Laparoscopic nerve-sparing radical hysterectomy without uterine manipulator for cervical cancer stage IB: description of the technique, our experience and results after the era of LACC trial.

PURPOSE: The aim of this study is to evaluate surgical data and oncological outcome of laparoscopic nerve-sparing radical hysterectomy without uterine manipulator for cervical cancer stage IB, over the last 8 years. METHODS: This retrospective study includes 32 patients with cervical cancer Figo stage (2009) IB who underwent laparoscopic nerve-sparing radical hysterectomy without using any kind of uterine manipulator. Patients were eligible if they had squamous cell carcinoma, adenocarcinoma, or adeno-squamous carcinoma, and no para-aortic lymph node involvement by imaging or after frozen section. The median value and range were assessed for operative outcomes and relapse rate and disease-free survival rate were evaluated using the Kaplan-Meier method. RESULTS: In the study, 32 patients were included and among them 27 women were stage IB1 (18 cases with tumor size 2-4 cm) and 5 women stage IB2 (Figo stage 2009). The median age of patients was 50.5 years (range 31-68) and median body mass index (B.M.I) was 25.3 kg/m2 (range 19-33.5 kg/m2). The average operating time was 228 min (range 147-310 min) and median hospital stay was 2.7 days (range 2-7 days). Approximate blood loss was 188 ml (range 120-300 ml). After a median follow-up of 37 months, we had 2 recurrences out of 32 cases and no death. Especially for patients with Figo stage (2009) IB1, the recurrence rate was 3.7% (1/27). The 3-year PFS was 93.7% and the number at risk 23 (71.8%) and especially for the IB1 stage (2009) women, the 3-year PFS was 96.1% and the number at risk 21 (77.7%). The 3-year OS was 100% with no. at risk 71.8%. CONCLUSIONS: Laparoscopic nerve-sparing radical hysterectomy without uterine manipulator is feasible and safe surgical procedure for cervical cancer with acceptable surgical and oncological outcomes in the hands of well-trained and experienced laparoscopic surgeons. Our retrospective study reveals better oncological outcome compared to other studies on the minimally invasive approach, where uterine manipulator was routinely used and no vaginal sealing of the tumor was made.

Laparoendoscopic single-site surgery (LESS) - is it feasible in gynecological surgery?

Increases in technical expertise in gynecological surgery and advances in surgical instrumentation have led to the development of laparoendoscopic single-site surgery (LESS). Between March and September 2009, 24 patients underwent adnexal surgery at our institution with laparoendoscopic single-site surgery. The LESS technique was performed using the TriPort through an umbilical incision of 10 mm and bent laparoscopic instruments. We furthermore compared the LESS technique with a control group of 24 patients operated consecutively in the same period and for the same procedures with conventional multiport laparoscopy. Comparing the two techniques we found differences between the operation time and mean hospital stay. The surgeon must master the use of novel bent instruments in close proximity to each another. The LESS technique for benign adnexal surgery is technically feasible and safe, representing a reproducible alternative to conventional multiport laparoscopy.

Standardized technique of laparoscopic pelvic and para-aortic lymphadenectomy in gynecologic cancer optimizes the perioperative outcomes.

INTRODUCTION: The main objective of this study is to illustrate the effectiveness and the safety of standardized technique of laparoscopic lymphadenectomy (LNE), newly introduced in a University Hospital, in patients with gynecologic malignancy. MATERIALS AND METHODS: A cohort of 104 patients with gynaecologic malignancies (71 with endometrial and 33 with cervical cancer), who underwent laparoscopic pelvic with or without para-aortic LNE between September 2008 and March 2010, were analyzed. Total laparoscopic hysterectomy with bilateral salpingo-oophorectomy (TLH & BSO) was the standard approach for patients with endometrial cancer (n = 71), while laparoscopic (nerve sparing) radical hysterectomy (n = 29), laparoscopic-assisted radical vaginal hysterectomy (n = 2) and radical trachelectomy was the treatment for patients with cervical cancer. All LNE were performed by a learning team under the supervision of an expert surgeon, familiar with the technique. RESULTS: The median number of pelvic lymph nodes yielded was 22 (range 16-34) and of para-aortic 14 (range 12-24). The mean operative time ± standard deviation for pelvic LNE for each side was 29 ± 17 and 64 ± 29 min for para-aortic LNE. The overall complication rate was 7.6% (n = 8). Two patients were reoperated laparoscopically, one because of postoperative hemorrhage and the other because of lymphocyst formation; laparoconversion was not necessary. DISCUSSION: Laparoscopic lymphadenectomy performed by a learning team with standardized technique is effective with adequate number of harvested nodes, in acceptable operative time and with low rate of perioperative complications.

