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Background Although surgery represents the cornerstone treatment of endometrial cancer at initial diagnosis, scarce data are available in recurrent setting. The purpose of this study was to review the outcome of surgery in these patients. Methods Medical records of all patients undergoing surgery for recurrent endometrial cancer at NCI Milano between January 2003 and January 2014 were reviewed. Survival was determined from the time of surgery for recurrence to last follow-up. Survival was estimated using Kaplan–Meier methods. Differences in survival were analyzed using the log-rank test. The Fisher’s exact test was used to compare optimal versus suboptimal cytoreduction against possible predictive factors. Results Sixty-four patients were identified. Median age was 66 years. Recurrences were multiple in 38 % of the cases. Optimal cytoreduction was achieved in 65.6 %. Median OR time was 165 min, median postoperative hemoglobin drop was 2.4 g/dl, and median length hospital stay was 5.5 days. Eleven patients developed postoperative complications, but only four required surgical management. Estimated 5-year progression-free survival (PFS) was 42 and 19 % in optimally and suboptimally cytoreduced patients, respectively. At multivariate analysis, only residual disease was associated with PFS. Estimated 5-year overall survival (OS) was 60 and 30 % in optimally and suboptimally cytoreduced patients, respectively. At multivariate analysis, residual disease and histotype were associated with OS. At multivariate analysis, only performance status was associated with optimal cytoreduction. Conclusions Secondary cytoreduction in endometrial cancer is associated with long PFS and OS. The only factors associated with improved long-term outcome are the absence of residual disease at the end of surgical resection and histotype.

The widespread introduction of screening methods allow to identify cervical dysplasia before having invasive cancer. The risk of developing cervical dysplasia persistence/ recurrence following conization represent a major health issue. Although several studies tried to identify predictors for cervical dysplasia persistence/recurrence, no previous study has been conducted to develop a risk calculator. The current study aimed to identify predictors of cervical dysplasia persistence/recurrence among women undergoing primary conization. We aimed to build nomograms estimating the risk of developing cervical dysplasia recurrence. Data of consecutive women with diagnosis of high-risk human papillomavirus (HPV) undergoing conization were retrospectively evaluated (1503 patients). The risk of developing cervical dysplasia persistence/recurrence was assessed with Kaplan–Meier and Cox’s hazard models. Additionally, two nomograms were built to estimate likelihood of cervical dysplasia recurrence: the first based on baseline and operative parameters and the second focusing on type-specific HPV detected. The performance of the above nomograms was assessed using concordance index. A total of 1503 patients were analyzed. After a mean (SD) follow-up of 48.6 ( ± 17.5) months, 84 (5.6%) patients required secondary conization. By multivariate analysis, HIV infection [hazard ratio (HR): 7.78; 95% confidence interval (CI): 2.77–21.81; P < 0.001], positive margins (HR: 26.2; 95% CI: 14.1–48.71; P < 0.001) and persistence of HPV (HR: 6.82; 95% CI: 4.15–11.21; P < 0.001) correlated with cervical intraepithelial neoplasia 2+ persistence/recurrence. The importance of those variables was corroborated by our first nomogram. The second nomogram suggested the impact of type-specific HPV infection in predicting cervical dysplasia persistence/ recurrence. HPV16, HPV18, HPV33, HPV35 and HPV45 were the HPV types most commonly associated with cervical dysplasia persistence/recurrence. The concordance index was greater than 0.70 for both nomograms, thus suggesting the reproducibility of our models. We developed the first two nomograms predicting this risk. The findings of this study require external validation. Once validated our data might be useful to plan a tailored postoperative surveillance of women receiving primary conization.

