Rectosigmoid Mesorectal-Sparing Resection in Advanced Ovarian Cancer Surgery.

Ovarian cancer is the most lethal of all gynecologic cancers.1 Primary debulking surgery (PDS) with achievement of no residual tumor (RT, 0) still is the recommended treatment, and the one with the greatest prognostic impact.2,3 Given the usual disease spread, several surgical procedures often are needed, and one of the most frequent is rectosigmoid resection.4 Anastomotic leak is the most feared complication. Other common complications are persistent urinary, defecatory, and sexual dysfunction due to autonomic nervous system injuries during surgery.5 Even if mesorectal resection is not deemed part of the treatment paradigm for advanced ovarian cancer (AOC), total mesorectal excision (TME) is the most common surgical technique used. However, for selected cases, with detection of no lymphadenopathies at the origin of the of the inferior mesenteric artery and a favorable ratio between the length of the left colon and the extent of the bowel carcinomatosis, a mesorectal-sparing resection with the preservation of the superior rectal artery and the mesorectal tissue should be pursued. This report presents the case of a 54-year-old woman with a diagnosis of FIGO stage 3C AOC who underwent PDS. The video (video 1) provides a step-by-step description of the surgical technique adopted for colorectal resection with mesorectal-sparing technique. Rectosigmoid mesorectal-sparing resection is feasible and could be a viable option for selected cases of AOC, maximizing the blood supply to colorectal anastomosis while minimizing the risk of both anastomotic leak and pelvic autonomic nervous system dysfunction.6.

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.

A laparoscopic risk-adjusted model to predict major complications after primary debulking surgery in ovarian cancer: A single-institution assessment.

OBJECTIVE: To develop and validate a simple adjusted laparoscopic score to predict major postoperative complications after primary debulking surgery (PDS) in advanced epithelial ovarian cancer (AEOC). METHODS: From January 2006 to June 2015, preoperative, intraoperative, and post-operative outcome data from patients undergoing staging laparoscopy (S-LPS) before receiving PDS (n=555) were prospectively collected in an electronic database and retrospectively analyzed. Major complications were defined as levels 3 to 5 of MSKCC classification. On the basis of a multivariate regression model, the score was developed using a random two-thirds of the population (n=370) and was validated on the remaining one-third patients (n=185). RESULTS: Major complication rate was 18.3% (102/555). Significant predictors included in the scoring system were: poor performance status, presence of ascites (>500cm(3)), CA125 serum level (>1000U/ml), and high laparoscopic tumor load (predictive index value, PIV ≥8). The mean risk of developing major postoperative complications was 3.7% in patients with score 0 to 2, 13.2% in patients with score 3 to 5, 37.1% in patients with score 6 to 8. In the validation population, the predicted risk of major complications was 17.8% (33/185) versus a 16.7% (31/185) observed risk (C-statistic index=0.790). CONCLUSION: This new score may accurately predict a patient's postoperative outcome. Early identification of high-risk patients could help the surgeon to adopt tailored strategies on individual basis.

Minimally invasive versus standard laparotomic interval debulking surgery in ovarian neoplasm: A single-institution retrospective case-control study.

OBJECTIVE: To further investigate the role of MIS comparing patients submitted to MI-IDS with a balanced population treated by standard laparotomy. METHODS: The investigational arm (Cases) includes 30 AEOC patients treated with MI-IDS. The Control arm included a consecutive series of 65 AEOC patients submitted to laparotomic IDS. Inclusion criteria were: age>18years, histologically proven EOC, clinical complete/partial response after NACT, and ECOG PS <2. Preoperative clinical data, perioperative and oncological outcomes were analyzed. General Well-Being Schedule (GWBS) was administered to evaluate quality of life before and after surgery. RESULTS: Both groups were well-balanced. A higher percentage of women among Cases received bevacizumab-containing NACT compared with Controls. No statistical differences were registered in terms of surgical procedures and residual tumor. A significantly longer median OT in Cases was counterbalanced by more favorable EBL and median length of stay and TTC. No statistically significant differences were registered in terms of postoperative complications. Cases showed a 6months longer PFS compared to Controls. However, in multivariate analysis only the administration of Bevacizumab and a shorter TTC were independently associated with a longer PFS. Regarding QoL, no statistically significant differences were registered in Cases between pre- and postoperative GWBS score. Differently from Controls where this difference was statistically significant and a more intense distress were recorded. CONCLUSIONS: Minimally invasive approach could represent an advantageous alternative surgical way to perform interval debulking surgery in this specific subset of patients, with no impact on PFS. Based on these findings a randomized clinical trial is now under evaluation in our Institution.

