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Surgical treatment of obese female patients represents a real challenge. Over the last decade, minimally invasive techniques for hysterectomy have emerged. These approaches reduce the invasiveness of standard surgical procedures while maintaining efficacy and feasibility.To evaluate the rates of perioperative, early, mid-term and late postoperative complications in very obese [body mass index (BMI) ≥ 35 and 40 kg/mA prospective comparative multi-centre non-randomized study.In total, 328 consecutive total (non-radical) hysterectomies were performed at seven teaching gynaecological centres. Of these, 153 (46.6%) were performed using an open laparotomy (LT) approach and 175 (53.4%) were performed laparoscopically (LS). All data were collected by medical specialists at the pre-operative examination prior to surgery, during surgery and three times postoperatively (during hospital stay, at 6-week follow-up and 6 months following surgery). Another analysis considered a total of 206 women who underwent laparoscopic hysterectomy. The subjects were divided according to BMI into 120 very obese women (BMI ≥ 35 and 40 kg/mThe total number of composite perioperative complications was significantly lower in the LS group (p = 0.006). Composite complications occurred significantly more often in patients in the LT group compared with the LS group in the early (p 0.001) and mid-term (p 0.001) postoperative periods. In the late postoperative period, the total number of composite postoperative complications did not differ significantly between the groups (p 0.396). Among 206 patients who underwent laparoscopic hysterectomy, the number of complications was generally low; the rates of composite perioperative (p = 0.393), early (p = 0.642), mid-term (p = 0.738) and late (p = 1) postoperative complications were generally low; and frequency did not differ significantly with BMI.The LS approach does not increase intra-operative morbidity associated with surgery, and has significantly better outcomes in terms of the postoperative complication rate.

Purpose: The successful implementation of immune checkpoint inhibitors (ICI) in the clinical management of various solid tumors has raised considerable expectations for patients with epithelial ovarian carcinoma (EOC). However, EOC is poorly responsive to ICIs due to immunologic features including limited tumor mutational burden (TMB) and poor lymphocytic infiltration. An autologous dendritic cell (DC)-based vaccine (DCVAC) has recently been shown to be safe and to significantly improve progression-free survival (PFS) in a randomized phase II clinical trial enrolling patients with EOC (SOV01, NCT02107937). Patients and Methods: We harnessed sequencing, flow cytometry, multispectral immunofluorescence microscopy, and IHC to analyze (pretreatment) tumor and (pretreatment and posttreatment) peripheral blood samples from 82 patients enrolled in SOV01, with the aim of identifying immunologic biomarkers that would improve the clinical management of patients with EOC treated with DCVAC. Results: Although higher-than-median TMB and abundant CD8+ T-cell infiltration were associated with superior clinical benefits in patients with EOC receiving standard-of-care chemotherapy, the same did not hold true in women receiving DCVAC. Conversely, superior clinical responses to DCVAC were observed in patients with lower-than-median TMB and scarce CD8+ T-cell infiltration. Such responses were accompanied by signs of improved effector functions and tumor-specific cytotoxicity in the peripheral blood. Conclusions: Our findings suggest that while patients with highly infiltrated, “hot” EOCs benefit from chemotherapy, women with “cold” EOCs may instead require DC-based vaccination to jumpstart clinically relevant anticancer immune responses.

Purpose:The successful implementation of immune checkpoint inhibitors (ICI) in the clinical management of various solid tumors has raised considerable expectations for patients with epithelial ovarian carcinoma (EOC). However, EOC is poorly responsive to ICIs due to immunologic features including limited tumor mutational burden (TMB) and poor lymphocytic infiltration. An autologous dendritic cell (DC)-based vaccine (DCVAC) has recently been shown to be safe and to significantly improve progression-free survival (PFS) in a randomized phase II clinical trial enrolling patients with EOC (SOV01, NCT02107937).Patients and Methods:We harnessed sequencing, flow cytometry, multispectral immunofluorescence microscopy, and IHC to analyze (pretreatment) tumor and (pretreatment and posttreatment) peripheral blood samples from 82 patients enrolled in SOV01, with the aim of identifying immunologic biomarkers that would improve the clinical management of patients with EOC treated with DCVAC.Results:Although higher-than-median TMB and abundant CD8+ T-cell infiltration were associated with superior clinical benefits in patients with EOC receiving standard-of-care chemotherapy, the same did not hold true in women receiving DCVAC. Conversely, superior clinical responses to DCVAC were observed in patients with lower-than-median TMB and scarce CD8+ T-cell infiltration. Such responses were accompanied by signs of improved effector functions and tumor-specific cytotoxicity in the peripheral blood.Conclusions:Our findings suggest that while patients with highly infiltrated, “hot” EOCs benefit from chemotherapy, women with “cold” EOCs may instead require DC-based vaccination to jumpstart clinically relevant anticancer immune responses.

Supplementary Figure from An Autologous Dendritic Cell Vaccine Promotes Anticancer Immunity in Patients with Ovarian Cancer with Low Mutational Burden and Cold Tumors

Supplementary Data from An Autologous Dendritic Cell Vaccine Promotes Anticancer Immunity in Patients with Ovarian Cancer with Low Mutational Burden and Cold Tumors

Purpose:In multiple oncological settings, expression of the coinhibitory ligand PD-L1 by malignant cells and tumor infiltration by immune cells expressing coinhibitory receptors such as PD-1, CTLA4, LAG-3, or TIM-3 conveys prognostic or predictive information. Conversely, the impact of these features of the tumor microenvironment on disease outcome among high-grade serous carcinoma (HGSC) patients remains controversial.Experimental Design:We harnessed a retrospective cohort of 80 chemotherapy-naïve HGSC patients to investigate PD-L1 expression and tumor infiltration by CD8+ T cells, CD20+ B cells, DC-LAMP+ dendritic cells as well as by PD-1+, CTLA4+, LAG-3+, and TIM-3+ cells in relation with prognosis and function orientation of the tumor microenvironment. IHC data were complemented with transcriptomic and functional studies on a second prospective cohort of freshly resected HGSC samples. In silico analysis of publicly available RNA expression data from 308 HGSC samples was used as a confirmatory approach.Results:High levels of PD-L1 and high densities of PD-1+ cells in the microenvironment of HGSCs were strongly associated with an immune contexture characterized by a robust TH1 polarization and cytotoxic orientation that enabled superior clinical benefits. Moreover, PD-1+TIM-3+CD8+ T cells presented all features of functional exhaustion and correlated with poor disease outcome. However, although PD-L1 levels and tumor infiltration by TIM-3+ cells improved patient stratification based on the intratumoral abundance of CD8+ T cells, the amount of PD-1+ cells failed to do so.Conclusions:Our data indicate that PD-L1 and TIM-3 constitute prognostically relevant biomarkers of active and suppressed immune responses against HGSC, respectively.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.This multicenter cohort study reports on the long-term effects of prenatal exposure to maternal cancer and its treatment on cognitive and behavioral outcomes in 9-year-old children. In total, 151 children (mean age, 9.3 years; range, 7.8-10.6 years) were assessed using a neurocognitive test battery and parent-report behavioral questionnaires. During pregnancy, 109 children (72.2%) were exposed to chemotherapy (only or in combination with other treatment modalities), 18 (11.9%) to surgery only, 16 (10.6%) to radiotherapy, one to trastuzumab, and 16 (10.6%) were not exposed to oncologic treatment. Mean cognitive and behavioral outcomes were within normal ranges. Gestational age at birth showed a positive association with Full Scale Intelligence Quotient (FSIQ), with the average FSIQ score increasing by 1.6 points for each week increase in gestational age (95% CI, 0.7 to 2.5; P < .001). No difference in FSIQ was found between treatment types (F[4,140] = 0.45, P = .776). In children prenatally exposed to chemotherapy, no associations were found between FSIQ and chemotherapeutic agent, exposure level, or timing during pregnancy. These results indicate a reassuring follow-up during the critical maturational period of late childhood, when complex functions develop and rely on the integrity of early brain development. However, associations were observed with preterm birth, maternal death, and maternal education. ispartof: JOURNAL OF CLINICAL ONCOLOGY vol:41 issue:8 pages:1527-+ ispartof: location:United States status: published

