Population-based norms for the human papillomavirus-quality of life (HPV-QoL) questionnaire: A cross-sectional multicenter study.

INTRODUCTION: Human papillomavirus (HPV) diagnosis has a considerable emotional and psychological impact on women. To evaluate the impairment this infection leads to regarding quality of life (QoL), several scales have been suggested, such as the human-papillomavirus-quality-of-life (HPV-QoL) questionnaire. This has been validated for the Spanish population and measures the impact of HPV on health-related-quality-of-life (HR-QoL). However, normative values are yet to be developed. Thus, the objective was to describe the population-based norms of the HPV-QoL for Spanish women aged 25-65 years and to test the questionnaire's construct validity. MATERIAL AND METHODS: This was a cross-sectional nationwide multicenter study. Women from outpatient clinics in Spain aged 25-65 years, with a diagnosis of past or active HPV infection were recruited. The central tendency, dispersion, and percentiles were calculated for the total score and its dimensions for each age group. Construct validity was tested by analyzing age groups and their correlations with other related scales (12-Item General Health Questionnaire [GHQ-12], Female Sexual Function Index [FSFI], and Hospital Anxiety and Depression Scale [HADS]). RESULTS: A total of 1352 women were included in the study. The norms showed moderate and significant coefficients of correlation with other related scales. Significant differences between age strata groups were found according to educational level, sexual dysfunction, sexual activity, mental deterioration, and severity of anxiety and depression symptoms (p < 0.001 in all cases). The total score differed significantly between the groups (p = 0.006). Significant differences in the contagiousness, health, and sexuality dimensions (p < 0.05) were found among the groups. It was seen that HPV infection impaired women's QoL. Dimensions within all test age groups (p < 0.001 in all cases) were significantly different, with the health dimension being the highest contributor to women's QoL impairment, whereas social well-being was the main determinant of QoL. CONCLUSIONS: Population-based norms for the novel HPV-QoL questionnaire showed adequate validity and could be a useful tool for assessing the impact of QoL among women with HPV in Spain.

Procalcitonin and C-reactive protein as early markers of anastomotic leakage in intestinal resections for advanced ovarian cancer (EDMOCS).

INTRODUCTION: Serum levels of procalcitonin and C-reactive protein (CRP) have been used to predict anastomotic leakage after colorectal surgery, but information is scarce in advanced ovarian cancer (AOC) surgery with bowel resection. This study aimed to assess the predictive value of procalcitonin and CRP in detecting anastomotic leakage after AOC surgery with bowel resection. The study also aimed to determine the optimal postoperative reference values and the best day for evaluating these markers. MATERIAL AND METHODS: This prospective, observational and multicentric trial included 92 patients with AOC undergoing debulking surgery with bowel resection between 2017 and 2020 in 10 reference hospitals in Spain. Procalcitonin and CRP levels were measured at baseline and on postoperative days 1-6. Receiver operating characteristic analysis was performed to evaluate the predictive value of procalcitonin and CRP at each postoperative day. Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: Anastomotic leakage was detected in six patients (6.5%). Procalcitonin and CRP values were consistently higher in patients with anastomotic leakage at all postoperative days. The maximum area under the curve (AUC) for procalcitonin was observed at postoperative day 1 (AUC = 0.823) with a cutoff value of 3.8 ng/mL (83.3% sensitivity, 81.3% specificity). For CRP, the maximum AUC was found at postoperative day 3 (AUC = 0.833) with a cutoff level of 30.5 mg/dL (100% sensitivity, 80.4% specificity). CONCLUSIONS: Procalcitonin and C-reactive protein are potential biomarkers for early detection of anastomotic leakage after ovarian cancer surgery with bowel resection. Further prospective studies with a larger sample size are needed to confirm these findings.

A combination of molecular and clinical parameters provides a new strategy for high-grade serous ovarian cancer patient management.

