Unilateral inguinofemoral lymphadenectomy in patients with early-stage vulvar squamous cell carcinoma and a unilateral metastatic sentinel lymph node is safe.

OBJECTIVE: Optimal management of the contralateral groin in patients with early-stage vulvar squamous cell carcinoma (VSCC) and a metastatic unilateral inguinal sentinel lymph node (SN) is unclear. We analyzed patients who participated in GROINSS-V I or II to determine whether treatment of the contralateral groin can safely be omitted in patients with a unilateral metastatic SN. METHODS: We selected the patients with a unilateral metastatic SN from the GROINSS-V I and II databases. We determined the incidence of contralateral additional non-SN metastases in patients with unilateral SN-metastasis who underwent bilateral inguinofemoral lymphadenectomy (IFL). In those who underwent only ipsilateral groin treatment or no further treatment, we determined the incidence of contralateral groin recurrences during follow-up. RESULTS: Of 1912 patients with early-stage VSCC, 366 had a unilateral metastatic SN. Subsequently, 244 had an IFL or no treatment of the contralateral groin. In seven patients (7/244; 2.9% [95% CI: 1.4%-5.8%]) disease was diagnosed in the contralateral groin: five had contralateral non-SN metastasis at IFL and two developed an isolated contralateral groin recurrence after no further treatment. Five of them had a primary tumor ≥30 mm. Bilateral radiotherapy was administered in 122 patients, of whom one (1/122; 0.8% [95% CI: 0.1%-4.5%]) had a contralateral groin recurrence. CONCLUSION: The risk of contralateral lymph node metastases in patients with early-stage VSCC and a unilateral metastatic SN is low. It appears safe to limit groin treatment to unilateral IFL or inguinofemoral radiotherapy in these cases.

Cervical re-injection of indocyanine green to improve sentinel lymph node detection in endometrial cancer.

OBJECTIVES: To evaluate the role of cervical re-injection of indocyanine green (ICG) to increase the detection rate of sentinel lymph node (SLN) in patients with endometrial cancer (EC) who underwent robotic-assisted surgical staging. METHODS: We retrospectively identified consecutive EC patients undergoing robotic-assisted staging with SLN biopsy at our Institution between June 2016 and April 2020. Patients were excluded if they had open abdominal surgical approach, neoadjuvant chemotherapy, and advanced stage [International Federation of Gynecology and Obstetrics (FIGO) stage III-IV] at diagnosis. According to our SLN protocol, in case of either unilateral or no SLN detection, we performed an ipsilateral or bilateral cervical re-injection of ICG. RESULTS: In total, 251 patients meeting inclusion criteria were included in the analysis. At first injection, bilateral detection was achieved in 184 (73.3%), unilateral detection in 57 (22.7%), and no detection in 10 (4.0%) patients. Cervical re-injection was performed in 51 of 67 patients with failed bilateral mapping. After cervical re-injection, bilateral detection rate increased to 94.5% (222/235), while unilateral and no detection were 5.1% (12/235) and 0.4% (1/235), respectively. CONCLUSIONS: Our results suggest that cervical re-injection of ICG, in case of failed bilateral mapping of SLN, brings about a significant improvement in SLN detection rates, therefore reducing the number of side-specific required lymphadenectomies.

Comparison between laparoscopy and laparotomy in the surgical re-staging of granulosa cell tumors of the ovary.

OBJECTIVE: To evaluate the role of laparoscopic (LPS) and laparotomic (LPT) re-staging in patients with incompletely surgically staged ovarian granulosa cell tumors (OGCT). METHODS: We conducted a medical chart retrospective analysis of all patients with sex cord stromal tumors (SCSTs) who were managed in our division between March 1994 and March 2017. After a complete review of surgical and pathological notes, patients with incomplete staging were restaged according to the FIGO guidelines. Statistical analysis was conducted using Statistical Package version 20.0 for Windows (SPSS, Inc., Chicago, Illinois). RESULTS: Out of a total of 170 patients SCSTs, 84 patients (49,5%) received primary surgery that included a hysterectomy; 86 patients (50,5%) underwent fertility-sparing surgery. Eighty-one patients (48%) with diagnosis of OGCT were incompletely surgically staged at another institution. We evaluated our results in terms of laparoscopic approach (56 patients) and open treatment (25 patients). Among the IA patient's group, 1 was upstaged to IIB stage and 2 to IIIB; among patients with IC stage, 1 was upstaged to IIA, 2 to IIB and 1 to IIIB stage. Adjuvant chemotherapy was given to the upstaged patients with final stage IIB-IIIC. No statistically significant difference between laparoscopy and open-surgery was detected in terms of upstaged patients after second surgery (p = 0,36). CONCLUSION: According to our series, laparoscopic restaging compared to the open approach seems to be a feasible and efficient technique to complete surgical staging in patients with GCTs incorrectly staged. Surgical restaging seems to upstage a considerable number of OGCT, mainly in the initial stage IC group of patients. However, the impact of restaging on final outcome and survival remains to be demonstrated.