The most common cancer in women worldwide is cervical cancer. For early-stage disease the standard treatment is radical hysterectomy. One of the main issues faced by surgeons performing a radical hysterectomy is the wide variation in the terminology used to define the procedure and the nomenclature used to describe the anatomical spaces critical to the success of the surgery. The aim of this review was to synthesize currently used anatomical landmarks with relation to surgical avascular spaces for the performance of radical hysterectomy.A computer-based comprehensive review of the MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, and SciSearch databases, as well as National Comprehensive Cancer Network and European Society of Gynaecological Oncology guidelines, was performed. With all relevant data collected, and previous anatomical studies during surgeries and on cadavers performed by authors, a manuscript of the definition of avascular spaces, methods of dissection, and anatomical limits was prepared.Avascular pelvic spaces developed during radical hysterectomy, such as the paravesical, pararectal, ureter tunnel, and paravaginal, were considered and included in the manuscript. A clear definition of avascular spaces may aid a better understanding of the anatomical aspects of the radical hysterectomy. It could improve surgeon knowledge of the structures that need to be preserved and those that need to be resected during a radical hysterectomy. Additionally, the detailed exposure of anatomical boundaries will facilitate the appropriate tailored radicality depending on the risk factors of the disease. Moreover, knowledge of these spaces could make pelvic surgery safer and easier for other types of gynecological and non-gynecological procedures.

ObjectiveThe objective of this systematic review was to assess the oncologic and fertility outcomes of patients with cervix-confined cancer >4 cm who underwent neo-adjuvant chemotherapy followed by fertility-sparing surgery.MethodsThis study was registered in PROSPERO (registration number CRD42021254816). PubMed/MEDLINE, ClinicalTrials, EMBASE, Cochrane Central Register of Controlled Trials, SCOPUS, and OVID databases were searched from inception to July 2021. The included patients were those with cancer confined to the cervix and tumor diameter >4 cm (International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB3) with squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma who underwent intra-venous neo-adjuvant chemotherapy followed by successful fertility-sparing surgery.ResultsThe initial search identified 2990 articles. A total of 40 patients from 11 studies had attempted fertility preservation surgery (conization, simple or radical trachelectomy) and in 26 patients (65%) it was successful. All patients received platinum-based chemotherapy. A complete pathological response occurred in 56% of patients and two patients (7.7%) had a recurrence. The 4.5-year disease-free survival was 92.3% and the 4.5-year overall survival rate was 100%. Of six patients who tried to conceive, four (67%) achieved at least one pregnancy and three of the five pregnancies (60%) were pre-term deliveries (all after radical trachelectomy). All patients with recurrence received cisplatin and ifosfamide instead of cisplatin and paclitaxel, underwent non-radical surgery, and had residual disease in the final specimen.ConclusionsEvidence for fertility-sparing surgery after neo-adjuvant chemotherapy in patients with cervical cancer and tumors >4 cm is limited, and this approach should be considered as an experimental intervention. As the use of non-radical surgery could be a risk factor, if neo-adjuvant chemotherapy is used, patients should undergo fertility-sparing radical surgery.

BACKGROUND: Outcomes for mother and child following a diagnosis of Hodgkin lymphoma during pregnancy are underinvestigated, and antenatal management of the disease has not been reported on widely. The aim of this study was to assess obstetric outcomes, antenatal management, and maternal survival in patients with Hodgkin lymphoma diagnosed during pregnancy who were registered in the International Network on Cancer, Infertility and Pregnancy (INCIP) database. METHODS: We did a multicentre, retrospective cohort study including oncological and obstetric data from 134 pregnant patients diagnosed with Hodgkin lymphoma between Jan 1, 1969, and Aug 1, 2018. Data collected from the INCIP database were obtained from 17 academic centres in Belgium, Czech Republic, Denmark, Greece, Israel, Italy, Mexico, the Netherlands, Russia, the UK, and the USA. We analysed patients' management over three epochs (before 1995, 1995-2004, and 2005-18). Obstetric outcomes (birthweight, obstetric or neonatal complications, and admission to a neonatal intensive care unit [NICU]) of patients who received antenatal chemotherapy were compared to those of patients who did not receive antenatal treatment. Maternal progression-free and overall survival was assessed by disease stage at diagnosis in pregnant patients and compared with outcomes of non-pregnant patients with Hodgkin lymphoma selected from databases of three tertiary centres, matched for stage and prognostic score. All patients included in survival analyses received standard doxorubicin, bleomycin, vinblastine and dacarbazone (ABVD) therapy since Jan 1, 1997. FINDINGS: Of the 134 pregnant patients diagnosed with Hodgkin lymphoma during pregnancy. 72 (54%) patients initiated antenatal chemotherapy, 56 (42%) did not receive treatment during pregnancy, and 6 (4%) received only radiotherapy. Over the years, chemotherapy was increasingly commenced during pregnancy. The incidence of neonates who were small for gestational age did not differ between chemotherapy-exposed neonates (15 [22%] of 69) and non-exposed neonates (six [16%] of 42; p=0·455). Admission to NICU also did not differ between groups (19 [29%] exposed to antenatal chemotherapy vs 12 [35%] unexposed to antenatal chemotherapy). Birthweight percentiles were lower in neonates prenatally exposed to chemotherapy compared with non-exposed neonates (p=0·035). Patients receiving antenatal therapy had more obstetric complications than those without antenatal therapy (p=0·005), the most common complications being preterm contractions (nine [12%] vs three [7%]) and preterm rupture of membranes (four [5%] vs 0). For the maternal survival analyses, we compared 77 pregnant patients and 211 non-pregnant, matched controls. 5-year progression-free survival for patients with early-stage Hodgkin lymphoma was 82·6% (95% CI 67·4-91·1) for 62 pregnant patients and 88·3% (81·6-92·7) for 142 controls (hazard ratio [HR] 1·80, 95% CI 0·84-3·87; p=0·130; 5-year overall survival was 97·3% (82·3-99·6) and 98·4% (93·6-99·6; HR 1·63, 0·35-7·65; p=0·534). In patients with advanced-stage disease (15 pregnant patients and 69 non-pregnant controls), 5-year progression-free survival was 90·9% (95% CI 50·8-98·7) versus 74·0% (60·9-83·3); HR 0·36, 95% CI 0·04-2·90; p=0·334. 5-year overall survival was 100% (no events occurred) and 96·2% (95% CI 85·5-99·1; HR cannot be estimated; p=0·146). INTERPRETATION: Occurrence of preterm contractions or preterm rupture of membranes was higher in patients with Hodgkin lymphoma receiving antenatal treatment compared with those who did not initiate treatment during pregnancy. Maternal survival did not differ between pregnant and non-pregnant patients with Hodgkin lymphoma, suggesting that antenatal chemotherapy or deferral of treatment until postpartum in selected patients can be considered, with regular obstetric follow-up to safeguard foetal growth. FUNDING: European Research Council, Research foundation Flanders, and Charles University Ministry of Health of the Czech Republic. ispartof: LANCET HAEMATOLOGY vol:6 issue:11 pages:E551-E561 ispartof: location:England status: published