BACKGROUND: High-grade serous carcinoma (HGSC) is the most common and deadly subtype of ovarian cancer. Although most patients will initially respond to first-line treatment with a combination of surgery and platinum-based chemotherapy, up to a quarter will be resistant to treatment. We aimed to identify a new strategy to improve HGSC patient management at the time of cancer diagnosis (HGSC-1LTR). METHODS: A total of 109 ready-available formalin-fixed paraffin-embedded HGSC tissues obtained at the time of HGSC diagnosis were selected for proteomic analysis. Clinical data, treatment approach and outcomes were collected for all patients. An initial discovery cohort (n = 21) were divided into chemoresistant and chemosensitive groups and evaluated using discovery mass-spectrometry (MS)-based proteomics. Proteins showing differential abundance between groups were verified in a verification cohort (n = 88) using targeted MS-based proteomics. A logistic regression model was used to select those proteins able to correctly classify patients into chemoresistant and chemosensitive. The classification performance of the protein and clinical data combinations were assessed through the generation of receiver operating characteristic (ROC) curves. RESULTS: Using the HGSC-1LTR strategy we have identified a molecular signature (TKT, LAMC1 and FUCO) that combined with ready available clinical data (patients' age, menopausal status, serum CA125 levels, and treatment approach) is able to predict patient response to first-line treatment with an AUC: 0.82 (95% CI 0.72-0.92). CONCLUSIONS: We have established a new strategy that combines molecular and clinical parameters to predict the response to first-line treatment in HGSC patients (HGSC-1LTR). This strategy can allow the identification of chemoresistance at the time of diagnosis providing the optimization of therapeutic decision making and the evaluation of alternative treatment strategies. Thus, advancing towards the improvement of patient outcome and the individualization of HGSC patients' care.

Can We Reduce Overtreatment of Cervical High-Grade Squamous Intraepithelial Lesions?

OBJECTIVE: The aim was to evaluate the cytology, colposcopic, and pathological factors associated with the absence of high-grade squamous intraepithelial lesion (HSIL)/cervical intraepithelial neoplasia (CIN) 2-3 lesion on loop electrosurgical excision procedure (LEEP) specimens in women with high-grade cytology and/or HSIL/CIN 2-3 biopsy and the risk of disease persistence/recurrence. MATERIALS AND METHODS: Two-center retrospective study of women undergoing LEEP for high-grade cervical disease between January 2014 and December 2019. Clinical, cytology, colposcopy, and pathology results were evaluated to identify independent predictive factors associated with CIN 1/negative LEEP results. Univariate and multivariate logistic regression models were performed. Follow-up data was evaluated to assess the risk of HSIL/CIN 2-3 persistence/recurrence. RESULTS: Six hundred thirty-nine of 801 women (79.8%) had high-grade cytology and 631 (78.8%) HSIL/CIN 2-3 biopsy. High-risk human papillomavirus test was positive in 98% of women. Loop electrosurgical excision procedure specimen showing CIN 1 or less was found in 27%-31%. Normal/low-grade colposcopy (odds ratio [OR] = 2.17, CI = 1.39-3.39, p = .001) and CIN 1/negative biopsy (OR = 3.25, CI = 2.12-4.99, p < .001) were predictors of negative/CIN 1 LEEP result in women with high-grade cytology. Normal/low-grade cytology (OR = 1.77, CI = 1.19-2.64, p = .005), normal/low-grade colposcopy (OR = 1.66, CI = 1.11-2.49, p = .013), and CIN 2 biopsy (OR = 2.75, CI = 1.73-4.39, p < .001) were predictors in women with HSIL/CIN 2-3 biopsy. Women with a negative/CIN 1 LEEP had lower recurrence/persistence than those with confirmed HSIL/CIN 2-3(1 vs 31, p = .002). Positive endocervical margin (OR = 2.85, CI = 1.10-7.36, p = .03) and high-risk human papillomavirus persistence (OR = 41.3, CI = 16-106.7, p < .01) were predictors of HSIL/CIN 2-3 persistence/recurrence. CONCLUSIONS: A CIN 1/negative LEEP specimen in women with high-grade cytology and/or HSIL/CIN 2-3 biopsy is associated with negative/low-grade cytology, normal/low-grade colposcopic findings and CIN 2 biopsy result before treatment. The HSIL/CIN 2-3 disease persistence/recurrence is low when LEEP specimen does not confirm HSIL/CIN 2-3.

Importance of Enhanced Recovery After Surgery (ERAS) Protocol Compliance for Length of Stay in Ovarian Cancer Surgery.

