Somatostatin and somatostatin analogues reduce PDGF-induced endometrial cell proliferation and motility.

BACKGROUND: Endometriosis is characterized by ectopic implantation of endometrial cells, which show increased proliferation and migration. Somatostatin (SST) and its analogues inhibit normal and cancer cell growth and motility through the SST receptors, sst1-5. Cortistatin (CST), which displays high structural and functional homology with SST, binds all ssts, as well as MrgX2. Our objective was to investigate the gene expression of the SST/CST system and to determine the effect of SST and its analogues on platelet-derived growth factor (PDGF)-induced proliferation and motility in telomerase-immortalized human endometrial stromal cell (T HESC) line and in primary endometrial stromal cell (ESCs) isolated from human endometriotic tissues. METHODS: Ectopic endometrial tissues were collected from women (n= 23) undergoing laparoscopic surgery for endometriosis (Stage III/IV). Gene expression was evaluated by real-time PCR, cell motility by wound healing assay, protein expression and ß-actin rearrangement by immunofluorescence, cell proliferation by the Alamar blue assay and ERK1/2 and Akt phosphorylation by western blot. RESULTS: Human endometriotic tissues, primary ESCs and T HESCs expressed SST, CST and ssts. SST, its analogues SOM230 and octreotide, as well as CST, counteracted PDGF-induced proliferation and migration in both ESCs and T HESCs. SST also inhibited vascular endothelial growth factor and metalloprotease-2 mRNA expression, and reduced basal and PDGF-induced ERK1/2 phosphorylation. CONCLUSION: These results indicate that the SST/CST system is expressed in endometriotic tissues and cells. The inhibitory effects of SST and its analogues on PDGF-induced proliferation and motility suggest that these peptides may represent promising tools in the treatment of endometriosis.

Laparoscopic stripping of endometriomas negatively affects ovarian follicular reserve even if performed by experienced surgeons.

In order to estimate the impact of laparoscopic stripping of endometriomas on the ovarian follicular reserve, 43 normo-ovulatory women were studied by endocrine (anti-Müllerian hormone (AMH), FSH, LH, inhibin B, oestradiol) and ultrasonographic (antral follicle count (AFC)) methods before surgery, and 3 and 9 months after surgery. The operation was performed by experienced laparoscopists, particularly aware of the need to avoid damaging the healthy part of the ovary. Serum AMH concentrations significantly decreased after the operation (1.4±0.2 ng/ml after 3 months and 1.3±0.3 ng/ml after 9 months versus 3.0±0.4 ng/ml before surgery; P<0.0001), whereas basal FSH, LH, oestradiol and inhibin B concentrations remained unchanged. The volume of the operated ovary significantly diminished after surgery (P<0.0001), whereas the AFC was not significantly altered. Overall, the data show that laparoscopic stripping of endometriomas reduces ovarian reserve. The significant decrease of AMH after surgery confirms that part of the healthy ovarian pericapsular tissue, containing primordial and preantral follicles, is removed or damaged despite all the surgical efforts to be atraumatic. This must be carefully considered when laparoscopic cystectomy surgery is scheduled for patients with no relevant symptoms besides infertility or with already small ovarian reserve.

Elastosonography: a possible new tool for diagnosis of adenomyosis?

OBJECTIVES: Adenomyosis is a disorder defined by the presence of ectopic endometrial glands and stroma within the myometrium. Transvaginal ultrasound (TVU) is currently the first-line examination for this condition and the aim of this paper is to relate a pilot experience that was conducted using TVU to evaluate adenomyosis and which started from the assumption that tissues with anatomopathological differences show different elasticity values. METHODS: Using standard B-mode analysis and elastosonography, we evaluated 30 consecutive women with suspected uterine adenomyosis. In 15 cases the diagnosis was confirmed by histology. RESULTS: The adenomyotic area presented more softness (red and green) compared with the surrounding uterine tissue (blue); the borders of the adenomyotic area corresponded to the borders of the green area. CONCLUSIONS: These preliminary results suggest that elastosonography could be considered a useful tool in the diagnosis of adenomyosis because it is non-invasive, easy to understand, easy to perform, and has a short learning curve towards becoming skilled at the procedure.

Effectiveness and Safety of Posterior Vaginal Repair with Single-Incision, Ultralightweight, Monofilament Propylene Mesh: First Evidence from a Case Series with Short-Term Results.