Purpose: In multiple oncological settings, expression of the coinhibitory ligand PD-L1 by malignant cells and tumor infiltration by immune cells expressing coinhibitory receptors such as PD-1, CTLA4, LAG-3, or TIM-3 conveys prognostic or predictive information. Conversely, the impact of these features of the tumor microenvironment on disease outcome among high-grade serous carcinoma (HGSC) patients remains controversial. Experimental Design: We harnessed a retrospective cohort of 80 chemotherapy-naïve HGSC patients to investigate PD-L1 expression and tumor infiltration by CD8+ T cells, CD20+ B cells, DC-LAMP+ dendritic cells as well as by PD-1+, CTLA4+, LAG-3+, and TIM-3+ cells in relation with prognosis and function orientation of the tumor microenvironment. IHC data were complemented with transcriptomic and functional studies on a second prospective cohort of freshly resected HGSC samples. In silico analysis of publicly available RNA expression data from 308 HGSC samples was used as a confirmatory approach. Results: High levels of PD-L1 and high densities of PD-1+ cells in the microenvironment of HGSCs were strongly associated with an immune contexture characterized by a robust TH1 polarization and cytotoxic orientation that enabled superior clinical benefits. Moreover, PD-1+TIM-3+CD8+ T cells presented all features of functional exhaustion and correlated with poor disease outcome. However, although PD-L1 levels and tumor infiltration by TIM-3+ cells improved patient stratification based on the intratumoral abundance of CD8+ T cells, the amount of PD-1+ cells failed to do so. Conclusions: Our data indicate that PD-L1 and TIM-3 constitute prognostically relevant biomarkers of active and suppressed immune responses against HGSC, respectively.

The standard procedure in cervical cancer is radical hysterectomy (RH) and pelvic lymphadenectomy (PLND). Because of the increasing age of women at childbirth, fertility becomes a major challenge. We present 20 years of experience with two-step less radical fertility-sparing surgery in women with IA1, LVSI positive, IA2 and IB1 (2 cm, infiltration less than half of stromal invasions.Preoperative workout consisted of histopathological diagnosis and magnetic resonance imaging along with ultrasonographic volumetry. We then performed laparoscopic sentinel lymph node mapping (SLNM) with frozen section (FS) followed by PLND and "selective parametrectomy" (removal of afferent lymphatic channels from the paracervix) in case of a negative result. If verified by definitive histopathology, patients were treated by simple trachelectomy (IB1) or large cone (IA1/IA2) biopsy 1 week after primary surgery.From 1999 to 2018, 91 women were enrolled in the study (median age 29.1 years, range 21-40). Of these 91 women, 51 (56.0%) were nulliparous. The detection rate of SLNs was 100% per patient and the specific side detection rate 96.7%. Positive lymph nodes were diagnosed in nine cases (9.8%). These women then underwent RH. Fertility was spared in 80 women but 4 recurred locally (5.0%). The mortality rate was 0.0%. The median follow-up was 149 months.Less radical fertility-sparing surgery with SLNM is safe in cervical cancers2 cm at the largest diameter and infiltrating less than half of the cervical stroma. The recurrence rate is acceptable with no mortality. Morbidity with this procedure is low. Extended and accurate follow-up is necessary and human papillomavirus - high risk (HPV-HR tests seem to be useful in such follow-up assessment.

The article focuses on fertility-sparing management during pregnancy and obstetrical management after fertility-sparing surgery. Over the years, more women in developed countries tend to delay childbirth to a later age, which leads to cervical cancer more often diagnosed during pregnancy. The advances in our understanding of prognosis and treatment options in these patients have helped us to address avenues and to circumvent standard therapy and fetal demise, respecting maternal and fetal chances. Childbearing trends also lead to an increase in the number of patients considering fertility-sparing management when diagnosed with cervical cancer. Such management represents a challenge for obstetricians as prior cervical surgery is a known risk factor for various adverse events. These include decreased fertility, second trimester miscarriage, preterm labor, or preterm premature rupture of membranes. Watchful follow-up and various prophylactic measures are keys when striving for the best possible outcome.

BACKGROUND: Based on reassuring short-term foetal and maternal safety data, there is an increasing trend to administer chemotherapy during the second and third trimesters of pregnancy. The pharmacokinetics (PK) of drugs might change as a result of several physiological changes that occur during pregnancy, potentially affecting the efficacy and safety of chemotherapy. OBJECTIVE: With this analysis, we aimed to quantitatively describe the changes in the PK of docetaxel, paclitaxel, doxorubicin and epirubicin in pregnant women compared with non-pregnant women. METHODS: PK data from 9, 20, 22 and 16 pregnant cancer patients from the International Network of Cancer, Infertility and Pregnancy (INCIP) were available for docetaxel, paclitaxel, doxorubicin and epirubicin, respectively. These samples were combined with available PK data from non-pregnant patients. Empirical non-linear mixed-effects models were developed, evaluating fixed pregnancy effects and gestational age as covariates. RESULTS: Overall, 82, 189, 271, and 227 plasma samples were collected from pregnant patients treated with docetaxel, paclitaxel, doxorubicin and epirubicin, respectively. The plasma PK data were adequately described by the respective models for all cytotoxic drugs. Typical increases in central and peripheral volumes of distribution of pregnant women were identified for docetaxel, paclitaxel, doxorubicin and epirubicin. Additionally, docetaxel, doxorubicin and paclitaxel clearance were increased in pregnant patients, resulting in lower exposure in pregnant women compared with non-pregnant patients. CONCLUSION: Given the interpatient variability, the identified pregnancy-induced changes in PK do not directly warrant dose adjustments for the studied drugs. Nevertheless, these results underscore the need to investigate the efficacy of chemotherapy, when administered during pregnancy. ispartof: CLINICAL PHARMACOKINETICS vol:60 issue:6 pages:775-784 ispartof: location:Switzerland status: published

Background Data on the long-term effects of prenatal exposure to maternal cancer and its treatment on child development are scarce. Methods In a multicenter cohort study, the neurologic and cardiac outcomes of 6-year-old children born to women diagnosed with cancer during pregnancy were compared with the outcome of children born after an uncomplicated pregnancy. Assessment included clinical evaluation, comprehensive neuropsychological testing, electrocardiography and echocardiography. Results In total, 132 study children and 132 controls were included. In the study group, 97 children (73.5%) were prenatally exposed to chemotherapy (alone or in combination with other treatments), 14 (10.6%) to radiotherapy (alone or in combination), 1 (0.8%) to trastuzumab, 12 (9.1%) to surgery alone and 16 (12.1%) to no treatment. Although within normal ranges, statistically significant differences were found in mean verbal IQ and visuospatial long-term memory, with lower scores in the study versus control group (98.1, 95% confidence interval [CI]: 94.5–101.8, versus 104.4, 95% CI: 100.4–108.4, P = 0.001, Q, Highlights • Cancer treatment including chemotherapy is possible during pregnancy. • Children are at risk for lower verbal IQ and visuospatial long-term memory scores. • Other cognitive functions and cardiac outcomes were normal at the age of 6 years. • We documented ototoxicity in three children exposed to cisplatin. • Follow-up until adulthood is recommended.