OBJECTIVES: Enhanced Recovery After Surgery (ERAS) programs include multiple perioperative care elements, which when implemented together are designed to improve recovery after surgery with subsequent reduction in hospital length of stay (LOS). The aim of this study is to examine the impact of ERAS protocol compliance on LOS in patients undergoing advanced ovarian cancer surgery within the context of a randomized clinical trial. METHODS: Patients were enrolled in a prospective, consecutive, interventional randomized clinical trial between June 2014 and March 2018. Women with either suspected or confirmed advanced ovarian cancer with International Federation of Gynecology and Obstetrics (FIGO) stages IIB-IVA and recurrent ovarian cancer, who underwent cytoreduction surgery, were randomly assigned to either a conventional management (CM) protocol or an ERAS protocol. Demographic items, preoperative clinical data, and surgical characteristics of patients were recorded, as were LOS and ERAS protocol compliance. Negative binomial regression was used to model the relation between length of stay and ERAS protocol compliance. RESULTS: We included 49 patients in the CM group and 50 patients in the ERAS group. The overall rate of ERAS compliance was 92%. We observed that increasing ERAS protocol compliance was associated with shorter median LOS, and in patients who underwent higher complex surgeries, the length of stay reduction was greater. CONCLUSION: This study identifies a correlation between increasing ERAS protocol compliance and decreasing LOS in ovarian cancer surgery. This finding underlines the necessity to implement as many ERAS protocol elements as possible to achieve optimal clinical outcome improvements.

Robot-assisted Extraperitoneal Para-aortic Lymphadenectomy Is Associated with Fewer Surgical Complications: A Post Hoc Analysis of the STELLA-2 Randomized Trial.

STUDY OBJECTIVE: To evaluate if extraperitoneal para-aortic lymphadenectomy (PALND) using a robot-assisted approach was associated with fewer complications than all other approaches (conventional laparoscopic transperitoneal or extraperitoneal and robot-assisted transperitoneal) without compromising lymph node yield, operative time, or length of stay. DESIGN: Post hoc analysis of the prospective randomized open-label multicenter trial (STELLA-2). SETTING: Three academic referral hospitals. PATIENTS: Two hundred and three eligible patients from the STELLA-2 trial were included. INTERVENTIONS: The patients were randomized to extraperitoneal or transperitoneal PALND using a minimally invasive approach (either laparoscopic or robot-assisted) for surgical staging of endometrial or ovarian cancer. The minimally invasive approaches were not subjected to randomization. MEASUREMENTS AND MAIN RESULTS: The primary end point was evaluated through a composite variable that included at least 1 of the following events: blood loss ≥500 mL during PALND, any intraoperative complication related to PALND, severe postoperative complication (Clavien-Dindo ≥grade IIIA), impossibility of completing the procedure, or conversion to laparotomy. Of the 203 patients analyzed, 68 were assigned to the extraperitoneal laparoscopic group (X-L), 62 to the transperitoneal laparoscopic group (T-L), 35 to the extraperitoneal robotic group (X-R), and 38 to the transperitoneal robotic group (T-R). A reduced trend in complications was observed in the extraperitoneal robot-assisted arm when considering the primary end point (X-L: 25.0%, T-L: 24.2%, X-R: 5.7%, T-R: 28.9%; p = .073). In a multivariable analysis, age (odds ratio [OR] 1.05; 95% confidence interval [CI], 1.00-1.09), body mass index (OR 1.09; 95% CI, 1.03-1.16), and waist-to-hip ratio (OR 1.66; 95% CI, 1.12-2.47) were found to independently increase the risk of PALND complications, whereas the extraperitoneal robotic approach (OR 0.13; 95% CI, 0.02-0.64) was an independent protective factor for complication occurrence. CONCLUSION: Robot-assisted extraperitoneal PALND is associated with fewer surgical complications, without compromising lymph node retrieval, operative time, or length of stay. Robot-enhanced 3D visualization, surgeon ergonomics, or hemostatic precision could explain our results.

Clinical Challenges in Managing Cervical Intraepithelial Neoplasia 2: A Report From a Cross-sectional Survey.

