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Objective: To describe the clinical and ultrasound characteristics of ovarian carcinosarcoma. Methods: This was a retrospective multicenter study. Patients with a histological diagnosis of ovarian carcinosarcoma, who had undergone preoperative ultrasound examination between 2010 and 2019, were identified from the International Ovarian Tumor Analysis (IOTA) database. Additional patients who were examined outside of the IOTA study were identified from the databases of the participating centers. The masses were described using the terms and definitions of the IOTA group. Additionally, two experienced ultrasound examiners reviewed all available images to identify typical ultrasound features using pattern recognition. Results: Ninety-one patients with ovarian carcinosarcoma who had undergone ultrasound examination were identified, of whom 24 were examined within the IOTA studies and 67 were examined outside of the IOTA studies. Median age at diagnosis was 66 (range, 33–91) years and 84/91 (92.3%) patients were postmenopausal. Most patients (67/91, 73.6%) were symptomatic, with the most common complaint being pain (51/91, 56.0%). Most tumors (67/91, 73.6%) were International Federation of Gynecology and Obstetrics (FIGO) Stage III or IV. Bilateral lesions were observed on ultrasound in 46/91 (50.5%) patients. Ascites was present in 38/91 (41.8%) patients. The median largest tumor diameter was 100 (range, 18–260) mm. All ovarian carcinosarcomas contained solid components, and most were described as solid (66/91, 72.5%) or multilocular-solid (22/91, 24.2%). The median diameter of the largest solid component was 77.5 (range, 11–238) mm. Moderate or rich vascularization was found in 78/91 (85.7%) cases. Retrospective analysis of ultrasound images and videoclips using pattern recognition in 73 cases revealed that all tumors had irregular margins and inhomogeneous echogenicity of the solid components. Forty-seven of 73 (64.4%) masses appeared as a solid tumor with cystic areas.

Pregnancies are rare in women with pituitary adenomas, which may relate to hormone excess from secretory subtypes such as prolactinomas or corticotroph adenomas. Decreased fertility may also result from pituitary hormone deficiencies due to compression of the gland by large tumours and/or surgical or radiation treatment of the lesion. Counselling premenopausal women with pituitary adenomas about their chance of conceiving spontaneously or with assisted reproductive technology, and the optimal pre-conception treatment, should start at the time of initial diagnosis. The normal physiological changes during pregnancy need to be considered when interpreting endocrine tests in women with pituitary adenomas. Dose adjustments in hormone substitution therapies may be needed across the trimesters. When medical therapy is used for pituitary hormone excess, consideration should be given to the known efficacy and safety data specific to pregnant women for each therapeutic option. In healthy women, pituitary gland size increases during pregnancy. Since some pituitary adenomas also enlarge during pregnancy, there is a risk of visual impairment, especially in women with macroadenomas or tumours near the optic chiasm. Pituitary apoplexy represents a rare acute complication of adenomas requiring surveillance, with surgical intervention needed in some cases. This guideline describes the choice and timing of diagnostic tests and treatments from the pre-conception stage until after delivery, taking into account adenoma size, location and endocrine activity. In most cases, pregnant women with pituitary adenomas should be managed by a multidisciplinary team in a centre specialised in the treatment of such tumours.