To investigate differences and similarities in the clinical approach of young clinicians managing women with endometrial cancer (EC) conservatively.A web-based survey was carried out. A platform of the European Network of Young Gynaecological Oncologists (ENYGO) database was used. A 38-item multiple-choice questionnaire was used to evaluate current practice in fertility-sparing management of EC. The survey covered investigations, treatment options, follow-up and management of recurrence and future family planning. Descriptive statistics were used.Overall, 116 out of 650 (17.84%) ENYGO members responded to the survey. In 92 (79.3%) centres, the caseload of early stage EC treated conservatively was less than 10 per year. One hundred and seven responders (93.8%) believe that treatment with progestins could be offered in grade 1 EC without myometrial invasion, but a minority would recommend it even for grade 2 tumours with no myometrial invasion or grade 1 with superficial invasion. The diagnostic tool for establishing grade of tumour was hysteroscopy with dilatation and curettage in 64 (55%) centres. Medroxyprogesterone acetate represents the most commonly prescribed progestogen (55, 47.4%). In 78 (67.2%) centres, a repeat endometrial biopsy was offered after 3 months of treatment commencement. Recurrences are treated mostly with hysterectomy (81, 69.9%) with only a small number of responders recommending to repeat progestin treatment. Lynch syndrome is a contraindication for conservative management in half of the responders (57, 49.1%). Most clinicians agree that patients should be referred promptly for assisted reproductive techniques once complete response has been achieved (68, 58.6%).Our study shows that conservative management is increasingly offered to women affected by early stage EC wishing to preserve their fertility. Further studies and joint registries are required to evaluate safety and effectiveness of this approach in this probably growing number of patients.

Objective To show 3 different techniques for achieving an endobag morcellation without adding extra-time and cost to the surgery. Design Stepwise demonstration of the 3 techniques with narrated video footage. Setting Morcellation is a useful procedure for fragmenting and extracting specimens during laparoscopic surgery without the need to perform a laparotomy. In this sense, patients that otherwise would not be eligible for minimally invasive surgery (i.e. large uterus or fibroids) could benefit from laparoscopic advantages. However, morcellation has a major limitation: the risk of dissemination of unsuspected malignancies. In 2017 the Food and Drugs Administration (FDA), released an updated assessment of the use of laparoscopic power morcellators for treatment of leiomyomas. A total of 23 studies were included in the analysis, and 20 studies (90,910 women) contributed to the estimated prevalence of leiomyosarcoma at the time of surgery for presumed leiomyomas. Depending on the modeling methodology used the estimated prevalence of uterine sarcoma was 1 in 305 to 1 in 360 women, and for leiomyosarcoma the estimated prevalence was 1 in 570 to 1 in 750 women. [1] Currently available evidence suggests that if an undiagnosed uterine malignancy is intraabdominally morcellated, there is risk of intraperitoneal dissemination of the disease. [2] Therefore, European Society of Gynecological Oncology (ESGO) emitted a statement in 2016 recommending avoiding morcellation if there is any suspicion of sarcoma and using endobag containers for morcellation of surgical removed uterine fibroids [3]. Additionally, in the United States, the FDA recommends performing laparoscopic power morcellation for myomectomy or hysterectomy only with a tissue containment system, legally marketed in the U.S. [4] INTERVENTIONS: There are several techniques described in the literature for contained uterine fibroids morcellation [5]. In this video, we present 3 of them: First, indirect view morcellation is described. In this technique we place the fibroid in the bag and exteriorize it through one of the trocars. Once outside the abdomen we will place the morcellator through the bag opening and do the morcellation inside the bag while checking through the umbilicus camera. Special attention must be paid in order to avoid any damage to the bag, as the visualization is limited in this technique. Second, direct view technique is described, where we exteriorize the opening of a 15mm bag through the suprapubic trocar and a closed end of the bag through the umbilicus. A hole must be made in the umbilicus end of the bag and we should introduce the camera trocar through it. Once done, we introduce the morcellator trough the opening and the camera in the umbilicus port. Third, single-port contained morcellation is explained. The bag is exteriorized through the umbilicus, and a skin retractor is placed. A glove is placed outside the retractor to isolate the bag. Once placed, two of the fingers are opened and used as trocars (one for the morcellator a the other for a 30-degree camera). After using this technique, the scope should be replaced in order to minimize the risk of contamination. The limitations of each technique could be the next: in the indirect view technique, due to the limited visualization, the surgeon must pay special attention to avoid bag tearing while morcellating the specimen. In the single port technique, the surgeon must have previous experience in this type of approach, minimizing the risk of contamination by changing the scope after the morcellation process. Finally, in the third method, the surgeon needs to ensure the proper closure of the bag before removing it from the abdomen to avoid possible dissemination risk. Conclusion Laparoscopic power morcellation may provide several benefits for our patients, when performing a hysterectomy or a multiple myomectomy. We present 3 different and feasible techniques for laparoscopic power morcellation using an endobag container.

BACKGROUND: Awareness is growing that cancer can be treated during pregnancy, but the effect of this change on maternal and neonatal outcomes is unknown. The International Network on Cancer, Infertility and Pregnancy (INCIP) registers the incidence and maternal, obstetric, oncological, and neonatal outcomes of cancer occurring during pregnancy. We aimed to describe the oncological management and obstetric and neonatal outcomes of patients registered in INCIP and treated in the past 20 years, and assess associations between cancer type or treatment modality and obstetric and neonatal outcomes. METHODS: This descriptive cohort study included pregnant patients with cancer registered from all 37 centres (from 16 countries) participating in the INCIP registry. Oncological, obstetric, and neonatal outcome data of consecutive patients diagnosed with primary invasive cancer during pregnancy between Jan 1, 1996, and Nov 1, 2016, were retrospectively and prospectively collected. We analysed changes over time in categorical patient characteristics, outcomes, and treatment methods with log-binomial regression. We used multiple logistic regression to analyse preterm, prelabour rupture of membranes (PPROM) or preterm contractions, small for gestational age, and admission to the neonatal intensive care unit (NICU). The INCIP registry study is registered with ClinicalTrials.gov, number NCT00330447, and is ongoing. FINDINGS: 1170 patients were included in the analysis and 779 (67%) received treatment during pregnancy. Breast cancer was the most common malignant disease (462 [39%]). Every 5 years, the likelihood of receiving treatment during pregnancy increased (relative risk [RR] 1·10, 95% CI 1·05-1·15), mainly related to an increase of chemotherapeutic treatment (1·31, 1·20-1·43). Overall, 955 (88%) of 1089 singleton pregnancies ended in a livebirth, of which 430 (48%) of 887 pregnancies ended preterm. Each 5 years, we observed more livebirths (RR 1·04, 95% CI 1·01-1·06) and fewer iatrogenic preterm deliveries (0·91, 0·84-0·98). Our data suggest a relationship between platinum-based chemotherapy and small for gestational age (odds ratio [OR] 3·12, 95% CI 1·45-6·70), and between taxane chemotherapy and NICU admission (OR 2·37, 95% CI 1·31-4·28). NICU admission seemed to depend on cancer type, with gastrointestinal cancers having highest risk (OR 7·13, 95% CI 2·86-17·7) and thyroid cancers having lowest risk (0·14, 0·02-0·90) when compared with breast cancer. Unexpectedly, the data suggested that abdominal or cervical surgery was associated with a reduced likelihood of NICU admission (OR 0·30, 95% CI 0·17-0·55). Other associations between treatment or cancer type and outcomes were less clear. INTERPRETATION: Over the years, the proportion of patients with cancer during pregnancy who received antenatal treatment increased, especially treatment with chemotherapy. Our data indicate that babies exposed to antenatal chemotherapy might be more likely to develop complications, specifically small for gestational age and NICU admission, than babies not exposed. We therefore recommend involving hospitals with obstetric high-care units in the management of these patients. FUNDING: Research Foundation-Flanders, European Research Council, Charles University, Ministry of Health of the Czech Republic. ispartof: The Lancet Oncology vol:19 issue:3 pages:337-346 ispartof: location:England status: published

