Alicia Hernández

Urinary Tract Endometriosis: Clinical, Diagnostic, and Therapeutic Aspects

OBJECTIVES To describe our experience at La Paz University Hospital with 12 patients with urinary tract endometriosis, an uncommon pathologic finding, the most extensive series published by Spanish investigators to our knowledge. METHODS We performed a retrospective analysis of 12 cases of urinary tract endometriosis diagnosed from 1993 to 2008. RESULTS The mean patient age was 37.75 years. Of the 12 patients, 5 had bladder involvement and 7 had ureteral involvement, 2 bilateral, 2 left, and 3 right. In those with bladder endometriosis, the diagnosis was made by cystoscopy and biopsy in 4 patients. Treatment consisted of laparoscopic hysterectomy and partial cystectomy in 1 patient and exploratory laparotomy, transvesical resection, and transurethral resection of the bladder in 3 patients. One of the patients who underwent transurethral resection of the bladder experienced 2 relapses. The first relapse was treated with transurethral resection of the bladder and the second with laparoscopic partial cystectomy. In the patients with ureteral endometriosis, the diagnosis was mainly established by magnetic resonance imaging. Treatment consisted of ureteroneocystostomy in 5 patients (bilateral in 1) and laparoscopic ureterolysis in 2, with later ureteral resection and end-to-end anastomosis in 1 of them. The patient who underwent bilateral ureteroneocystostomy finally required right autotransplantation because of early ureteral relapses. CONCLUSIONS Urinary tract endometriosis is an uncommon pathologic finding. Surgery is the treatment of choice. We believe partial cystectomy should be considered as an initial option in selected cases, depending on the extent and location of lesions. For cases of ureteral endometriosis, the initial technique depends on the location and depth of the lesion.

Prognostic factors associated with local recurrence in squamous cell carcinoma of the vulva

Objective To analyze the prognostic factors related to the recurrence rate of vulvar cancer. Methods Retrospective study of 87 patients diagnosed of vulvar squamous cell carcinoma diagnosed at a tertiary hospital in Madrid between January 2000 and December 2010. Results The pathological mean tumor size was 35.1±22.8 mm, with stromal invasion of 7.7±6.6 mm. The mean free margin after surgery was 16.8±10.5 mm. Among all patients, 31 (35.6%) presented local recurrence (mean time 10 months; range, 1 to 114 months) and 7 (8%) had distant metastases (mean time, 5 months; range, 1 to 114 months). We found significant differences in the mean tumor size between patients who presented a relapse and those who did not (37.6±21.3 mm vs. 28.9±12.1 mm; p=0.05). Patients with free margins equal or less than 8 mm presented a relapse rate of 52.6% vs. 43.5% of those with free margin greater than 8 mm (p=0.50). However, with a cut-off of 15 mm, we observed a local recurrence rate of 55.6% vs. 34.5%, respectively (p=0.09). When the stromal invasion cut-off was >4 mm, local recurrence rate increased up to 52.9% compared to 37.5% when the stromal invasion was ≤4 mm (p=0.20). Conclusion Tumor size, pathologic margin distance and stromal invasion seem to be the most important predictors of local vulvar recurrence. We consider the cut-off of 35 mm of tumor size, 15 mm tumor-free surgical margin and stromal invasion >4 mm, high risk predictors of local recurrence rate.

The efficacy of robotic driven handheld instruments for the acquisition of basic laparoscopic suturing skills

OBJECTIVE To evaluate the efficacy of robotic-driven handheld laparoscopic instruments for the acquisition and improvement of basic laparoscopic suturing skills. STUDY DESIGN A prospective study was carried out on 15 physicians grouped by previous experience. They were evaluated on the completion of basic surgical laparoscopic skills. First, they used traditional non-articulating laparoscopic instruments, and later they used robotic-driven articulating instruments. RESULTS Significant time reduction was observed in the group of inexperienced physicians when they used robotic-driven instruments for needle loading and placing stitches. An 8.3% time reduction was observed in the same group when considering total times for the completion of all exercises. No significant differences for the experienced groups were found. CONCLUSIONS Robotic-driven handheld instruments could help inexperienced physicians acquire basic skills in laparoscopic techniques. No benefit has been observed when previous laparoscopic experience is present.