Purpose To investigate whether the total number of removed lymph nodes (LNs) and the number of metastatic LNs would prove to be independent prognostic factors for survival in patients with cervical cancer (CC). Methods Data from patients with CC who underwent radical surgery between March 1980 and September 2009 were reviewed. A total of 526 patients were included in the statistical analysis. Full pathologic evaluation was performed. The total number of examined LNs and their histopathological status were analyzed for their prognostic effect on survival by means of multivariable Cox proportional hazard regression models. Results The median number (interquartile range) of total, pelvic, and para-aortic nodes removed was 37 (29–47), 34 (27–42), and 19 (14–24), respectively. Positive pelvic nodes were found in 102 of 526 (19 %) patients. All 8 patients with para-aortic metastases had also pelvic node metastases. At multivariable analysis, vaginal involvement, type of lymphadenectomy and LN status all significantly negatively affected disease-free survival and overall survival, whereas the number of total LNs removed did not affect survival. Conclusions LN metastasis and number of LN metastases confer an independent risk for worse survival in patients with CC. Pelvic lymphadenectomy is important for staging and regional disease control when LNs are involved. If a standardized complete lymphadenectomy is performed, the number of LNs is not a significant factor per se.

Purpose To investigate oncological outcomes and patterns of recurrence of patients undergoing adjuvant “sandwich” chemo-radio-chemotherapy for locally advanced endometrial cancer. Methods This is a multi-institutional retrospective study evaluating chart of consecutive patients undergoing chemo-radio-chemotherapy for FIGO stage III–IVA endometrial caner. Results The study population included 45 patients who had adjuvant sandwich regimen. Median age of the study population was 66 years. The majority of patients were diagnosed with endometrioid histology and with stage III disease. After a median follow-up of 35 months, 15 patients developed recurrent disease. Three-year disease-free and overall survivals was 45% and 81%, respectively. Three-years site-specific disease-free survival was 85%, 92% and 48% for local, loco-regional, and distant recurrence, respectively. All patients included in the study had nodal dissection. Nodal assessment included: sentinel node mapping, sentinel node mapping plus backup lymphadenectomy and lymphadenectomy in 15, 6 and 24 patients, respectively. The latter group included four patients detected by suspected enlarged nodes, intraoperatively. Even after the exclusion of patients with enlarged nodes, the type of nodal assessment did not impact on survival outcomes ( p  > 0.2). Positive peritoneal cytology was the only factor associated with an increased risk of developing (any site) recurrence and distant-specific recurrence, independently. No factor predicted for overall survival. Conclusion Adjuvant “sandwich” chemo-radio-chemotherapy for locally advanced endometrial cancer guarantee promising local and loco-regional controls, but distant failure rate is high, thus suggesting the need for applying other systemic treatment strategies for these patients.

VLPs contain repetitive, high-density displays of viral surface proteins that present conformational viral epitopes that can elicit strong T cell and B cell immune responses [2]. [...]VLPs would be adopted for delivery of genes and other therapeutic agents [3]. Bogani, G.; Maggiore, U.L.R.; Signorelli, M. The role of human papillomavirus vaccines in cervical cancer: Hanna, D.L. CMP-001 and INCAGN01949 for Patients with Stage IV Pancreatic Cancer and Other Cancers Except Melanoma.

Background The purpose of this observational study was to evaluate disease-free survival, overall survival, local recurrence rate, and morbidities in patients submitted to class III nerve-sparing radical hysterectomy (NSRH) compared with standard radical hysterectomy (RH) in cervical cancer (CC). This was a comparative study in the context of multimodal therapies. Materials and Methods We investigated patients with CC admitted to the National Cancer Institute of Milan between January 4, 2001, and September 29, 2009, treated with NSRH. We compared patients operated with RH between March 20, 1980, and December 28, 1995. A total of 496 patients were enrolled. The median follow-up was 93 months (42 and 159 months for the NSRH and RH groups, respectively). Results The overall number of relapses was 30 out of 185 and 60 out of 311 for NSRH and RH, respectively. Five-year disease-free survival estimate was 78.9% (95% confidence interval [CI] 72.0–85.7) in NSRH and 79.8% (95% CI 75.3–84.3) in RH ( P  = 0.519). Five-year overall survival estimate was 90.8% (95% CI 85.9–95.6) in NSRH and 84.1% (95% CI 8.0–88.3) in RH ( P  = 0.192). Rates of postoperative serious complications were 9.7% and 19.6% for NSRH and RH, respectively ( P  = 0.004). Positive pelvic lymph node and vagina status were significant ( P  < 0.01) independent predictors by multivariable analyses. Conclusions The oncologic results were comparable between NSRH and conventional class III RH in the context of two multimodal treatments. Bladder function and postoperative complications rate are improved by nerve-sparing technique. The nerve-sparing technique should be considered in all CC patients addressed to surgery because it improves functional outcome and preserves radicality without compromising overall survival.

