Adjuvant chemotherapy does not improve disease-free survival in FIGO stage IC ovarian granulosa cell tumors: The MITO-9 study.

OBJECTIVE: Evidence-based management of granulosa cell tumors of the ovary (GCT) has been not yet standardized: surgery, including fertility-sparing procedures for young women, has been traditionally the standard treatment; on the other hand, chemotherapy has been used for treatment of advanced and/or recurrent disease. However, very limited experience, has been selectively focused on the role of adjuvant chemotherapy in stage IC patients. The objective of this retrospective study was to assess the efficacy of first line postoperative chemotherapy in patients with stage IC treated at the Italian Centers involved in the MITO (Multicenter Italian Trials in Ovarian cancer) Group. PATIENTS AND METHODS: A retrospective multi-institutional review of patients with GCT of the ovary at FIGO stage IC treated or referred to MITO centers was conducted. Surgical outcome, pathological findings and follow-up data were analysed. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors factors for disease free survival. RESULTS: A total of 40 patients with primary GCT of the ovary at FIGO stage IC were identified. The median follow-up period was 96months (range 7-300). At multivariate analysis, surgical treatment outside MITO centers and incomplete surgical staging were independent poor prognostic indicators for recurrence; adjuvant chemotherapy did not retain significant predictive value for recurrence. CONCLUSIONS: This study raises the question about the value of adjuvant chemotherapy in stage IC GCT: a comprehensive evaluation of a larger series is urgently needed in order to characterize stage IC substages who can be spared treatment toxicity.

Radical hysterectomy after chemoradiation in FIGO stage III cervical cancer patients versus chemoradiation and brachytherapy: Complications and 3-years survival.

BACKGROUND: To compare patterns and rates of early and late complications, and survival outcome in FIGO stage III cervical cancer patients underwent to radical hysterectomy after chemo-radiation (CT-RT) vs. chemo-radiation alone. METHODS: Between May 1996 and April 2013 150 FIGO stage III cervical cancer patients were treated. We divide patients according to type of treatment: 77 were submitted to standard treatment (Group A), and 73 to completion hysterectomy after chemo-radiation (Group B). RESULTS: The baseline characteristics of the 2 groups were superimposable. We observed lower intra-operative and treatment-related early urinary and gastro-intestinal complications in Group B with respect to Group A (p < 0.001). Vascular complications were registered only in Group B (p < 0.001). We found a significantly higher rate of local recurrences in the Group A than in the Group B (p < 0.002). We registered 29 deaths in the Group A and 22 in the Group B (p = 0.021). The 3-years disease-free survival rate in the Group A and in the Group B was 62.9% and 68.3%, respectively (p = 0.686), and the 3-years overall survival rate in the Group A and in the Group B was 63.2% and 67.7%, respectively (p = 0.675). CONCLUSIONS: This study confirms that radical hysterectomy after CT-RT is an effective therapeutic approach for advanced cervical cancer. Further prospective and randomized studies should be performed in order to solve the question about the standard approach, and how the different pattern of complication could impact on the quality of life.

Long-Term Survival for Platinum-Sensitive Recurrent Ovarian Cancer Patients Treated with Secondary Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