Management of thoracic endometriosis: single institution experience

OBJECTIVE Thoracic endometriosis is a relatively rare type of endometriosis and includes catamenial pneumothorax, hemothorax and hemoptysis, and presence of intrathoracic endometriotic nodules. We want to clarify and resume the most appropriate management of this pathology. STUDY DESIGN We retrospectively reviewed all the cases of thoracic endometriosis diagnosed and followed up in our Unit from 2005 to 2013. This search revealed five women, with a mean age of 34.5 (26-44). Four had previous history of endometriosis or severe dysmenorrhea. One patient complained of chronic shoulder pain with diaphragmatic implants, another one presented catamenial hemoptysis, and three women suffered from catamenial pneumothorax, with right-side preference. RESULTS Three patients underwent surgery and all of them were treated with GnRH agonists at least during 6 month referring improvement in symptoms. After 1-8 years follow-up, all these patients remain asymptomatic. CONCLUSION The optimal management of thoracic endometriosis needs further evaluation but the combined approach by hormonal therapy and surgery could be the best option.

Single-port laparoscopic extraperitoneal para-aortic lymphadenectomy.

Objective The aim of this study was to evaluate the feasibility and the safety of single-port extraperitoneal laparoscopic para-aortic lymphadenectomy for patients with gynecologic cancer. Methods From July 2012 to January 2013, a total of 7 patients with gynecologic cancer underwent a laparoscopic pelvic and para-aortic lymphadenectomy with a single-port device. An extraperitoneal approach was performed for para-aortic lymphadenectomy using only one 2.5-cm incision on the left side. In 6 patients, additionally, hysterectomy and pelvic lymphadenectomy with conventional laparoscopy were performed to complete the treatment. Results Aortic dissection was complete in all cases without complications. The median age of the patients was 63 years (range, 48–78 years), and the median patient body mass index was 31 kg/m2 (range, 19–38 kg/m2). The median number of para-aortic nodes was 17 (range, 10–25); the median operative time was 204 minutes (range, 120–300 minutes). The median hospital stay was 4 days (range, 3–6 days). No patient encountered postoperative complications. Conclusions This study demonstrates the feasibility of single-port laparoscopic extraperitoneal para-aortic lymphadenectomy.

Pelvic Exenteration in Gynecologic Cancer: La Paz University Hospital Experience.

Background Pelvic exenteration is an ultraradical surgery involving the en bloc resection of the pelvic organs, including the internal reproductive organs, the distal urinary tract (ureters, bladder, urethra), and/or anorectum. It is mainly applied as a salvage surgery for recurrent gynecologic tumors of any origin (vulva, vagina, cervix, uterine, and also ovary). Our aim was to establish the most favorable cases for this type of surgery by means of a review of our institution experience. Methods Retrospective analyses of all patients treated with pelvic exenteration for recurrent gynecologic cancer from 2008 to 2014 at La Paz University Hospital. Results Ten patients underwent pelvic exenteration for recurrent gynecologic cancers including uterine, cervical, vaginal, vulvar, and ovarian cancer. All patients had received prior treatment: surgery, radiotherapy, and/or chemotherapy. Eight patients underwent total pelvic exenteration, one anterior and one posterior pelvic exenteration. Urinary diversions technique consisted of ileal conduits in all cases. Permanent colostomy was performed in all cases. Postoperative complications were related to the urinary diversion in 50% of the cases, to the reconstructive technique in 30%, and to systemic or pelvic infections in 20%. Conclusions Despite the high morbidity and mortality rates, pelvic exenteration is feasible, and in selected cases of cancer recurrence is the last possible treatment.

Abstract 392: Predictive value of angiogenesis related genes in advanced ovarian carcinoma

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Management of advanced ovarian cancer (AOC) involves surgery in order to achieve surgical cytoreduction followed by chemotherapy. Combination platinum (C) - paclitaxel (P) chemotherapy has become a standard first line treatment for the advanced-stage disease. Outcome is significantly improved with this regimen and 40 to 50% achieve complete clinical remission. Classical parameters such as age at diagnosis, extent of disease residual disease after surgery, and the histopathological features of the tumor are imperfect predictors of response. Angiogenesis plays a major rol in ovarian carcinogenesis and antiangiogenic compounds such as bevacizumab proved efficacy in AOC in early phase trials. The aim of this study is to build a profile able to predict clinical response to multimodal first line therapy. Materials and Methods: 61 patients with III/IV FIGO stage ovarian cancer who underwent surgical cytoreduction and received a C plus P regimen were included. RNAs were collected from formalin-fixed paraffin-embedded AOC samples. Expression levels of 82 angiogenesis related genes were measured using quantitative real time polymerase chain reaction. Clinical response was evaluated using CT after the completion of multimodal therapy. Statistical analysis was performed using a regression method to generate multiple models based on the significant genes. The accuracy of the models was evaluated using Receiver Operating Characteristic (ROC) curves. The Akaike Information Criterion based selection was used to find the most accurate one. Results: The median age at diagnosis was 53 years (range, 21 to 82 years). All patients had advanced disease (FIGO stages III/IV). Most of them had FIGO stage III (51, 83.6%), grade 3 tumors (35, 57.4%), and serous histology (42, 68.9%). 52 patients (85.2%) achieved an initial response (complete response or partial response by RECIST criteria) to this therapy. It was found an independent model able to predict any degree of response to therapy comprising 8 genes with an Area Under the Curve (AUC) of 0.955 (p<0.001). Leave-one-out cross validation was applied to avoid overfitting of the model, obtaining a corrected AUC of 0.880, 95%IC: 0,776-0,985. Conclusions: It is possible to generate a predictive model of clinical response for ovarian cancer based on angiogenesis related genes using formalin-fixed paraffin-embedded samples. The present results are consistent with the increasing weight of several angiogenesis genes in prognosis of ovarian cancer. Although these results should be validated prospectively in larger series of ovarian cancer patients, this model could identify those patients that would achieve any degree of response to standard treatment. So it could be used to tailor therapy in those patients with no response at all to treatment. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 392.