Sentinel nodes in vulvar cancer: Long-term follow-up of the GROningen INternational Study on Sentinel nodes in Vulvar cancer (GROINSS-V) I.

OBJECTIVE: In 2008 GROINSS-V-I, the largest validation trial on the sentinel node (SN) procedure in vulvar cancer, showed that application of the SN-procedure in patients with early-stage vulvar cancer is safe. The current study aimed to evaluate long-term follow-up of these patients regarding recurrences and survival. METHODS: From 2000 until 2006 GROINSS-V-I included 377 patients with unifocal squamous cell carcinoma of the vulva (T1, <4 cm), who underwent the SN-procedure. Only in case of SN metastases an inguinofemoral lymphadenectomy was performed. For the present study follow-up was completed until March 2015. RESULTS: Themedian follow-up was 105 months (range 0­179). The overall local recurrence ratewas 27.2% at 5 years and 39.5% at 10 years after primary treatment, while for SN-negative patients 24.6% and 36.4%, and for SN-positive patients 33.2% and 46.4% respectively (p = 0.03). In 39/253 SN-negative patients (15.4%) an inguinofemoral lymphadenectomy was performed, because of a local recurrence. Isolated groin recurrence rate was 2.5% for SN-negative patients and 8.0% for SN-positive patients at 5 years. Disease-specific 10-year survival was 91% for SN-negative patients compared to 65% for SN-positive patients (p b .0001). For all patients, 10-year disease-specific survival decreased from 90% for patients without to 69% for patients with a local recurrence (p b .0001).

Is there a role for postoperative treatment in patients with stage Ib2-IIb cervical cancer treated with neo-adjuvant chemotherapy and radical surgery? An Italian multicenter retrospective study.

PURPOSE: Neoadjuvant chemotherapy [NACT] followed by radical hysterectomy is an alternative therapeutic option to concurrent chemotherapy-radiotherapy for locally advanced cervical cancer. However there are very few data about the effectiveness of any post-operative treatment in this clinical setting. The purpose of this study was to correlate the patterns of recurrence and the clinical outcomes of cervical cancer patients who received NACT, with postoperative adjuvant treatment. PATIENTS AND METHODS: This retrospective multicenter study included 333 patients with FIGO stage Ib2-IIb cervical cancer who underwent platinum-based NACT followed by radical surgery. Pathological responses were retrospectively assessed as complete; optimal partial; and suboptimal response. Overall optimal response rate was the sum of complete and optimal partial response rates. RESULTS: On the whole series, recurrence-free survival was significantly longer in patients who achieved an overall optimal response than in those who did not (p<0.0001), and in patients who received adjuvant chemotherapy compared to those who did not (p=0.0001). On multivariate analysis, consolidation therapy (p=0.0012) was the only independent prognostic variable for recurrence-free survival; whereas FIGO stage (p=0.0169) and consolidation therapy (p=0.0016) were independent prognostic variables for overall survival. CONCLUSION: Optimal responders after chemo-surgical treatment for FIGO stage Ib2-IIb cervical cancer do not need any further treatment. Additional cycles of chemotherapy could be of benefit for patients with suboptimal response and intra-cervical residual disease. Both adjuvant chemotherapy and adjuvant radiation treatments do not seem to improve the clinical outcome of patients with extra-cervical residual disease compared to no further treatment.

Neoadjuvant chemotherapy prior to pelvic exenteration in patients with recurrent cervical cancer: single institution experience.

