Christianne Lok

Pediatric Outcome after Maternal Cancer Diagnosed during Pregnancy.

BACKGROUND Data on the long-term outcome of children who are exposed to maternal cancer with or without treatment during pregnancy are lacking. METHODS In this multicenter case-control study, we compared children whose mothers received a diagnosis of cancer during the pregnancy with matched children of women without a cancer diagnosis. We used a health questionnaire and medical files to collect data regarding neonatal and general health. All children were prospectively assessed (by means of a neurologic examination and the Bayley Scales of Infant Development) at 18 months, 36 months, or both. A cardiac assessment was performed at 36 months. RESULTS A total of 129 children (median age, 22 months; range, 12 to 42) were included in the group whose mother had cancer (prenatal-exposure group) with a matching number in the control group. During pregnancy, 96 children (74.4%) were exposed to chemotherapy (alone or in combination with other treatments), 11 (8.5%) to radiotherapy (alone or in combination), 13 (10.1%) to surgery alone, 2 (1.6%) to other drug treatments, and 14 (10.9%) to no treatment. Birth weight was below the 10th percentile in 28 of 127 children (22.0%) in the prenatal-exposure group and in 19 of 125 children (15.2%) in the control group (P=0.16). There was no significant between-group difference in cognitive development on the basis of the Bayley score (P=0.08) or in subgroup analyses. The gestational age at birth was correlated with the cognitive outcome in the two study groups. Cardiologic evaluation among 47 children at 36 months of age showed normal cardiac findings. CONCLUSIONS Prenatal exposure to maternal cancer with or without treatment did not impair the cognitive, cardiac, or general development of children in early childhood. Prematurity was correlated with a worse cognitive outcome, but this effect was independent of cancer treatment. (Funded by Research Foundation-Flanders and others; ClinicalTrials.gov number, NCT00330447.).

Microparticles and exosomes: impact on normal and complicated pregnancy.

Eukaryotic cells release vesicles into their environment by membrane shedding (ectosomes or microparticles) and secretion (exosomes). Microparticles and exosomes occur commonly in vitro and in vivo. The occurrence, composition and function(s) of these vesicles change during disease (progression). During the last decade, the scientific and clinical interest increased tremendously. Evidence is accumulating that microparticles and exosomes may be of pathophysiological relevance in autoimmune, cardiovascular and thromboembolic diseases, as well as inflammatory and infectious disorders. In this review, we will summarize the discovery, biology, structure and function of microparticles and exosomes, and discuss their (patho‐) physiological role during normal and complicated pregnancy.

Leukocyte activation and circulating leukocyte-derived microparticles in preeclampsia.

Problem  Preeclampsia shows characteristics of an inflammatory disease including leukocyte activation. Analyses of leukocyte‐derived microparticles (MP) and mRNA expression of inflammation‐related genes in leukocytes may establish which subgroups of leukocytes contribute to the development of preeclampsia.

The Functions of Microparticles in Pre-Eclampsia

Pre-eclampsia (P-EC), a heterogenic multisystem disorder characterized by hypertension and proteinuria, usually develops in the second half of pregnancy. The incidence is 2 to 5%, and P-EC is therefore a major cause of maternal and perinatal morbidity and mortality. Although the exact etiology is unknown, placental factors released into the maternal circulation lead to systemic maternal inflammation and endothelial dysfunction. Growing evidence indicates that placenta-derived microparticles, best known as syncytiotrophoblast microparticles (STBM), are important among these factors. This review provides an overview of the presence and function(s) of STBM and other cell-derived microparticles and exosomes.

The histophysiology and pathophysiology of the peritoneum

The peritoneum is an extensive serous organ with both epithelial and mesenchymal features and a variety of functions. Diseases such as inflammatory peritonitis and peritoneal carcinomatosis can induce disturbance of the complex physiological functions. To understand the peritoneal response in disease, normal embryonic development, anatomy in healthy conditions and physiology of the peritoneum have to be understood. This review aims to summarize and discuss the literature on these basic peritoneal characteristics. The peritoneum is a dynamic organ capable of adapting its structure and functions to various physiological and pathological conditions. It is a key element in regulation of inflammatory responses, exchange of peritoneal fluid and prevention of fibrosis in the abdominal cavity. Disturbance of these mechanisms may lead to serious conditions such as the production of large amounts of ascites, the generation of fibrotic adhesions, inflammatory peritonitis and peritoneal carcinomatosis. The difficulty to treat diseases, such as inflammatory peritonitis and peritoneal carcinomatosis, stresses the necessity for new therapeutic strategies. This review provides a detailed background on the peritoneal anatomy, microenvironment and immunologic responses which is essential to generate new hypotheses for future research.