Minimally invasive secondary cytoreduction plus HIPEC for recurrent ovarian cancer: a case series.

OBJECTIVE: To analyze the feasibility of laparoscopic/robotic secondary cytoreductive surgery and hyperthermic intraperitoneal intra-operative chemotherapy (SCS+HIPEC) in a retrospective series of isolated platinum sensitive recurrent ovarian cancer. METHODS: We retrospectively evaluated a consecutive series of ovarian cancer patients with isolated platinum sensitive relapse. Isolated relapse was defined as the presence of a single nodule, in a single anatomic site. In all cases the presence of isolated relapse was assessed at pre-operative FDG-PET/CT scan, and confirmed with staging laparoscopy performed immediately before SCS+HIPEC. RESULTS: 84 women with platinum sensitive relapse received SCS+HIPEC during a 4-year period. Among them, 10 cases (11.9%) showed isolated relapse and were treated with laparoscopic/robotic SCS+HIPEC. In all cases complete debulking was achieved. In HIPEC treatment, 9 women received cisplatin at 75 mg/m(2), and the remaining patient oxaliplatin 460 mg/m(2). In 7 patients SCS was performed through the laparoscopic route, and in 3 cases with a robotic approach. The median operative time from skin incision to the end of cytoreductive surgery was 122 min (95-140), estimated blood loss was 50 cm(3) (50-100), and the median length of hospital stay was 4 days (3-7). The interval from surgery to adjuvant chemotherapy was 21 days (19-32). No grade 3/4 surgical, metabolic, or hematologic complications occurred. In all cases post-operative FDG-PET/CT scan was negative, and after a median time of 10 months (6-37) from SCS+HIPEC no secondary recurrence was observed. CONCLUSIONS: Minimally invasive SCS+HIPEC can be safely performed in selected ovarian cancer patients with platinum sensitive isolated relapse.

Ovarian cancer patients with localized relapse: clinical outcome and prognostic factors.

OBJECTIVE: We evaluated the clinical outcome and prognostic factors for post-relapse survival (PRS) in a large retrospective series of ovarian cancer patients with localized relapse. PATIENTS AND METHODS: The following radiological inclusion criteria were adopted: relapse in single anatomic site and ≤ 3 nodules. All cases were followed for at least 24 months after recurrent disease. RESULTS: Two hundred twenty ovarian cancer patients met the inclusion criteria. Serous histotype and G3 tumors were observed in 173 (78.6%) and 151 (77.4%) cases, respectively. All women received platinum-based first-line chemotherapy. Overall, the median follow-up was 46 (8-249) months, and platinum-resistant relapse was documented in 51 women (23.2%). Eighty-one patients (36.8%) recurred in the peritoneum (LPeR), 76 patients (34.5%) in the abdominal lymph nodes (LLNR), and 63 patients (28.7%) in parenchymal organs (LPaR); 142 patients (64.5%) recurred with a single nodule; and 78 patients (35.5%) recurred with 2-3 nodules. Secondary cytoreductive surgery (SCS) was attempted in 73 cases (33.2%), and complete debulking was achieved in all patients. On multivariate analysis, platinum-free interval (PFI, χ(2)=13.457, p value=0.001), complete SCS (median PRS, 69 months vs 25 months, p=0.001), anatomic site of relapse (median PRS, 41months in LPeRs, 63 months in LLNRs and 24 months in LPaRs, p=0.001), and number of nodules (median PRS, 58months in patients with one nodule, 24months in patients with 2-3 nodules, p=0.001) were identified as predictors of PRS. CONCLUSIONS: Beside the duration of PFI, the complete SCS, the anatomic site of relapse, and the number of nodules were independent prognostic factor for duration of PRS.

Introduction of staging laparoscopy in the management of advanced epithelial ovarian, tubal and peritoneal cancer: impact on prognosis in a single institution experience.

