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The choice of the technique to enter the peritoneal cavity, during a laparoscopy, depends on a lot of variables which hinder a standardized method and, actually, it appears impossible to show, with certainty, the best method to choose for the first abdominal access in gynecological laparoscopy. The preference for one or another technique depends on the operator experience, school and speciality of the surgeon, laparoscopical upgrading and the work environment; many surgical techniques are not yet used due the limits and fears of some surgeons to change the preference in first access approaching and for the lack of operating versatility by a method or another one. A review of the scientific literature, underlines that the major problems during the first laparoscopical abdominal access are two, vascular and intestinal and their percentage is variable. In this paper we describe the large range of methods for open and closed laparoscopy and for direct access, that permit to perform a first abdominal laparoscopical access, and their major possible problems.

OBJECTIVE: The aim of the present investigation was to evaluate the cervical conizations performed in the last 20 years in a single institution, with a particular interest in analyzing the trend of the length of cone excisions.PATIENTS AND METHODS: A retrospective cohort study of women who underwent a CO2-laser cervical conization between January 1996 and December 2015. Cytological abnormalities on referral pap smear, colposcopic findings and pertinent clinical and socio-demographic characteristics of each woman were collected. In particular, the length of cone specimen was evaluated, taking into account all the factors potentially influencing the length of excision.RESULTS: A total of 1270 women who underwent cervical conization from January 1996 to December 2015 were included in the analysis. A mean cone length of 15.1 ± 5.7 mm was reported, and we observed a significant decrease in the length of cone excisions over the whole study period. Age (rpartial = 0.1543, p < 0.0001), see & treat procedure (rpartial = -0.1945, p < 0.0001) and grade II colposcopic findings (rpartial = 0.1540, p < 0.0001) were significantly associated with the length of cone excision on multivariate analysis.CONCLUSIONS: In the last 20 years, a significant decrease in the length of cone excision was observed. In our opinion, this can be due to the acquired awareness by the gynecologists of the potential disadvantages of wide cone excision in term of adverse obstetric outcomes in future pregnancies.

Intestinal obstruction is a frequent cause of death in patients suffering from gynecological cancer, who have undergone multiple treatment in the form of surgery and/or chemotherapy and/or radiotherapy. The usual form of rescue treatment consists in the use of a nasogastric tube to administer support and analgesic treatment. Surgical gastrostomy is not a viable proposition in these extremely weak patients with large masses compressing and displacing the stomach. Percutaneous endoscopic gastrostomy (PEG), a technique first introduced for nutritional purposes, can be beneficially used to achieve decompression in these patients.PEG was performed in a total of 67 patients who had already undergone multiple treatment for abdominal-pelvic neoplasia with upper gastrointestinal obstruction, who could no longer be operated and who had a life expectancy of less than sixty days. In three cases positioning was not possible owing to the lack of transillumination of the gastric and abdominal wall. 54/64 patients had previously undergone at least two operations.Esophagogastric lesions were found in 29% of patients, some of which were attributed to the nasogastric tube. Symptomatic wellbeing was obtained in 76.5% a few days after PEG. PEG remained in situ from 4 to 472 days. Slight peristomal infection was observed in 9% of cases. In seven cases it was necessary to add octreotide owing to the reappearance of symptoms.PEG is relatively easy to use and allows obstructive symptoms to be resolved in the majority of patients. Special medical skills are not required and the patient may be easily managed at home together with support therapy and pain management. Once PEG has been performed, it is possible to take fluids and semi-liquid foods, offering the patient a chance to taste flavours which have often been forgotten. PEG enables neoadjuvant chemotherapy to be performed in patients with previously untreated intestinal obstruction.

Objective Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. Methods This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. Results Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p, Synopsis The prevalence of patients with early-stage endometrial cancer (EC) has been lower during coronavirus disease 2019 (COVID-19) pandemic than before its onset. Further evidence is needed to assess the impact of COVID-19 pandemic on survival outcomes of EC patients.