OBJECTIVES: The aims of the study were to determine the management strategies offered to women with cervical intraepithelial neoplasia 2 (CIN 2) and the attitude of colposcopists toward its histological diagnosis and to identify the criteria used to select women for conservative management. METHODS: Colposcopists working in Spain were invited to participate in an online questionnaire via the Spanish Gynecology and Colposcopy Societies. The survey included 42 questions covering the 3 objectives of the study. One hundred eighty-two colposcopists representing all autonomous regions in Spain responded. The response rate was 26.2%, considering the total number of members. RESULTS: Most colposcopists offer conservative management in selected cases (153/182). The preferred follow-up interval is 6 months (65%), followed by 3-4 months (30%). Observation was considered no longer appropriate after 24 months (29.5%) and 12 months (26.3%), and 24.3% expressed that it depended on women's plan to conceive. During conservative management, 93.9% always perform a cytology, 62.7% human papillomavirus testing, 96.8% colposcopy, 47.9% cervical biopsy, and 28.1% endocervical curettage. Forty-five percent consider that CIN 2 merely represents a misclassified CIN 1 or CIN 3, whereas 46.2% think that CIN 2 lesions are unlikely to regress. Most respondents considered that age older than 40 years (81.3%), human papillomavirus 16 infection (62.1%), HIV infection (76.8%), positive p16 immunostaining (60.2%), a large lesion occupying more than 50% of the cervix (87%), endocervical involvement (91.6%), and previous treatment for CIN 2-3 (77%) are contraindications for conservative management. CONCLUSIONS: Management of CIN 2 remains challenging for colposcopists, and a lack of consensus still exists in clinical practice. A better understanding of the natural history of CIN 2 and its clinical outcomes is still necessary to guide clinicians in its management.

Intraoperative Human Papillomavirus Test Predicts 24-Month High-Grade Squamous Intraepithelial Lesion Recurrence Saving Costs: A Prospective Cohort Study.

OBJECTIVES: The human papilloma virus (HPV) test is recommended in the posttreatment follow-up of cervical intraepithelial neoplasia. The aim of the study was to assess whether the intraoperative HPV (IOP-HPV) test had a similar diagnostic accuracy that HPV test performed at 6 months to predict high-grade squamous intraepithelial lesion (HSIL) recurrence. MATERIALS AND METHODS: In a prospective cohort study, 304 women diagnosed with HSIL by biopsy and/or endocervical curettage before treatment and/or confirmation in the histological specimen were included. Immediately after surgery, HPV testing was performed. This test was compared with the test at 6 months and other predictors of recurrence. Patients were followed for 24 months. An economic analysis was performed to compare the costs of IOP-HPV and HPV test at 6 months. RESULTS: Recurrence rate of HSIL was 6.2% (19 patients). The diagnostic accuracy of the IOP-HPV test to predict HSIL recurrence at 24 months was similar to the HPV test at 6 months, with comparative sensitivities of 100% versus 86.7%, specificities of 82.0% versus 77.9%, positive predictive values of 27.1% versus 18.1%, and negative predictive values of 100% versus 99.0%. Direct economic saving per high-grade intraepithelial lesion patient was 172.8 &OV0556;. CONCLUSIONS: The HPV test performed after loop electrosurgical resection procedure predicted recurrence of HSIL at 24 months with a similar diagnostic accuracy than the HPV test at 6 months. The use of the IOP-HPV test in the management of HSIL will allow early detection of the risk of recurrent disease and to save costs because of potential suppression of the need of HPV and follow-up controls at 6 months.

Vaginal Intraepithelial Neoplasia: Clinical Presentation, Management, and Outcomes in Relation to HIV Infection Status.

OBJECTIVES: The data available on vaginal intraepithelial neoplasia (VAIN) and infection by HIV are scarce. We therefore aimed to review the clinical presentation, management, and survival outcomes of VAIN in this group of women. MATERIALS AND METHODS: This is an observational cohort study of women diagnosed with VAIN for a 23-year period. Clinical characteristics and outcomes were analyzed according to women's HIV infection status. Disease-free and progression-free survival were compared between groups. RESULTS: Twenty-two of 87 women were HIV positive (25.3%) compared with the HIV-negative group, HIV-positive women were younger (median age = 39 vs 57 years, p < .001) and more frequently smokers (p < .001). They also presented with multifocal and multicentric disease more often (p = .004 and p = .033, respectively) in relation to infection by human papillomavirus. All HIV-positive women were receiving antiretroviral treatment. The median time from the diagnosis of HIV to the development of VAIN was 14 years (range = 1-22 years). There were no significant differences in survival outcomes between groups. CONCLUSIONS: HIV-positive women are at an increased risk of developing VAIN and frequently present at a younger age with multifocal and multicentric disease. Vaginal intraepithelial neoplasia lesions can develop many years after the initial diagnosis of HIV infection reason why prolonged surveillance is essential to enable prompt diagnosis and treatment.

Metastatic Involvement of Lesser Sac in Advanced Epithelial Ovarian Cancer.

