Maternal death by cancer in pregnancy: A descriptive study of the International Network on Cancer, Infertility and Pregnancy.

OBJECTIVE: To characterise pregnant women diagnosed with primary or recurrent cancer who died during pregnancy, during delivery or within 1 year postpartum. DESIGN: A descriptive study. SETTING: The registry of the International Network on Cancer, Infertility and Pregnancy (INCIP). POPULATION: Women diagnosed with cancer during pregnancy between 2000 and 2022. METHODS: Using the INCIP registry database, we compared the characteristics of all women with cancer who died during pregnancy, delivery or within 1 year postpartum with those of all women with cancer who survived the first year postpartum. MAIN OUTCOME MEASURES: Maternal and tumour characteristics and obstetrical and neonatal outcomes. RESULTS: Of the 2359 women registered in INCIP, there were 131 cases (5.6%) of maternal mortality. Lung cancer (9/14, 64.3% of all registered women with lung cancer), gastro-oesophageal cancer (13/21, 61.9%) and acute leukaemia (17/105, 16.2%) had the highest rates of maternal mortality. Maternal mortality was associated with fewer live births compared with the control group without maternal mortality (99/131, 75.6%, vs 1952/2163, 90.0%; P < 0.001), more elective caesarean sections (64/104, 60.4%, vs 756/1836, 41.2%; P < 0.001) and a lower gestational age at (induced) delivery (34.0 vs 37.1 weeks; P < 0.001), resulting in more preterm births. CONCLUSIONS: Maternal mortality occurred in 5.6% of cancer-in-pregnancy cases and is associated with adverse perinatal outcomes.

Middle cerebral artery peak systolic velocity monitoring of fetal anemia during chemotherapy in pregnancy.

INTRODUCTION: Chemotherapy during pregnancy can increase the risk of fetal anemia. Severe fetal anemia can lead to the development of hydrops fetalis and potentially fetal demise. Hence, it is imperative to implement consistent monitoring methods in the context of chemotherapy treatment. This study aimed to diagnose and monitor fetal anemia using middle cerebral artery peak systolic velocity (MCA-PSV) as a diagnostic tool during chemotherapy in pregnant women. MATERIAL AND METHODS: The study employed a prospective analysis involving a case series of 15 patients diagnosed with cancer during pregnancy and subsequently underwent chemotherapy. MCA-PSV was used to identify fetal anemia. The patients were scheduled for ultrasound examinations of the MCA-PSV. The first examination was performed on the same day as the administration of chemotherapy, while the second occurred on the 10th day after chemotherapy. The measurement technique used in the study was based on the methodology proposed by Mari and Barr. The multiples of the median were calculated using the calculators provided by Medicina Fetal Barcelona. Based on these values anemia severity was determined. When moderate or severe anemia was identified, chemotherapy was individually modified. Additionally, a blood count analysis was conducted immediately after the delivery of the newborn. RESULTS: Five patients were diagnosed with fetal or newborn anemia. With MCA-PSV, we identified moderate fetal anemia in two patients and severe fetal anemia in one. The complete blood count testing of newborns revealed mild anemia in three patients. One case was unrelated to chemotherapy-induced anemia. During treatment, fetal anemia did not corelate with maternal anemia. CONCLUSIONS: In four cases of anemia the combination of cisplatin and iphosphamide was used as a chemotherapy agent. No anemia was observed in other drug combinations. Our findings suggest that MCA-PSV is a reliable method for identifying anemia and should be included in the treatment protocol for chemotherapy-induced fetal anemia.

Complete tubal abortion which didn't require salpingectomy.