The Role of Hyperthermic Intraperitoneal Intraoperative Chemotherapy in Ovarian Cancer

Opinion statementEpithelial ovarian cancer (EOC) is the fourth most common gynecologic cancer in Europe and is the leading cause of death among women with gynecologic malignancies. This is due to the fact that the majority of the patients are diagnosed with advanced stage disease. In these stages, extensive intraperitoneal metastases are often present, making therapy more difficult. The current standard treatment involves primary or interval cytoreductive surgery and chemotherapy. However, many patients develop intraperitoneal (IP) recurrences despite complete surgery and chemotherapy. Therefore, alternative ways to deliver chemotherapy have been examined. Administration of the chemotherapy directly into the peritoneal cavity allows high doses of the cytotoxic agent at the site of the cancer, while minimizing the occurrence of systemic side effects. Theoretically, IP administration is most beneficial when only microscopic disease is present since penetration of the drug is limited to a few millimeters. IP chemotherapy can be administered during surgery under hyperthermic conditions (HIPEC) or during regular chemotherapy courses through a catheter placed into the abdominal cavity. IP administration results in an improved survival, although catheter-related morbidity is reported. Hyperthermia potentiates the cytotoxic effect of chemotherapy and may therefore have an additional positive effect on prognosis. Although recent observational studies show encouraging results with respect to effect on survival and rate of complications, it remains a challenge to identify those patients who would benefit most from adding HIPEC to the standard treatment. In this respect, age and timing of HIPEC during treatment might be important factors, although no convincing evidence is available yet. Currently, a total of 18 clinical trials are open and to answer the above-mentioned questions, it is adamant to complete these trials, especially the randomized phase III trials. Accrual is hampered by the fact that HIPEC is currently offered as standard treatment in some centers even though convincing evidence is not yet available. If these phase III trials show positive results in favor of HIPEC, subsequent trials comparing surgery and postoperative IP chemotherapy with surgery and HIPEC seem a logical next step.

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.

Primary brain tumours, meningiomas and brain metastases in pregnancy: report on 27 cases and review of literature

BACKGROUND The concurrence of intracranial tumours with pregnancy is rare. The purpose of this study was to describe all reported patients registered in the international Cancer in Pregnancy registration study (CIP study; http://www.cancerinpregnancy.org), and to review the literature in order to obtain better insight into outcome and possibilities of treatment in pregnancy. METHODS We collected all intracranial tumours (primary brain tumour, cerebral metastasis, or meningioma) diagnosed during pregnancy, registered prospectively and retrospectively by international collaboration since 1973. Patients diagnosed postpartum were excluded. We summarised the demographic features, treatment decisions, obstetrical and neonatal outcomes. RESULTS The mean age of the 27 eligible patients was 31years (range 23-41years), of which 13 and 12 patients were diagnosed in the second and third trimesters, respectively. Eight patients (30%) underwent brain surgery, seven patients (26%) had radiotherapy and in three patients (11%) chemotherapy was administered during gestation. Two patients died during pregnancy and four pregnancies were terminated. In 16 (59%) patients elective caesarean section was performed of which 14 (52%) were still preterm (range 30-36weeks, mean 33weeks). Five patients had a vaginal delivery (range 36-40weeks). Of the 21 ongoing pregnancies all children were born alive without visible congenital malformations and the available long-term follow-up data (range 2-25years) of six children were reassuring. CONCLUSION Adherence to standard protocol for the treatment of brain tumours during pregnancy appears to allow a term delivery and a higher probability of a vaginal delivery.

A predictive model combining human epididymal protein 4 and radiologic features for the diagnosis of ovarian cancer

OBJECTIVE Ovarian cancer is the leading cause of death in women with gynecologic cancer. CA125 is the commonly used biomarker in the diagnosis of ovarian cancer, but has limitations in both sensitivity and specificity. Human Epididymal secretory protein (HE4) is a promising biomarker and is included in the Risk of Ovarian Malignancy Algorithm (ROMA) score, which is suggested to further increase the diagnostic accuracy than either marker alone. However, information from ultrasound and CT-scan is not included in this algorithm. This study evaluated the diagnostic accuracy of HE4 in the pre-operative diagnosis of ovarian cancer and the predictive values of biomarkers, ultrasound and CT-scan and combinations hereof. METHODS HE4 and CA125 were measured in 361 subjects (34 benign, 147 ovarian cancer and 180 controls). Sensitivity, specificity and area under the curve (AUC) for CA125, HE4, ROMA and RMI scores were calculated using the receiver operating characteristic (ROC) methodology. The additional predictive value of ultrasound or CT-scan to the individual markers was analyzed using logistic regression. RESULTS The sensitivity in predicting ovarian cancer of CA125 was 91% and of HE4 90%. The specificity was 65% and 97% respectively. HE4 demonstrated the highest discrimination (ROC-AUC=0.96), compared to ROMA, RMI and CA125 (AUC=0.95, 0.89 and 0.90 respectively). ROMA did not improve when it was combined with different ultrasound factors. The presence of intra-abdominal metastasis on CT-scan improved the discriminative potential of HE4 (p=0.0004). CONCLUSION HE4 in combination with CT-scan may be incorporated in the diagnostic work-up in women with a pelvic mass.

Tongue cancers during pregnancy: Case reports and review of literature

Due to its rarity, there is no standard treatment for tongue cancers that concur with pregnancy. Treatment depends on the stage of cancer, gestational age of the pregnancy, and the wish of the mother to maintain the pregnancy. The purpose of this study was to review the literature and to report 5 new cases.