Supplemental Digital Content is available in the text.Objectives:The objectives of this study were to evaluate whether the international recommendations on the management of uterine papillary serous carcinoma arising in a polyp are uniformly followed in Italian Oncologic Centers and whether the strategy adopted is effective.Materials and Methods:Patients with uterine papillary serous carcinoma arising in a polyp and who had undergone a hysterectomy were identified in the 2003-2013 database of 7 Italian Gynecologic Oncology Centers. Clinical and pathologic characteristics and outcomes were compared between staging procedure types. Survival curves of the women were plotted using the Kaplan-Meier method and analyzed using Cox regression hazard model and the log-rank test. Associations between clinical parameters and the incidence of recurrence were assessed by generalized linear models and the Fisher test.Results:A total of 75 patients met the inclusion criteria. Recurrence-free survival was affected positively by type of surgical staging and negatively by preoperative diagnosis of hypertension. The association between surgical staging and recurrence-free survival resulted significant at univariate survival analysis (P=0.048 and 0.045) and maintained a trend of significance (P=0.070) in multivariate analysis, whereas hypertension was demonstrated to be the principal influencing factor.Conclusions:The international recommendations on the management of uterine papillary serous carcinoma are not uniformly followed in daily practice, although the extension of the surgery seems to be associated with lower recurrence rates also when uterine papillary serous carcinoma is confined to a polyp or endometrial surface.

Objective: About 30% of Adult type granulosa cell tumors of the ovary (AGCTs) are diagnosed in fertile age. In stage I, conservative surgery (fertility-sparing surgery, FSS), either unilateral salpingo-oophorectomy (USO) or cystectomy are possible options. The aim of this study is to compare oncological outcomes of FSS and radical surgery (RS) in apparently stage I AGCTs treated within the MITO group (Multicenter Italian Trials in Ovarian cancer). Methods: Survival curves were calculated using the Kaplan-Meier method and compared with log-rank test. The role of clinicopathological variables as prognostic factors for survival was assessed using Cox's regression. Results: Two-hundred and twenty-nine patients were included; 32.6% received FSS, 67.4% RS. In the FSS group, 62.8% underwent USO, 16.7% cystectomy, 20.5% cystectomy followed by USO. After a median follow up of 84 months, median DFS was significantly worse in the FSS-group (10 yr DFS 50% vs 74%, in FSS and RS group, p = 0.006). No significant difference was detected between RS and USO (10 yr DFS 75% vs 70%, p = 0.5).Cystectomy-group showed a significantly worse DFS compared to USO (10 yr DFS 16% vs 70%, p < 0.001). Patients receiving cystectomy and subsequent USO showed a better prognosis, even though significantly worse compared to USO (10 yr DFS 41% vs 70%, p = 0.05). Between FSS and RS, no difference in OS was detected. At multivariate analysis, FIGO stage IC and cystectomy retained significant predictive value for worse survival. Conclusions: This study supports the oncological safety of FSS in stage I AGCTs, provided that cystectomy is avoided; USO should be the preferred approach.

Objective Surgery represents the mainstay of treatment of stage I adult type granulosa cell tumors of the ovary (AGCTs). Because of the rarity and indolent course of the disease, no prospective trials are available. Open surgery has long been considered the traditional approach; oncological safety of laparoscopy is only supported by small series or case reports. The aim of this study was to compare the oncological outcomes between laparoscopic and open surgery in stage I AGCTs treated within the MITO (Multicenter Italian Trials in Ovarian cancer) Group. Methods Data from patients with stage I AGCTs were retrospectively collected. Clinicopathological features were evaluated for association with relapse and death. Survival curves were calculated using the Kaplan-Meier method and compared with the log-rank test. The role of clinicopathological variables as prognostic factors for survival was evaluated using Cox's regression model. Results 223 patients were identified. Stage 1A, 1B and 1C were 61.5%, 1.3% and 29.6% respectively. 7.6% were apparently stage I. Surgical approach was laparoscopic for 93 patients (41.7%) and open for 130 (58.3%). 5-years DFS was 84% and 82%, 10-years DFS was 68% and 64% for the laparoscopic and open-group (p = 0.6).5-years OS was 100% and 99%, 10 years OS was 98% and 97% for the laparoscopic and open-surgery group (p = 0.8). At multivariate analyses stage IC, incomplete staging, site of primary surgery retained significant prognostic value. Conclusion The present study suggests that surgical route does not affect the oncological safety of patients with stage I AGCTs, with comparable outcomes between laparoscopic and open approach.

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. Copyright © 2016. Published by Elsevier Inc.