Tubal abortion is characterized by the extrusion of the foetus into the abdominal (peritoneal) cavity. It can either be a complete extrusion or incomplete with residual tissue remaining in the fallopian tube. It is a type of ectopic pregnancy that is difficult to determine the exact incidence of tubal pregnancies. Identifying cases of tubal abortions is crucial for individualized care since it can lead to a more conservative treatment approach. The diagnosis should be based on ultrasound imaging, b-hCG levels and visual conformation during exploratory surgery, either open or laparoscopic. The article describes the case of a 30-year old patient who presented with lower abdominal pain and was admitted for a suspected ectopic pregnancy. Ultrasound imaging showed a mass resembling a tubal pregnancy next to the uterus with b-hCG levels of 111.8 U/L. During laparoscopic surgery, a tubal abortion was detected in the pouch of Douglas (Rectouterine pouch). This finding led us to preserve both fallopian tubes. Histopathology confirmed our clinical findings. A conservative approach can be sufficient in case of tubal abortions, which can lead to preserved fertility and tubal functions.

Chronic endometritis - a constantly discussed issue in infertile women.

OBJECTIVE: A review of current knowledge on the pathophysiology, diagnostic and treatment options for chronic endometritis in infertile women. METHODS AND RESULTS: One of the major causes of failed in vitro fertilization (IVF) is undiagnosed intrauterine pathologies, including chronic inflammation of the uterine mucosa - chronic endometritis. However, some authors relativize the negative impact of chronic endometritis on reproductive outcomes. The etiopathogenesis of chronic endometritis is due to qualitative and quantitative changes in the endometrial microbiome with abnormal multiplication of microorganisms naturally occurring in the uterine cavity or vagina. There is no uniform consensus on the most common pathogen causing chronic endometritis. It is characterized by infiltration of plasma cells into the endometrial stroma outside the menstrual cycle, accompanied by hyperaemia and endometrial oedema. Clinical symptoms are very mild or absent. The diagnosis of chronic endometritis is often difficult because there is no specific clinical or laboratory diagnostic method. The following investigative options are commonly used for the diagnosis of chronic endometritis: diagnostic hysteroscopy, histopathological examination of the endometrium including CD 138 immunohistochemistry and culture from the uterine cavity. However, standardised international hysteroscopic and histopathological criteria for accurate diagnosis of chronic endometritis are still lacking. Empirically administered antibiotic therapy improves the success rate of pregnancy and delivery of a viable foetus in infertile patients with proven chronic endometritis. In addition to reviewing the current knowledge of chronic endometritis, this article discusses the importance of hysteroscopy in the diagnostic process. CONCLUSION: Chronic endometritis is often a clinically silent disease with negative impact on reproduction in infertile women. Although there are still many unresolved issues, the introduction of hysteroscopy into the diagnostic process is important for clinical practice; however, hysteroscopy even in combination with histological examination of the endometrium, often does not allow an unequivocal diagnosis of chronic endometritis. Further prospective randomised studies in a selected group of women with proven chronic endometritis and repeated failure to implant proven euploid embryos should refine this knowledge.

New staging of endometrial carcinoma - FIGO 2023.

AIM: To review the changes in the new version of the FIGO 2023 staging system for endometrial cancer. METHODS AND RESULTS: The new FIGO 2023 endometrial cancer staging system provides key updates for the diagnosis and treatment of endometrial cancer. An important step in diagnosis is molecular classification, which allows more accurate risk stratification for recurrence and the identification of targeted therapies. The new staging system, based on the recommendations of the international societies ESGO, ESTRO and ESP, incorporates not only the description of the pathological and anatomical extent of the disease, but also the histopathological characteristics of the tumour, including the histological type and the presence of lymphovascular space invasion. In addition, the staging system uses molecular testing to classify endometrial cancers into four prognostic groups: POLEmut, MMRd, NSMP and p53abn. Each group has its own specific characteristics and prognosis. The most significant changes have occurred in stages I and II, in which the sub-staging better reflects the biological behaviour of the tumour. This update increases the accuracy of prognosis and improves individualized treatment options for patients with endometrial cancer. CONCLUSION: The updated FIGO staging of endometrial cancer for 2023 incorporates different histologic types, tumour features, and molecular classifications to better reflect the current improved understanding of the complex nature of several endometrial cancer types and their underlying bio logic behaviour. The aim of the new endometrial cancer staging system is to better define stages with similar prognosis, allowing for more precise indication of individualised adjuvant radiation or systemic treatment, including the use of immunotherapy.