BACKGROUND: To analyze the 5- and 7-year survival outcomes for women with platinum-sensitive recurrent epithelial ovarian cancer (REOC) who underwent secondary cytoreductive surgery (SCS) plus platinum-based hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: From the electronic databases of the Department of Obstetrics and Gynecology at the Catholic University of the Sacred Heart of Rome and of the S. Orsola Hospital, University of Bologna, a consecutive series of REOC patients were selected using the following inclusion criteria: primary platinum-free interval (PFI-1) of 6 months or longer, completeness of secondary cytoreduction score (CC) of 1 or lower, minimum follow-up period of 48 months, Eastern Cooperative Group (ECOG) performance status at recurrence of 1 or less, and platinum-based HIPEC. Progression-free survival (PFS) and post-relapse survival (PRS) were calculated as the time between SCS + HIPEC and secondary recurrence or death, respectively. RESULTS: The final study population included 70 women with platinum-sensitive REOC. The median follow-up time was 73 months (range 48-128 months), and the median PFI-1 was 19 months (range 6-100 months). At the time of recurrence, the median peritoneal cancer index was 7 (range 1-21), and a CC score of 0 was achieved for 62 patients (88.6 %). As the HIPEC drug, we used oxaliplatin in 17 cases (38.6 %) and cisplatin in 43 cases (61.4 %). No postoperative deaths were observed, and the complication rate for grades 3 and 4 disease was 8.6 %. The median PFS duration was 27 months (range 5-104 months), and the 5- and 7-year PRS rates were respectively 52.8 and 44.7 %, (median PRS 63 months). CONCLUSIONS: The current study demonstrated favorable 5- and 7-year PRS rates for platinum-sensitive REOC patients undergoing SCS + HIPEC, which encourages the inclusion of patients in randomized clinical trials for definitive conclusions to be drawn.

Occurrence of septic shock in a patient submitted to emergency cerclage following a negative amniocentesis: report of a case.

BACKGROUND: Second trimester emergency cerclage is an option for pregnant women presenting bulging fetal membranes. Despite a significant prolongation of pregnancy might be achieved, serious fetal and maternal events have been reported. Exclusion of infections through preprocedure amniocentesis has been proposed. METHODS: A 37-year-old woman, gravida 4 para 1, was admitted at 21 weeks of gestation to our University Hospital due to bulging fetal membranes. An amniocentesis was performed in order to exclude an actual amniotic infection. Our Microbiology Department found a negative amniotic culture for bacteria and Mycoplasma and a normal glucose and interleukin-6 level, so a cervical cerclage was performed. The patient was discharged home on oral erythromycin. RESULTS: After 48 h, the patient complained of hyperpyrexia, shivers and reduced fetal movements. Ultrasound at admission showed absent cardiac activity and after cerclage removal a non-viable fetus was delivered vaginally. Piperacillin and tazobactam were started, but the clinical course of the patient deteriorated and she developed a cold septic shock and was submitted to hysterectomy and transferred to the ICU of our hospital. CONCLUSION: This report heralds that even after negative amniocentesis, a life-threatening infection may not be excluded in women candidate for emergency cerclage due to bulging fetal membranes.

Laparoscopic versus laparotomic approach to endometrial cancer.

OBJECTIVE: The aim of our study was to compare the feasibility, morbidity, long-term safety, disease-free survival, and overall survival of the laparoscopic (LPS) approach to early-stage endometrial cancer (EC) compared to the traditional laparotomic approach. METHODS: We reviewed retrospective data of patients who underwent primary surgery from 1997 to 2009. We recorded clinical parameters, surgical stage, histological type, operative and peri-operative complications, time to resumption of normal functions, conversion to laparotomy, overall survival, and disease-free survival. RESULTS: LPS, did not increase operative risk and peri-operative complications even in obese and older women. The number of pelvic lymph and aortic nodes removed was similar for the two groups. One hundred and eight patients had a follow-up of 60 months. The two groups were similar for disease-free survival and overall survival. CONCLUSIONS: Laparoscopic approach to EC provides a reduction in postoperative complications and hospital stay compared to the laparotomic approach.

[Laparoscopic surgery for endometrial cancer in overweight women]. / Utilizzo della laparoscopia nel trattamento chirurgico delle sovrappese affette da cancro dell' endometrio.