OBJECTIVES/HYPOTHESIS: Thyroid cancer, with 6% to 10% of cancer diagnoses, is one of the most common malignancies during pregnancy. Its treatment poses a risk for the pregnancy, as the thyroid gland plays a crucial role in the evolution of pregnancy. The aim of this study is to evaluate treatment of primary well-differentiated thyroid carcinoma during pregnancy and fetal and maternal outcomes.STUDY DESIGN: This is an international cohort study.METHODS: Primary thyroid cancer patients were identified from the database of the International Network on Cancer, Infertility, and Pregnancy registration study. Data on histopathological characteristics, diagnostic and therapeutic interventions, outcome (obstetrical, neonatal, and maternal) and maternal follow-up were analyzed.RESULTS: Thirty-five patients with well-differentiated thyroid carcinoma were eligible. All 35 patients underwent surgery, 29 (83%) of which during pregnancy. Procedures during pregnancy were mainly total thyroidectomies (n = 24). The median number of days between diagnosis and surgical treatment was different between the groups with surgery during and after pregnancy (27 vs. 139 days, P < .001). Both maternal and neonatal outcomes were uncomplicated, regardless of gestational age during surgery.CONCLUSIONS: Well-differentiated thyroid carcinoma diagnosed during pregnancy has a favorable outcome for both mother and child. Surgical management during pregnancy has no negative impact on the pregnancy regardless of the trimester at the time of surgery. However, the potential negative effects of thyroid surgery early in pregnancy demand management of these patients in an experienced multidisciplinary team to provide the best possible care for these patients and their unborn babies.LEVEL OF EVIDENCE: 4 Laryngoscope, 2017.

Purpose of Review Cancer diagnosis in young pregnant women challenges oncological decision-making. The International Network on Cancer, Infertility and Pregnancy (INCIP) aims to build on clinical recommendations based on worldwide collaborative research. Recent Findings A pregnancy may complicate diagnostic and therapeutic oncological options, as the unborn child must be protected from potentially hazardous exposures. Pregnant patients should as much as possible be treated as non-pregnant patients, in order to preserve maternal prognosis. Some approaches need adaptations when compared with standard treatment for fetal reasons. Depending on the gestational age, surgery, radiotherapy, and chemotherapy are possible during pregnancy. A multidisciplinary approach is the best guarantee for experience-driven decisions. A setting with a high-risk obstetrical unit is strongly advised to safeguard fetal growth and health. Research wise, the INCIP invests in clinical follow-up of children, as cardiac function, neurodevelopment, cancer occurrence, and fertility theoretically may be affected. Furthermore, parental psychological coping strategies, (epi)genetic alterations, and pathophysiological placental changes secondary to cancer (treatment) are topics of ongoing research. Summary Further international research is needed to provide patients diagnosed with cancer during pregnancy with the best individualized management plan to optimize obstetrical and oncological care.

INTRODUCTION: Gastric cancer during pregnancy is extremely rare and data on optimal treatment and possible chemotherapeutic regimens are scarce. The aim of this study is to describe the obstetric and maternal outcome of women with gastric cancer during pregnancy and review the literature on antenatal chemotherapy for gastric cancer. MATERIAL AND METHODS: Treatment and outcome of patients registered in the International Network on Cancer, Infertility and Pregnancy database with gastric cancer diagnosed during pregnancy were analyzed. RESULTS: In total, 13 women with gastric cancer during pregnancy were registered between 2002 and 2018. Median gestational age at diagnosis was 22 weeks (range 6-30 weeks). Twelve women were diagnosed with advanced disease and died within 2 years after pregnancy, most within 6 months. In total, eight out of 10 live births ended in a preterm delivery because of preeclampsia, maternal deterioration, or therapy planning. Two out of six women who initiated chemotherapy during pregnancy delivered at term. Two neonates prenatally exposed to chemotherapy were growth restricted and one of them developed a systemic infection with brain abscess after preterm delivery for preeclampsia 2 weeks after chemotherapy. No malformations were reported. CONCLUSIONS: The prognosis of gastric cancer during pregnancy is poor, mainly due to advanced disease at diagnosis, emphasizing the need for early diagnosis. Antenatal chemotherapy can be considered to reach fetal maturity, taking possible complications such as growth restriction, preterm delivery, and hematopoietic suppression at birth into account. ispartof: ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA vol:99 issue:1 pages:79-88 ispartof: location:United States status: published

Introduction/Background The purpose of this study was to assess obstetric and maternal outcome of pregnant patients with diagnosis of Hodgkin lymphoma (HL) to guide physicians in clinical management. Methodology Clinical data of pregnant patients diagnosed with HL between 1969 and 2018 were collected from the registry of the International Network on Cancer, Infertility and Pregnancy (INCIP). For survival analysis of classical HL treated with an ABVD-based regimen, non-pregnant controls were selected based on stage and prognostic score at diagnosis. Results The median gestational age at diagnosis of 134 eligible patients was 20 weeks (range: 3–37). Antenatal chemotherapy was initiated in 53.7% of patients. Ten (7.5%) early pregnancies were terminated. One foetus deceased in the third trimester after three cycles of chemotherapy. In total, 120 (89.6%) pregnancies ended in a live birth. Preterm delivery was observed in 47 (40.1%) singleton pregnancies. Birth weight percentiles were lower in children prenatally exposed to oncological treatment and 17.9% were small for gestational age at birth (figure 1). Four children (3.5%) had major congenital malformations. Five-year progression-free survival (PFS) for HL during pregnancy was 82.5% and 90.9% for early (n=62) and advanced stage (n=15). Five-year overall survival (OS) was 97.3% and 100%, respectively. Although not significant, patients with early stage HL appeared to have inferior PFS compared with matched non-pregnant controls (n=62, figure 2), more clearly seen in the subgroup that initiated chemotherapy during pregnancy (n=45). OS was comparable between both groups, supporting the effectiveness of salvage therapy. For advanced stage HL survival was similar to controls, albeit small numbers. Conclusion Survival of patients diagnosed with early stage HL during pregnancy appears not statistically different from matched non-pregnant controls, however future prospective research is necessary to investigate the efficacy of chemotherapy during pregnancy. Awareness of complications as preterm delivery and low birth weight is important. Disclosure This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 647047. We are grateful to the Research Foundation-Flanders (FWO., grant no G070514N) and ESGO (European Society of Gynaecological Oncology) for their support. FA is senior clinical investigator of the F.W.O. MJH was supported by Charles University research project Progres Q28 and Q34 and by grant MH CZ - DRO (‘Kralovske Vinohrady University Hospital - FNKV, 00064173’). The funding sources did not influence study design. There are no conflicting interests to declare.

Objectives Purpose of study was to determine long term experience of less radical surgery, sentinel lymph node identification (SLNI) with Tc99+blue day with laparoscopic surgery. Methods From 1999 to 2018, 91 women with tumor less than 20 mm in largest diameter, infiltration less than half of cervical stroma underwent SLNI, frozen section (FS) of SLN, extirpation of afferent parametrial lymphatic channel, pelvic lymphadenectomy or only SLN. FS SLN positive patients underwent radical hysterectomy. Seven days after final histopathological processing of dissected nodes, large cone or simple trachelectomy was performed. Results 15 women (16.5%) lost fertility. 9 women had positive lymph nodes (9.9%), 2 close invasive margin (2.2%), so radical hysterectomy was performed. Four cases had SIL in margin or patient decision, had laparoscopic hysterectomy. One patient N1 had recurrence and died of disease. All other are in complete remission. Fertility was save in 76 cases. Three central recurrences (isthmic part of uterus) were observed (3.9%), one died (1.3%), 2 are in CR 15 and 7 years. We have no distant recurrence. 62 of 76 women whose reproductive ability had been maintained tried to conceive (82%). Of these 62 women, 49 became pregnant (79%) in total 76 pregnancies. 43 mothers gave birth to 48 children, two children were by surrogate mothers. Conclusions Less radical fertility sparing surgery in early cervical cancer can be feasible method that yields high, successful pregnancy rate. This work was supported by the Charles University research program PROGRES Q 28 (Oncology).