Preoperative and postoperative staging in endometrial cancer - a prospective study.

OBJECTIVE: The aim of this study was to determine how often changes the stage of the tumour in definitive histology against preoperative clinical stage in patient cohort with diagnosed endometrial cancer. METHODS: We evaluated prospectively a cohort of 166 patients with endometrial cancer. They all underwent abdominal hysterectomy, bilateral salpingo-oophorectomy, sentinel lymph node biopsy. Patients with high-risk tumours also pelvic lymfadenectomy. We collected data of preoperative diagnostic biopsy and postoperative definitive histology. The data were statistically processed. RESULTS: Detection of sentinel lymph node was successful in 71.1%, bilateral successful detection was in 40.6%. Discrepancy of tumour grade between preoperative biopsy and definitive histology was generally 31.4%. Upgrading of the tumour was in 22 (14.4%) cases, downgrading in 26 (17%) cases. Upgrade from low-risk to high-risk group of tumours was noticed in eight cases. Histopathological tumour type changed in 6.6%, 4.6% moved to histopathologic high-risk group. The tumour stage changed in definite histology in 57.3%, in 19.2% of cases moved from stage low/intermediate-risk group to intermediate-high/high-risk disease group. CONCLUSION: Correct assessment of preoperative clinical stage and histological grade of endometrial cancer is burdened with a high inaccuracy rate. A lot of cases is up-staged after surgical staging and moved to intermediate-high/high-risk disease group. Results confirm the importance of oncogynaecologic centre II. evaluation of histopathology findings from diagnostic biopsies made in referring hospitals. Sentinel lymph node biopsy should be performed even in clinically low/intermediate-risk disease group.

Twenty years of experience with less radical fertility-sparing surgery in early-stage cervical cancer: Pregnancy outcomes.

INTRODUCTION: The standard procedure in cervical cancer is radical hysterectomy and pelvic lymphadenectomy (PLND). Because of the increasing age of women bearing children, fertility has become a major challenge. We present pregnancy results after less radical fertility-sparing surgery in women with IA1, LVSI positive, IA2 and IB1 (<2 cm, infiltration less than half of the cervical stroma). MATERIALS AND METHOD: All women (n = 91) underwent laparoscopic sentinel lymph node mapping with frozen section followed by PLND and "selective parametrectomy" (removal of afferent lymphatic channels from the paracervix) if sentinel nodes (SLN) are negative. If lymph nodes were verified negative by definitive histopathology, patients were treated by simple trachelectomy (IB1) or large cone (IA1/IA2) biopsy 1 week after primary surgery. RESULTS: From 1999 to 2018, 91 women were enrolled in the study (median age 29.1 years, range 21-40). Fertility was spared in 76 (83.5%) women; 13 (17.1%) women did not plan future pregnancy and 63 (82.9%) had pregnancy desires. Fifty-four of 63 women conceived (pregnancy rate 85.7%) and 48 of 63 delivered 58 babies (delivery rate 76.2%). Thirty-nine women delivered in term (67.2%): 13 women between 32 and 36 + 6 weeks of pregnancy, 3 between 28 and 31 + 6 weeks and 3 between 24 and 27 + 6 weeks. Only one woman still plans pregnancy. One woman is currently pregnant. CONCLUSION: The goal of fertility-sparing surgery is to produce good oncological results and promising pregnancy outcomes. Pregnancy results after less radical fertility-sparing procedures show promise (pregnancy rate 82.9% and delivery rate 76.2%).

Avascular spaces in radical hysterectomy.

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.

The efficacy of human papillomavirus vaccination in the prevention of recurrence of severe cervical lesions.