High-throughput 3-dimensional culture of epithelial ovarian cancer cells as preclinical model of disease

Background Recent reports have identified distinct genomic patterns in ovarian carcinoma, including proliferative and mesenchymal-like groups, with worse outcome. The exact mechanisms driving the onset and progression of these tumors are still poorly understood. Additionally, researchers are concerned about the correct subtype stratification of the available cell line models, and the exploration of alternatives to monolayer culture. Identification of biomarkers to stratify cell lines, characterization of important processes as epithelial-mesenchymal transition (EMT), and the use of three-dimensional (3D) cultures as alternative models could be useful for cell line classification. Methods and Results In this work, we present a descriptive analysis of 16 commonly used ovarian cancer cell lines. We have studied their morphology in 2- and 3D culture, and their response to cisplatin, observing in the majority of them an increased resistance in 3D. We have also performed an immunohistochemical analysis for proliferation marker Ki-67, and EMT related markers to establish phenotypes. Epithelial cells tend to show higher proliferative rates, and mesenchymal cells show an increase in EMT related markers, especially when cultured in 3D conditions. Conclusions We have stated the complex heterogeneity of ovarian cancer models, resembling primary tumors, agreeing with the argument that the cell line model for in vitro experiments must be carefully chosen. Our results also support that tridimensional culture could be a very helpful alternative in ovarian cancer research. Regarding EMT, a very important process for the development of this disease, some related biomarkers might be further characterized for their role in this disease development.

Predicting Response to Standard First-line Treatment in High-grade Serous Ovarian Carcinoma by Angiogenesis-related Genes

Background/Aim: Predicting response to treatment in high-grade serous ovarian carcinoma (HGSOC) still remains a clinical challenge. The standard-of-care for first-line chemotherapy, based on a combination of carboplatin and paclitaxel, achieves a high response rate. However, the development of drug resistance is one of the major limitations to efficacy. Therefore, identification of biomarkers able to predict response to chemotherapy in patients with HGSOC is a critical step for prognosis and treatment of the disease. Several studies suggest that angiogenesis is an important process in the development of ovarian carcinoma and chemoresistance. The aim of this study was to identify a profile of angiogenesis-related genes as a biomarker for response to first-line chemotherapy in HGSOC. Materials and Methods: Formalin-fixed paraffin-embedded samples from 39 patients with HGSOC who underwent surgical cytoreduction and received a first-line chemotherapy with carboplatin and paclitaxel were included in this study. Expression levels of 82 angiogenesis-related genes were measured by quantitative real-time polymerase chain reaction using TaqMan low-density arrays. Results: Univariate analysis identified five genes [angiopoietin 1 (ANGPT1), aryl hydrocarbon receptor nuclear translocator (ARNT), CD34, epidermal growth factor (EGF) and matrix metallopeptidase 3 (MMP3)] as being statistically associated with response to treatment. Multivariable analysis by Lasso-penalized Cox regression generated a model with the combined expression of seven genes [angiotensinogen (AGT), CD34, EGF, erythropoietin receptor (EPOR), interleukin 8 (IL8), MMP3 and MMP7)]. The area under the receiver operating characteristics curve (0.679) and cross-validated Kaplan–Meier survival curves were used to estimate the accuracy of these predictors. Conclusion: An angiogenesis-related gene expression profile useful for response prediction in HGSOC was identified, supporting the important role of angiogenesis in HGSOC.

398 Influence of Nutritional Status at 36 Weeks Postmenstrual Age on Body Composition of Vlbw Infants on the First Two Years

398 Influence of Nutritional Status at 36 Weeks Postmenstrual Age on Body Composition of Vlbw Infants on the First Two Years