OBJECTIVES: In advanced epithelial ovarian cancer (AOC), lesser sac (LS) metastasis particularly to the supragastric LS (SGLS) may be overlooked, resulting in unrecognized residual disease. We aimed to identify the frequency, distribution, and predictors of LS metastasis using laparoscopic evaluation at laparotomy and perioperative surgical complications associated with evaluation and resection/ablation. METHODS: Prospective observational study in consecutive patients with AOC undergoing laparotomy for primary or interval cytoreductive surgery in 2 centers between November 2013 and December 2016. RESULTS: Of 182 AOC patients undergoing laparotomy, 150 were eligible for metastasis distribution analysis; 96/150 (64%) had LS metastasis with 90/150 (60%) involving the SGLS, including lesser omentum (47.3%), floor (42%), upper recess (24.6%), and caudate lobe (22.6%), with 62/90 (68.8%) being less than 1 cm in dimension. Of 144 undergoing cytoreductive surgery, 92 (64%) had LS metastasis, which was completely resected/ablated in 77/92 (83.6%).The strongest multivariate predictors of LS metastasis were involvement of Morison pouch (P < 0.001) and peritoneal cancer index of 17 or greater (P < 0.001). The LS metastasis was significantly associated with diaphragmatic surgery (84% vs 54%), cholecystectomy (33% vs 2%), splenectomy (50% vs 14%), retroperitoneal nodal metastasis (75% vs 49%), and surgical complexity score of 8 or higher (75% vs 35%). Morbidity related to treatment of LS metastasis was minimal. CONCLUSIONS: Lesser sac metastasis and SGLS metastasis are present in almost two thirds of cases of AOC and often small in size. Systematic exploration is necessary to detect and treat metastases to LS to prevent unrecognized incomplete cytoreduction.

Laparoscopic Isthmocele Repair with Hysteroscopic Assistance.

OBJECTIVE: To demonstrate our experience with hysteroscopic assistance in the laparoscopic repair of an isthmocele. DESIGN: Surgical video article (Canadian Task Force classification III). SETTING: University hospital. INTERVENTION: A 42-year-old woman with a history of previous caesarean section presented as an emergency with a large, seriously infected isthmocele. Once the infection was cured with antibiotics, sonography revealed a 23 × 14-mm isthmocele with 1.4-mm residual myometrium thickness. She reported postmenstrual spotting and dysmenorrhea of several years duration, as well as previous dyspareunia that had worsened after her cesarean section. Given her symptomatic isthmocele with thin residual myometrium and desire for childbearing, laparoscopic repair was offered. First, the bladder was dissected to expose the isthmus. Uterine arteries were dissected. Hysteroscopic guidance and transillumination revealed the edges of the defect. The isthmocele and fibrotic tissue were excised with cold scissors, minimizing cauterization. A hysterometer was placed in the uterine cavity to respect the cervical canal and posterior uterine wall, and the myometrium was then closed in 2 layers. The total surgical time was 120 minutes. The postoperative period was uneventful. At 2 months after surgery, sonography confirmed restoration, with a myometrium thickness of 8.3 mm. The patient was asymptomatic, except for dyspareunia. At 6 months after surgery, hysteroscopic examination was normal. We recommended that the patient avoid attempting pregnancy for 9 months. CONCLUSION: Hysteroscopic simultaneous assistance during laparoscopic isthmocele repair can be of great help in identifying the edges of the defect, especially in large cavities and in first cases, in which edges might not be clear otherwise. Resecting all of the fibrotic tissue while respecting healthy myometrium is essential. Excessive cauterization and ischemic suturing could prevent proper healing of the myometrium.

Pathological Risk Factors and Outcomes in Women With Stage IB2 Cervical Cancer Treated With Primary Radical Surgery Versus Chemoradiotherapy.