OBJECTIVES: The aim of the study is to evaluate the response to neoadjuvant chemotherapy (NACHT) of patients with recurrent cervical cancer who were poor candidates for pelvic exenteration (PE), and the impact on DFS and OS. METHODS: A retrospective data collection extracted from medical records of 61 patients submitted to pelvic exenteration was performed: 30 underwent up-front exenterative procedure whereas 31 received NACHT. RESULTS: The median tumor size was significantly (P=0.0006) larger in the NACHT group compared to the up-front PE one (43.9 mm vs 28 mm), and a significant (P=0.04) higher percentage of patients (45 vs 20%) had lateral pelvic wall invasion in the NACHT group. No statistically significant difference in early and late complications was observed in the two groups. Median overall survival in study population was 42.9 months (95% CI: 22.2, 180.8). Median overall survival times as well as recurrence free survival times were not significantly different between NACHT (42.9 months and 36.1 months for OS and DFS respectively) vs. No NACHT (111.9 months and 48.1 months for OS and DFS respectively). There was an overall significant difference in DFS between negative and positive margins but the curves were similar for NACHT and up-front PE groups stratified by resection margin status. CONCLUSIONS: In our series, though small and retrospective, NACHT prior to PE represents a feasible therapeutic option without intra-operative and early post-operative mortality or worsening of early and late complication rate and with acceptable long-term survival and DFS for recurrent cervical cancer patients who are poor candidates for up-front pelvic exenteration.

Robotic surgery for endometrial cancer: comparison of perioperative outcomes and recurrence with laparoscopy, vaginal/laparoscopy and laparotomy.

INTRODUCTION: Comparison of perioperative outcomes and recurrence in patients undergoing primary surgical treatment for endometrial cancer by robotics, laparoscopy, vaginal/laparoscopy, or laparotomy approaches. METHODS: Prospective analysis of 67 patients undergoing robotic surgery for endometrial cancer between March 2004 and December 2007. Comparison was made with similar patients operated between November 1999 and December 2006 by laparoscopy (37 cases), laparotomy (99 cases) and vaginal/laparoscopy approach (vaginal hysterectomy, bilateral adnexectomy/laparoscopic lymphadenectomy) (47 cases) and matched by age, body mass index (BMI), histological type and International Federation of Gynecologists and Obstetricians (FIGO) staging. RESULTS: Mean operating times for patients undergoing robotic, laparoscopy, vaginal/laparoscopy or laparotomy approach were 181.9, 189.5, 202.7 and 162.7 min, respectively (p = 0.006); mean blood loss was 141.4, 300.8, 300.0 and 472.6 ml, respectively (p <0.001); mean number of nodes was 24.7, 27.1, 28.6, and 30.9, respectively (p = 0.008); mean length of hospital stay was 1.9, 3.4, 3.5 and 5.6 days, respectively (p < 0.001). There were no significant differences in intra- or postoperative complications among the four groups. The conversion rate was 2.9% for robotics and 10.8% for the laparoscopy group (0.001). There were no differences relative to recurrence rates among the four groups: 9%, 14%, 11% and 15% for robotics, laparoscopy, vaginal/laparoscopy, and laparotomy, respectively. CONCLUSION: Robotics, laparoscopy and vaginal/laparoscopy techniques are preferable to laparotomy for suitable patients with endometrial cancer. Robotics is preferable to laparoscopy due to a shorter hospital stay and lower conversion rate and preferable to vaginal/laparoscopy due to a reduced hospitalization.

Early oral versus "traditional" postoperative feeding in gynecologic oncology patients undergoing intestinal resection: a randomized controlled trial.

BACKGROUND: A randomized controlled trial was performed to assess the outcome of early oral postoperative feeding (EOF) compared with traditional oral feeding (TOF) in gynecologic oncology patients undergoing laparotomy with associated intestinal resection. METHODS: Patients aged 18-75 years, undergoing elective laparotomy, and with preoperative diagnosis of gynecologic malignancy, were eligible. Exclusion criteria included infectious conditions, intestinal obstruction, severe malnutrition, American Society of Anesthesiologists (ASA) score > or =4, and postoperative stay in the intensive care unit lasting >24 h. Patients allocated to EOF received liquid diet in the first postoperative day and then regular diet. Patients received traditional feeding scheme until resolution of postoperative ileus to start liquid diet. The primary end-point of the trial was length of hospital stay. RESULTS: Between January 1st, 2007 and March 15th, 2008, 40 patients were randomized to receive either EOF or TOF. Hospital stay in patients who received EOF (n = 18) was 6.9 days versus 9.1 days in the TOF group (n = 22) (P = 0.022). Requirements for analgesic and antiemetic drugs, intensity of pain, intestinal function recovery, mean levels of postoperative satisfaction, postoperative complications, and quality-of-life scores did not differ between the two groups. CONCLUSION: Early resumption of oral intake is feasible and safe in gynecologic oncology patients undergoing intestinal resection as part of a planned surgical procedure. Moreover, significant reduction in length of hospital stay was demonstrated.

