A systematic review and meta-analysis of the prevalence of therapeutic targets in cervical cancer.

Cervical Cancer (CC) is a significantly prevalent disease in developing countries. Currently, targeted therapies are not a primary standard of care in CC. This information could be crucial for developing directed therapies and patient screening for biomarkers that would allow personalised treatment of CC. This systematic review aimed to estimate the prevalence of potential therapeutic targets such as the epidermal growth factor receptor (EGFR) and the PI3K/Akt/mTOR and Ras/Raf/MAPK pathways in patients with CC, identified through genomic and non-genomic testing. Studies were identified through an ad-hoc search strategy from the available on MEDLINE (Ovid), CENTRAL, LILACS, SCOPUS, through the Clinical Trial registry on Clinicaltrials.gov, International Clinical Trials Registry Platform, RENIS (Argentine National Registry of Health Research) and grey literature sources. We included 74 studies which represented a total pool of 7,862 participants. Forty-five studies informed mutations of EGFR, with a combined positivity rate of 53% (95%CI: 45%-60%; I2 = 95%). Twenty studies informed the presence of mutations in PIK3CA with a combined positivity rate of 30% (95%CI: 21%-39%; I2 = 96%). Twenty-three studies reported a mutation in Ras, with a combined positivity rate of 14% (95%CI: 8%-21%; I2 = 95%). Raf mutations were informed in six studies. Six studies informed the presence of Akt mutations, two studies informed mTOR mutations and only one study reported mutations of MAPK. The most frequently described therapeutic targets were EGFR, and the PIK3CA and Ras pathways, though inconsistency in positivity rates was significant. Our study did not allow the identification of any specific clinical characteristics that might explain the observed heterogeneity. Despite the overall good quality of the included studies, the applicability of these results to patients' general population with CC is still unclear.

Extra-uterine endometrial stromal sarcoma arising from deep infiltrating endometriosis.

We present a compelling case of a 45-year-old female with a history of endometriosis and leiomyomas, who presented to her gynecologist with chronic pelvic pain complaints. Both a transvaginal ultrasound (US) and an MRI (magnetic resonance imaging) were ordered. The US demonstrated multiple uterine lesions, likely fibroids, and an endometrioma within the right ovary. The MRI of the pelvis with and without gadolinium identified a mass within the right ovary with homogenous intermediate T2-signal, restricted diffusion, and delayed enhancement relative to the myometrium. Several irregular-shaped lesions were also noted within the external myometrium, anterior pelvic wall, and the peritoneum, which were intermediate signal on T2-weighted images, restricted diffusion, and an enhancement pattern similar to the myometrium. The patient underwent a right adnexectomy. The histopathology findings were consistent with a low-grade endometrial stromal sarcoma (low grade-ESS) arising from the endometrial stroma of the right ovary. A debulking surgery confirmed the involvement of external myometrium, anterior pelvic wall, and the peritoneum secondary to a low-grade ESS without the endometrial cavity's involvement. The underlying hypothesis is that the endometriosis stroma from extra-uterine structures such as the right ovary, pelvic and anterior peritoneum, and external myometrium may have subsequently resulted in a low-grade ESS. Low-grade extra-uterine ESS without endometrial involvement is a rare entity. Based on our literature search, this is one of the few reports covering the radiological features of low-grade extra-uterine ESS arising outside the uterus with a concomitant deep infiltrating endometriosis, but without the involvement of the endometrial cavity.

Incidence of Lymph Node Metastases in Women With Low-Risk Early Cervical Cancer (<2 cm) Without Lymph-Vascular Invasion.

OBJECTIVE: To determine the incidence of lymph node metastasis in women with low-risk cervical cancer stage IA2 or IB1 (<2 cm) without lymph-vascular space invasion. METHODS: A multicenter retrospective study was performed in patients who underwent radical or simple hysterectomy, conization, or trachelectomy plus pelvic lymphadenectomy for cervical cancer between January 2000 and June 2016. RESULTS: A total of 271 patients were included in the study. Median age and body mass index were 46 years (range, 23-77 years) and 24 kg/m (range, 18-48 kg/m), respectively. Twenty-two patients had stage IA2 (8.1%), and 249 (91.9%) had stage IB1. The median tumor size was 14 mm (range, 5-20 mm). Tumor grades were 1 (n = 63 [23.2%]), 2 (n = 120 [44.3%]), 3 (n = 63 [23.2%]), and unknown (25 [9.2%]). Median depth stromal invasion was 6 mm (range, 3-20 mm). Histologic subtypes included squamous (n = 171 [63.1%]), adenocarcinoma (n = 92 [33.9%]), and adenosquamous (n = 8 [3.0%]). Overall incidence of lymph node metastasis was 2.9% (n = 8). The incidence of lymph node involvement in G1, G2, and G3 was 0% (0/63), 5% (6/120), and 3.1% (2/63), respectively. No patient with stage IA2 (regardless of grade or histology) or G1 cervical cancer less than 2 cm (stage IB1) had lymph node metastasis. CONCLUSIONS: Patients with stage IA2 or IB1 (G1) with tumor size of less than 2 cm and no lymph-vascular space invasion may not need lymph node evaluation. On the other hand, 95% and 98% of patients with grade 2 or 3 tumors, respectively, could potentially undergo an unnecessary lymphadenectomy. Further studies with bigger sample size are required to confirm these results.