Background. To evaluate the impact of the Laparoscopic Approach to Cervical Cancer (LACC) Trial on patterns of care and surgery-related morbidity in early-stage cervical cancer. Methods. This is a retrospective, a multi-institutional study evaluating 90-day surgery-related outcomes of patients undergoing treatment for early-stage cervical cancer before (period I: 01/01/2016-06/01/2018) and after (period II: 01/01/2019-06/01/2021) the publication of the results of the LACC trial. Results. Charts of 1295 patients were evaluated: 581 (44.9%) and 714 (55.1%) before and after the publication of the LACC trial, respectively. After the publication of the LACC trial, the number of patients treated with minimally invasive radical hysterectomy decreased from 64.9% to 30.4% (p < 0.001). Overall, 90-day complications occurred in 110 (18.9%) and 119 (16.6%) patients in the period I and period II, respectively (p = 0.795). Similarly, the number of severe (grade 3 or worse) complications did not differ between the two periods (38 (6.5%) vs. 37 (5.1%); p = 0.297). Overall and severe 90-day complications were consistent between periods even evaluating stage IA (p = 0.471), IB1 (p = 0.929), and IB2 (p = 0.074), separately. Conclusions. The present investigation highlighted that in referral centers the shift from minimally invasive to open radical hysterectomy does not influence 90-day surgery-related morbidity. (c) 2022 Elsevier Inc. All rights reserved.

BACKGROUND: Treatment for patients with recurrent ovarian cancer has been mainly based on systemic therapy. The role of secondary cytoreductive surgery is unclear. METHODS: We randomly assigned patients with recurrent ovarian cancer who had a first relapse after a platinum-free interval (an interval during which no platinum-based chemotherapy was used) of 6 months or more to undergo secondary cytoreductive surgery and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone. Patients were eligible if they presented with a positive Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) score, defined as an Eastern Cooperative Oncology Group performance-status score of 0 (on a 5-point scale, with higher scores indicating greater disability), ascites of less than 500 ml, and complete resection at initial surgery. A positive AGO score is used to identify patients in whom a complete resection might be achieved. The primary end point was overall survival. We also assessed quality of life and prognostic factors for survival. RESULTS: A total of 407 patients underwent randomization: 206 were assigned to cytoreductive surgery and chemotherapy, and 201 to chemotherapy alone. A complete resection was achieved in 75.5% of the patients in the surgery group who underwent the procedure. The median overall survival was 53.7 months in the surgery group and 46.0 months in the no-surgery group (hazard ratio for death, 0.75; 95% confidence interval, 0.59 to 0.96; P = 0.02). Patients with a complete resection had the most favorable outcome, with a median overall survival of 61.9 months. A benefit from surgery was seen in all analyses in subgroups according to prognostic factors. Quality-of-life measures through 1 year of follow-up did not differ between the two groups, and we observed no perioperative mortality within 30 days after surgery. CONCLUSIONS: In women with recurrent ovarian cancer, cytoreductive surgery followed by chemotherapy resulted in longer overall survival than chemotherapy alone. (Funded by the AGO Study Group and others; DESKTOP III ClinicalTrials.gov number, NCT01166737.).

BACKGROUND CIN2 is considered a biologically equivocal lesion falling between low and high grade cervical dysplasia, but it is often managed with cervical conization as a high-grade lesion. However, since cervical conization can lead to an increased risk of adverse obstetric events, it might be interesting to identify, by colposcopy, a subgroup of women with a low risk of "occult" CIN3 who could be managed with a "wait and see" approach. METHODS All the women with CIN2 cervical biopsy from 1999 to 2019 were retrospectively identified. Their colposcopic patterns at the time of biopsy and the histopathological findings on the final cone specimen were compared. RESULTS Among the 354 women with CIN2 biopsy included, the overall CIN3+ lesion rate on final cone specimen was 21.4%. The rate of CIN3 on final specimen was higher in women with G2 colposcopy compared to G1 (27,2% vs 15.9%, p= 0.01). Among women with G1 colposcopy, the rate of CIN3+ lesions was significantly higher in women with fine punctation (p=0.02) while no differences in women with thin acetowhite epithelium or fine mosaic emerged. CONCLUSIONS In women with CIN2 biopsy, when a G2 pattern or G1 with fine punctation on colposcopy is detected, there is an increased risk of CIN3+ on final histology, therefore an excisional treatment should be preferred. Otherwise, in women with CIN2 biopsy and other G1 patterns on colposcopy, a "wait and see" approach could be considered.

