Giorgia Perniola

Secondary Cytoreductive Surgery in Patients with Platinum-Sensitive Recurrent Ovarian Cancer

ABSTRACTBackgroundSecondary surgical cytoreduction (SCR) represents a promising therapeutic strategy for patients affected by ovarian cancer disease recurrence. The aim of this prospective observational trial was to analyze the role of SCR in patients with platinum-sensitive ovarian cancer.MethodsPatients with platinum-sensitive ovarian cancer underwent SCR by a single surgical team. Clinical and oncologic data were prospectively recorded. A total of 47 patients underwent SCR from 1999 to 2003.ResultsThe mean operating time was 210 minutes, and mean blood loss was 500 mL. The most frequent surgical procedures carried out were splenectomy, lymphadenectomy, bowel resection, and extensive peritonectomy. Optimal cytoreduction was achieved in 41 patients. Thirty-seven patients had no visible tumor at the end of SCR. Overall median survival was 49 months. Patients who achieved optimal residual disease had a median survival of 61 months, whereas patients who had residual disease >1 cm had a median survival of 19 months.ConclusionsPositive CA-125 (cancer antigen 125) was identified as a negative prognostic factor at multivariate analysis. After careful selection, optimal cytoreduction can be achieved in most patients who are subjected to SCR with acceptable morbidity. Residual tumor and CA-125 represent the most important prognostic factors.

The effect of surgery for endometrioma on ovarian reserve evaluated by antral follicle count: a systematic review and meta-analysis

STUDY QUESTION Does surgical treatment of endometriomas impact on the ovarian reserve as evaluated with antral follicle count (AFC)? SUMMARY ANSWER This meta-analysis of published data shows that surgery for endometrioma does not significantly affect ovarian reserve as evaluated by AFC. WHAT IS KNOWN ALREADY Surgical excision of an ovarian endometrioma significantly affects ovarian reserve evaluated with anti-Mullerian hormone (AMH) levels. Data for other reliable markers of ovarian reserve, such as AFC, have not been pooled in meta-analyses. STUDY DESIGN, SIZE, DURATION A systematic review with electronic searches of PubMed, MEDLINE and Embase up to April 2014 was conducted to identify articles evaluating AFC before and after surgery for ovarian endometriomas, or before or after surgery for the affected versus the contralateral ovary. PARTICIPANTS/MATERIALS, SETTING, METHODS Of the 24 studies evaluated in detail, 13 were included for data extraction and meta-analysis, including a total of 597 patients. The primary outcome at pooled analysis was AFC (mean and SD) for affected ovaries before and after surgery. Secondary outcomes were AFC for the affected ovary versus the contralateral ovary before surgery, and AFC for the operated versus the contralateral ovary after surgery. The data were pooled using the RevMan software by the Cochrane Collaboration. Heterogeneity between studies was based on the results of the χ(2) and I(2) statistics. A random-effect model was used for the meta-analysis because of high heterogeneity between studies. MAIN RESULTS AND THE ROLE OF CHANCE AFC for the operated ovary did not change significantly after surgery (mean difference 0.10, 95% CI -1.45 to 1.65; P = 0.90). Lower AFC for the diseased ovary compared with the contralateral one was present before surgery, although the difference was not significant (mean difference -2.79, 95% CI -7.10 to 1.51; P = 0.20). After surgery, the operated ovary showed a significantly lower AFC compared with the contralateral ovary (mean difference -1.40, 95% CI -2.27 to -0.52; P = 0.002). LIMITATIONS, REASONS FOR CAUTION Heterogeneity among the selected studies was high; therefore, limiting the conclusions of the present systematic review. WIDER IMPLICATIONS OF THE FINDINGS Ovarian reserve evaluated with AFC is not reduced after surgical treatment of an endometrioma. A lower AFC is present for the affected ovary both before and after surgery. Recently, concerns have been raised as to the reliability of AMH as a marker of ovarian reserve. Based on the present findings, surgical treatment of an endometrioma may be considered safer for the ovarian reserve than previously thought. STUDY FUNDING/COMPETING INTERESTS No external funding was sought or obtained for this study. No conflicts of interest are declared.