Several scientific papers report clinical symptoms, indications, complications and outcomes of brainstem cavernous malformation (BSCM) surgery without reporting on the occurrence of postoperative Holmes tremor (HT). Our purpose is to report our experience with HT in a monocentric series of resected brainstem cavernomas. We reviewed all the BSCM surgical records between 2002 and 2018 at Saint-Luc University Hospital's Department of Neurosurgery, Brussels and selected patients developing HT postoperatively. Patients' demographics, symptoms, pre- and postoperative imaging, recurrence and complications were analysed. A PubMed literature review was performed to compare our results with those in the existing literature. In a total series of 18 resected BSCM, 5 patients: 1 male and 4 females, with a median age of 51 years (range 29-59 years), developed HT. The median preoperative mRS score was 2 (range 1-4). GTR was achieved in all patients without surgery-related death. BSCM were located in the mesencephalon in 4 patients (80%) who developed HT. Tremor was noticed between ten days and one year after surgery. One patient saw significant improvements to the point of stopping treatment. The median follow-up period was 2 years (range 1-14 years). At the last follow-up, 40% of our patients showed a worse mRS score, 40% stayed unchanged, and 20% improved. We are reporting an original single-center series of patients suffering from HT after BSCM surgery. The risk for HT after surgery is significant for midbrain BSCM. A spontaneous favorable evolution is possible.

Cancer during pregnancy is increasingly diagnosed due to the trend of delaying pregnancy to a later age and probably also because of increased use of non-invasive prenatal testing for fetal aneuploidy screening with incidental finding of maternal cancer. Pregnant women pose higher challenges in imaging, diagnosis, and staging of cancer. Physiological tissue changes related to pregnancy makes image interpretation more difficult. Moreover, uncertainty about the safety of imaging modalities, fear of (unnecessary) fetal radiation, and lack of standardized imaging protocols may result in underutilization of the necessary imaging tests resulting in suboptimal staging. Due to the absence of radiation exposure, ultrasound and MRI are obvious first-line imaging modalities for detailed locoregional disease assessment. MRI has the added advantage of a more reproducible comprehensive organ or body region assessment, the ability of distant staging through whole-body evaluation, and the combination of anatomical and functional information by diffusion-weighted imaging which obviates the need for a gadolinium-based contrast-agent. Imaging modalities with inherent radiation exposure such as CT and nuclear imaging should only be performed when the maternal benefit outweighs fetal risk. The cumulative radiation exposure should not exceed the fetal radiation threshold of 100 mGy. Imaging should only be performed when necessary for diagnosis and likely to guide or change management. Radiologists play an important role in the multidisciplinary team in order to select the most optimal imaging strategies that balance maternal benefit with fetal risk and that are most likely to guide treatment decisions. Our aim is to provide an overview of possibilities and concerns in current clinical applications and developments in the imaging of patients with cancer during pregnancy.

OBJECTIVE: To provide contemporary gestational age-specific recommendations for management, a retrospective series of patients with renal or bladder cancer during pregnancy is reported. METHODS: Obstetric and oncological data of pregnant patients with a diagnosis of renal or bladder cancer were selected from the worldwide registry of the International Network of Cancer, Infertility and Pregnancy. In addition, the literature was reviewed for recent case reports since last reviews in 2014 for renal cancer and 2004 for bladder cancer. RESULTS: International Network of Cancer, Infertility and Pregnancy registered 22 cases (14 renal cancer and 8 bladder cancer), diagnosed between 1999 and 2017, and the literature reported 15 cases with renal cancer and 10 cases with bladder cancer between 2004 and 2019. Most common symptoms for renal and bladder cancer were pain (28%) and hematuria (66%), respectively. In more than half of the patients, surgical treatment was performed during pregnancy. Preterm deliveries were mostly medically induced (12 of 17, 71%) and all patients with a planned delivery before 34 weeks had advanced cancer. For renal and bladder cancer respectively, 79% and 87% of patients obtained complete remission. Advanced cancer stages had worse prognosis; 3 of 7 patients with known follow-up deceased within 15 months after diagnosis. CONCLUSION: Gestational age at diagnosis determines further management of renal and bladder cancers during pregnancy. Advanced stages challenge decision-making. The maternal needs for immediate treatment, and the neonatal risks including the impact of a preterm delivery should be discussed in a multidisciplinary setting while respecting the patient's autonomy.