BackgroundTreatment of cervical cancer during pregnancy is often complex and challenging. This study aimed to analyze current patterns of practice in the management of pregnant patients diagnosed with cervical cancer.MethodsThis was a matched cohort study comprising patients managed for cervical cancer during pregnancy from six European centers. Patient information was retrieved from the dataset of the International Network for Cancer, Infertility and Pregnancy from 1990 to 2012. Each center matched its patients with two non-pregnant controls for age (±5 years) and International Federation of Gynecology and Obstetrics (FIGO) 2009 stage. Information on age, histological type, grade, lymphovascular space invasion, stage, tumor size, method of diagnosis, site of recurrence, delivery, date of recurrence, and date of death was recorded. Progression-free survival was compared using multivariable Cox proportional hazards regression.ResultsA total of 132 pregnant patients and 256 controls were analyzed. The pregnant patients (median age 34 years, range 21–43) were diagnosed at a median gestational age of 18.4 weeks of pregnancy (range 7–39). Stage distribution during pregnancy was 14.4% for stage IA, 47.0% for IB1, 18.9% for IB2, and 19.7% for II-IV. For treatment during pregnancy, 17.4% of the patients underwent surgery, 16.7% received neoadjuvant chemotherapy, 26.5% delayed their treatment, 12.9% had a premature delivery, and 26.5% had their pregnancy terminated. Median follow-up was 84 months (67 months for pregnant and 95 months for non-pregnant patients). The unadjusted hazard ratio of pregnancy for progression-free survival was 1.18 (95% confidence interval 0.74 to 1.88).ConclusionSurgery and chemotherapy is increasingly used in the management of pregnant patients with cervical cancer and prognosis is similar to that of non-pregnant patients.

IntroductionAdvanced minimal access surgical training is an important component of training in gynecological oncology (GO). Europe-wide data on this topic are lacking. We present data on availability and trainee experience of advanced laparoscopic surgical (ALS) and robotic surgical (RS) training in GO across Europe.MethodA prospective web-based anonymized survey of European GO trainees was sent to the European Network of Young Gynaecological Oncologists members/trainees. It included sociodemographic information and specific questions pertaining to training experience or satisfaction in laparoscopic and robotic surgery. χ2test was used for evaluating categorical variables and Mann-Whitney/Kruskal-Wallis (nonparametric) tests for continuous variables between 2 and more independent groups.ResultsA total of 113 GO trainees from 29 countries responded. The mean (standard deviation) age was 35.2 (6.1) years, 59.3% were men, 40.7% were women, and 46% were in accredited training posts. The ALS and RS training was offered in only 43% and 23% of institutes respectively, and 54% and 23% of trainees had undergone some form of formal or informal training in ALS and RS respectively. A total of 62.4% felt that RS should be a formal component of GO training programs. A total of 61% and 35% planned to go outside their institute for ALS or RS training respectively. Trainees rating (1–5 scale) of their open surgery and ALS or RS skills (3.3/2.6/1.9) and training experience (3.5/2.8/2.1), respectively, were higher for open surgery than ALS or RS (P< 0.0005). Accredited posts were more likely than nonaccredited posts to offer ALS training (60%/31%,P= 0.002), formal training schedules (27.9%/4.4%,P= 0.003), and use of logbooks (46%/23%,P= 0.035).ConclusionsTraining and experience in ALS and RS are poorly rated by GO trainees across Europe, and only few centers offer this. There is an urgent need to expand and harmonize training opportunities for ALS and RS. Most trainees want RS included as a formal component of their training.

Because of a notable increase in age at delivery, the incidence of malignancy diagnosed during pregnancy has substantially increased. This review aims to summarize the literature and expert knowledge on gynecologic cancers diagnosed in pregnancy regarding epidemiology, examination and staging procedures, description of treatment modalities and management of gynecological malignancies with special interest in cervical and ovarian cancer. Thorough attention is paid to the surgery and chemotherapy administration for early-stage cervical cancer diagnosed during pregnancy.

We aimed to provide comprehensive protocols and promote effective management of pregnant women with gynecological cancers. New insights and more experience have been gained since the previous guidelines were published in 2014. Members of the International Network on Cancer, Infertility and Pregnancy (INCIP), in collaboration with other international experts, reviewed existing literature on their respective areas of expertise. Summaries were subsequently merged into a manuscript that served as a basis for discussion during the consensus meeting. Treatment of gynecological cancers during pregnancy is attainable if management is achieved by collaboration of a multidisciplinary team of health care providers. This allows further optimization of maternal treatment, while considering fetal development and providing psychological support and long-term follow-up of the infants. Nonionizing imaging procedures are preferred diagnostic procedures, but limited ionizing imaging methods can be allowed if indispensable for treatment plans. In contrast to other cancers, standard surgery for gynecological cancers often needs to be adapted according to cancer type and gestational age. Most standard regimens of chemotherapy can be administered after 14 weeks gestational age but are not recommended beyond 35 weeks. C-section is recommended for most cervical and vulvar cancers, whereas vaginal delivery is allowed in most ovarian cancers. Breast-feeding should be avoided with ongoing chemotherapeutic, endocrine or targeted treatment. More studies that focus on the long-term toxic effects of gynecologic cancer treatments are needed to provide a full understanding of their fetal impact. In particular, data on targeted therapies that are becoming standard of care in certain gynecological malignancies is still limited. Furthermore, more studies aimed at the definition of the exact prognosis of patients after antenatal cancer treatment are warranted. Participation in existing registries (www.cancerinpregnancy.org) and the creation of national tumor boards with multidisciplinary teams of care providers (supplementary Box S1, available at Annals of Oncology online) is encouraged. ispartof: ANNALS OF ONCOLOGY vol:30 issue:10 pages:1601-1612 ispartof: location:England status: published

A high density of tumor-infiltrating CD8+ T cells and CD20+ B cells correlates with prolonged survival in patients with a wide variety of human cancers, including high-grade serous ovarian carcinoma (HGSC). However, the potential impact of mature dendritic cells (DCs) in shaping the immune contexture of HGSC, their role in the establishment of T cell-dependent antitumor immunity, and their potential prognostic value for HGSC patients remain unclear. We harnessed immunohistochemical tests and biomolecular analyses to demonstrate that a high density of tumor-infiltrating DC-LAMP+ DCs is robustly associated with an immune contexture characterized by TH1 polarization and cytotoxic activity. We showed that both mature DCs and CD20+ B cells play a critical role in the generation of a clinically favorable cytotoxic immune response in HGSC microenvironment. In line with this notion, robust tumor infiltration by both DC-LAMP+ DCs and CD20+ B cells was associated with most favorable overall survival in two independent cohorts of chemotherapy-naive HGSC patients. Our findings suggest that the presence of mature, DC-LAMP+ DCs in the tumor microenvironment may represent a novel, powerful prognostic biomarker for HGSC patients that reflects the activation of clinically relevant anticancer immunity. Citation Format: Iva Truxova, Lenka Kasikova, Michal Hensler, Petr Skapa, Jan Laco, Ladislav Pecen, Lucie Belicova, Ivan Praznovec, Michael J. Halaska, Tomas Brtnicky, Eva Salkova, Lukas Rob, Roman Kodet, Jeremy Goc, Catherine Sautes-Fridman, Wolf Herman Fridman, Ales Ryska, Lorenzo Galluzzi, Radek Spisek, Jitka Fucikova. Mature dendritic cells correlate with favorable immune infiltrate and improved prognosis in ovarian carcinoma patients [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr B76.