Risk-reducing salpingo-oophorectomy: a meta-analysis on impact on ovarian cancer risk and all cause mortality in BRCA 1 and BRCA 2 mutation carriers.

BackgroundWomen with BRCA1 and BRCA2 mutation carriers are at substantially elevated risk of developing ovarian cancer. The aim of the meta-analysis is to clarify the role of risk-reducing salpingo-oophorectomy (RRSO) to reduce ovarian cancer risk and mortality in women with BRCA 1 and BRCA 2 mutation carriers.MethodsPubmed, Medline and Scopus were searched to select English-language articles. Two investigators independently extracted characteristics and results of selected studies. Articles were included only if prospective and if absolute numbers of ovarian cancer and death events were available or derivable from the test. Pooled hazard ratio (HR) with 95% confidence interval (CI) was calculated using fixed effects model.ResultsMeta-analysis of 3 prospective studies demonstrated a significant risk reduction of ovarian cancer with RRSO in BRCA 1 and BRCA 2 mutation carriers, as well as benefit in all-causes mortality incidence.ConclusionsIt may be justified to recommend RRSO to reduce ovarian cancer risk and all-causes mortality in women with a mutation in BRCA 1 and BRCA 2.

Optimizing the Total Laparoscopic Hysterectomy Procedure for Benign Uterine Pathology

STUDY OBJECTIVE To evaluate the influence of the learning curve in total laparoscopic hysterectomy on short- and long-term clinical results. DESIGN Retrospective comparative analysis (Canadian Task Force classification II-2). SETTING Malzoni Medical Center of Avellino, university-affiliated hospital. PATIENTS Three hundred and ninety-six women in the first time period (1997-1999) and 624 women in the second time period (2000-2002) were treated, using different techniques, by the same surgeon. Patients suffered from symptomatic myomas and uterine fibromatosis. No case was considered suitable for a vaginal procedure. INTERVENTION Total laparoscopic hysterectomy. MEASUREMENTS AND MAIN RESULTS No statistical differences were found between the two groups for patient age, parity, body mass index, and indications for surgery (p = NS), except for uterine weight (395 g vs. 408 g; p <.01). In the first time period, the average operating time was 105 +/- 27 minutes (range, from 65-190). In the second time period, the average operating time was 80 +/- 21 minutes (range, 45-170) (p <.001). The postoperative hemoglobin drop was 1.44 g/dL (range, 0.8-6.1) and 1.39 g/d (range, 0.7-4.3) in the first series and second series, respectively (p = NS). In the first series, the mean postoperative hospital stay was 2.4 +/- 1 days (range, 2-7). In the second series, the mean postoperative hospital stay was 2.3 +/- 1 days (range, 2-6). A significant decrease in short-term complications occurred between the first and second time period, 7.7% and 5.55% respectively (p <.03). We performed three (0.75%) and four (0.6%) conversion to laparotomy procedures, respectively, in the first and second groups (p = NS). During the first period, two reoperations were necessary; in the second period, one patient (0.15%) required a reoperation (p = NS). The rate of postoperative blood transfusion was 0.5% (n = 2) in the first period versus 0.15% (n = 1) in the second period (p = NS). Significant decrease of long-term complications occurred between first and second series, 2.0% and 0.45% respectively (p <.05). There were no differences between the two groups regarding sexual symptoms p = NS). CONCLUSION Laparoscopic hysterectomy is a safe, effective, and reproducible technique after completion of a period of training necessary to standardize the procedure. The results support the importance of optimizing some steps of the surgical technique to reduce severe complications.

Simple extrafascial trachelectomy and pelvic bilateral lymphadenectomy in early stage cervical cancer.