Recommendations for a standardised educational program in robot assisted gynaecological surgery: Consensus from the Society of European Robotic Gynaecological Surgery (SERGS).

BACKGROUND: The Society of European Robotic Gynaecological Surgery (SERGS) aims at developing a European consensus on core components of a curriculum for training and assessment in robot assisted gynaecological surgery. METHODS: A Delphi process was initiated among a panel of 12 experts in robot assisted surgery invited through the SERGS. An online questionnaire survey was based on a literature search for standards in education in gynaecological robot assisted surgery. The survey was performed in three consecutive rounds to reach optimal consensus. The results of this survey were discussed by the panel and led to consensus recommendations on 39 issues, adhering to general principles of medical education. RESULTS: On review there appeared to be no accredited training programs in Europe, and few in the USA. Recommendations for requirements of training centres, educational tools and assessment of proficiency varied widely. Stepwise and structured training together with validated assessment based on competencies rather than on volume emerged as prerequisites for adequate and safe learning. An appropriate educational environment and tools for training were defined. Although certification should be competence based, the panel recommended additional volume based criteria for both accreditation of training centres and certification of individual surgeons. CONCLUSIONS: Consensus was reached on minimum criteria for training in robot assisted gynaecological surgery. To transfer results into clinical practice, experts recommended a curriculum and guidelines that have now been endorsed by SERGS to be used to establish training programmes for robot assisted surgery.

Feasibility of robotic radical hysterectomy after neoadjuvant chemotherapy in women with locally advanced cervical cancer.

OBJECTIVE: To evaluate the safety and feasibility of robotic radical hysterectomy (RRH) in women with locally advanced cervical cancer (LACC) after neoadjuvant chemotherapy (NACT). MATERIAL AND METHODS: A retrospective comparative longitudinal observational study was performed in 30 patients with LACC FIGO stage IB2-IIB who underwent RRH after NACT between February 2008 and September 2014. This group was compared with a cohort of 176 patients underwent RRH with cervical cancer FIGO stage IA2-IB1 in the same period of time. RESULTS: Patients' age, BMI, ASA score, comorbidity, and previous abdominal surgery, was similar between groups. FIGO stage significantly differed between groups; 29 (96.6%) of patients had FIGO stage IB2 in NACT group and 163 (92.6%) were FIGO stag IB1 in women without NACT, p < 0.001. Type of RRH was also significantly different between groups. Type C1 RRH was significantly more common in NACT group, p = 0.015. Mean (SD) tumor size was significantly bigger in NACT, 27.0 (13.7) mm versus 20.9 (9.0) mm in early stage versus LACC, respectively. p = 0.023. Mean (SD) surgical time was significantly longer in NACT group (307.8 (40.2) min versus 277.4 (45.4) min, p = 0.001). Estimated blood loss and length of the hospital stay were similar between groups. There were no significant differences in terms of intraoperative and postoperative complications. CONCLUSIONS: RRH after NACT in women with LACC seems to be safe and feasible. These results need to be confirmed in studies with a larger patients sample.

Neourethral meatus reconstruction for vulvectomies requiring resection of the distal part of the urethra.