The diagnosis of breast cancer (BC) during pregnancy is uncommon. It has varied among different studies from 1:10,000 to 1:3000 of all pregnancies, with a median age of 33 years. Pregnancy-associated BC represents a challenge in terms of clinical management to guarantee both maternal and fetal security in choosing the right treatment. This situation is complex and requires a multidisciplinary approach, including the surgeon, anesthesiologist, oncologist, radiotherapist, psychologist, and maternal–fetal medicine specialist. In the present review, we examined the management of pregnancy-associated BC, focusing on pathophysiologic background, risk factors, diagnosis, staging procedures, anesthesia, surgical management, and systemic treatment.

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 < 0.001 [Q refers to the false discovery rate adjusted P value], and 3.9, 95% CI: 3.6-4.3, versus 4.5, 95% CI: 4.1-4.9, P = 0.005, Q = 0.045, respectively). A significant difference in diastolic blood pressure was found, with higher values in chemotherapy-exposed (61.1, 95% CI: 59.0 to 63.2) versus control children (56.0, 95% CI 54.1 to 57.8) (P < 0.001, Q < 0.001) and in a subgroup of 59 anthracycline-exposed (61.8, 95% CI: 59.3 to 64.4) versus control children (55.9, 95% CI: 53.6 to 58.1) (P < 0.001, Q = 0.02). CONCLUSIONS: Children prenatally exposed to maternal cancer and its treatment are at risk for lower verbal IQ and visuospatial long-term memory scores and for higher diastolic blood pressure, but other cognitive functions and cardiac outcomes were normal at the age of 6 years. CLINICAL TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov, NCT00330447.

Cancer associated with pregnancy is defined by diagnosis during pregnancy, lactation, or the first year after delivery. The decision about type of treatment depends on the cancer stage and gestational age. Termination of pregnancy does not seem to modify the maternal prognosis for breast cancers. Interdisciplinary meetings and discussions are needed to evaluate and balance the maternal and fetal risks. In this chapter, we discuss about how to prevent or treat maternal and fetal complications of surgery and chemotherapy in pregnancy-associated breast cancer.

Limited data are available on the frequency and time trends of pregnancy-associated cancers, particularly from Southern European countries. The aim of this study was to analyze the frequency and time trends of pregnancy-associated cancer in Italy. Methods This was a population-based linkage study using the regional hospital discharge forms database of four Italian regions with more than 17 million inhabitants. All resident women with a hospital discharge form reporting a birth or abortion in the time period under consideration were identified. The time period of the study was 2003-2015 for the Piemonte and Puglia region, 2006-2015 for the Tuscany region, and 2005-2015 for the Veneto region. Risk of developing a pregnancy-associated cancer was calculated as the ratio of the number of pregnancy-related cancers to the total number of pregnancies. Results A total of 2 297 648 pregnancies were identified. Overall, the pregnancy-associated cancer frequency was 134.8 per 100 000 pregnancies: the frequency ranged from 127.1 in Puglia to 157.3 in Tuscany. The frequency for 100 000 pregnancies was 66.4 in women aged <30 years; the risk increased with age, with a frequency of 275.6 among women aged 40+ years. Approximately two-thirds of cancers were associated with pregnancies resulting in a delivery and one-third with pregnancies resulting in a termination of pregnancy or spontaneous pregnancy loss. No clear trend emerged in the risk of pregnancy-associated cancer per 100 000 pregnancies and calendar year. Conclusion No clear time trend was observed in the frequency of pregnancy-associated cancers in Italy during the last 10 years, the rates being 104, 164, and 130 per 100 000 pregnancies, respectively, in 2003, 2010, and 2015.

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

A case of stage IB2 cervical cancer at 27 weeks of pregnancy, treated with neoadjuvant chemotherapy followed by radical Cesarean hysterectomy with full pelvic and infra-mesenteric lymphadenectomy, and adjuvant chemo-radiation is described. While she remains without disease, her baby was diagnosed with acute myelogenous leukemia. We highlight the pre-operative work-up, treatment options, safety, feasibility, and outcomes for the mother and her fetus.