ObjectiveTransfusions represent one of the main progresses of modern medicine. However, accumulating evidence supports that transfusions correlate with worse survival outcomes in patients affected by solid cancers. In the present study, we aimed to investigate the effects of perioperative blood transfusion in locally advanced cervical cancer.MethodsData of consecutive patients affected by locally advanced cervical cancer scheduled to undergo neoadjuvant chemotherapy plus radical surgery were retrospectively searched to test the impact of perioperative transfusions on survival outcomes. Five-year survival outcomes were evaluated using Kaplan-Meier and Cox models.ResultsThe study included 275 patients. Overall, 170 (62%) patients had blood transfusion. Via univariate analysis, we observed that transfusion correlated with an increased risk of developing recurrence (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.09–4.40; P = 0.02). Other factors associated with 5-year disease-free survival were noncomplete clinical response after neoadjuvant chemotherapy (HR, 2.99; 95% CI, 0.92–9.63; P = 0.06) and pathological (P = 0.03) response at neoadjuvant chemotherapy as well as parametrial (P = 0.004), vaginal (P < 0.001), and lymph node (P = 0.002) involvements. However, via multivariate analysis, only vaginal (HR, 3.07; 95% CI, 1.20–7.85; P = 0.01) and lymph node involvements (HR, 2.4; 95% CI, 1.00–6.06; P = 0.05) correlate with worse disease-free survival. No association with worse outcomes was observed for patients undergoing blood transfusion (HR, 2.71; 95% CI, 0.91–8.03; P = 0.07). Looking at factors influencing overall survival, we observed that lymph node status (P = 0.01) and vaginal involvement (P = 0.06) were independently associated with survival.ConclusionsThe role of blood transfusions in increasing the risk of developing recurrence in LAAC patients treated by neoadjuvant chemotherapy plus radical surgery remains unclear; further prospective studies are warranted.

Epithelial ovarian cancer (EOC) is the gynecological disease with the highest death rate. We applied an automatic class discovery procedure based on gene expression profiling to stages III–IV tumors to search for molecular signatures associated with the biological properties and progression of EOC. Using a complementary DNA microarray containing 4451 cancer-related, sequence-verified features, we identified a subset of EOC characterized by the expression of numerous genes related to the extracellular matrix (ECM) and its remodeling, along with elements of the fibroblast growth factor 2 (FGF2) signaling pathway. A total of 10 genes were validated by quantitative real-time polymerase chain reaction, and coexpression of FGF2 and fibroblast growth factor receptor 4 in tumor cells was revealed by immunohistochemistry, confirming the reliability of gene expression by cDNA microarray. Since the functional relationships among these genes clearly suggested involvement of the identified molecular signature in processes related to epithelial–stromal interactions and/or epithelial–mesenchymal cellular plasticity, we applied supervised learning analysis on ovarian-derived cell lines showing distinct cellular phenotypes in culture. This procedure enabled construction of a gene classifier able to discriminate mesenchymal-like from epithelial-like cells. Genes overexpressed in mesenchymal-like cells proved to match the FGF2 signaling and ECM molecular signature, as identified by unsupervised class discovery on advanced tumor samples. In vitro functional analysis of the cell plasticity classifier was carried out using two isogenic and immortalized cell lines derived from ovarian surface epithelium and displaying mesenchymal and epithelial morphology, respectively. The results indicated the autocrine, but not intracrine stimulation of mesenchymal conversion and cohort/scatter migration of cells by FGF2, suggesting a central role for FGF2 signaling in the maintenance of cellular plasticity of ovary-derived cells throughout the carcinogenesis process. These findings raise mechanistic hypotheses on EOC pathogenesis and progression that might provide a rational underpinning for new therapeutic modalities.