AIM: The aim of this study was to investigate the feasibility and safety of laparoscopic staging of overweight women with endometrial cancer and to compare the surgical outcomes among these patients with those managed by laparotomy. METHODS: This was a retrospective analysis (Canadian Task-force Classification II-3). We reviewed operative and hospital records of 70 patients with a body mass index >25 kg/m2 who underwent surgical treatment for endometrial cancer between 2001 and 2008. Thirty-five patients treated laparoscopically were compared to an equivalent group of patients treated by laparotomy. Operative and postoperative variables were afterwards assessed. RESULTS: Women in laparoscopic group had a significantly lower blood loss (median, 25th-75th percentiles: 1.2, 0.8-2.0 in laparoscopic versus 1.8, 1.0-2.8 in laparotomic group, P<0.05). No differences between both group in terms of operative time (median, 25th-75th percentiles: 165 min, 130-183 in laparoscopic versus 135 min, 110-170 in laparotomic; P>0.05) and mean number of pelvic and para-aortic lymph nodes removed (22 ± 8.4 versus 24 ± 6.2 and 9.2 ± 2.5 versus 9.3 ± 5 respectively; P>0.05). Length of urethral catheter and hospital stay were statistically higher in laparotomic group (two days versus three days; four days versus seven days respectively; P<0.05). CONCLUSION: Laparoscopic surgery in overweight women with endometrial cancer had equivalent surgical staging than women operated by laparotomy. With regard to postsurgical variables, overweight women who underwent laparoscopic surgery had better results than those treated by laparotomy.

[18F]FDG-PET/CT monitoring early identifies advanced ovarian cancer patients who will benefit from prolonged neo-adjuvant chemotherapy.

AIM: The most accepted standard duration of neoadjuvant chemotherapy (na-CHT) before debulking surgery for advanced ovarian cancer (AOC) is 3 courses. However a percentage of patients could benefit from additional courses. [(18)F]FDG-PET/CT monitoring during na-CHT could predict early pathological response and allow the delivery of an optimal na-CHT duration. METHODS: Consecutive patients with AOC unsuitable for optimal up front surgery and fit for na-CHT were monitored by FDG-PET/CT at baseline and after 3 and 6 courses of carboplatin-paclitaxel CHT. At the end of na-CHT patients were re-evaluated to undergo definitive optimal surgery (i.e. without post-surgical residual disease). Percentage changes in maximal standardized uptake value (∆-SUVmax) were compared with the pathological response. Only patients with pathological complete response (pCR) or minimal residual disease (pMRD) were considered as pathological responders (pR), while all the other cases were considered non-responders (NR). RESULTS: Baseline FDG-PET/CT was abnormal in all 42 enrolled patients (median SUVmax 11, range 3-20). After 3 and 6 courses median SUVmax decreased to 3 (<2-21) and <2, i.e. value equal to normal surrounding tissues uptake (<2-17), respectively. After 3 courses, 17 (40%) patients presented ∆-SUVmax=100%, (i.e. SUVmax <2): 15 of them (88%) subsequently resulted pR and achieved no postsurgical residual disease at the end of na-CHT, while 2 (12%) were NR with postsurgical residual tumor ≤ 1cm. Out of 25 patients with ∆-SUVmax <100% after 3 courses, 6 (24%) were pR and 19 (76%) NR at the end of na-CHT. CONCLUSION: Patients with AOC who present normalization of SUVmax after 3 courses of na-CT have a high likelihood of benefiting from 3 additional courses in order to obtain pCR or pMDR and receiving optimal surgery.

Behaviour of ovarian tumors of low malignant potential treated with conservative surgery.

OBJECTIVE: Fertility-sparing surgery has been proposed for the treatment of borderline ovarian tumors. The aim of this study was to evaluate the outcome of patients submitted to cystectomy (CYS) compared with patients treated by unilateral salpingo-oophorectomy (USO) or bilateral salpingo-oophorectomy with/without total hysterectomy (radical surgery, RS). METHODS: We reviewed retrospectively the data of patients treated in 3 institutions for borderline ovarian tumors. One hundred and sixty-eight patients underwent laparoscopic or laparotomic surgical treatment from 1985 to 2006. Tumor recurrence rate, disease-free survival and site of recurrences were evaluated. Specific prognostic factors, such as stage, histology, micropapillary subtype, exophytic tumor growth, intraoperative spillage, endosalpingiosis, staging procedures, and route of surgery were analysed. RESULTS: Thirty-five patients underwent cystectomy, 50 unilateral salpingo-oopohorectomy, and 83 radical surgery. Twelve patients in the CYS group (34.3%), 10 in the USO group (20.0%), and 5 (6.0%) in RS group relapsed. Five-year progression-free survival (PFS) was 59.6%, 78.4%, and 93.5% in CYS, USO and RS groups, respectively. None of the relapsed patients died of disease. CONCLUSIONS: Cystectomy is an effective surgical strategy for patients with borderline ovarian tumor. The higher risk of local relapses is not associated with a reduction in the overall survival. The procedure should be offered to young patients with bilateral tumors and to very young ones, considering the higher risk of local relapse.