Objectives The aims of this study were to estimate the occurrence of pregnancy-associated cancer overall and by site, to evaluate if the risk increases over time, and to investigate some major determinants. Methods: This is a population-based linkage study using the regional hospital discharge forms [Scheda di Dimissione Ospedaliera (SDO)] database of Lombardy, Italy, a region with 10 million inhabitants. All resident women with a SDO reporting a birth or abortion between 2001 and 2012 were identified. Pregnancy-associated cancers were defined as a cancer occurring during pregnancy or within 12 months after pregnancy and were identified by selecting all SDOs reporting a first diagnosis of cancer. Risk of developing a pregnancy-related cancer was calculated as the ratio of the number of pregnancy-related cancers to the total number of pregnancies. The effect of potential predictors on the risk was estimated using a logistic regression model, and odds ratios (OR) were estimated. Results: During the period 2001-2012, the risk of pregnancy-related cancer was 122.9 per 100,000 pregnancies. The most common cancers were breast cancer (479 cases, 39.9/100,000 pregnancies), thyroid cancer (186 cases, 15.5/100,000), and lymphomas (157 cases, 13.1/100,000). Skin cancer accounted for 177 cases (14.8/100,000), half of which were melanomas. The risk of developing a pregnancy-related cancer increased significantly with age, from 60 of 100,000 for women less than 30 years old to 265 of 100,000 for women aged more than 40 years. Italian women had a higher risk than foreign ones (OR, 1.6), and the pregnancy outcome was more frequently an abortion (OR, 1.2), whereas no trend in risk was observed with calendar year (P = 0.249). Conclusions: This study confirms previously reported incidence estimates but does not show increases over time.

Cancer is the leading cause of death in women of reproductive age. During the last decades and especially in developed countries, the incidence of cancer is increasing dramatically, with an incidence of 1 in 1,000 pregnancies. This is mostly related to delay of pregnancy into the late reproductive years. The aim of this study was to investigate the outcome of pregnancy in women with diagnosis of cancer; in particular, neonatal morbidity and mortality, after in utero exposure to chemotherapy, were evaluated. A total of 59 singletons and one twin pregnancy complicated by cancer were followed at our tertiary centre over the last 15 years. A different treatment, based on surgery and/or chemotherapy in pregnancy or delayed to the postpartum period, was employed. There were 59 live births (97%), one foetal loss and one stillbirth at 28 weeks. The congenital malformation rate was 5% (n = 3). The rate of preterm birth was 83%. The mean birthweight and mean birthweight percentile were 2,098 g (740–3930) and 46 (7–93), respectively; 32% of neonates were small for gestational age (SGA). Dividing the population into treated or untreated with chemotherapy, the rate of SGA was not statistically significant different between the two groups. Our results showed that chemotherapy administered during the second trimester or later did not influence intrauterine foetal growth, but the high prevalence of SGA neonates in the two groups, exposed or not exposed to chemotherapy, suggests an influence of maternal cancer per se on foetal growth.

Prolactinoma is a common cause of infertility in young women and treatment with dopamine agonists (DA) allows restoration of fertility in over 90% of the cases. Both bromocriptine and cabergoline have shown a good safety profile when administered during early pregnancy. In particular, data on exposure of the fetus or embryo to cabergoline during the first weeks of pregnancy have now been reported in more than 900 cases, and do indicate that cabergoline is safe in this context. There is no increase in the frequency of spontaneous miscarriage, premature delivery, multiple births or neonatal malformations, and follow-up studies of the children for up to 12years after fetal exposure to cabergoline did not show any physical or developmental abnormalities. These women should therefore continue DA treatment until pregnancy has been initiated. Treatment discontinuation is recommended at that time in women with microprolactinoma or non-compressive macroprolactinoma. For microprolactinomas, the risk of symptomatic tumour enlargement during pregnancy is very low (2-3%). It is higher for macroprolactinomas (20-30%) and careful follow-up is advised, including MRI without contrast injection if symptoms or visual disturbances develop. If a symptomatic tumour enlargement does occur, reinitiation of the dopamine agonist (BRC or CAB) is indicated rather than surgery. Breast-feeding has no harmful effect on tumour growth and DA treatment, if still needed, may be postponed as long as breast-feeding is desired. Finally, about 40% of women with a microprolactinoma or an intermediate size macroprolactinoma may be in prolonged remission after one or more pregnancies.