OBJECTIVE: The use of transvaginal mesh is controversial, and over time, multiple surgical methods for the treatment of posterior vaginal prolapse (PVP) have been proposed including different surgical approaches and techniques. To date, no clear conclusion has been reached about the use of mesh for reinforcing transvaginal posterior repair. The aim of this study was to evaluate the feasibility, safety, and effectiveness of a novel, ultralightweight mesh for the treatment of PVP. METHODS: We performed a single-center, prospective observational study on consecutive patients referred for primary or recurrent, symptomatic stage II PVP (according to the international Pelvic Organ Prolapse Quantification System) from April 2017 to September 2018. In all patients, transvaginal posterior repair was augmented with a single-incision, isoelastic polypropylene mesh. Data about the postoperative outcomes were collected until December 2019. RESULTS: A total number of 15 patients were included. The median follow-up after surgery was 18 months (IQR = 14). Surgery was completed in all cases without complications. Regarding the anatomical outcomes (as measured according to POP-q classification), a significant improvement was observed in terms of Bp, D, and C (p < 0.05). The functional outcomes were significantly ameliorated after surgery, with a reduction of bulge symptom, stypsis, incomplete evacuation, and excessive staining (p < 0.05). The quality of life was significantly improved in the majority of patients (p < 0.05). Median patients' satisfaction rate was 100% (IQR = 22.5%). Neither early nor late postoperative complications occurred. CONCLUSIONS: Single-incision, ultralightweight polypropylene meshes were safe and highly effective in the treatment of PVP. As our study has some limitations, further large, controlled studies are needed.

Laparoscopic conservative management of ureteral endometriosis.

PURPOSE OF REVIEW: The surgical management of deeply infiltrating endometriosis involving the ureter is a complex procedure that requires an accurate balance between the need for complete excision of endometriotic foci and the need to avoid any morbidity associated with radical surgery. Owing to its rarity, a clear surgical strategy to deal with this condition (e.g. ureterolysis vs. ureteroneocystostomy) has not as yet been identified. RECENT FINDINGS: A few studies present data about the conservative management of ureteral endometriosis. We reported the experience of some surgical topics dealing with ureteral endometriosis and their strategies for the conservative treatment of this condition. SUMMARY: Ureterolysis could be used as the initial surgical step for patients with ureteral endometriosis. For patients displaying extended severe ureteral involvement, stenosis, or moderate or severe hydronephrosis with a high risk of having intrinsic ureteral disease, ureteroneocystostomy is likely to be a wiser surgical strategy. Moreover the crucial role of the primary surgeon in the treatment definition will hardly be replaced by objective reproducible referral pattern.

Laparoscopic conservative management of ureteral endometriosis: a survey of eighty patients submitted to ureterolysis.

BACKGROUND: this study aims to evaluate the effectiveness and safety of laparoscopic conservative management of ureteral endometriosis. METHODS: Eighty cases of histologically confirmed endometriosis affecting the ureter, 10 of which with bladder involvement were prospectively studied. In detail, patients were 13 women with ureteral stenosis (7 with hydronephrosis), 32 with circular lesions totally encasing the ureter, and 35 with endometriotic foci on the ureteral wall, but not completely encasing it. They were submitted to laparoscopic ureterolysis with or without partial cystectomy, ureteroneocistostomy. The rate of surgical complications, the recurrence rate, the patients' satisfaction rate was assessed during 22 months (median) follow-up. RESULTS: Laparoscopic ureterolysis was employed for all patients and set free the ureter from the disease in 95% of cases, whereas ureteroneocystostomy was necessary for 4 patients showing severe stenosis with hydronephrosis, among which 2 had intrinsic endometriosis of the ureteral muscularis. Three post-surgery ureteral fistulae occurred in cases with ureteral involvement longer than 4 cm: two cases were successfully treated placing double J catheter, the third needed ureteroneocistostomy. During follow-up, ureteral endometriosis recurred in 2 patients who consequently underwent ureteroneocystostomy. Most patients expressed high satisfaction rate throughout the whole follow-up period. CONCLUSION: laparoscopic ureterolysis is effective and well tolerated in most cases of ureteral endometriosis. Ureteroneocystostomy is a better strategy for patients with extended (more than 4 cm) ureteral involvement or with severe stenosis with or without hydronephrosis.

Prophylactic bilateral oophorectomy during vaginal hysterectomy for benign pathology.