Cotyledonoid leiomyoma of the uterus is a rare variant of benign uterine leiomyoma. It has a favorable attitude, despite some ultrasound presentations. A bulky uterus with a heterogeneous mass with irregular margins, high vascularity, and infiltration of the myometrium can induce the suspicion of a malignant mesenchymal tumor and lead to a radical surgical treatment. If present, some imaging features may suggest this rare type of leiomyoma, thus avoiding extensive surgery, especially in young nulliparous women. We report 13 cases of cotyledonoid leiomyoma with clinical characteristics, imaging features, and a literature review.

ObjectiveThe aim of this study was to analyze the oncological outcome of stage I malignant ovarian germ cell tumors patients included in the MITO-9 study to identify those who might be recommended routine surveillance alone after complete surgical staging.MethodsMITO-9 was a prospective observational study analyzing data collected between January 2013 and December 2019. Three groups were identified: group A included 13 patients stage IA dysgerminoma and IAG1 immature teratoma; group B included 29 patients with stage IB–C dysgerminomas, IA–C G2–G3 immature teratomas and stage IA mixed malignant ovarian germ cell tumors and yolk sac tumors; and group C included five patients (two patients with stage IC1 and one patient with stage IC2 yolk sac tumors and two patients with mixed-stage IC2 malignant ovarian germ cell tumors).ResultsA total of 47 patients with stage I conservatively treated malignant ovarian germ cell tumors were analyzed. Two patients in group B were excluded from the routine surveillance alone group due to positive surgical restaging. Therefore, a total of 45 patients were included in the study. Median follow-up was 46.2 months (range; 6–83). In total, 14 of 45 patients (31.1%) received chemotherapy, while 31 (68.9%%) underwent surveillance alone. One patient in group A, with stage IA dysgerminoma had a relapse, successfully managed with conservative surgery and chemotherapy. None of the patients in group B and C relapsed. All patients were alive at completion of the study. Overall, among 31 patients (68.9%) who underwent surveillance alone, only one patient relapsed but was treated successfully.ConclusionsOur data showed that close surveillance alone could be an alternative option to avoid adjuvant chemotherapy in properly staged IB–C dysgerminomas, IA–IC G2–G3 immature teratomas, and IA mixed malignant ovarian germ cell tumors with yolk sac tumor component.

The CDKN1B gene, encoding for the CDK inhibitor p27kip1, is mutated in defined human cancer subtypes, including breast, prostate carcinomas and small intestine neuroendocrine tumors. Lessons learned from small intestine neuroendocrine tumors suggest that CDKN1B mutations could be subclonal, raising the question of whether a deeper sequencing approach could lead to the identification of higher numbers of patients with mutations. Here, we addressed this question and analyzed human cancer biopsies from breast (n = 396), ovarian (n = 110) and head and neck squamous carcinoma (n = 202) patients, using an ultra‐deep sequencing approach. Notwithstanding this effort, the mutation rate of CDKN1B remained substantially aligned with values from the literature, showing that essentially only hormone receptor‐positive breast cancer displayed CDKN1B mutations in a relevant number of cases (3%). However, the analysis of copy number variation showed that another fraction of luminal breast cancer displayed loss (8%) or gain (6%) of the CDKN1B gene, further reinforcing the idea that the function of p27kip1 is important in this type of tumor. Intriguingly, an enrichment for CDKN1B alterations was found in samples from premenopausal luminal breast cancer patients (n = 227, 4%) and in circulating cell‐free DNA from metastatic luminal breast cancer patients (n = 59, 8.5%), suggesting that CDKN1B alterations could correlate with tumor aggressiveness and/or occur later during disease progression. Notably, many of the identified somatic mutations resulted in p27kip1 protein truncation, leading to loss of most of the protein or of its C‐terminal domain. Using a gene‐editing approach in a luminal breast cancer cell line, MCF‐7, we observed that the expression of p27kip1 truncating mutants that lose the C‐terminal domains failed to rescue most of the phenotypes induced by CDKN1B gene knockout, indicating that the functions retained by the C‐terminal portion are critical for its role as an oncosuppressor, at least in luminal breast cancer. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Objective Coronavirus disease 2019 (COVID-19) has caused rapid and drastic changes in cancer management. The Italian Society of Gynecology and Obstetrics (SIGO), and the Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) promoted a national survey aiming to evaluate the impact of COVID-19 on clinical activity of gynecologist oncologists and to assess the implementation of containment measures against COVID-19 diffusion. Methods The survey consisted of a self-administered, anonymous, online questionnaire. The survey was sent via email to all the members of the SIGO, and MITO groups on April 7, 2020, and was closed on April 20, 2020. Results Overall, 604 participants completed the questionnaire with a response-rate of 70%. The results of this survey suggest that gynecologic oncology units had set a proactive approach to COVID-19 outbreak. Triage methods were adopted in order to minimize in-hospital diffusion of COVID-19. Only 38% of gynecologic surgeons were concerned about COVID-19 outbreak. Although 73% of the participants stated that COVID-19 has not significantly modified their everyday practice, 21% declared a decrease of the use of laparoscopy in favor of open surgery (19%). However, less than 50% of surgeons adopted specific protection against COVID-19. Additionally, responders suggested to delay cancer treatment (10%-15%), and to perform less radical surgical procedures (20%-25%) during COVID-19 pandemic. Conclusions National guidelines should be implemented to further promote the safety of patients and health care providers. International cooperation is of paramount importance, as heavily affected nations can serve as an example to find out ways to safely preserve clinical activity during the COVID-19 outbreak.