OBJECTIVE To determine the feasibility and safety of simple extra-fascial trachelectomy plus pelvic lymphadenectomy in young patients affected by early stage cervical cancer. METHODS We have prospectively identified all patients with early-stage cervical cancer (stages IA2-IB1) referred to our department. Inclusion criteria were: age ≤ 38 years, strong desire to maintain fertility, FIGO stage ≤ IB1, tumor size<2 cm, no LVSI, no evidence of nodal metastasis. Surgical technique included two steps: laparoscopic pelvic lymphadenectomy and vaginal simple extrafascial trachelectomy. Patients were followed up for oncological and obstetrical outcomes. RESULTS Fourteen patients were enrolled in the study. Median age was 32 years (range 28-37); histotype was squamous in 11/14 (79%) cases and adenocarcinoma in 3/14 cases (21%); FIGO stage was IA2 in 5/14 (36%) patients, IB1 in 9/14 (64%) patients; median tumor size was 17 mm (range 14-19); median operative time was 120 min (range 95-210). No severe intraoperative complications were recorded. Postoperative complications were observed in two patients. No recurrences were detected. One patient died for other disease. Eight patients became pregnant and 3 of them had a term delivery. CONCLUSION Low risk early-cervical cancer patients could be safely treated by simple extrafascial trachelectomy in order to maintain fertility. More studies are needed to better define the role of conservative and ultraconservative surgical approaches (i.e. conization) in this setting, either for fertility purposes or to minimize surgical complications.

Neoadjuvant chemotherapy followed by radical surgery in patients affected by vaginal carcinoma.

BACKGROUND Radiotherapy represents the standard treatment for patients affected by FIGO stage II vaginal cancer. Several authors have suggested that neoadjuvant chemotherapy followed by radical surgery might be a valid treatment option in patients affected by cervical cancer. The objective of this study was to analyse the feasibility and results obtained by neoadjuvant chemotherapy followed by surgery in patients affected by invasive vaginal cancer with paravaginal tissue involvement not reaching the pelvic side wall. METHODS Eleven patients affected by FIGO stage II vaginal cancer were treated with paclitaxel 175 mg/m(2) and cisplatin 75 mg/m(2) every 21 days for three courses followed by radical surgery. RESULTS All patients were subjected to the 3 planned chemotherapy courses. Three (27%) patients achieved a complete clinical response and seven (64 %) patients achieved a partial clinical response. All patients were subjected to radical hysterectomy and vaginectomy. At a median follow up of 75 months two (18%) patients suffered a disease recurrence and one of these died of disease. CONCLUSIONS Neoadjuvant chemotherapy followed by radical surgery is a feasible therapeutic strategy with good short- and long-term results. In women affected by vaginal cancer, a larger series reporting the result of this therapeutic strategy or the results obtained by surgery alone will aid physicians to choose the best therapeutic strategy for each individual patient.

Hormone therapy in oophorectomized BRCA1/2 mutation carriers.

ObjectiveBRCA1/2 mutation carriers have greatly elevated lifetime risks of breast, ovarian, and fallopian tube cancers. Bilateral prophylactic salpingo-oophorectomy is recommended to prevent cancer in these women. As it is often performed before natural menopause, it may be accompanied by menopausal symptoms, impaired quality of life, and increased cardiovascular risk. MethodsIn this review, we describe the indications, timing, and implications of salpingo-oophorectomy for BRCA-positive women, with a special focus on the risks and benefits of hormone therapy (HT). Furthermore, retrospective and prospective trials of HT in BRCA mutation carriers undergoing prophylactic salpingo-oophorectomy are debated. ResultsHormonal deprivation after prophylactic salpingo-oophorectomy may negatively impact health and quality of life; most women experience menopausal symptoms shortly after surgical operation. Literature data suggest that HT generally reduces vasomotor symptoms related to surgical menopause, improving sexual functioning without affecting survival. ConclusionsDespite the limitations of retrospective and prospective observational studies, short-term HT seems to improve quality of life and does not seem to have an adverse effect on oncologic outcomes in BRCA1 and BRCA2 mutation carriers without a personal history of breast cancer. Therefore, randomized and larger trials are urgently needed.