Preoperative local staging of endometrial cancer: transvaginal sonography vs. magnetic resonance imaging.

OBJECTIVES: To compare the accuracy of transvaginal sonography (TVS) and magnetic resonance imaging (MRI) in the preoperative staging of endometrial carcinoma. METHODS: This was a prospective study in which 74 women consecutively diagnosed with endometrial carcinoma were examined using TVS by physicians trained in gynecological sonography and MRI by radiologists with a special interest in gynecology. All patients underwent surgical-pathological staging after removal of the uterus, adnexa and pelvic lymph nodes. Sensitivity, specificity, and positive and negative predictive values were calculated for each imaging modality with regard to detection of neoplastic invasion of the outer half of the myometrium and cervical involvement. RESULTS: TVS and MRI performed equally well in the preoperative staging of endometrial cancer, with no statistically significant differences between the two techniques. The sensitivity, specificity, positive and negative predictive values, and overall diagnostic accuracy for TVS in the evaluation of myometrial infiltration were 84%, 83%, 79%, 88% and 84%, respectively. Respective values for MRI were 84%, 81%, 77%, 87% and 82%. The corresponding statistics for detection of cervical involvement were 93%, 92%, 72%, 98% and 92% for TVS; and 79%, 87%, 58%, 95% and 85% for MRI. CONCLUSIONS: When carried out by expert practitioners, TVS shows good accuracy in the local staging of endometrial carcinoma. Because of its high costs, MRI should be offered only to those in whom TVS produces images of poor quality.

Paraovarian/paratubal cysts: comparison of transvaginal sonographic and pathological findings to establish diagnostic criteria.

OBJECTIVES: To describe the sonographic features of paraovarian cysts and to compare these features with pathological findings in order to define the best treatment options (surgical vs. conservative). METHODS: Fifty patients (mean age 48 (range, 14-68) years), each with a surgically proven paraovarian cyst, were retrospectively recruited. Preoperative transvaginal ultrasonographic B-mode and power Doppler observations were re-evaluated and histological reports were analyzed. RESULTS: All cysts were correctly diagnosed as paraovarian at preoperative transvaginal sonography (TVS). Paraovarian cysts appeared as unilocular ('simple') cysts in 33 (66%) cases and multilocular in two (4%). In 15 patients (30%) the cyst showed a variable number of papillary projections growing from the cyst wall (unilocular-solid cysts). Power Doppler examination of the papillae showed the presence of blood vessels in four of these patients (27%). Histological analysis of the masses containing papillary projections diagnosed eight cystadenofibromas, five cystadenomas and two serous papillary borderline tumors, while analysis of paraovarian cysts without papillations revealed benign, serous cysts of paramesonephric or mesothelial origin. CONCLUSIONS: Paraovarian cysts can show a wide range of sonographic features. Their risk of malignancy is low if no papillary projections are detected at transvaginal sonography, but when mural proliferations are present a borderline tumor can be found at pathological examination.

Uterine vascularization and pregnancy outcome in patients undergoing intracytoplasmatic sperm injection: the role of nitric oxide.