Role of Fallopian Tubes in the Development of Ovarian Cancer.

Ovarian cancer is the leading cause of death from gynecologic malignancy and the fifth cause of cancer death in women in the United States. The most common and lethal histologic subtype of epithelial ovarian cancer is high-grade serous carcinoma (HGSC), which generally presents at an advanced stage. HGSC may be associated with BRCA1 and BRCA2 mutations. Historically, HGSC was believed to originate from the ovarian epithelial cells. However, more recent evidence supports the idea that most ovarian cancers originate in the fallopian tube epithelium in both high-risk women and in the general population. Serous tubal intraepithelial carcinomas may ultimately evolve into ovarian or peritoneal cancer. As a result, prophylactic salpingectomy with conservation of the ovaries has become an increasingly more common practice for premenopausal women undergoing risk-reducing surgery. Because the fallopian tube is now recognized as the most common potential site of origin of ovarian carcinoma, there is ongoing research to explore molecular and genetic factors that may be critical in the development of this disease. Further research is needed to identify novel opportunities for early detection and screening of ovarian cancer with the ultimate goal of increasing overall survival.

Robotic Versus Open Radical Hysterectomy in Women With Locally Advanced Cervical Cancer After Neoadjuvant Chemotherapy: A Single-institution Experience of Surgical and Oncologic Outcomes.

STUDY OBJECTIVE: To compare the surgical and oncologic outcomes of robotic radical hysterectomy (RRH) versus laparotomy in women with locally advanced cervical cancer (LACC) after neoadjuvant chemotherapy (NACT). SETTING: Oncology referral center. DESIGN: A retrospective comparative observational study was performed in 30 patients with LACC Fédération Internationale de Gynécologie et d'Obstétrique stage IB2-IIB who underwent RRH after NACT between February 2008 and December 2014. This group was compared with a cohort of 44 patients with similar characteristics who underwent abdominal radical hysterectomy after NACT (Canadian Task Force classification II2). PATIENTS: Patients with LACC FIGO stage IB2-IIB. INTERVENTIONS: A retrospective comparative observational study. MEASUREMENTS AND MAIN RESULTS: The mean (standard deviation [SD]) operative time was significantly longer in the robotic group (307.8 minutes [40.2] vs 233.7 minutes [61.9], p ≤ .001). On the contrary, the mean (SD) estimated blood loss was significantly lower in the robotic group (111.0 mL [69.6] vs 286.9 mL [159.1], p ≤ .001), and length of stay was significantly shorter (4.1 [2.4] days vs 5.8 days [3.3], p = .015). The incidence of intraoperative and early and late complications was not statistically significantly different between the 2 groups. The mean (SD) follow-up of patients was 35.6 months (28.4) and 43.7 months (23.2) in the open and robotic groups, respectively (p = .137). The disease recurrence rate (27.2% vs 20%) was similar between the 2 groups; sites and types of recurrences were also similar. Kaplan-Meier survival analysis for median progression-free survival and median overall survival were not statistically different comparing cohorts by surgery type. CONCLUSIONS: RRH after NACT in women with LACC is associated with similar perioperative and oncologic outcomes to open procedure. These results require further investigation to establish a more robust conclusion.

Use of TachoSil® to Prevent Symptomatic Lymphocele after an Aggressive Tumor Debulking with Lymphadenectomy for Advanced Stage Ovarian Cancer. A Pilot Study.

OBJECTIVE: To describe the incidence of symptomatic lymphocele (SLC) after an aggressive tumor debulking surgery and lymphadenectomy in patients with ovarian cancer and peritoneal carcinomatosis with or without TachoSil®. MATERIAL AND METHODS: A pilot retrospective comparative observational study was performed between patients with advanced ovarian cancer International Federation of Gynecology and Obstetrics stages III-IV who underwent complete debulking surgery and radical retroperitoneal lymphadenectomy. In 18 patients, 4 TachoSil® patches were placed in the retroperitoneal area, since January 2014-October 2014. This group was compared with other 18 consecutive patients matched by age, International Federation of Gynecology and Obstetrics stage, surgical complexity, American Society of Anesthesiologists score, comorbidity, and BMI without the use of TachoSil®. RESULTS: Baseline characteristics were similar between groups. There were no statistically significant differences in terms of surgical complexity, surgical time, estimated blood loss, node removed, length of hospital stay, and complications between groups. SLC was diagnosed in 7 patients (38.8%) without TachoSil®, and in 2 patients (11.1%) with TachoSil® (p = 0.121). The use of TachoSil® was associated with a statistically significant lower re-admission rate (p = 0.041) and with a significantly shorter time to adjuvant chemotherapy (p = 0.02). CONCLUSIONS: Using TachoSil® in women with advanced stage ovarian cancer who underwent radical debulking with retroperitoneal lymph node dissection is associated with a non-statistically significant reduction in the incidence of SLC. A larger-scale randomized controlled study should be conducted to confirm our preliminary results.