Secondary analyses from a randomized clinical trial: age as the key prognostic factor in endometrial carcinoma

OBJECTIVE The purpose of this study was to explore in greater depth the outcomes of the Italian randomized trial investigating the role of pelvic lymphadenectomy in clinical early stage endometrial cancer. In the attempt to identify the patients with poorer prognosis, the impact of age and body mass index were also thoroughly investigated by cancer-specific survival (CSS) analyses. STUDY DESIGN Survival outcomes of trial patients were analyzed in relation to age (≤65 years and >65 years) in the 2 arms (lymphadenectomy and no lymphadenectomy) and in the whole population of the trial. RESULTS Univariate and multivariable analyses of CSS and overall survival (OS) of patients showed that age >65 years is a strong independent poor prognostic factor (5-y OS 92.1% and 78.4% in ≤65 years and >65 years patients, respectively, P < .0001; 5-y CSS 93.8% and 83.5% in ≤65 years and >65 years patients, respectively, P = .003). Among women ≤65 years, node negative patients had 94.4% 5-y OS and 96.3% 5-y CSS vs 74.3% 5-y OS and 74.3% 5-y CSS for node positive patients (P = .009 and P = .002, respectively), while among women >65 y, node negative patients had 75.7% 5-y OS and 83.6% 5-y CSS vs 74.1% 5-y OS and 83.3% 5-y CSS for node positive patients (P = .55 and P = .58, respectively). Univariate and multivariable survival analyses in the whole trial population showed that older age, and higher tumor grade and stage were significantly associated to a worse prognosis. CONCLUSION Older women faced an intrinsic poorer survival whether or not they underwent lymphadenectomy, and, unexpectedly, irrespective of the presence of nodal metastasis. Only in older patients was obesity (body mass index >30) significantly associated with scarce prognosis.

Modified gluteal fold advancement V-Y flap for vulvar reconstruction after surgery for vulvar malignancies

OBJECTIVE The aim of the study is to assess the feasibility and complications of the modified V-Y advancement gluteal flap in the vulvo-perineal reconstruction among women operated for vulvar malignancies. METHODS From December 2008 to April 2012 women who underwent radical surgery for invasive vulvar cancer were considered for the study. Patients after demolitive procedure were submitted to reconstructive step (Group A) consisting of bilateral or monolateral V-Y advancement fascio-cutaneous flap, from gluteal fold. Surgical results were compared to those of a historical group of patients (Group B) with the same characteristics but not submitted to the reconstructive step. RESULTS Twenty-nine patients were considered for the study and submitted to radical surgery followed by V-Y flap. Surgical results were compared to those of 78 patients submitted to demolitive surgery only. There were no differences in terms of clinical characteristics between the two groups. The average length of hospital stay was 7 and 10 days, respectively for Groups A and B (P=0.0067). Mean operating time was higher in Group A, 210 vs 120 min (P<0.00001). Among women with tumor size larger than 4 cm (27 Group A, 30 Group B), Group A had lower complication rate (dehiscence 11% vs 40%; P=0.0172). CONCLUSIONS Modified gluteal fold advancement V-Y flap is a safe and simple procedure and can be harvested in a single surgery session. It could be able to reduce hospital stay and in patients with large loss of substance could reduce rate of complications.

Predictors of postoperative morbidity after cytoreduction for advanced ovarian cancer: Analysis and management of complications in upper abdominal surgery

OBJECTIVE To evaluate the complication rate and its impact in patients who have undergone upper abdominal surgery for treatment of advanced ovarian cancer. METHODS Patients who have undergone upper abdominal surgery including diaphragm surgery, splenectomy, distal pancreatectomy, gastric resection, liver resection and biliary surgery were considered for the study. Perioperative complications were evaluated and graded according to Clavien-Dindo. RESULTS One hundred and twenty one patients were included. Two hundred and twelve surgical procedures were performed. Thirty-six patients reported at least one complication, but 61.1% of these the complication was mild. Median hospital stay for patients with and without complication was 7 vs. 13days respectively (p<0.001). There was a significant correlation between post-operative hospital stay and the total number of surgical procedures (R=0.445, p<0.001). At multivariate analysis, diaphragmatic resection and pancreatic resection were associated with a significant increase of postoperative hospital stay, furthermore diaphragmatic resection (p=0.004), hepatic resection (p=0.004), pancreatectomy (p=0.011) and biliary surgery (p=0.049) were independent predictors of severe (G3-G4) complication. CONCLUSIONS Rate of complications of patients submitted to upper abdominal surgery for ovarian cancer is acceptable. Prediction of severe complications is the goal for its optimal management. Extensive procedures should be avoided with those patients in which optimal residual tumor could not be reached.