OBJECTIVE: The aim of this study was to assess the feasibility and safety of vaginal removal of ovaries at the time of vaginal hysterectomy. MATERIALS AND METHODS: All patients candidate to hystero-salpingo-oophorectomy by transvaginal approach, between 1 March 2004 and 28 February 2007, were admitted in the study. RESULTS: Of the 472 women included in the study, 432 (91.5%) underwent hysterectomy and bilateral oophorectomy by vaginal approach. There was only one case of major vessel injury, but no patients required blood transfusion. All the operations were performed only by vaginal route and no conversion to the abdominal route was required. CONCLUSION: The need to perform oophorectomy should not be considered a contraindication to vaginal hysterectomy.

Safety and efficacy of vaginal hysterectomy in the large uterus with the LigaSure bipolar diathermy system.

OBJECTIVE: This study was undertaken to assess safety and efficacy of vaginal hysterectomy in case of large uterine size (> or = 250 g) using the LigaSure bipolar diathermy (Valleylab, Boulder, CO). STUDY DESIGN: In a retrospective study, medical records of 102 patients who underwent vaginal hysterectomy and who had uterine weight (evaluated after surgery) 250 g or greater were reviewed. All hysterectomies were performed by using the LigaSure vessel sealing system to secure vascular pedicles (uterosacral-cardinal, uterine and ovarian and round ligaments). RESULTS: Of the 102 vaginal hysterectomies, 99 were successfully performed (97.1%; 95% confidence interval, 91.6-99.4%), whereas a conversion from the vaginal to the abdominal route was required in 3 cases. The median uterine weight was 455 g (range, 241-1913 g). The weight of the largest uterus successfully removed vaginally was 1600 g, without intraoperative and postoperative complications. The median operative time was 50 minutes (range, 25-50 minutes). CONCLUSION: The current study confirms that very large uterine volume does not represent a real obstacle to perform vaginal hysterectomy and that results in a safe and effective technique in cases of uterine weight 250 g or greater.

Breast cancer preoperative staging: does contrast-enhanced magnetic resonance mammography modify surgery?

Women with newly diagnosed breast cancer may have lesions undetected by conventional imaging. Recently contrast-enhanced magnetic resonance mammography (CE-MRM) showed higher sensitivity in breast lesions detection. The present analysis was aimed at evaluating the benefit of preoperative CE-MRM in the surgical planning. From 2005 to 2009, 525 consecutive women (25-75 years) with breast cancer, newly diagnosed by mammography, ultrasound, and needle-biopsy, underwent CE-MRM. The median invasive tumour size was 19 mm. In 144 patients, CE-MRM identified additional lesions. After secondlook, 119 patients underwent additional biopsy. CE-MRM altered surgery in 118 patients: 57 received double lumpectomy or wider excision (41 beneficial), 41 required mastectomy (40 beneficial), and 20 underwent contra lateral surgery (18 beneficial). The overall false-positive rate was 27.1% (39/144). CE-MRM contributed significantly to the management of breast cancer, suggesting more extensive disease in 144/525 (27.4%) patients and changing the surgical plan in 118/525 (22.5%) patients (99/525, 18.8% beneficial).

Laparoscopy and body mass index: feasibility and outcome in obese patients treated for gynecologic diseases.

STUDY OBJECTIVE: To compare feasibility and surgical outcome of laparoscopic gynecologic surgery between obese, overweight, normal-weight, and underweight women. DESIGN: Retrospective case control study (Canadian Task Force classification II-3). SETTING: Surgery Unit of Minimally Invasive Gynaecology. PATIENTS: A total of 503 women who underwent laparoscopic procedures for both benign disease and malignancies. INTERVENTIONS: Four main categories of gynecologic disease were identified: uterine fibroids, benign adnexal masses, endometriosis, and endometrial cancer (stage I). For each category patients were divided into 4 groups: underweight (BMI <18.5 kg/m(2)), normal-weight (BMI 18.5-24.9 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)), and obese (BMI ≥30 kg/m(2)). MEASUREMENTS AND MAIN RESULTS: Selected outcomes were duration of surgery, rate of laparotomy conversion, intraoperative and postoperative complications, and duration of hospital stay. No statistical difference regarding demographic data, surgical and medical history, and intraoperative findings was present between groups. No laparotomy conversion occurred. Regarding duration of surgery, we found no statistical difference among the BMI groups with regard to benign diseases, whereas pelvic lymphadenectomy in obese patients with endometrial cancer had a statistically significant longer duration than in the control group (122 +/- 47 min vs 65 +/- 21 min, p <.001). The postoperative complication rate was 0.01%: 3 cases of blood transfusion and 1 case of hemoperitoneum among myomectomies; 1 ureteral fistula in surgery for pelvic endometriosis; and 1 case of postoperative lymphocele in endometrial cancer group. No statistically significant difference was found in duration of hospital stay among the BMI groups in any of the categories of disease. For each category we conducted an analysis to identify any possible risk factors other than BMI in the surgical outcomes. CONCLUSION: Laparoscopic approach in the various applications of gynecologic surgery does not appear to be significantly influenced by BMI in terms of surgical outcomes, laparotomy conversion rate, intraoperative and postoperative complications rate, and duration of hospital stay. The technical difficulties can be solved if skilled surgeons and anesthetists are available.