Laparoscopic-assisted vaginal hysterectomy with and without laparoscopic transsection of the uterine artery: an analysis of 1,255 cases.

INTRODUCTION: To evaluate the operative outcomes of patients managed by laparoscopic-assisted vaginal hysterectomy (LAVH) with and without laparoscopic transsection of the uterine artery for benign gynaecologic diseases. PATIENTS AND METHODS: A retrospective analysis of 1,255 women from two different centers undergoing hysterectomy between 1998 and 2009 with benign indications is presented. 856 patients were treated by LAVH type I (vaginal transsection of the uterine artery) and 399 patients by LAVH type II (laparoscopic transsection of the uterine artery). Operative outcomes, intraoperative and postoperative complications, as well as laparoconversion rates were the main objectives of the study. RESULTS: Median operative time was similar between LAVH type I and II (136 vs. 126 min, respectively, P = NS). Intraoperative complication rate was not significantly different between the two groups of the study (LAVH type I: 1.5% vs. LAVH type II: 1.26%, respectively, P = NS). The injury of the urinary tract, especially of the bladder, was the most common intraoperative complication for both the groups of the study. Laparoconversion rate was similar in LAVH type I and II (0.5 vs. 0.35%, respectively, P = NS), while postoperative complications were significantly higher in LAVH type I (2.25%) compared to LAVH type II (1.16%), mainly because of postoperative vaginal and intrabdominal haemorrhage in the group of the LAVH type I. CONCLUSION: LAVH with laparoscopic transsection of the uterine artery is an effective and safe technique with less postoperative complication compared to LAVH with vaginal transsection of the uterine vessels.

Prognostic value of follicular fluid 25-OH vitamin D and glucose levels in the IVF outcome.

OBJECTIVES: The aim of the present study was to measure serum and follicular fluid 25-OH vitamin D and glucose levels in women who underwent IVF-ET treatment and to further investigate whether the circulating 25-OH vitamin D and glucose levels correlate with IVF success. METHODS: This prospective observational study included 101 consecutive women who underwent 101 IVF-ICSI ovarian stimulation cycles and were allocated to one of the three groups according to their follicular fluid 25-OH vitamin D concentrations. Group A (n = 31) with less than 20 ng/ml, group B (n = 49) with vitamin levels between 20.1 and 30 ng/ml and group C (n = 21) with more than 30 ng/ml vitamin concentration. RESULTS: Follicular fluid vitamin levels significantly correlated with the quality of embryos in total (r = -0.27, p = 0.027), while the quality of embryos of group C were of lower quality as compared to those of groups A and B (p = 0.009). Follicular fluid glucose levels were lower in women of group C as compared to the respective levels of groups A and B (p = 0.003). Clinical pregnancy rate demonstrated in 14.5% in women of group C and 32.3% and 32.7% in groups A and B, respectively (p = 0.047). CONCLUSION: The data suggests that excess serum and follicular fluid vitamin levels in combination with decreased follicular fluid glucose levels have a detrimental impact on the IVF outcome.

Seven years' experience in laparoscopic dissection of intact ovarian dermoid cysts.

A large case series on laparoscopic removal of dermoid cysts with a diameter between 3 and 12 cm, via an endobag, is reported (127 cysts in 121 premenopausal women). The incidence of spillage and recurrence rate of laparoscopic ovarian dermoid cystectomy, the duration of the surgical procedure, the length of hospitalization, the incidence of recurrence and pregnancies was evaluated. In 2.5% of cases, the endobag ruptured during removal, and a total spillage rate of 12% was seen. No signs or symptoms of peritonitis were observed regardless of cystic spillage or not. Laparoscopic cystectomy of dermoid cysts in premenopausal women is safe and effective and appears to be a valuable alternative to laparotomy. Controlled intraperitoneal spillage of cyst contents does not increase postoperative morbidity as long as an endobag is used and the peritoneal cavity is washed out thoroughly.

Total laparoscopic hysterectomy without uterine manipulator. A retrospective study of 1023 cases.