Objective: Catecholamine-secreting tumors (pheochromocytomas and paragangliomas) presenting during pregnancy are extremely rare, but they can be fatal to both mother and fetus. Recent discoveries in the genetic background of these tumors are expected to address an increasing number of at-risk women to prenatal diagnosis. Methods: The literature was reviewed in order to provide clinicians with a practical and updated guide on how to manage this life-threatening condition. Results: The clinical presentation of catecholamine-secreting tumors can be deceptive and mimic common disorders of pregnancy. Silent catecholamine-secreting tumors can become evident during pregnancy, and hypertension cannot be considered a hallmark for this condition: some women may be normotensive or develop orthostatic hypotension. Biochemical screening includes measurement of plasma free metanephrines or urinary fractioned metanephrines. Measurement of catecholamines, dopamine, and methoxytyramine can provide further information on tumor biology, location, and prognosis. Diagnostic imaging is limited, and medical treatment requires a cautious balance between hemodynamic control and effects on the fetoplacental unit. Several genes have been associated with syndromes including catecholamine-secreting tumors, and positive genetic testing can correlate with tumor behavior. Timing and modalities for tumor removal and delivery, including anesthetic management, depend on gestational age, maternal and fetal wellbeing, control of catecholamine excess, suspicion of multiple or malignant disease, and surgical accessibility to the tumor. Conclusion: A timely diagnosis and a multidisciplinary approach are the keys to improve pregnancy outcomes in patients with a catecholamine-secreting tumor; each case should be managed in a tertiary referral center.

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.).

A multidisciplinary discussion is necessary to tackle a complex and infrequent medical problem such as cancer occurring during pregnancy. Pregnancy does not predispose to cancer, but cancers occurring in women of reproductive age are encountered during pregnancy. Ultrasonography and magnetic resonance imaging are the preferred staging examinations, but also a sentinel node staging procedure is possible during pregnancy. Standard cancer treatment is aimed for. Operations can safely be performed during pregnancy, but surgery of genital cancers can be challenging. The observation that chemotherapy administered during the second or third trimester of pregnancy, that is, after the period of organogenesis, has little effect on the long-term outcome of children adds to the therapeutic armamentarium during pregnancy. Cancer treatment during pregnancy adds in the continuation of the pregnancy and the prevention of prematurity.

A multidisciplinary discussion is necessary to tackle a complex and infrequent medical problem such as cancer occurring during pregnancy. Pregnancy does not predispose to cancer, but cancers occurring in women of reproductive age are encountered during pregnancy. Ultrasonography and magnetic resonance imaging are the preferred staging examinations, but also a sentinel node staging procedure is possible during pregnancy. Standard cancer treatment is aimed for. Operations can safely be performed during pregnancy, but surgery of genital cancers can be challenging. The observation that chemotherapy administered during the second or third trimester of pregnancy, that is, after the period of organogenesis, has little effect on the long-term outcome of children adds to the therapeutic armamentarium during pregnancy. Cancer treatment during pregnancy adds in the continuation of the pregnancy and the prevention of prematurity.

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.