Aim During the last years, the role of sentinel lymph node mapping (SLNM) for endometrial cancer (EC) surgical treatment has increased in popularity. However, several controversies remain about different technical steps of SLNM. Thus, a randomised control trial was designed to compare cervical (CI) and hysteroscopic (HI) indocyanine green (ICG) injection for SLNM of newly diagnosed EC undergoing surgical staging. The primary end-point of the study was to compare these two techniques in terms of para-aortic detection rate. Methods Patients with apparent stage I or II histologically confirmed EC undergoing surgery were included in the study. This randomised trial distinguished patients in two study groups according to two different techniques of ICG SLNM: CI versus HI injection. Patients who met the inclusion criteria were randomly assigned to CI or HI injection in a 1:1 ratio. The central randomisation system allocated patient randomisation numbers sequentially in the order in which the patients were enrolled. This randomised trial was not blinded for either patients or the surgeons. Results From March 2017 until April 2019, a total of 165 patients were randomised in this study: 85 (51.5%) in the CI group and 80 (48.5%) in the HI group. After randomisation, 14 (8.5%) patients were excluded from the study. Finally, 151 patients were included in the analysis: 82 (54.3%) in the CI group and 69 (45.7%) in the HI group. Hysteroscopy injection shows an ability to detect Sentinel nodes (SNLs) in the para-aortic area of about 10% greater compared with CI injection, although this difference did not reach statistical significance. The HI technique was superior in detecting isolated para-aortic SLNs (5.8% Versus 0%). The CI injection was correlated with higher SLN detection rates at the pelvic level compared with HI injection. Pelvic and overall detection was higher in the CI group. Conclusions The present study supports the adoption of CI instead of HI injection because the former allows better identification of sentinel nodes (especially in the pelvic area). Detection of SLN in the para-aortic area was slightly higher in patients receiving a HI injection, but the difference with the CI route was not statistically significant.

Carboplatin/paclitaxel is the reference regimen in the treatment of advanced high-grade serous ovarian cancer (HGSOC) in neo-adjuvant chemotherapy (NACT) before interval debulking surgery (IDS). To identify new genetic markers of platinum-resistance, next-generation sequencing (NGS) analysis of 26 cancer-genes was performed on paired matched pre- and post-NACT tumor and blood samples in a patient with stage IV HGSOC treated with NACT-IDS, showing platinum-refractory/resistance and poor prognosis. Only the TP53 c.375+1G>A somatic mutation was identified in both tumor samples. This variant, associated with aberrant splicing, was in trans configuration with the 72Arg allele of the known germline polymorphism TP53 c.215C>G (p. Pro72Arg). In the post-NACT tumor sample we observed the complete expansion of the TP53 c.375+1G>A driver mutant clone with somatic loss of the treatment-sensitive 72Arg allele. NGS results were confirmed with Sanger method and immunostaining for p53, BRCA1, p16, WT1, and Ki-67 markers were evaluated. This study showed that (i) the splice mutation in TP53 was present as an early driver mutation at diagnosis; (ii) the mutational profile was shared in pre- and post-NACT tumor samples; (iii) the complete expansion of a single dominant mutant clone through loss of heterozygosity (LOH) had occurred, suggesting a possible mechanism of platinum-resistance in HGSOC under the pressure of NACT.