OBJECTIVE: Vulvar cancer is a relatively rare tumour accounting for just 5% of all gynaecological malignancies. Radical excision can sometimes involve the distal one-third to one-half of the urethra leading to postoperative problems with micturition, asymmetries and psychosexual distress. Although this topic has been largely addressed, no specific method for distal urethra reconstruction has been described. The aim of this paper is to assess the safety and reliability of our reconstructive technique. METHODS: We conducted a retrospective study of 47 consecutive patients who underwent neourethral meatus reconstruction with vaginal mucosa flap. The surgical technique is described step-by-step. We reviewed the patients' demographics, operative characteristics, as well as immediate complications and long-term outcomes. RESULTS: Neo-meatal reconstruction was combined to direct vulvar closure in 2 patients, rhomboid flaps in 3 cases, 1 bilateral lotus flap and 36 V-Y fasciocutaneous flaps, 4 rectus abdominis and 1 gracilis flap. Wound dehiscence at the site of the neourethral reconstruction occurred in only 4.3%, partial necrosis of the vaginal mucosa flap in 2.1%. Totally post-operative early complication rate including the whole procedures was 29.8% with a re-operation rate of 4.3%. Long-term outcomes were evaluated in 68.1% patients, including 18.7% of urinary incontinence, no urethral stenosis and 25% of narrowed vaginal introitus. CONCLUSION: Neourethral meatus reconstruction using the vaginal mucosa flap is a simple, safe and reliable technique with a very low early complication rate. We suggest that this flap could be a good option to preserve and restore urinary function in case of distal urethral amputation.

Effects of a gonadotropin-releasing hormone analog on rabbit ovarian function.

This study was undertaken to elucidate the effects of a GnRH analog (GnRH-a) on rabbit ovulation, oocyte maturation, and steroidogenesis, and to verify whether treatment with a GnRH-a interferes with ovarian response to exogenous gonadotropin (hCG), both in vivo and in vitro. Three approaches were used. In the first, adult New Zealand White (NZW) rabbits were divided into two groups. Both received PMSG and hCG administered 72 h after PMSG. In the test group a GnRH-a, leuprolide acetate (LA; 20 microg/kg) was administered s.c. every 24 h. Treated rabbits showed a significant decrease in ovulatory efficiency (control = 88%; treated = 72%), and an increase in degeneration rate of preimplantation embryos (control = 30% vs. treated = 40%). For the second approach, in vitro perfusion experiments were designed to compare the direct effects of LA (10.000 ng/ml) and hCG (50 IU) on ovarian function and to verify whether the presence of a GnRH-a in the perfusate modifies the actions of hCG. LA reduced the ovulatory efficiency of hCG-treated ovaries perfused in vitro (hCG-treated = 87%; hCG-treated LA-perfused = 70%), reduced the potential for preimplantation development (morula stage: hCG-treated = 53%; hCG-treated LA-perfused = 31%; LA-perfused = 12%), and increased the degeneration rate of early embryos (21%, 48%, and 56% respectively). In the third approach, the direct effect of LA (Group I: control, Group II:1.000 ng/ml, and Group III:10.000 ng/ml) on the in vitro maturation of denuded rabbit oocytes was evaluated. LA induced meiotic maturation, but increased oocyte degeneration rate. The potential for preimplantation development was reduced (Morula stage: control = 16%, Group II = 8%, and Group III = 6%), and degeneration rate was increased (38%, 65%, 63% respectively). This study suggests that pharmacological doses of LA may exert a negative effect on oocyte function by direct action on the oocyte, indirectly via alteration of the intrafollicular environment and/or through interference with gonadotropin-induced biological effects within the ovary.

Estradiol regulation of the rabbit corpus luteum: in vivo and in vitro studies.

The objective of this study was to determine whether estradiol has a direct effect on progesterone secretion by the rabbit corpus luteum. Empty or estradiol-filled Silastic capsules were implanted sc into pseudopregnant rabbits (day 0). Ten days later (day 10), peripheral blood was obtained via the marginal ear vein, and Silastic capsules were removed. Twenty-four hours after capsule removal (day 11), blood samples were obtained and ovaries removed for in vitro perfusion. The artery and vein of each ovary were individually cannulated, and ovaries were perfused in vitro for 6 h. Mean progesterone secretion rates were determined from perfusate samples taken every 30 min. On day 10, serum progesterone concentrations were similar in control and estradiol-treated animals. On day 11, 24 h after withdrawal of Silastic capsules, serum progesterone concentration in the estradiol-treated rabbits decreased significantly compared to controls. The withdrawal of estradiol also significantly reduced the secretion of progesterone by in vitro perfused ovaries in estradiol-withdrawn rabbits compared to empty capsule controls. Addition of estradiol or 25-hydroxycholesterol (25-OH) to the perfusion medium significantly increased progesterone secretion by ovaries from estradiol-withdrawn rabbits but not to control values. In contrast, a combination of estradiol plus 25-OH restored progesterone secretion to control levels. Although estradiol together with 25-OH stimulated progesterone secretion 24 h after estradiol withdrawal, progesterone secretion in vitro was unaffected 48 h after capsule removal, whereas pregnenolone stimulated secretion 5-fold. These results demonstrate that estradiol has a direct and acute stimulatory effect on progesterone secretion by the rabbit corpus luteum.