Monoclonal antibodies (mAbs) are the cornerstone of the treatment of several types of tumors, but their use in pregnant women is not clearly defined. Here, we report and analyze all available data on mAb treatment in pregnant cancer patients. A literature search was performed from 2000 until January 2013 and all articles addressing safety of mAbs during pregnancy were reviewed. We found very few data on the use of bevacizumab in pregnant women. However, owing to its antiangiogenic effects and possible consequences on fetal development, it should be avoided during pregnancy. Trastuzumab administration has been associated with an elevated incidence of oligohydramnios and poor neonatal outcomes, particularly when prescribed after the first trimester for repeated infusions, and therefore it is not recommended. Rituximab does not seem to be teratogenic, but a transient prolonged neutropenia in the newborns was reported, without major infectious consequences in most cases. Few data are available about other mAbs, and hence their use during pregnancy remains discouraged. © 2013 Future Medicine Ltd.

To evaluate physicians' attitudes and knowledge regarding the treatment possibilities for patients with cancer in pregnancy.

Lung cancer is an uncommon diagnosis during pregnancy. The combination of smoking in young women, increased maternal age during pregnancy, and increasing incidence of lung cancer worldwide may cause an increase of pregnancy associated lung cancer. The aim of this study was to describe all cases of lung cancer during pregnancy, registered in the international Cancer in Pregnancy registration study (CIP study; www.cancerinpregnancy.org).

Mature cystic teratomas, commonly known as dermoid cysts, are the most frequent ovarian tumors discovered during pregnancy. They are present in 0.3% of pregnancies from weeks 16-20 of gestation. The diagnosis of mature cystic teratomas during pregnancy presents the vexing problem of weighing the risks of surgery under general anesthetic against the risks of an untreated persistent adnexal mass.

BACKGROUND: Chemotherapy for the treatment of maternal cancers during pregnancy has become more acceptable in the past decade; however, the effect of prenatal exposure to chemotherapy on cardiac and neurodevelopmental outcomes of the offspring is still uncertain. We aimed to record the general health, cardiac function, and neurodevelopmental outcomes of children who were prenatally exposed to chemotherapy. METHODS: We did an interim analysis of a multicentre observational cohort study assessing children who were prenatally exposed to maternal cancer staging and treatment, including chemotherapy. We assessed children at birth, at age 18 months, and at age 5-6, 8-9, 11-12, 14-15, or 18 years. We did clinical neurological examinations, tests of the general level of cognitive functioning (Bayley or intelligence quotient [IQ] test), electrocardiography and echocardiography, and administered a questionnaire on general health and development. From age 5 years, we also did audiometry, the Auditory Verbal Learning Test, and subtasks of the Children's Memory Scale, and the Test of Everyday Attention for Children, and we also completed the Child Behavior Checklist. This study is registered with ClinicalTrials.gov, number NCT00330447. FINDINGS: 236 cycles of chemotherapy were administered in 68 pregnancies. We assessed 70 children, born at a median gestational age of 35·7 weeks (range 28·3-41·0; IQR 3·3; 47 women at <37 weeks), with a median follow-up period of 22·3 months (range 16·8-211·6; IQR 54·9). Although neurocognitive outcomes were within normal ranges, cognitive development scores were lower for children who were born preterm than for those born at full term. When controlling for age, sex, and country, the score for IQ increased by an average 11·6 points (95% CI 6·0-17·1) for each additional month of gestation (p<0·0001). Our measurements of the children's behaviour, general health, hearing, and growth corresponded with those of the general population. Cardiac dimensio