OBJECTIVE: To evaluate the prognostic impact of routinely use of staging laparoscopy (S-LPS) in patients with primary advanced epithelial ovarian cancer (AEOC). METHODS: All women were submitted to S-LPS before receiving primary debulking surgery (PDS) or neoadjuvant treatment (NACT). The surgical and survival outcome were evaluated by univariate and multivariate analysis. RESULTS: Among 300 consecutive patients submitted to S-LPS no complications related to the surgical procedure were registered. The laparoscopic evaluation showed that almost half of the patients (46.3%) had a high tumor load. One-hundred forty-eight (49.3%) women were considered suitable for PDS and the remaining 152 (50.7%) were submitted to NACT. The percentages of complete (residual tumor, RT=0) and optimal (RT<1cm) cytoreduction of PDS and interval debulking surgery (IDS) were 62.1% and 57.5%, 22.5% and 27.7%, respectively, p=0.07. The post-operative complications of NACT/IDS group were lower than PDS group (p=0.01). The median progression free survival in women with RT=0 at PDS was 25 months (95% CI, 15.1-34.8), which was statistically significant longer than in all other patients, irrespective of the type of treatment they received (p=0.0001). At multivariate analysis, residual disease (p=0.011) and performance status (p=0.016) maintained an independent association with the PFS. CONCLUSIONS: Including S-LPS in a tertiary referral center for the management AEOC does not appear to have a negative impact in terms of survival and it may be helpful to individualize the treatment avoiding unnecessary laparotomies and surgical complications.

The new surgical robot Hugo™ RAS for total hysterectomy: a pilot study.

Background: With the rising popularity of robotic surgery, Hugo™ RAS is one of the newest surgical robotic platforms. Investigating the reliability of this tool is the first step toward validating its use in clinical practice; and presently there arelimited data available regarding this. The literature is constantly enriched with initial experiences, however no study has demonstrated the safety of this platform yet. Objectives: This study aimed to investigate its reliability during total hysterectomy. Materials and Methods: A series of 20 consecutive patients scheduled for minimally invasive total hysterectomy with or without salpingo-oophorectomy for benign disease or prophylactic surgery were selected to undergo surgery with Hugo™ RAS. Data regarding any malfunction or breakdown of the robotic system as well as intra- and post-operative complications were prospectively recorded. Results: Fifteen of the twenty patients (75.0%) underwent surgery for benign uterine diseases, and five (25.0%) underwent prophylactic surgery. Among the entire series, an instrument fault occurred in one case (5.0%). The problem was solved in 4.8 minutes and without complications for the patient. The median total operative time was 127 min (range, 98-255 min). The median estimated blood loss was 50 mL (range:30-125 mL). No intraoperative complications were observed. One patient (5.0%) developed Clavien-Dindo grade 2 post-operative complication. Conclusions: In this pilot study, Hugo™ RAS showed high reliability, similar to other robotic devices. What is new?: Present findings suggest that Hugo™ RAS is a viable option for major surgical procedures and deserves further investigation in clinical practice.

Should laparoscopy be included in the work-up of advanced ovarian cancer patients attempting interval debulking surgery?

OBJECTIVES: Primary: To investigate whether S-LPS could contribute to a better identification of patients to submit to IDS. Secondary: To identify the most appropriate level of laparoscopic index value (PIV) to identify inoperable patients in this subset of patients. METHODS: A prospective single-institutional study including patients with advanced ovarian/peritoneal cancer (FIGO stage IIIC-IV) to be submitted to IDS after NACT. Patients have been considered eligible for surgical exploration in case of complete/partial radiological or serological response; stable disease if primary surgery had been performed in a different hospital; progressive radiological disease in the presence of serological response, young age, and good performance status (ECOG <1); and progressive serological disease with stable clinical and radiological disease. A laparoscopic assessment for each patient has been performed. RESULTS: Ninety-eight consecutive AOC patients submitted to NACT have been eligible for the study. With the addition of S-LPS to the RECIST criteria, a surgical exploration is performed in all patients and the percentage of explorative laparotomies drops to about 10%. The use of S-LPS after the GCIG criteria can reduce the risk of both explorative laparotomies from 30% to 13%, and inappropriate unexplorations from 18% to 0%. Moreover, at a PIV >4 the probability of optimally resecting the disease at laparotomy is equal to 0. CONCLUSIONS: Present data suggest that S-LPS can play a relevant role to discriminate patients with partially/stable disease or referred from other Institutions after NACT, which can be susceptible of successful IDS.