Laparoscopic surgical staging in women with early stage epithelial ovarian cancer performed by recently certified gynecologic oncologists.

OBJECTIVE: To compare the surgical and oncological outcomes of laparoscopic versus open surgical staging in patients with early stage ovarian cancer performed by recently certified gynecologic oncologists. STUDY DESIGN: A retrospective comparative observational study was performed, which included women who had undergone laparoscopic comprehensive surgical staging for early stage epithelial ovarian cancer between June, 2008 and January, 2014. Patients were compared with women who had undergone laparotomic staging between June, 2006 and January, 2014. RESULTS: A total of 50 and 58 patients underwent, laparoscopic and laparotomy surgical staging, respectively. The patients' baseline characteristics were similar in both groups. Women in the laparoscopy group had a significantly lower preoperative CA-125 value (p=0.01). The operative time was similar between groups. The patients in the laparotomy group had significantly higher estimated blood loss (p≤0.001) and larger ovarian masses (p=0.001). Estimated blood loss was significantly higher in laparotomy versus laparoscopy; median (IQ range) 200 (200-225) ml and 500 (300-1000) ml (p≤0.0001). Intraoperative complications and postoperative complication rate was similar in both groups regardless of the type of surgical procedure; and laparoscopy was associated with a significantly shorter length of the hospital stay (p≤0.001). The number of lymph node retrieved and upstaging rate, as well as progression free survival and overall survival rates, were similar in both groups. CONCLUSIONS: Laparoscopic surgical staging of apparent early stage ovarian cancer has similar surgical and oncological outcomes to laparotomy when recently certified gynecologic oncologists perform the procedures.

Laparoscopic surgery for treating adnexal masses during the first trimester of pregnancy.

OBJECTIVE: To evaluate the feasibility and safety of laparoscopic surgery for treating adnexal masses during the first trimester of pregnancy. STUDY DESIGN: An observational study of a prospective collection of data of all pregnant women who underwent laparoscopic surgery for adnexal masses during the first trimester of pregnancy between January 1999 and November 2012 at the Obstetrics and Gynecology Department of the Italian Hospital of Buenos Aires, Buenos Aires, Argentina was performed. RESULTS: A total of 13 women were included. The median (range) gestational age at the moment of surgical procedure was 7 weeks (range: 5-12 weeks). The main indication of surgery was cyst torsion in four cases (30.7%) and rupture of ovarian cysts in four cases (30.7%). Other indications included persistent ovarian cyst in three patients (23%) and heterotopic pregnancy in two cases (15.3%). Neither surgical complications nor spontaneous abortions occurred in any of the cases and the post-operative period was uneventful in all the cases. No cases of intrauterine growth retardation, preterm delivery, congenital defects, or neonatal complications were registered. CONCLUSION: The treatment of complicated adnexal masses by laparoscopic surgery during the first trimester of pregnancy appears to be a safe procedure both for the mother and for the foetus. Additional research on a larger number of cases is still needed to support these conclusions.

Clinical outcomes in patients with isolated serous tubal intraepithelial carcinoma (STIC): A comprehensive review.

OBJECTIVE. Serous tubal intraepithelial carcinoma (STIC) is currently considered the precursor lesion of pelvic (i.e., ovarian or peritoneal) high-grade serous carcinoma. The incidence of STIC has been reported to range from 0.6% to 7% in BRCA mutations carriers. However, the clinical outcome of patients with 'isolated' STIC remains elusive. The aim of this study is to review the published literature on isolated STIC to determine outcomes of these ients and present a summary of management strategies. METHODS. A systematic English-language literature search was conducted in PubMed, MEDLINE-Ovid, Scopus, EBSCO host, Cochrane Library of articles published from February 2006 to April 2015. Study inclusion criteria for review were the following: risk-reducing salpingo-oophorectomy (RRSO), BRCA mutation carriers, non-BRCA mutation carriers, and benign surgical indication. Exclusion criteria were as follows: the presence of synchronous gynecological cancers, concurrent non-gynecological malignancies, the presence of ovarian intraepithelial lesions, and articles that did not include any clinical information and were restricted to pathology information only. RESULTS. A total of 78 patients with isolated STIC were included in our analysis. The median age for all patients was 53.7 years (range; 37-83). Surgical indication was RRSO in 67 patients with BRCA mutations or high-risk personal or family history. In the other 11 patients, an incidental STIC was detected after surgery for non-cancerous indications. Eleven (16.4%) patients received chemotherapy after the diagnosis of STIC. The follow-up time ranged from 2 to 150 months. Three (4.5%) patients with BRCA mutations were diagnosed with primary peritoneal carcinoma (PPC) during the follow-up at 43, 48 and 72 months after RRSO. CONCLUSIONS. The rate of primary peritoneal carcinoma in patients with BRCA mutations and isolated STIC is 4.5%. The role of adjuvant therapy remains elusive and routine surveillance with tumor markers and imaging is not warranted.