Objective: To compare the efficacy and safety of mirabegron 50 mg and solifenacin 5 mg in overactive bladder (OAB) patients dissatisfied with previous antimuscarinic treatment due to lack of efficacy. Patients and methods: This randomized, double-blind, phase IIIb, noninferiority study, enrolled male and female patients aged ⩾18 years old, with symptoms of OAB for ⩾3 months, who were dissatisfied with their previous antimuscarinic drug due to lack of efficacy. A total of 1887 patients were randomized to receive mirabegron 50 mg ( n = 943) or solifenacin 5 mg ( n = 944) daily for 12 weeks. The primary efficacy endpoint was change from baseline to end of treatment in mean number of micturitions/24 h. Noninferiority was confirmed if the lower limit of the two-sided 95% confidence interval (CI) for the treatment difference between solifenacin and mirabegron was > −0.20. Secondary efficacy endpoints, which included change from baseline in mean number of incontinence episodes/24 h, urgency incontinence episodes/24 h, urgency episodes (grade 3 or 4)/24 h and nocturia episodes/24 h, were analyzed using analysis of covariance. Results: For the primary endpoint, adjusted mean treatment difference (95% CI) in mean number of micturitions/24 h was −0.18 (−0.42, 0.06) and therefore noninferiority of mirabegron to solifenacin was not demonstrated. Both treatments demonstrated clinically meaningful reductions in efficacy variables and were well tolerated, with a lower incidence of dry mouth with mirabegron. Conclusions: Noninferiority of mirabegron compared with solifenacin for reduction in micturition frequency could not be demonstrated in this population of OAB patients who were dissatisfied with previous antimuscarinic therapy due to lack of efficacy. Both mirabegron and solifenacin improved key OAB symptoms with no statistically significant differences observed between the two treatments. Both drugs were well tolerated.

Incidence nadorových onemocněni v těhotenstvi stoupa vzhledem ke starnouci populaci rodicek. Onkologicka prognoza těchto pacientek se nelisi oproti netěhotným. Diky aktualnim poznatkům je ve velkem procentu připadů možne pokracovat v graviditě a soucasně zahajit protinadorovou lecbu. Tato prace shrnuje zakladni fakta týkajici se diagnostiky a lecby nadorových onemocněni v těhotenstvi vcetně podavani chemoterapie v graviditě.

Introduction: Fetal growth restriction (FGR) carries an increased risk of perinatal mortality and morbidity. A major cause of FGR is placental insufficiency. After in utero chemotherapy-exposure, an increased incidence of FGR has been reported. In a prospective cohort study we aimed to explore which pathways may contribute to chemotherapy-associated FGR. Methods: Placental biopsies were collected from 25 cancer patients treated with chemotherapy during pregnancy, and from 66 control patients. Differentially expressed pathways between chemotherapy-exposed patients and controls were examined by whole transcriptome shotgun sequencing (WTSS) and Ingenuity Pathway Analysis (IPA). Immunohistochemical studies for 8-OHdG and eNOS (oxidative DNA damage), proliferation (PCNA) and apoptosis (Cleaved Caspase 3) were performed. The expression level of eNOS, PCNA and IGFBP6 was verified by real-time quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR). Results: Most differential expressed genes between chemotherapy-exposed patients and controls were related to growth, developmental processes, and radical scavenging networks. The duration of chemotherapy exposure had an additional impact on the expression of genes related to the superoxide radicals degeneration network. Immunohistochemical analyses showed a significantly increased expression of 8-OHdG (P = 0.003) and a decreased expression of eNOS (P=0.015) in the syncytiotrophoblast of the placenta of cancer patients. A decreased expression of PCNA was detected by immunohistochemistry as RT-qPCR (NS). Conclusion: Chemotherapy exposure during pregnancy results in an increase of oxidative DNA damage and might impact the placental cellular growth and development, resulting in an increased incidence of FGR in this specific population. Further large prospective cohort studies and longitudinal statistical analyses are needed.

ObjectiveThe aim of this study was to prospectively monitor the patients’ quality of life (QoL) after vulvar cancer surgery.DesignThe design was prospective clinical study.SettingThe study was set in the Department of Obstetrics and Gynecology, 2nd Medical Faculty of the Charles University and University Hospital Motol, Prague, Czech Republic.MethodsA group of 36 patients underwent vulvar cancer surgery: 24 patients were subject to inguinofemoral lymphadenectomy (RAD) and 12 to sentinel lymph node biopsy. To evaluate QoL, the European Organisation for Research and Treatment of Cancer, QoL questionnaires (QLQ-C30 and QLQ-CX24) were administered to patients before and 6 and 12 months after surgery.ResultsIn patients with vulvar cancer after inguinofemoral lymphadenectomy, increased fatigue and impaired lymphedema were observed. In the group of patients after sentinel lymph node biopsy, none of the QoL variables worsened postoperatively. Comparing both groups 12 months after surgery, the RAD group had significantly worse outcomes in body image and cognitive functioning than the sentinel lymph node biopsy group.Patients in the RAD group, who received adjuvant radiotherapy (n = 13), had worse QoL in symptom experience (P < 0.05) at 6 and 12 months after the surgery than patients without radiotherapy (n = 11).ConclusionsLess radical surgery showed objectively better QoL results.

Objective 28 women under 35years with early-stage cervical cancer and strong desire for fertility preservation that do not fulfil standard criteria for fertility-sparing surgery (tumour larger than 2cm or with deep of infiltration more than half of stroma) were included in prospective study. Methods Dose-dense neoadjuvant chemotherapy (NAC) was performed on all 28 patients in 10-day intervals: cisplatin plus ifosfamide in squamous cell cancer (15 women—53.6%) or cisplatin plus doxorubicin in adenocarcinoma (13 women—46.3%). Patients underwent laparoscopic lymphadenectomy and vaginal simple trachelectomy after NAC. Patients with positive lymph nodes or inadequate free surgical margins underwent radical hysterectomy. Results No residual disease was found in 6 women (21.4%), microscopic disease was observed in 11 women (39.3%) and macroscopic tumour in was observed in 11 women (39.3%). Ten women (35.7%) lost fertility. Four women (20%) after fertility-sparing surgery recurred, two died of the disease (10%). Fertility was spared in 20 (71.4%) women and 10 of them became pregnant (50%). Eight women delivered ten babies (6 term and four preterm deliveries). There were two miscarriages in second trimester (in one woman) and one in first trimester. One woman underwent four unsuccessful cycles of IVF, one failed to become pregnant and one recurred too early. Two women underwent chemoradiotherapy for recurrence and lost chance for pregnancy. Conclusions Downstaging by NAC in IB1 and IB2 cervical cancer before fertility-sparing surgery is still an experimental procedure, but shows some promise. Long-term results in relation to oncological outcome for this concept are still needed.