OBJECTIVE: The aim of this study was to evaluate the feasibility and safety of a total laparoscopic hysterectomy (TLH) without the use of a uterine manipulator in women with benign indications for hysterectomy. STUDY DESIGN: Between January 2011 and January 2020, 1023 patients underwent a TLH without the use of any type of uterine manipulator. The indications for hysterectomy were all benign conditions. The patients' details were obtained from the hospital medical records and the indications for hysterectomy, the surgical data and the intra and postoperative complications were evaluated. All operations were performed by the same surgical team. RESULTS: The median age was 48.2 years, while the BMI ranged from between 26.2 kg/m2 and 47.8 kg/m2. A small percentage of the women were menopausal (278, 27 %) and, following a detailed consultation with 563 (55 %) of the patients, we performed a TLH with adnexectomy. The mean operative time was 78 min (43-168 min), while the estimated blood loss was 59 mL (20-260 ml) and the mean uterine weight was 255 g (40-1510 g). There was no case of conversion to laparotomy. A blood transfusion was required for 14 patients (1.4 %), while there was one case of ureteral injury and three cases where the bladder was opened and fixed laparoscopically. The average hospital stay was 1.1 days, with only 38 patients staying for two or more days. In the long term, we had five cases (0.5 %) of vaginal vault dehiscence and one case of vaginal vault hematoma. CONCLUSION: A TLH without the use of a uterine manipulator is a feasible and safe procedure. While it is perhaps a more demanding procedure for young doctors, when performed by well-trained and experienced laparoscopic surgeons, the procedure entails a short operative time and a low complications rate. As such, it should be the first step in the training of young doctors for performing laparoscopic radical hysterectomies.

Growth hormone and prolactin response to ghrelin during the normal menstrual cycle.

OBJECTIVE: It has been suggested that exogenous oestradiol augments ghrelin-induced growth hormone (GH) secretion in postmenopausal women. Whether endogenous oestrogens exert a similar effect during the normal menstrual cycle is not known. The aim of this study was to test the hypothesis that physiological changes in ovarian steroids during the normal menstrual cycle modulate GH and prolactin (PRL) response to ghrelin. DESIGN: Healthy women were studied in three phases of the normal menstrual cycle. PATIENTS: Ten healthy normally cycling women. MEASUREMENTS: A single dose of ghrelin (1 microg/kg) was administered intravenously in the early and late follicular phases and in the mid-luteal phase of the cycle. Saline was injected in the preceding cycle. Blood samples were taken before ghrelin or saline injection (time 0) and also at -15, 15, 30, 45, 60, 75, 90 and 120 min. The GH and PRL responses were assessed. RESULTS: Serum oestradiol and progesterone concentrations showed the variations of a normal menstrual cycle. After ghrelin administration, in the three phases of the cycle, plasma ghrelin and serum GH and PRL levels increased rapidly, peaking at 30 min and declining gradually thereafter (P < 0.001). There were no significant differences in the hormone levels between the three phases at all time points. No changes in GH and PRL levels were seen after saline injection. CONCLUSIONS: These results demonstrate that GH and PRL responses to ghrelin do not change across the menstrual cycle. It is suggested that the action of ghrelin on the pituitary somatotrophs is modulated differentially by endogenous and exogenous ovarian steroids.

Effect of ghrelin on gonadotrophin secretion in women during the menstrual cycle.

BACKGROUND: It has been suggested that ghrelin may affect reproduction in animals by decreasing pituitary LH secretion. The role of ghrelin on LH secretion in women has not been investigated. Our aim was to assess the effect of ghrelin administration on basal and GnRH-induced LH secretion during the menstrual cycle. METHODS: Normally cycling women (n = 10) received on Day 3 of three consecutive cycles a single bolus i.v. of either ghrelin (1 microg/kg, cycle 1) or GnRH (100 microg, cycle 2) or GnRH plus ghrelin (cycle 3). In cycle 1, ghrelin was also injected in late follicular and mid-luteal phase of the cycle. Saline was injected in a preceding cycle (cycle 1, control). Blood samples were taken before drugs or saline injection (time 0) as well as at -15, 15, 30, 45, 60, 75, 90 and 120 min. RESULTS: Plasma ghrelin levels increased rapidly, peaking at 15 or 30 min (P < 0.001), then decreased steadily, approaching pre-injection levels at 120 min. Serum FSH, LH, estradiol and progesterone levels remained unchanged. The stimulating effect of GnRH on LH and FSH secretion was unaffected by ghrelin injection. In contrast to saline, ghrelin stimulated a significant increase in growth hormone levels. CONCLUSIONS: Under these experimental conditions, our results demonstrate for the first time the inability of a bolus of ghrelin to affect basal and GnRH-induced LH and FSH secretion. It is suggested that ghrelin does not play a major physiological role in gonadotrophin secretion in women.