Metformin improves endothelial function in normoinsulinemic PCOS patients: a new prospective.

BACKGROUND: Metformin was reported to improve the alterations of endothelial reactivity in normal-weight subjects with polycystic ovary syndrome (PCOS). The aim of the present study was to investigate the mechanisms of action of this drug on the vascular function of this population. METHODS: Thirteen normal-weight, normoinsulinemic and normolipemic PCOS women were studied before and after 6 months of metformin treatment (1000 mg/day). The endothelial function was assessed by evaluating the flow-mediated dilatation (FMD) of the brachial artery. We correlated this parameter with the endocrine-metabolic features of the patients. RESULTS: Metformin significantly reduced testosterone (1.56 +/- 0.52 after 6 months versus 2.98 +/- 1.00 at baseline) and 17-hydroxyprogesterone (0.03 +/- 0.01 versus 0.06 +/- 0.02 nmol/ml) levels, without affecting gluco-insulinemic parameters. Concomitantly, the basal vessel diameter and the FMD significantly increased (4.12 +/- 0.68 versus 3.2 +/- 0.41 and 5.2 +/- 0.6 versus 3.76 +/- 0.5 mm, respectively), thus documenting an improved endothelial function. CONCLUSIONS: Our data confirm the positive effects of metformin on the altered vascular reactivity, a precocious marker of cardiovascular risk, in normoinsulinemic PCOS subjects. This improvement seems to be mediated through hormonal changes, thus highlighting the detrimental role of hyperandrogenemia on the endothelial function, even beyond the metabolic factors. However, a direct effect of metformin on the endothelium should not be excluded.

Low- and standard-estrogen dosage in oral therapy: dose-dependent effects on insulin and lipid metabolism in healthy postmenopausal women.

OBJECTIVE: To evaluate the influences of different doses of daily oral unopposed 17beta-estradiol compared with placebo, both on glucose tolerance and lipid metabolism in healthy postmenopausal women. PATIENTS AND METHODS: Forty-eight normoinsulinemic postmenopausal women were enrolled in the study. Patients were assigned to receive randomly 1 mg (group A) or 2 mg (group B) of oral micronized estradiol therapy daily or to the placebo (group C), for 12 weeks. RESULTS: The low-dose estradiol treatment determined an improvement of the peripheral insulin sensitivity, made evident by a significant increase both in the metabolic index and oral glucose insulin sensitivity index (p < 0.01 and p < 0.05, respectively) as well as a decrease in the homeostasis model assessment-estimated insulin resistance (p < 0.01). Conversely, in the standard-dose group, the metabolic index significantly decreased (p < 0.05), showing a slight deterioration in insulin sensitivity. For lipid metabolism, the 1 mg dose showed a neutral effect, while 2 mg had a beneficial effect on low density lipoprotein cholesterol, but caused an increase in triglycerides (p < 0.01 and p < 0.05, respectively). CONCLUSIONS: The oral low dose of unopposed estradiol therapy had a favorable effect on glycoinsulinemic metabolism in healthy postmenopausal women; however, the standard dose caused a slight but significant deterioration in insulin sensitivity.

Urologic surgery in gynecologic oncology: a large single-institution experience.

OBJECTIVE: The increasing tendency to a tailored treatment in gynecologic oncology has required the extension of the intervention to other non-gynecological structures, as the urinary district. Moreover the role of the urological surgery in gynecologic oncology is still not completely explored. The objective of the study is to evaluate the occurrence of urological procedures in gynecologic oncology surgery. METHODS: Patients admitted to the Division of Gynecologic Oncology, Catholic University of Sacred Hearth, Rome, Italy, between January 2009 and December 2012, were retrospectively analyzed. Clinical charts identified the occurrence of urological procedures in major gynecological surgery. RESULTS: A total of 728 patients were analyzed for the study. A total of 204 urologic procedures were carried out in 83 patients. In all patients, preoperative hydronephrosis appears to be the only statistically significant predisposing factor to urological procedures. At multivariate analysis, stratifying data for different neoplasm, recurrence was the only adjunctive significant variable for ovarian cancer, as well as neo-adjuvant treatment and recurrence for cervical cancer. CONCLUSIONS: This study has identified preoperative factors influencing the needing of urological procedures in different gynecologic neoplasms, allowing a proper planning of surgical treatment, tailored on each patient.