Epidermal growth factor inhibits follicular response to human chorionic gonadotropin: possible role of cell to cell communication in the response to gonadotropin.

Epidermal growth factor (EGF) affects follicular steroidogenesis and expression of gonadotropin receptors. The effects of EGF on hCG-induced estradiol and progesterone secretion and ovulation were examined in the in vitro perfused rabbit ovary. We also examined the effects of EGF on hCG-induced progesterone secretion by isolated granulosa cells. In addition, distribution of hCG within the follicle was probed by immunohistochemical means 30 min after its administration to the in vitro perfused ovary. EGF significantly (P less than 0.05) reduced hCG-induced secretion of estradiol (control, 117 +/- 12 pg/min.follicle; 10 ng/ml EGF, 55 +/- 10) and progesterone (control, 18.2 +/- 1.2 ng/min.follicle; 10 ng/ml EGF, 11.9 +/- 0.8) by the perfused ovary. In contrast, EGF did not inhibit hCG-induced progesterone secretion by isolated granulosa cells. Ovulatory efficiency (number of ovulated ova per number of mature follicles x 100) when EGF was given 30 min before hCG was reduced dose-dependently from 58.2% with no EGF to 8.3% with 10 ng/ml EGF (P less than 0.001). Ovulation was not inhibited by EGF when it was given 30 min after hCG. Distribution of hCG in the preovulatory follicle was confined to the basement membrane, thecal cell layer, and a small fraction of the outer granulosa cell layer. These observations suggest that gonadotropin stimulates the follicle through the release of a secondary signal(s) from ligand-bound granulosa cells near the follicle wall to unexposed cells of the inner avascular area. EGF may inhibit the follicular response to hCG by attenuation of this cell to cell communication.

Requirement of oestrogens for the sensitivity of prolactin cells to vasoactive intestinal peptide in rats and man.

Vasoactive intestinal peptide (VIP) is a prolactin-releasing hormone which is involved in the multifactorial modulation of prolactin secretion in mammals. Intravenous injection of VIP (1 microgram/kg) to fertile women increased plasma prolactin levels and heart rate and reduced diastolic pressure. The same treatment to menopausal women caused similar cardiovascular effects but did not modify plasma prolactin levels. In contrast, TRH (200 micrograms, i.v.) induced a significant increase in plasma prolactin levels in both fertile and menopausal women. The relevance of oestrogens in affecting VIP-stimulated prolactin secretion was evaluated in vitro by measuring prolactin release from pituitary cells of control and ovariectomized rats. The sensitivity of rat mammotrophs to VIP, but not to TRH, was completely suppressed 3 or 4 weeks after ovariectomy. Furthermore, implantation of rats with a silastic capsule containing oestradiol-17 beta during ovariectomy, preserved the cell responsiveness to VIP. The prolactin-releasing property of VIP was also restored when pituitary cells from ovariectomized rats were cultured for 3 days in the presence of 10 nmol oestradiol-17 beta/l before being used for prolactin release experiments. The present study shows that the ability of prolactin-secreting cells to respond to the stimulatory action of VIP requires high levels of circulating oestrogens, both in man and rats.

Effects of acetylsalicylic acid (aspirin) and naproxen sodium (naproxen) on ovulation, prostaglandin, and progesterone production in the rabbit.