PURPOSE: To evaluate whether, after pituitary desensitisation, the impedance to flow in the uterine vessels may be an indicator of an ICSI programme outcome, and to test the relationship between intrafollicular nitric oxide and oocyte/embryo quality. METHODS: Thirty-eight women, on the basis of impedance to flow at the level of uterine artery, evaluated on the first day of COH, were divided in patients with normal (Pulsatility Index--PI, 2.5; Group II, n=27) PI values. The patients were submitted to hormonal, ultrasonographic and Doppler evaluations. Plasma and follicular fluid concentrations of nitrites/nitrate (NO(2) (-)/NO(3) (-)) were assayed. RESULTS: In the Group I, the impedance to flow remained lower than in Group II and was associated to good quality embryos and to a higher pregnancy rate. Follicular fluid NO(2) (-)/NO(3) (-) levels were inversely correlated with the embryo quality. The uterine artery PI and the pregnancy rate were inversely correlated. The PIs analysed on the day 1 of stimulation, were positively correlated with those registered on day 8 and on the day of ovum pick-up. CONCLUSIONS: A Doppler analysis done on day 1 of controlled ovarian hyperstimulation may be an useful indicator of ART outcome.

Female precocious puberty, obesity and polycystic-like ovaries.

OBJECTIVE: To evaluate the characteristics of obese girls with gonadotropin releasing hormone-dependent precocious puberty with and without polycystic-like ovaries. METHODS: Forty-seven overweight (> 75(th) centile of the Italian reference data) girls with a diagnosis of isosexual precocious puberty underwent auxological analysis, hormonal assay and utero-ovarian sonographic and Doppler evaluation. On the basis of sonography the patients were subdivided into two groups, girls presenting normal ovaries (Group I; n = 31) and those with polycystic-like ovaries (Group II; n = 16). RESULTS: The mean body weight was significantly higher (P = 0.003) in Group II than it was in Group I. In addition, the patients with polycystic-like ovaries fell within our definition of superobese (> or = 97(th) centile of the Italian reference data) in 44% of cases. The uterine and ovarian volumes were significantly greater in Group II compared with Group I patients. The Doppler evaluation showed intraparenchymal ovarian vascularization and low downstream impedance to flow in all patients in Group II. CONCLUSIONS: Girls with precocious puberty and polycystic ovaries, compared with those without polycystic ovaries, have a higher incidence of body weight exceeding the 85(th) centile of the Italian reference data (obesity).

Transdermal HRT and Doppler findings in normotensive and hypertensive postmenopausal patients.

OBJECTIVE: To evaluate the effects of transdermal hormone replacement therapy (HRT) on plasma viscosity, serum levels of thromboxane B2 (TXB2) and vascular impedance in the uterine, bladder wall, internal carotid and ophthalmic arteries in normotensive and hypertensive postmenopausal patients. METHODS: Thirty postmenopausal patients underwent continuous estradiol transdermal supplementation at a dose of 50 microg/day and 12-day courses of medroxyprogesterone acetate 10 mg/day every 2 months. The women were divided into two groups according to their blood pressure: normotensive women (Group 1, n=14) and hypertensive subjects (Group 2, n=16). Before starting HRT and after 6 months of therapy, the patients underwent: transvaginal ultrasonographic examination of the pelvic organs; Doppler examination of the blood flow velocities in the uterine, bladder wall, internal carotid and ophthalmic arteries; and analysis of plasma viscosity and plasma TXB2. RESULTS: After 6 months of HRT plasma viscosity had decreased in both groups (mean reduction in Group 1, (14+/-1)%, P=0.005; mean reduction in Group 2, (10+/-1)%, P=0.005) as had the TXB2 levels (mean reduction in Group 1, (93+/-2)%, P<0.001; mean reduction in Group 2, (92+/-3)%, P<0.001). The mean percentage reduction in plasma viscosity was smaller in hypertensive women than in normotensive women (P<0.05). There was also a significant reduction in vascular impedance in the uterine artery (mean reduction in Group 1, (16+/-1)%, P=0.005; mean reduction in Group 2, (19+/-1)%, P=0.005), the bladder wall arteries (mean reduction in Group 1, (23+/-2)%, P=0.005; mean reduction in Group 2, (18+/-1)%, P=0.005), the internal carotid artery (mean reduction in Group 1, (25+/-1)%, P=0.005; mean reduction in Group 2, (26+/-1)%, P=0.005) and the ophthalmic artery (mean reduction in Group 1, (24+/-2)%, P=0.005; mean reduction in Group 2, (16+/-1)%, P=0.005). The percentage reduction in vascular impedance did not differ significantly between the two groups. CONCLUSIONS: Our results show that transdermal HRT is effective in reducing plasma viscosity, TXB2 levels and vascular impedance in the peripheral and central vessels both in normotensive and hypertensive postmenopausal patients.