Metformin reduces the expression of corticotropin-releasing hormone and urocortin in the endometrium of healthy women.

OBJECTIVE: To investigate the effect of metformin administration on the expression of endometrial corticotrophin-releasing hormone (CRH) and urocortin (UCN) in the midluteal phase of the cycle. DESIGN: Experimental study, performed in 2010-2011. SETTING: University hospital. PATIENT(S): Eight healthy, normally cycling and parous women volunteered for the study. INTERVENTION(S): All women were investigated in two nonconsecutive cycles (control cycle, untreated and after one cycle break; trial cycle, oral administration of metformin [850 mg × 2]). Endometrial pipelle biopsies were obtained on day LH+7. MAIN OUTCOME MEASURE(S): The endometrial biopsies were immunohistochemically assessed for CRH and UCN expression. Evaluation of positivity was performed by applying the immunoreactive score. RESULT(S): Compared with samples from control cycles, CRH and UCN were significantly reduced in endometrial samples obtained during metformin treatment. This down-regulation was significant both in the endometrial cells and in the endometrial stroma. CONCLUSION(S): This is the first study showing that during the midluteal phase of the cycle, metformin may decrease the production of CRH and UCN in the endometrium. Metformin interference to decidualization could happen by CRH/UCN modification.

Blockage of ghrelin-induced prolactin secretion in women by bromocriptine.

OBJECTIVE: To investigate the effect of bromocriptine on ghrelin-induced PRL secretion in women. DESIGN: Longitudinal study. SETTING: University hospital. PATIENT(S): Ten healthy, normally cycling women. INTERVENTION(S): The women were injected IV on day 3 of three cycles with a single dose of normal saline (cycle 1) or ghrelin (1 microg/kg) after pretreatment for 2 days either with placebo (cycle 2) or with bromocriptine (cycle 3) per os. Blood samples were taken before and frequently after drugs administration for 120 minutes. MAIN OUTCOME MEASURE(S): The PRL and GH responses to ghrelin were assessed. RESULT(S): Bromocriptine suppressed basal PRL levels significantly. The injection of ghrelin stimulated a significant increase in serum PRL levels in cycle 2 but not in cycle 3, in which PRL levels remained stable. The response of GH to gherlin was significantly attenuated in cycle 3 as compared with cycle 2. CONCLUSION(S): The present study demonstrates for the first time that bromocriptine blocked the stimulating effect of ghrelin on PRL release and attenuated the GH response to the same stimulus. The mechanism of these interactions needs to be clarified.

Effect of ovarian hormones on serum adiponectin and resistin concentrations.

OBJECTIVE: To investigate the effect of ovarian hormones on adiponectin and resistin levels in women. DESIGN: Experimental study. SETTING: University hospital. PATIENT(S): Thirteen normally cycling women (7 in group 1 and 6 in group 2) and 8 postmenopausal women (group 3). INTERVENTION(S): Women of group 1 were investigated in a control cycle and in a subsequent cycle in which total abdominal hysterectomy plus bilateral salpingooophorectomy (TAH+BSO) was performed on day 3. In both cycles, the women received increasing doses of E(2) from days 3 to 5. Women of group 2 underwent TAH+BSO on day 3 without receiving any hormonal treatment. Women of group 3 received increasing doses of E(2) for 15 days. MAIN OUTCOME MEASURE(S): Adiponectin, resistin, and E(2) concentrations. RESULT(S): In group 1, serum adiponectin and resistin levels did not show any significant changes for the week following day 3 and were similar in the two cycles. In group 2, adiponectin and resistin levels were similar before and after TAH+BSO and remained stable during the first postoperative week. In group 3, no significant changes in adiponectin and resistin levels were seen during the 15 days of E(2) administration. CONCLUSION(S): Adiponectin and resistin values were not affected either by estrogen treatment or after ovariectomy in women. It is suggested that ovarian hormones are not involved in the regulation of adiponectin and resistin secretion in women.