The growth hormone-releasing hormone (GHRH) antagonist JV-1-36 inhibits proliferation and survival of human ectopic endometriotic stromal cells (ESCs) and the T HESC cell line.

OBJECTIVE: To determine the effect of the GHRH antagonist JV-1-36 on proliferation and survival of primary ectopic human endometriotic stromal cells (ESCs) and the T HESC cell line. DESIGN: Prospective laboratory study. SETTING: University hospital. PATIENT(S): 22 women with endometriosis (aged 34.8+/-5.7 years) undergoing therapeutic laparoscopy. INTERVENTION(S): Eutopic (n=10) and ectopic (n=22) endometrial tissues were collected from women who underwent therapeutic laparoscopic surgery for endometriosis (stage III/IV). MAIN OUTCOME MEASURE(S): Expression of GHRH, GHRH receptor (GHRH-R) and GHRH-R splice variant (SV) 1 mRNA was determined by reverse-transcription polymerase chain reaction (RT-PCR). The ESC proliferation was assessed by 5-bromo-2-deoxyuridine incorporation, cell survival by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and Trypan blue assay. The T HESC survival was evaluated by MTT, cyclic adenosine monophosphate (cAMP) levels by ELISA, extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation by Western blot, and insulin-like growth factor (IGF)-2 mRNA by real-time PCR. RESULT(S): The ESCs and T HESCs, but not normal endometrial tissues, expressed GHRH-R mRNA; SV1 mRNA was determined in normal endometrial tissues, ESCs, and T HESCs; GHRH mRNAwas found in T HESCs; JV-1-36 inhibited ESC proliferation and ESC and T HESC survival. In T HESCs, JV-1-36 reduced cAMP production and ERK1/2 phosphorylation but had no effect on IGF-2 mRNA expression. CONCLUSION(S): The GHRH antagonist JV-1-36 inhibits endometriotic cell proliferation and survival, suggesting that GHRH antagonist may represent promising tools for treatment of endometriosis.

Cost/accuracy ratio analysis in breast cancer patients undergoing ultrasound-guided fine-needle aspiration cytology, sentinel node biopsy, and frozen section of node.

We evaluated the effectiveness and the cost of axillary staging in breast cancer patients by ultrasound-guided fine-needle aspiration cytology (US-FNAC), sentinel node biopsy (SNB), and frozen sections of the sentinel node to achieve the target of the highest number of immediate axillary dissections. From January 2003 through October 2005, a total of 404 consecutive eligible breast cancer patients underwent US-FNAC of suspicious axillary lymph nodes. If tumor cells were found, immediate axillary dissection was proposed (33% of node-positive cases). If US or cytology was negative, SNB was performed. Frozen sections of the sentinel node allowed immediate axillary dissection in 31% of node-positive cases. The remaining 36% underwent delayed axillary dissection. We compared our policy with clinical evaluation of the axilla, showing better specificity of US-FNAC, the cost balanced by a 12% reduction of SNBs, and a marked reduction of unnecessary axillary dissections resulting from false-positive clinical staging. Moreover, the comparison between our policy and permanent histology of the sentinel node showed an 8% cost saving, mainly associated with the immediate axillary dissections. US-FNAC of axillary lymph nodes in breast cancer patients reliably predicts the presence of metastases and therefore refers a significant number of patients to the appropriate surgical treatment, avoiding an SNB. As cost saving to the health care system in our study is mainly related to one-step axillary surgery, US-FNAC of axillary lymph nodes and frozen section of the sentinel node generate significant cost saving for patients who have metastatic nodes.