OBJECTIVE: Both radical hysterectomy with pelvic lymphadenectomy and primary chemoradiotherapy have been shown to be effective in the management of women with stage IB2 cervical cancer. This study aims to review the outcomes related to each treatment modality and the effects of pathological risk factors on overall survival (OS) and disease-free survival. METHODS: We performed a retrospective study of 92 women with stage IB2 cervical cancer who were treated at the Northern Gynecological Oncology Center (Gateshead, United Kingdom) across a 22-year period between January 1991 and July 2013. Women were divided into those undergoing primary surgery and those undergoing primary radiotherapy/chemoradiotherapy. The main outcome measures were OS and progression-free survival (PFS). Pathological risk factors of survival were assessed using multivariate analysis. RESULTS: Sixty-seven women (72.8%) underwent primary surgery, and 25 women (27.2%) had primary radiotherapy/chemoradiotherapy. Thirty-one of 67 women (46.3%) required adjuvant radiotherapy/chemoradiotherapy after surgery because of positive lymph nodes in 77.4% of cases. The median follow-up was 57.5 months (range, 3-137 months). Thirty-two women (34.8%) had disease recurrence: 6 women (16.7%) in the group undergoing surgery alone, 15 women (48.4%) in the group requiring adjuvant treatment after surgery, and 11 women (44%) in the group having primary radiotherapy/chemoradiotherapy. Overall survival and PFS were higher for women undergoing surgery alone (91.7% and 83.3%) compared with women requiring adjuvant treatment after surgery (54.8% and 51.4%) and those having primary radiotherapy/chemoradiotherapy (60% and 56%) (P = 0.0004 and P = 0.005, respectively). Lymph node metastasis was a significant pathological risk factor of OS and PFS in multivariate analysis. CONCLUSIONS: Most women require adjuvant treatment after surgery because of positive lymph nodes. Because survival outcomes for women requiring dual treatment are similar to those for women undergoing primary chemoradiotherapy, nodal assessment before definitive treatment should guide the management of these women and identify a low-risk group that can be treated with surgery alone.

Patterns of First Recurrence and Oncological Outcomes in Locally Advanced Cervical Cancer Patients: Does Surgical Staging Play a Role?

BACKGROUND: We aimed to determine whether surgical aortic staging by minimally invasive paraaortic lymphadenectomy (PALND) affects the pattern of first recurrence and survival in treated locally advanced cervical cancer (LACC) patients when compared to patients staged by imaging (noPALND). METHODS: This study was a multicenter observational retrospective cohort study of patients with LACC treated at tertiary care hospitals throughout Spain. The inclusion criteria were histological diagnosis of squamous carcinoma, adenosquamous carcinoma, and/or adenocarcinoma; FIGO stages IB2, IIA2-IVA (FIGO 2009); and planned treatment with primary chemoradiotherapy between 2000 and 2016. Propensity score matching (PSM) was performed before the analysis. RESULTS: After PSM and sample replacement, 1092 patients were included for analysis (noPALND n = 546, PALND n = 546). Twenty-one percent of patients recurred during follow-up, with the PALND group having almost double the recurrences of the noPALND group (noPALND: 15.0%, PALND: 28.0%, p < 0.001). Nodal (regional) recurrences were more frequently observed in PALND patients (noPALND:2.4%, PALND: 11.2%, p < 0.001). Among those who recurred regionally, 57.1% recurred at the pelvic nodes, 37.1% recurred at the aortic nodes, and 5.7% recurred simultaneously at both the pelvic and aortic nodes. Patients who underwent a staging PALND were more frequently diagnosed with a distant recurrence (noPALND: 7.0%, PALND: 15.6%, p < 0.001). PALND patients presented poorer overall, cancer-specific, and disease-free survival when compared to patients in the noPALND group. CONCLUSION: After treatment, surgically staged patients with LACC recurred more frequently and showed worse survival rates.

Can the microcystic, elongated and fragmented pattern of invasion influence the evaluation of the depth of myometrial invasion in low-grade endometrioid endometrial cancer using imaging techniques?

Objectives: The microcystic, elongated and fragmented pattern of invasion can be associated with an underestimation of the depth of myometrial invasion by imaging techniques. We aimed to evaluate the influence of microcystic, elongated and fragmented pattern of invasion in the diagnostic performance of transvaginal ultrasound scan and magnetic resonance imaging for the prediction of the depth of myometrial invasion in low-grade endometrioid endometrial carcinomas. Methods: Prospective and consecutive study including all low-grade (G1-G2) endometrioid endometrial carcinomas diagnosed between October 2013 and July 2018 in a tertiary hospital. Preoperative staging was performed with transvaginal ultrasound scan and/or magnetic resonance imaging followed by surgical staging. Final histology was considered as the reference standard. Sensitivity, specificity and diagnostic accuracy for the prediction of depth of myometrial invasion was calculated for both imaging techniques. The STARD 2015 guidelines were used. Results: A total of 136 patients were consecutively included. Transvaginal ultrasound scan was performed in 132 patients and magnetic resonance imaging in 119 patients. The diagnostic accuracy of transvaginal ultrasound scan for the prediction of depth of myometrial invasion in the microcystic, elongated and fragmented negative group (82% (95% confidence interval = 73-88)) was higher compared to the microcystic, elongated and fragmented positive group (61% (95% confidence interval = 36-83)). The diagnostic accuracy of magnetic resonance imaging was also higher in the microcystic, elongated and fragmented negative group (80% (95% confidence interval = 71-87)) compared to the microcystic, elongated and fragmented positive (47% (95% confidence interval = 21-73)). Conclusions: In low-grade endometrioid endometrial carcinomas with a positive microcystic, elongated and fragmented pattern of invasion, the evaluation of the depth of myometrial invasion using transvaginal ultrasound scan and magnetic resonance imaging may be underestimated.