OBJECTIVE: To determine the effects of acetylsalicylic acid (aspirin) and naproxen sodium (naproxen) on ovulation, ovarian prostaglandins (PG), and P production in the rabbit via in vivo and in vitro studies. DESIGN: Aspirin and naproxen were administered i.v. 6.5 and 7 hours, respectively, after hCG administration to New Zealand White adult female rabbits. Laparotomy was performed 24 hours after hCG administration. For in vitro experiments, control animals underwent laparotomy 6.5 (aspirin) and 7 hours (naproxen) after hCG administration. The treated animal received aspirin and naproxen; laparotomy was performed 1 hour later. One ovary was perfused for 6 hours with aspirin or naproxen whereas the contralateral ovary served as a control and was perfused with control medium (M199; GIBCO, Grand Island, New York). Perfusate samples were collected at 1-hour intervals for PG and P determination. SETTING: A conventional laboratory setting. INTERVENTIONS: In vivo experiments used i.v. administration of 100 mg/kg aspirin and 10 and 50 mg/kg naproxen. In vitro perfusion was also carried out with 100 micrograms/mL aspirin and 10 and 50 micrograms/mL naproxen added to the perfusate. MAIN OUTCOME MEASURES: Ovulatory efficiency (no. of ovulations/no mature follicles) and ovarian vein PG and P concentration were determined. RESULTS: Ovulatory efficiency was 88% for control, 41% for in vivo aspirin-treated, and 40% (10 mg/kg) and 0% (50 mg/kg) for naproxen-treated rabbits. Aspirin and naproxen were associated with decreased ovulatory efficiency when administered in vitro to both in vivo control and in vivo treated ovaries (control-medium = 70%; control-aspirin = 14%; aspirin-medium = 34%; aspirin-aspirin = 0%; control-naproxen = 25%; naproxen-medium = 38%; naproxen = 0% with 10 microgram/mL, and control-naproxen = 13%; naproxen-medium = 0%; naproxen = 0% with 50 micrograms/mL). Prostaglandin F2 alpha was undetectable in the perfusate of those ovaries perfused of those ovaries perfused either with aspirin or naproxen. Ovarian venous concentration of P in the perfusate was similar in all groups. CONCLUSIONS: Aspirin and naproxen significantly reduced ovulatory efficiency and PG production both in vivo and in vitro in hCG-treated rabbits. A critical period of 6.5 and 7 hours after hCG administration was established.

Time-related effects of gonadotropin-releasing hormone analog treatment in experimentally induced endometriosis in the rat.

The purpose of our study was to characterize the time-dependent effect of gonadotropin-releasing hormone analog (GnRH-a) therapy on endometriosis explant using the rat model. Endometriosis was induced in 60 mature female rats. One group of treated animals as well as controls were killed at 2, 4, 6 and 8 weeks of treatment at which time the explant was evaluated. Explant volume was significantly reduced in all treatment groups, an effect that was more significant in animals treated for greater than or equal to 4 weeks compared with those treated for only 2 weeks. We conclude that GnRH-a treatment caused gradual regression of endometrial explant that was effectively complete by 4 weeks of treatment. We further conclude that this experimental model may be useful in the evaluation of other modes of endometriosis therapy.

Clinical review of 63 cases of sex cord stromal tumors.

PURPOSE OF INVESTIGATION: A retrospective analysis of 63 cases of sex cord stromal tumors treated in a 22-year period to evaluate the prognostic impact of different clinical parameters. METHODS: Sixty-three cases of sex cord stromal tumors were studied. These neoplasms are characteristically detected at an early stage and may recur locally years after the initial diagnosis. The most frequent cell type was adult granulosa cell tumor (75%); a total of 37 patients (62%) had Stage IA lesions. RESULTS: The cornerstone of treatment is surgery. Conservative surgical treatment was performed in 11 out of 47 cases (23%) of early stage tumor and in one of 13 patients affected by advanced neoplasm. Five of these 12 patients became pregnant after the treatment. Endometrial hyperplasia and uterine adenocarcinoma were diagnosed in 26.5% and 8.8% of the cases, respectively. Twenty-one patients (35%) received adjuvant therapy: 20 chemotherapy and one chemo-radiation treatment. Eight patients (13%) either progressed or recurred. All the recurrent patients but one had been treated with adjuvant chemotherapy (VAC and/or PVB). Overall survival by stage was 88.2% for Stage I and 30% for Stage III-IV. CONCLUSION: Tumor stage is the most important clinical parameter of prognostic relevance. Tumor size and laterality significantly affected prognosis in terms of overall survival; survival rate did not seem to be affected either by the age of the patients or by the modality of surgical treatment.