Clinical outcomes after fast-track care in women undergoing laparoscopic hysterectomy.

OBJECTIVE: To evaluate the feasibility and safety of multimodal perioperative care after laparoscopic hysterectomy. METHODS: A prospective observational study was performed at Clara Campal Comprehensive Cancer Center, Madrid, Spain, between April 1, 2011, and July 30, 2014, and included women who were scheduled to undergo a laparoscopic hysterectomy. Fast-track (multimodal) care included provision of full preoperative verbal and written information, intravenous dexamethasone (8 mg) during surgery, removal of the urinary catheter at the end of surgery, and early mobilization and solid food intake. The main outcome was the length of hospital stay. RESULTS: Overall, 88 patients were included. The median hospital stay was 22.7 hours (range 5-72). Same-day discharge was feasible in 24 (27%) patients. A total of 51 (58%) women were discharged after overnight stay, 46 (90%) of whom elected to do so because of personal preference. Finally, 13 (15%) patients were discharged at least 36 hours after surgery. Eleven (13%) women visited the emergency unit after discharge and 3 (3%) were readmitted. CONCLUSION: The perioperative multimodal recovery program is safe and feasible in a selected group of women after an elective laparoscopic hysterectomy.

Surgical outcomes and complications of prophylactic salpingectomy at the time of benign hysterectomy in premenopausal women.

STUDY OBJECTIVE: To compare the surgical outcome and short-term postoperative complications in premenopausal women who had undergone hysterectomies for benign indication with or without prophylactic bilateral salpingectomy. DESIGN: A cohort of consecutive women who had undergone hysterectomy plus bilateral salpingectomy between May 2012 and July 2014 (group A) were compared with the same number of consecutive premenopausal patients who had undergone simple hysterectomy operated on before May 2012 (group B). Inclusion criteria included premenopausal women and benign indication for surgery (Canadian Task Force classification III). SETTING: tertiary care hospital. INTERVENTION: Salpingectomy versus no salpingectomy at the time of benign hysterectomy. MEASUREMENTS AND MAIN RESULTS: A total of 97 and 71 patients were included in groups A and B, respectively. No differences between the 2 groups were observed regarding patient characteristics. The average operative time, estimated blood loss, uterine size, and intraoperative complications were similar between groups. The mean (standard deviation) length of hospitalization time was 43.7 (22.4) hours in group A and 53.9 (83.5) hours in group B (p = .008). There were no significant differences in terms of the incidence of postoperative complications, emergency visits after readmission, and hospital readmission between both groups of patients. CONCLUSION: Prophylactic salpingectomy at the time of benign hysterectomy in premenopausal women is safe and feasible and does not worsen surgical outcomes or the incidence of intraoperative and postoperative complications.

Different strategies of treatment for uterine cervical carcinoma stage IB2-IIB.

Uterine cervical cancer is the second most common gynecological malignancy. It is estimated that over 35% of tumors are diagnosed at locally advanced disease, stage IB2-IIB with an estimated 5-year overall survival of 60%. During the last decades, the initial treatment for these women has been debated and largely varies through different countries. Thus, radical concurrent chemoradiation is the standard of care in United Sated and Canada, and neoadjuvant chemotherapy followed by radical surgery is the first line of treatment in some institutions of Europe, Asia and Latin America. Until today, there is no evidence of which strategy is better over the other. This article describe the evidence as well as the advantages and disadvantages of the main strategies of treatment for women affected by uterine cervical cancer stage IB2-IIB.

Borderline tumours of the ovary, current controversies regarding their diagnosis and treatment.

Borderline ovarian tumours generally affect women of reproductive age. The positive prognosis is related to the fact that over 80% of cases are diagnosed at an early stage of the disease. Although radical surgery is the standard of care for this disease, fertility-sparing surgery can be performed in selected cases. Since it was first described in 1929, the knowledge of the molecular and histologic characteristics has been significantly improved. In this review, advances in the clinical behaviour, pathologic characteristics, prognostics factors, and different strategies of treatment are discussed.