Struma ovarii (SO), a rare tumor containing at least 50% of thyroid tissue, represents approximately 5% of all ovarian teratomas; its malignant transformation rate is reported to occur in up to 10% of cases and metastases occur in about 5-6% of them. We describe a 36-year old woman who underwent laparoscopic left annessectomy two years earlier because of an ovarian cyst. Follow-up imaging revealed a right adnexal mass, ascitis and peritoneal nodes that were diagnosed as comprising a malignant SO with peritoneal secondary localizations at histopathology performed after intervention. Restaging with F-18-FDG-PE T/CT scan, abdominal CT and ultrasonography showed abnormalities in the perihepatic region and presacral space and left hypochondrium localizations. The patient underwent thyroidectomy, hepatic nodulectomy and cytoreductive peritonectomy: histopathological examination did not show any malignant disease in the thyroid and confirmed the presence of peritoneal localizations due to malignant SO; molecular analysis detected NRAS Q61K mutation in exon 3, whereas no mutations were identified on the BRAF gene. The patient underwent radioiodine treatment: serum Tg was decreased at first follow-up after three months of I-131-therapy. We believe that our case raises some interesting considerations. First, pathologists should be aware of this entity and should check for the presence of point mutations suggesting an aggressive disease behavior, which could be beneficial for an optimal therapeutic approach. Second, although most of the knowledge in this field comes from case reports, efforts should be made to standardize the management of patients affected by malignant SO, including use of practice guidelines.

Objective: The aim of this study is to evaluate the long-term outcome of granulosa cell tumour (GCT) of the ovary in a large series of patients treated in MITO centres (Multicentre Italian Trials in Ovarian Cancer) and to define prognostic parameters for relapse and survival. Methods: A retrospective multi-institutional review of patients with GCTs of the ovary treated or referred to MITO centres was conducted. Surgical outcome, intraoperative and pathological findings and follow-up data were analysed. Kaplan–Meier and Cox proportional hazards analyses were used to determine the predictors for survival and recurrence. Results: A total of 97 patients with primary GCT of the ovary were identified. The median follow-up period was 88 months (range 6–498). Of these, 33 patients had at least one episode of disease recurrence, with a median time to recurrence of 53 months (range 9–332). Also, 47% of recurrences occurred after 5 years from initial diagnosis. At multivariate analysis, age and stage were independent poor prognostic indicators for survival; surgical treatment outside MITO centres and incomplete surgical staging retained significant predictive value for recurrence in both univariate and multivariate analyses. Conclusions: This study confirms the generally favourable prognosis of GCTs of the ovary, with 5-year overall survival approaching 97%. Nevertheless, prognosis after 20 years was significantly poorer, with 20-year survival rate of 66.8% and a global mortality of 30–35. These findings support the need for lifelong follow-up even in early-stage GCT.

Objective. Granulosa cell tumors (GCTs) are the most common estrogen-secreting ovarian tumors; perhaps due to the persistent hyperestrogenism, a wide spectrum of associated endometrial pathologies ranging from endometrial hyperplasia to carcinoma has been documented in patients with GCTs. The aim of this study is to evaluate the incidence of endometrial pathologies in a large series of GCT patients treated in MITO centers. Methods. A retrospective multi-institutional review of patients with granulosa cell tumors of the ovary treated or referred to MITO centers was conducted. Descriptive statistics were used to characterize the patient population and to assess the association of GCT and endometrial abnormalities at the time of diagnosis; multivariate regression analysis was also performed to identify independent predictors of endometrial abnormalities. Results. A total of 150 patients with primary adult GCT was identified. During the preoperative assessment, endometrial pathology was found in 35.9% of symptomatic patients and in 90.9% of asymptomatic women with endometrial thickening at transvaginal ultrasound. At the time of surgery, hyperplasia was documented in 29.2% of patients, whereas endometrial cancer occurred in 7.5% of patients. Almost all of the patients (97.6%) with endometrial hyperplasia were older than 40 years. All patients with endometrial cancer were older than 40 years and postmenopausal. Conclusions. Endometrial carcinoma/atypical hyperplasia were commonly observed in GCT patients > 40 years; based on these data, endometrial sampling should be performed in symptomatic women at least 40 years of age. In asymptomatic women < 40 years, endometrial sampling is of low yield.