OBJECTIVE: A review of current knowledge on the efficacy of human papillomavirus (HPV) vaccination in preventing recurrent severe cervical lesions after excisional surgical treatment. METHODS AND RESULTS: HPV infection is necessary for the development of most cervical precancerous lesions and cervical cancers. Currently, three prophylactic vaccines against HPV infection are available on the market: bivalent Cervarix, quadrivalent Gardasil (formerly Silgard) and nonavalent Gardasil9. All three prophylactic vaccines show high effect in preventing the development of precancerous lesions. The highest efficacy is achieved in the HPV naive population. The surgical excision of severe cervical precancers is the standard approach. However, guidelines regarding HPV vaccination at the time of conisation are not clearly determined. Women diagnosed with severe cervical lesions have mostly not been vaccinated against HPV so far. Therefore, it is beneficial to understand the importance and efficacy of HPV vaccination at the time of conisation in preventing recurrent precancerous lesions. The exact value of HPV vaccination in the context of surgical excision of precancerous lesions remains unclear, but vaccination is definitely valuable in reducing the risk of recurrence. Vaccination timing seems to be more favorable before surgery. However, the ideal timing of vaccination is not established. Some of these questions are likely to be answered by the results of ongoing randomized controlled trials. CONCLUSION: Adjuvant HPV vaccination in the setting of surgical treatment for cervical precancerous lesion is significantly associated with a reduced risk of recurrence. HPV vaccination should be strongly considered as adjuvant therapy, especially in young patients undergoing conisation for a severe cervical lesion.

Fertility-sparing surgery after neo-adjuvant chemotherapy in women with cervical cancer larger than 4 cm: a systematic review.

OBJECTIVE: The 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. METHODS: This 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. RESULTS: The 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. CONCLUSIONS: Evidence 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.

Analysis of awareness and acceptance of SARS-CoV-2 vaccination among pregnant women.

Vaccination is a widely discussed topic during pregnancy and breastfeeding. Due to newly emerging covid-19 variants, vaccination has become more and more important. These new variants pose a risk for the development of maternal and neonatal complications. The aim of this study was to conduct a survey among pregnant women to assess the awareness of covid-19 and vaccination. Among the respondents, 58% were vaccinated with at least one dose and 51% were fully vaccinated. Also, 77% percent of responders thought that there was an increased risk of severe covid-19 infection among pregnant women versus non-pregnant women, while 71% were aware of the risk of fetal death associated with covid-19 infection. Although the rate of awareness among pregnant women is quite high (up to 87%), it is crucial to present the advantages of vaccination among gynecologists and doctors of other specialties as they are able to motivate women to be vaccinated.

Epidemiology and significance of surgical margins in the management of HPV-associated vulvar precancers (H-SIL) - analysis of own data.

OBJECTIVE: Epidemiology and evaluation of the importance of surgical margins in the treatment of vulvar H-SIL - analysis of own data. MATERIAL AND METHODS: The prospective study included women dia-gnosed with HPV-associated vulvar epithelial neoplasia from 10/2016 to 1/2022. A total of 65 women were included. After surgical treatment, the women were distributed to groups according to surgical margins and were followed-up at regular intervals. RESULTS: Seventeen women (26%) dia-gnosed with HPV-associated vulvar intraepithelial neoplasia were under 49 years, whereas 48 women (74%) were older than 49 years. Recurrence rates of HPV-associated precancers were 12.3%, 1.5% and 3.1% in excisions with positive margins up to 1mm peripheral margins and 1-3mm peripheral margins, respectively. The risk of recurrence when the lesion reaches the margin is statistically significant, compared to a healthy margin of 1-3mm. CONCLUSION: Keeping the minimal healthy margin (1-3mm) seems to be an acceptable risk of recurrence of HPV-associated vulvar intraepithelial neoplasia with positive cosmetic effect and minimal risk of disturbing the psychosexual functions of women. Long-term regular follow-up is necessary.

Twenty years of experience with less radical fertility-sparing surgery in early-stage cervical cancer: Oncological outcomes.

INTRODUCTION: 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. MATERIALS AND METHOD: 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. RESULTS: 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. CONCLUSION: Less radical fertility-sparing surgery with SLNM is safe in cervical cancers <2 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.

Laparoscopic Power Morcellation: Techniques to Avoid Tumoral Spread.