Surgical Outcomes of Laparoscopic Pelvic Lymph Node Debulking during Staging Aortic Lymphadenectomy in Locally Advanced Cervical Cancer: A Multicenter Study.

BACKGROUND: Few studies have evaluated laparoscopic pelvic lymph node (PLN) debulking during staging aortic lymphadenectomy in locally advanced cervical cancer (LACC). It allows us to know the lymph node status and facilitates the action of chemoradiotherapy (CRT) by reducing tumor burden. We evaluated its feasibility and compared the perioperative morbidity and the time to CRT with a control group. METHODS: This was a multicenter retrospective study of patients with LACC FIGO stage IIIC1r who were recipients of CRT. We compared two cohorts: group 1, which consisted of 164 patients with surgical staging by laparoscopic aortic lymphadenectomy and PLN debulking, and group 2, which consisted of 111 patients with aortic lymphadenectomy alone. RESULTS: Excision of the bulky nodes was possible in all patients in group 1 except for one. Surgery lasted a median of 82 min longer in group 1 but there was no greater intraoperative bleeding or increased hospital stay. There were no significant differences in intraoperative or postoperative complications between the groups. A significantly shorter time from surgery to the start of RT was observed in group 1. CONCLUSIONS: It is feasible to perform laparoscopic PLN debulking in the same procedure as the staging aortic lymphadenectomy in LACC without increasing surgical or postoperative complications and without delaying the start of CRT compared to single aortic lymphadenectomy.

BRCA1 mutations in high-grade serous ovarian cancer are associated with proteomic changes in DNA repair, splicing, transcription regulation and signaling.

Despite recent advances in the management of BRCA1 mutated high-grade serous ovarian cancer (HGSC), the physiology of these tumors remains poorly understood. Here we provide a comprehensive molecular understanding of the signaling processes that drive HGSC pathogenesis with the addition of valuable ubiquitination profiling, and their dependency on BRCA1 mutation-state directly in patient-derived tissues. Using a multilayered proteomic approach, we show the tight coordination between the ubiquitination and phosphorylation regulatory layers and their role in key cellular processes related to BRCA1-dependent HGSC pathogenesis. In addition, we identify key bridging proteins, kinase activity, and post-translational modifications responsible for molding distinct cancer phenotypes, thus providing new opportunities for therapeutic intervention, and ultimately advance towards a more personalized patient care.

Adjuvant therapy in early-stage cervical cancer after radical hysterectomy: are we overtreating our patients? A meta-analysis.

OBJECTIVE: There is a gap in knowledge regarding the ideal management of patients with early-stage cervical cancer and intermediate-risk features. Here, we present a meta-analysis of the published literature on oncological outcomes in these patients and determine trends in postoperative management. METHODS: MEDLINE and PubMed were used for literature searches. The inclusion criteria were: English language articles including ≥ 10 patients, patients who underwent radical hysterectomy, nodes negative, studies reporting oncological outcomes and complications treatment-related and compare a surgery-only cohort with a radiotherapy cohort. The PRISMA guidelines were followed. Combined relative risk was calculated using DerSimonian-Laird random-effects model and a forest plot was drawn. RESULTS: We collected 183 manuscripts on early-stage cervical cancer treated with radical hysterectomy alone or with adjuvant radiotherapy after surgery. A total of eight studies met the inclusion criteria. Regarding oncological outcomes, survival was reported in five studies. The relative risk of recurrence and the relative risk of mortality was similar in both groups independently whether receive or not adjuvant therapy. Most of the studies did not report significant differences regarding morbidity treatment related between the groups, except for a higher rate of lymphedema after radiotherapy. CONCLUSION: We found that the relative risk of recurrence and mortality was similar in both groups not depending on adjuvant therapy. Therefore, whether radiotherapy adjuvant treatment is indicated remains a topic of debate.