ObjectiveLymphoceles are among the most common postoperative complications of pelvic lymphadenectomy (PL), with a reported incidence of 1% to 50%. Symptoms are pelvic pain, leg edema, gastrointestinal obstruction, obstructive uropathy, and deep vein thrombosis, and severe complications such as sepsis and lymphatic fistula formation. After laparoscopic PL, we tested the prevention of lymphoceles using collagen patch coated with the human coagulation factors (TachoSil, Nycomed International Management GmbH, Zurich, Switzerland) on 55 patients with endometrial cancer stages IB to II who had undergone laparoscopy.Materials and MethodsThe authors divided the patients into 2 laparoscopy groups: PL plus TachoSil (group 1: 26 patients) and PL without TachoSil in a control group (group 2: 29 patients), as historical cohort of patients who underwent PL between 2010 and 2012. We collected surgical parameters, and the patients underwent ultrasound examination on postoperative days 7, 14, and 28. The main outcome measures were the development of symptomatic or asymptomatic lymphoceles, the need for further surgical intervention, as adverse effect of surgery, and the drainage volume and duration.ResultsThe same number of lymph nodes in both groups was removed; group 1 showed a lower drainage volume. Lymphoceles developed in 5 patients in group 1 and in 15 patients in group 2; of these, only 2 patients were symptomatic in group 1 and 5 patients were symptomatic in group 2, without statistical difference and no percutaneous drainage request.ConclusionsIn this preliminary investigation, the intraoperative laparoscopy application of TachoSil seems to reduce the rate of postoperative lymphoceles after PL, providing a useful additional treatment option for reducing drainage volume and preventing lymphocele development after PL.

Stathmin is a p53-target gene, frequently overexpressed in late stages of human cancer progression. Type II High Grade Epithelial Ovarian Carcinomas (HG-EOC) represents the only clear exception to this observation. Here, we show that stathmin expression is necessary for the survival of HG-EOC cells carrying a p53 mutant (p53(MUT) ) gene. At molecular level, stathmin favours the binding and the phosphorylation of p53(MUT) by DNA-PKCS , eventually modulating p53(MUT) stability and transcriptional activity. Inhibition of stathmin or DNA-PKCS impaired p53(MUT) -dependent transcription of several M phase regulators, resulting in M phase failure and EOC cell death, both in vitro and in vivo. In primary human EOC a strong correlation exists between stathmin, DNA-PKCS , p53(MUT) overexpression and its transcriptional targets, further strengthening the relevance of the new pathway here described. Overall our data support the hypothesis that the expression of stathmin and p53 could be useful for the identification of high risk patients that will benefit from a therapy specifically acting on mitotic cancer cells.

This study aimed to evaluate the efficiency of 18F-FDG PET/CT in suspected recurrence of epithelial ovarian cancer, after treatment, comparing outcomes of PET/CT with histological tumor subtype, CA-125 serum levels, and findings of conventional diagnostic imaging modalities (CI).Data from 121 women who underwent FDG PET/CT for suspected recurrence of epithelial ovarian cancer after treatment were reviewed retrospectively.Of all patients, 80% had recurrent disease and 20% were disease-free on the final clinical diagnosis. PET/CT showed true-positive findings in 82% of patients, whereas CI demonstrated true-positives in 70% of cases. At the time of PET/CT scanning, only 55 patients had serum CA-125 level greater than 35 U/mL, whereas 52 patients presented with CA-125 levels in a reference range. PET/CT sensitivity (82%) was significantly higher than that of CA-125 (59%), whereas difference in sensitivity between PET/CT and CI (69%) was limited. PET/CT specificity (87%) was significantly better than that of CI (47%), although no difference in specificity between PET/CT and CA-125 (80%) was found. However, no difference in CA-125 serum levels between patients with local tumor relapse and those with distant metastases was found. PET/CT showed the highest positive predictive value (96%) and negative predictive value (55%) when compared with other modalities. In high-grade tumors (n = 66), PET/CT accuracy was 80%, better than that of serum CA-125 (64%) and that of CI (62%). Equally in low-grade ovarian carcinomas (n = 55), PET/CT accuracy (87%) was significantly higher than that of the tumor marker (60%) and also higher than that of CI (70%).FDG PET/CT was proven to be more efficient than serum CA-125 assay and CI in detecting recurrences of ovarian cancer after treatment. The sensitivity of FDG PET/CT is not influenced by tumor histology. FDG PET/CT should be considered a useful diagnostic tool in the surveillance of patients that received treatment for epithelial ovarian carcinoma.