Comparison of optimal cytoreduction rates in emergency versus non-emergency admissions for advanced ovarian cancer: a multi-institutional study.

AIMS: to investigate whether first referral to the Emergency Department (ED) of a General Hospital is an independent risk-factor for suboptimal debulking compared to a similar population electively admitted to cytoreductive surgery, in a cohort of 307 AOC patients. METHODS: this is a multicentre case-control study, analyzing a cohort of 307 AOC patients treated at San Raffaele Hospital of Milan (111 Center A) and Gemelli Hospital of Rome (196 Center B) between January 2006/2008 and December 2010. Women are classified as patients admitted to the Hospital from ED (Cases) and out-patients (Controls). RESULTS: At univariate analysis, Cases significantly differ from Controls in terms of worse ECOG PS, larger ascites, pleuric effusion and peritoneal carcinomatosis. The rate of optimal cytoreduction is statistically lower in the Cases than Controls. At multivariate analysis, significant independent predictors for suboptimal residual disease resulted ED admission, peritoneal carcinosis and mesenteral involvement, supra radical surgery. CONCLUSIONS: Patients admitted from Emergency Department may have a lower likelihood of optimal cytoreduction, due to their poor clinical characteristics and large diffusion of the disease.

Effect of pioglitazone treatment on the adrenal androgen response to corticotrophin in obese patients with polycystic ovary syndrome.

BACKGROUND: To investigate the effect of pioglitazone on adrenal steroidogenesis in polycystic ovary syndrome (PCOS), we studied 11 obese (two with BMI >25 kg/m(2); nine with BMI >27 kg/m(2)) PCOS women before and after 6 months of treatment at a dose of 45 mg/day. METHODS: During the early follicular phase, ultrasonography and hormonal assays were performed. On separate days, all women underwent an oral glucose tolerance test (OGTT), a euglycaemic hyperinsulinaemic clamp and an adrenocorticotrophin hormone (ACTH) test. The same protocol was repeated after therapy. RESULTS: Pioglitazone treatment significantly reduced the insulin response to OGTT and improved the insulin sensitivity indices (P < 0.01 and P = 0.03 respectively). A significant decrease was found in LH (P < 0.05) and androstenedione (P < 0.01) levels after therapy, whereas the other hormonal parameters improved but not significantly. Pioglitazone administration reduced the response of 17alpha-hydroxyprogesterone (17OHP) and androstenedione to ACTH (P < 0.01 and P < 0.02 respectively), most likely through an inhibition of cytochrome P450. The same treatment was able to rebalance the relative activity of 17,20-lyase, as documented by an increase in the androstenedione:17OHP ratio (P < 0.05) after ACTH stimulation. CONCLUSIONS: Our data support the contention that insulin enhances ACTH-stimulated steroidogenesis, while inducing a relative impairment of 17,20-lyase activity. Whether the beneficial effects of pioglitazone on this imbalance could be related to the ameliorated glyco-insulinaemic metabolism or to a direct effect on the adrenal glands remains to be determined.

Second-order perturbation theory of rectangular waveguides and directional couplers.

Perturbation theory is applied to rectangular-core coupled waveguides, whose cladding can be homogeneous or not. Second-order corrections are evaluated for the phase constants of the guided modes and for the coupling coefficient. This requires the full spectrum of radiation modes, which are found within the same approximation as Marcatili's guided modes. It is found that the second-order terms are negligible in most cases of practical interest. However, there are cases for which these terms are so large that the usual first-order theory collapses.

Collisions between type II two-dimensional quadratic solitons.

We report experimental and numerical results that describe collisions between two-dimensional type II quadratic solitons excited in a KTP crystal by fundamental waves of orthogonal polarization. Our results provide experimental evidence of the possibility of both inelastic collision (when two quadratic solitons merge at input into a single soliton at output) and quasi-elastic collision.

Polarization-multiplexed x((2)) solitary-wave interactions.

We investigate interactions between vectorial solitary waves through typeII second-harmonic generation. We demonstrate that one can tune the collision distance of two initially codirectional solitary waves changing their polarization state. Moreover, by adiabatic perturbation analysis, it is possible to predict such a collision distance as a function of solitary-wave separation, in good agreement with numerical simulations.