STUDY 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. Patients who otherwise would not be eligible for minimally invasive surgery (i.e., those with a large uterus or myomas) could benefit from laparoscopic advantages. However, morcellation has a major limitation: the risk of dissemination of unsuspected malignancies. In 2017, the Food and Drug Administration 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 has suggested that if an undiagnosed uterine malignancy is intra-abdominally morcellated, there is a risk of intraperitoneal dissemination of the disease [2]. Therefore, the European Society of Gynecological Oncology emitted a statement in 2016 recommending avoiding morcellation if there is any suspicion of sarcoma and using endobag containers for morcellation of the surgically removed uterine myomas [3]. In addition, in the United States, the Food and Drug Administration recommends performing laparoscopic power morcellation for myomectomy or hysterectomy only with a tissue containment system, legally marketed in the United States [4]. INTERVENTIONS: There are several techniques described in the literature for contained uterine myomas morcellation [5]. In this video, we present 3 of them: First, an indirect-view morcellation is described. In this technique, we placed the myoma in the bag and exteriorize it through one of the trocars. Once outside the abdomen, we placed the morcellator through the bag opening and did the morcellation inside the bag while checking through the umbilicus camera. Special attention must be paid to avoid any damage to the bag because the visualization is limited in this technique. Second, a direct-view technique is described, in which we exteriorized the opening of a 15-mm bag through the suprapubic trocar and a closed end of the bag through the umbilicus. We made a hole in the umbilicus end of the bag and introduced the camera trocar through it. Once done, we introduced the morcellator through the opening and the camera in the umbilicus port. Third, a single-port-contained morcellation is explained. The bag was exteriorized through the umbilicus, and a skin retractor was placed. A glove was placed outside the retractor to isolate the bag. Once placed, 2 of the fingers were opened and used as trocars (one for the morcellator and the other for a 30° camera). After using this technique, the scope should be replaced to minimize the risk of contamination. The following are possible limitations of each technique: in the indirect-view technique, owing to the limited visualization, the surgeon must pay special attention to avoid tearing the bag while morcellating the specimen. In the direct-view technique method, the surgeon needs to ensure the proper closure of the bag before removing it from the abdomen to avoid possible dissemination risk. Finally, 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. CONCLUSION: Laparoscopic power morcellation may provide several benefits for our patients, when performing a hysterectomy or a multiple myomectomy. We presented 3 different and feasible techniques for laparoscopic power morcellation using an endobag container.

Morcellation of the Uterus: Is There Any Place?

PURPOSE OF REVIEW: This paper aims to review recent findings related to uterine morcellation. RECENT FINDINGS: In 2014, the US Food and Drug Administration (FDA) issued a safety communication warning against the use of laparoscopic power morcellators. A risk of occult uterine sarcoma in women is 1/770 to 1/10,000. Our goal is to minimize the risk of spillage due to morcellation and balance it with other risks due to different surgical approaches. In case of a presence of sarcoma risk factors, any form of morcellation should be contraindicated. Power morcellation should be limited to myomectomies. In peri- and postmenopausal age, an endometrial biopsy is highly recommended before surgery with expected morcellation. It is important to explain to the patient the risks of morcellation and the risks and benefits of different surgical approaches. Finally, women should be informed that the prognosis of leiomyosarcoma is poor regardless of the method of removal.

Pregnancy and Cancer: the INCIP Project.

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. 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.

Gastric cancer during pregnancy: A report on 13 cases and review of the literature with focus on chemotherapy during pregnancy.

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.

Characteristics of patients with cervical cancer during pregnancy: a multicenter matched cohort study. An initiative from the International Network on Cancer, Infertility and Pregnancy.

BACKGROUND: Treatment 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. METHODS: This 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. RESULTS: A 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). CONCLUSION: Surgery and chemotherapy is increasingly used in the management of pregnant patients with cervical cancer and prognosis is similar to that of non-pregnant patients.

Oncological management and obstetric and neonatal outcomes for women diagnosed with cancer during pregnancy: a 20-year international cohort study of 1170 patients.

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.