Background The purpose of this study was to assess obstetric and maternal outcome of pregnant patients with diagnosis of Hodgkin lymphoma (HL) registered by the International Network on Cancer, Infertility and Pregnancy (INCIP) to guide physicians in clinical management. Methods Clinical data of pregnant patients diagnosed with HL between 1969 and 2018 were collected from the INCIP registry. For survival analysis of classical HL treated with an ABVD-based regimen, non-pregnant controls were selected based on stage and prognostic score at diagnosis. Results The median gestational age at diagnosis of 134 eligible patients was 20 weeks (range: 3 – 37). Antenatal chemotherapy was initiated in 53.7% of patients. Ten (7.5%) early pregnancies were terminated. One foetus deceased in the third trimester after three cycles of chemotherapy. In total, 120 (89.6%) pregnancies ended in a live birth. Preterm delivery was observed in 47 (40.1%) singleton pregnancies. Birth weight percentiles were lower in children prenatally exposed to oncological treatment and 17.9% were small for gestational age at birth. Four children (3.5%) had major congenital malformations. Five-year progression-free survival (PFS) for HL during pregnancy was 82.5% and 90.9% for early (n = 62) and advanced stage (n = 15). Five-year overall survival (OS) was 97.3% and 100%, respectively. Although not significant, patients with early stage HL appeared to have inferior PFS compared with matched non-pregnant controls (n = 62), more clearly seen in the subgroup that initiated chemotherapy during pregnancy (n = 45). OS was comparable between both groups, supporting the effectiveness of salvage therapy. For advanced stage HL survival was similar to controls, albeit small numbers. Conclusions Although further prospective research on the efficacy of chemotherapy during pregnancy is necessary, survival of patients diagnosed with early stage HL during pregnancy appears not to be statistically different from matched non-pregnant controls, Awareness of complications as preterm delivery and low birth weight is important in this population. Clinical trial identification NTC00330447. Legal entity responsible for the study The authors. Funding European Union’s Horizon 2020 Research and Innovation Program under grant agreement No 647047 Research Foundation-Flanders (FWO., grant no G070514N) and ESGO (European Society of Gynaecological Oncology) Charles University Research Project Progres Q28 and Q34 and by grant MH CZ - DRO ("Kralovske Vinohrady University Hospital - FNKV, 00064173"). Disclosure All authors have declared no conflicts of interest.

Background The International Network of Cancer, Infertility and Pregnancy was launched in order to register women of reproductive age with a cancer diagnosis. Over the years, the project has expanded with currently 2653 cases registered by 114 centres and an annual registration rate of 150 patients. The expected rising numbers of cancer diagnosis during pregnancy as a result of an increased age at first childbirth and the possibility of early cancer detection by the non-invasive prenatal testing calls for an ongoing evaluation of clinical practice. Moreover, women might become pregnant while exposed to adjuvant or maintenance therapies that are increasingly being used. Methods The INCIP database consists of a secured on-line registration tool. Oncological, obstetric and neonatal data are registered by members. Annual scientific meetings give updates on the ongoing research projects. Results Most patients were registered in Belgium, the Netherlands, Italy and USA and one third of participating centres are non-European. Currently 2059 patients with a cancer diagnosis or treatment during pregnancy are registered, 395 women that received fertility preservation and 199 patients with a postnatal cancer diagnosis (Figure 1). Breast cancer, lymphoma and cervical cancer are the most frequent registered cancer types and the majority of patients (67%) received antenatal cancer treatment (Figure 2). Most women delivered a live born baby (88%), however 47% delivered preterm and 80% of preterm deliveries were medically induced. One-fifth of neonates (21%) were small for gestational age. Congenital malformations were reported in 3% of live births. Conclusions Cancer occurring in women endangers obstetrical and neonatal outcome and potentially future fertility. The INCIP registry is open for further collection of data since for such a relatively rare situation, only a large-scale project will provide better insights on maternal and foetal risks assessment, which is essential for optimal patient counselling and care. Clinical trial identification NCT00330447. Legal entity responsible for the study The authors. Funding European Union’s Horizon 2020 research and innovation program under grant agreement No 647047. Disclosure All authors have declared no conflicts of interest.

Background More than 90% of cases of anal cancers are caused by high-risk human papillomavirus (HR HPV) infection and a history of cervical intraepithelial neoplasia (CIN) is established as possible risk factor. Objectives To demonstrate relationship between anal and cervical HPV infection in women with different grades of CIN and microinvasive cervical cancer. Study design A total of 272 women were enrolled in the study. The study group included 172 women who underwent conization for high-grade CIN or microinvasive cervical cancer. The control group consisted of 100 women with non-neoplastic gynecologic diseases or biopsy-confirmed CIN 1. All participants completed a questionnaire detailing their medical history and sexual risk factors and were subjected to anal and cervical HPV genotyping using Cobas and Lynear array HPV test. Results Cervical, anal, and concurrent cervical and anal HPV infections were detected in 82.6%, 48.3% and 42.4% of women in the study group, and in 28.0%, 26.0% and 8.0% of women in the control group, respectively. The prevalence of the HR HPV genotypes was higher in the study group and significantly increased with the severity of cervical lesion. Concurrent infections of the cervix and anus occurred 5.3-fold more often in the study group than in the control group. Any contact with the anus was the only significant risk factor for development of concurrent HPV infection. Conclusions Concurrent anal and cervical HR HPV infection was found in nearly half of women with CIN 2+. The dominant genotype found in both anatomical locations was HPV 16. Any frequency and any type of contact with the anus were shown as the most important risk factor for concurrent HPV infection.

The aim of the study was to assess patterns in the use of social media (SM) platforms and to identify the training needs among European gynecologic oncology trainees.In 2014, a web-based survey was sent to 633 trainees from the European Network of Young Gynaecological Oncologists (ENYGO) database. The 14-item questionnaire (partially using a 1- to 5-point Likert scale) assessed respondents' use of SM and preference for workshop content and organization. Descriptive analysis was used to describe the mean scores reported for different items, and the internal reliability of the questionnaire was assessed by Cronbach α.In total, 170 ENYGO members (27%) responded to the survey. Of those, 91% said that they use SM platforms, mostly for private purposes. Twenty-three percent used SM professionally and 43% indicated that they would consider SM to be a clinical discussion forum. The respondents said that they would like updates on conferences and professional activities to be shared on SM platforms. Complication management, surgical anatomy, and state of the art in gynecologic oncology were identified as preferred workshops topics. The most frequently indicated hands-on workshops were laparoscopic techniques and surgical anatomy. Consultants attached a higher level of importance to palliative care education and communication training than trainees. The mean duration of the workshop preferred was 2 days.This report highlights the significance of ENYGO trainees' attachment to SM platforms. Most respondents expect ENYGO to use these online channels for promoting educational activities and other updates. Using SM for clinical discussion will require specific guidelines to secure professional and also consumer integrity. This survey confirms surgical management and the state of the art as important knowledge gaps, and ENYGO has tailored its activities according to these results. Future activities will further direct attention and resources to education in palliative care and molecular tumor biology.

Owing to their central role in the initiation and regulation of antitumor immunity, dendritic cells (DCs) have been widely tested for use in cancer immunotherapy. Despite several encouraging clinical applications, existing DC-based immunotherapy efforts have yielded inconsistent results. Recent work has identified strategies that may allow for more potent DC-based vaccines, such as the combination with antitumor agents that have the potential to synergistically enhance DC functions. Selected cytotoxic agents may stimulate DCs either by directly promoting their maturation or through the induction of immunogenic tumor cell death. Moreover, they may support DC-induced adaptive immune responses by disrupting tumor-induced immunosuppressive mechanisms via selective depletion or inhibition of regulatory subsets, such as myeloid-derived suppressor cells and/or regulatory T cells (Tregs). Here, we summarize our current knowledge on the capacity of anticancer chemotherapeutics to modulate DC phenotype and functions and the results of ongoing clinical trials evaluating the use of DC-based immunotherapy in combination with chemotherapy in cancer patients.