Transvaginal sonographic features of peritoneal carcinomatosis.

OBJECTIVES: Peritoneal carcinomatosis involves the dissemination of intra-abdominal tumor tissue often associated with gynecological malignancies. The objective of this study was to describe the transvaginal sonographic appearance of this condition. METHODS: The data of 60 patients with surgically and histologically proven peritoneal carcinomatosis were analyzed. Transvaginal sonograms performed within 7 days of admission to the operating theater were re-evaluated in order to identify the sonographic features associated with peritoneal carcinomatosis. RESULTS: Carcinomatosis was revealed in 53/60 cases (88%) by the presence of hypoechoic nodules attached to the peritoneum and visible on transvaginal sonography (TVS). The pouch of Douglas was the site most frequently involved. Power Doppler sonography showed the presence of blood vessels in 48 (91%) of these metastases. Ascites was found in 50 (83%) women. An adnexal mass suggestive of being the primary tumor was present in only 41 women (68%). CONCLUSIONS: Peritoneal carcinomatosis has typical features on TVS and, in the vast majority of cases, its genital origin can be correctly hypothesized. Power Doppler sonography strengthens the diagnosis by showing vascularity of the peritoneal implants. In a patient with a known pelvic malignancy or whenever peritoneal carcinomatosis is suspected, TVS can give useful information in order to better assess the presence and extension of metastatic nodules within the abdominal cavity.

Fitz-Hugh-Curtis-syndrome mimicking acute cholecystitis: value of new ultrasound findings in the differential diagnosis.

Fitz-Hugh-Curtis is a rare syndrome characterised by perihepatitis following pelvic inflammatory disease. We report the case of a patient with a right ovarian teratoma, abnormal liver tests and pain in the right abdomen and shoulder, initially attributed to an acalculous cholecystitis. Before gynaecological surgery, a repeat ultrasound scan found several small avascular peritoneal masses at the upper dome of the liver, not reported in the initial examination. This prompted laparoscopic exploration of the subdiaphragmatic space, and the final diagnosis of Fitz-Hugh-Curtis-syndrome was made. Such ultrasound finding appears to be a new diagnostic feature of this syndrome.

(18)F-FDG PET/CT in the evaluation of recurrent ovarian cancer: a prospective study on forty-one patients.

AIM: Many patients with ovarian cancer are at high risk of recurrence especially in the 2 years following first-line therapy. CA125 serum levels measurement associated to computed tomography (CT), ultrasound (US) and magnetic resonance imaging (MRI) are currently used during follow-up to detect recurrent disease. Unfortunately, in a relevant percentage of cases all of these traditional imaging techniques provide a significant number of doubtful/equivocal results or turn out negative even in presence of elevated Ca125 levels. Aim of our study was to evaluate sensitivity, specificity and accuracy of (18)F-FDG PET/CT in a group of patients with suspicion of ovarian cancer recurrence. METHODS: We prospectively evaluated 41 patients with a mean age of 59.4 years who had been previously treated for ovarian cancer with surgery and radio-chemotherapy or radio-chemotherapy alone. Following the performance of traditional radiologic imaging (US, CT, MRI) and Ca125 measurement, all patients underwent additional (18)F-FDG PET/CT. PET/CT results were compared with histologic findings or clinical, laboratory and repeated traditional imaging techniques during subsequent follow-up data. RESULTS: Of 41 patients 32 had a positive PET-CT (30 true positive, two false positive) whereas nine a negative PET/CT (five true negative, four false negative). Overall, in our experience (18)F-FDG PET/CT provided a good sensitivity (88.2%), specificity (71.4%) and accuracy (85.4%), superior to that reported in literature for traditional radiologic imaging. CONCLUSIONS: It can be concluded that (18)F-FDG PET/CT appears to be a useful and accurate tool in disclosing early recurrent ovarian cancer.