resulted in preterm delivery with early neonatal death of both twins, allowing assessment of the renin angiotensin system (RAS) status of each fetus, both by cord blood renin and aldosterone assay and by renal immunohistochemistry. The donor had severe oliguria/oligohydramnios, whereas the recipient, in addition to severe polyuria/polyhydramnios, had cardiomyopathy, atrioventricular regurgitation, and ascites. Although immunohistochemistry demonstrated that renal secretion of renin was up-regulated in the donor and down-regulated in the recipient, cord blood levels of renin and aldosterone were similar, with high renin levels in both twins. This observation supports the hypothesis that despite renal RAS down-regulation, the recipient is exposed to RAS effectors elaborated in the donor and transferred via placental shunts. This may contribute to cardiomyopathy and hypertension in the recipient, which cannot be accounted for by hypervolemia alone. We thus hypothesized that in TTTS, the recipient's hypertensive cardiomyopathy could be due to a mechanism similar to the classical model of hypertension referred to as "2 kidneys-1 clip." Thus the hypovolemic donor twin, comparable to the clipped kidney, produces vasoactive hormones that compromise the recipient, comparable to the normal kidney, causing hypertension and cardiomyopathy.

Increased apoptosis in cervical intraepithelial neoplasia associated with HIV infection: implication of oncogenic human papillomavirus, caspases, and Langerhans cells.

PURPOSE: Increasing risk of squamous cervical intraepithelial neoplasia (CIN) exits in HIV-infected women. However, the relatively low incidence of invasive carcinoma in the untreated HIV-infected population suggests an imbalance between cell proliferation and apoptosis. We investigated apoptosis and caspases in cervical samples from this population comparatively to non-HIV-infected and control subjects. EXPERIMENTAL DESIGN: Apoptotic terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method, immunohistochemistry for caspase-2, caspase-3, caspase-8, caspase-9, and other apoptosis markers were done on 12 normal cervical samples and 103 low- and high-grade cervical lesions, containing human papillomavirus(es) from 35 HIV-negative and 33 HIV-positive women before tritherapy advent. RESULTS: (a) The apoptotic index (AI) in epithelial cells did not vary between normal mucosa and condyloma acuminata infected or not with HIV. (b) AI augmented with the CIN severity in HIV-positive and HIV-negative women. (c) AI dramatically increased in oncogenic human papillomavirus-infected CIN of HIV-positive population compared with the CIN of similar grade in HIV-negative one. This was associated with a greater expression of caspase-8, active caspase-9, and active caspase-3 in those samples. Moreover, densities of Langerhans' cells, involved in apoptotic bodies engulfment, were greatly reduced in CIN of HIV-positive women. In samples, these densities were highly inversely correlated with AI (r = -0.88, P < 0.002). CONCLUSIONS: This study provides the first evidence for the strongly enhanced apoptosis levels and caspase expression in CIN of untreated HIV-infected women. We suggest that the reduction in Langerhans' cell number could contribute at least partly to apoptotic cell accumulation.