ObjectiveRecent evidence has suggested that laparoscopic radical hysterectomy is associated with an increased risk of recurrence in comparison with open abdominal radical hysterectomy. The aim of our study was to identify patterns of recurrence after laparoscopic and open abdominal radical hysterectomy for cervical cancer.MethodsThis a retrospective multi-institutional study evaluating patients with recurrent cervical cancer after laparoscopic and open abdominal surgery performed between January 1990 and December 2018. Inclusion criteria were: age ≥18 years old, radical hysterectomy (type B or type C), no recurrent disease, and clinical follow-up >30 days. The primary endpoint was to evaluate patterns of first recurrence following laparoscopic and open abdominal radical hysterectomy. The secondary endpoint was to estimate the effect of the primary surgical approach (laparoscopy and open surgery) in post-recurrence survival outcomes (event-free survival and overall survival). In order to reduce possible confounding factors, we applied a propensity-matching algorithm. Survival outcomes were estimated using the Kaplan-Meier model.ResultsA total of 1058 patients were included in the analysis (823 underwent open abdominal radical hysterectomy and 235 patients underwent laparoscopic radical hysterectomy). The study included 117 (14.2%) and 35 (14.9%) patients who developed recurrent cervical cancer after open or laparoscopic surgery, respectively. Applying a propensity matched comparison (1:2), we reduced the population to 105 patients (35 vs 70 patients with recurrence after laparoscopic and open radical hysterectomy). Median follow-up time was 39.1 (range 4–221) months and 32.3 (range 4–124) months for patients undergoing open and laparoscopic surgery, respectively. Patients undergoing laparoscopic radical hysterectomy had shorter progression-free survival than patients undergoing open abdominal surgery (HR 1.98, 95% CI 1.32 to 2.97; p=0.005). Patients undergoing laparoscopic radical hysterectomy were more likely to develop intrapelvic recurrences (74% vs 34%; p<0.001) and peritoneal carcinomatosis (17% vs 1%; p=0.005) than patients undergoing open surgery.ConclusionsPatients undergoing laparoscopic radical hysterectomy are at higher risk of developing intrapelvic recurrences and peritoneal carcinomatosis. Further evidence is needed in order to corroborate our findings.

Introduction/BackgroundDuring radical pelvic surgeries fibers of the autonomic pelvic nervous network can be accidentally damaged leading to significant visceral sequalae, which dramatically affect women’s quality of life because of urinary, anorectal, and sexual postoperative dysfunctions. Direct visualization seems to be the only way to preserve hypogastric nerves(HNs), pelvic splanchnic nerves(PSNs), and the bladder branches from the inferior hypogastric plexus(IHP). However, the literature lacks critical photos and/or illustrations that are necessary to understand the precise anatomy needed to preserve the pelvic autonomic fibers. Here, we performed laparoscopic surgery, before LACC era, identifying key anatomic landmarks useful to highlight the path of the most commonly encountered autonomic pelvic nerves in gynecologic radical surgery: during the narration we describe and illustrate the procedure to identify all autonomic pelvic nerves, the sympathetic fibers, the PSNs, and the bladder branch emerging from the IHP in order to preserve their anatomic and functional integrity.MethodologyNarrated laparoscopic video footage for identifying, dissecting, and preserving the autonomic nerve bundles during pelvic surgery.ResultsThis technique is anatomically and surgically valid for adequate removal of the parametrial issues and vagina while preserving the total pelvic nervous system.ConclusionNerve-sparing¬ surgery reduces bowel-, bladder- and sexual­ dysfunction without decreasing surgical efficacy. The comprehension of the three-dimensional structure of the vascular and nerve anatomy in the pelvis is the right way to perform nerve sparing radical surgery effectively and safely. This video provides a great resource to educate surgeons, especially the youngest ones, about the retroperitoneal nervous networking: we identified the autonomic nerve pathway from adjacent tissues along the pathway consisting of cardinal, sacro-uterine, rectouterine/vaginal, and vesico-uterine ligaments.DisclosuresNothing to disclose.