Proteomic Studies on the Management of High-Grade Serous Ovarian Cancer Patients: A Mini-Review.

High-grade serous ovarian cancer (HGSC) remains the most common and deadly subtype of ovarian cancer. It is characterized by its late diagnosis and frequent relapse despite standardized treatment with cytoreductive surgery and platinum-based chemotherapy. The past decade has seen significant advances in the clinical management and molecular understanding of HGSC following the publication of the Cancer Genome Atlas (TCGA) researchers and the introduction of targeted therapies with anti-angiogenic drugs and poly(ADP-ribose) polymerase inhibitors in specific subgroups of patients. We provide a comprehensive review of HGSC, focusing on the most important molecular advances aimed at providing a better understanding of the disease and its response to treatment. We emphasize the role that proteomic technologies are now playing in these two aspects of the disease, through the identification of proteins and their post-translational modifications in ovarian cancer tumors. Finally, we highlight how the integration of proteomics with genomics, exemplified by the work performed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC), can guide the development of new biomarkers and therapeutic targets.

Retro cervical tunneling to ensure correct placement for robotic-assisted transabdominal cerclage.

OBJECTIVE: To demonstrate the step-by-step surgical technique of robotic-assisted transabdominal cerclage, highlighting a new posterior compartment approach. DESIGN: Stepwise explanation of a surgical technique using surgical video. SETTING: The procedure was performed at the Obstetrics and Gynecology Department, Hospital Vall d'Hebron in Barcelona, Spain, a tertiary medical center. The local institutional review board considers that case reports are exempt from research approval. PATIENT(S): A 26-year-old non-pregnant patient, with a history of cervical incompetence, three second-trimester losses, and vaginal cerclage failure during her previous pregnancy. INTERVENTION(S): Robotic-assisted transabdominal cerclage placement was performed. An 8-mm, 30° scope; monopolar scissors; and Maryland bipolar graspers were used. A uterine manipulator was used for better exposure. First, a bladder flap was created, and the uterine vessels were identified and skeletonized. Next, a window between the uterine vessels and the uterine cervix at the level of the cervical-isthmic junction was created bilaterally. At the posterior compartment, the dissection of the root of the uterosacral ligaments was carefully performed. A retrocervical pocket was created with monopolar scissors and sharp dissection. The procedure was finished with the Mersilene tape placement. First, the tape was passed through the window created in the right broad ligament, with a posterior-to-anterior direction, the retro cervical pocket, and finally through the left broad ligament. The knot was placed anteriorly and reperitonization was performed. In addition to this operation, robotic-assisted transabdominal cerclage was successfully performed in another six patients with good surgical and obstetrics outcomes. MAIN OUTCOME MEASURE(S): Intraoperative technique to ensure successful robot-assisted abdominal cerclage placement. RESULT(S): The patient became pregnant six months following the robotic-assisted transabdominal cerclage. Her pregnancy was closely followed up at the High-Risk Obstetric Unit, and she had no complications during pregnancy. An elective cesarean section was performed at 36 weeks with a healthy newborn baby that was discharged with the mother three days after delivery. CONCLUSION(S): The development of a retro cervical pocket during robotic-assisted transabdominal cerclage can be performed safely and effectively. It may help prevent displacement of the Mersilene tape during endoscopic knotting.

Total laparoscopic radical hysterectomy for cervical cancer in prolapsed uterus.

PURPOSE: The association between cervical cancer and uterine prolapse is rare and sparsely represented in literature, despite the high incidence of the latter. The suitable treatment in this clinical situation is not defined. The objective of this article is to review published cases about this clinical condition. METHODS: We report a case of cervical cancer in prolapsed uterus treated with radical hysterectomy performed totally by laparoscopic approach, and review other case reports published about this clinical condition. RESULTS: We present the first case reported in literature in our knowledge of cervical cancer in prolapsed uterus treated with radical hysterectomy performed totally by laparoscopic approach. Treatments previously reported are vaginal hysterectomies with adjuvant radiotherapy or concomitant chemo-radiotherapy. CONCLUSIONS: Radical hysterectomy can be correctly performed totally by laparoscopic approach even when cervical cancer is associated with severe uterine prolapse.