BACKGROUND: Recent insights provide support for the treatment of cancer during pregnancy, a coincidence that poses both mother and fetus at risk. Our aim was to critically review studies on the physiologic variations during pregnancy, the most common tumor markers used in diagnosis and follow-up of gynecological cancers. METHODS: We conducted a systematic review of six tumor markers during normal pregnancy: carbohydrate antigen (CA) 15-3 (breast cancer); squamous cell carcinoma antigen (cervical cancer); and CA 125, anti-Müllerian hormone, inhibin B and lactate dehydrogenase (ovarian cancer). RESULTS: For CA 15-3, 3.3% to 20.0% of all measurements were above the cut-off (maximum 56 U/mL in the third trimester). Squamous cell carcinoma antigen values were above cut-off in 3.1% and 10.5% of the measurements (maximum 4.3 µg/L in the third trimester). Up to 35% of CA 125 levels were above cut-off: levels were highest in the first trimester, with a maximum value up to 550 U/mL. Inhibin B, anti-Müllerian hormone and lactate dehydrogenase levels were not elevated in maternal serum during normal pregnancy. CONCLUSION: During normal pregnancy, tumor markers including CA 15.3, squamous cell carcinoma antigen and CA 125 can be elevated; inhibin B, anti-Müllerian hormone and lactate dehydrogenase levels remain below normal cut-off values. Knowledge of physiological variations during pregnancy can be clinically important when managing gynecological cancers in pregnant patients.

PURPOSE OF REVIEW: Cancer during pregnancy is uncommon, although not rare. As women in developed societies defer childbearing and the incidence of most malignancies rises with increasing age, the situation in which cancer complicates pregnancy is expected to become more common. Cancer staging and treatment can be performed during pregnancy and should be defined in a multidisciplinary setting. Here, we describe the potential to use chemotherapy during pregnancy. RECENT FINDINGS: New insights add to the practice of administering chemotherapy from 14 weeks gestational age onwards. The placental barrier function protects the fetus. The physiologic gestational changes reduce the maternal serum levels of chemotherapy, although the pharmacodynamic impact remains unknown. Comedication to chemotherapy can be administered on strict indications. Chemotherapy after 35 weeks is not recommended as an interval of at least 3 weeks is preferred between chemotherapy administration and delivery. Recent data show that the long-term outcome of children antenatally exposed to chemotherapy is comparable to children of the same age. Nevertheless, a higher rate of neurodevelopmental problems was encountered after preterm birth, also in this selected patient population. SUMMARY: Administration of chemotherapy during pregnancy may decrease the need for early delivery, and thus prematurity.

BACKGROUND: Little is known about the treatment of breast cancer during pregnancy. We aimed to determine whether treatment for breast cancer during pregnancy is safe for both mother and child. METHODS: We recruited patients from seven European countries with a primary diagnosis of breast cancer during pregnancy; data were collected retrospectively if the patient was diagnosed before April, 2003 (when the registry began), or prospectively thereafter, irrespective of the outcome of pregnancy and the type and timing of treatment. The primary endpoint was fetal health for up to 4 weeks after delivery. The registry is ongoing. The study is registered with ClinicalTrials.gov, number NCT00196833. FINDINGS: From April, 2003, to December, 2011, 447 patients were registered, 413 of whom had early breast cancer. Median age was 33 years (range 22-51). At the time of diagnosis, median gestational age was 24 weeks (range 5-40). 197 (48%) of 413 women received chemotherapy during pregnancy with a median of four cycles (range one to eight). 178 received an anthracycline, 15 received cyclophosphamide, methotrexate, and fluorouracil, and 14 received a taxane. Birthweight was affected by chemotherapy exposure after adjustment for gestational age (p=0·018), but not by number of chemotherapy cycles (p=0·71). No statistical difference between the two groups was observed for premature deliveries before the 37th week of gestation. 40 (10%) of 386 infants had side-effects, malformations, or new-born complications; these events were more common in infants born before the 37th week of gestation than they were in infants born in the 37th week or later (31 [16%] of 191 infants vs nine [5%] of 195 infants; p=0·0002). In infants for whom maternal treatment was known, adverse events were more common in those who received chemotherapy in utero compared with those who were not exposed (31 [15%] of 203 vs seven [4%] of 170 infants; p=0·00045). Two infants died; both were exposed to chemotherapy and d

OBJECTIVE: The co-occurrence of cancer and pregnancy is more frequently diagnosed. The effects of cancer treatment on maternal and fetal outcomes are less well known. The cardiotoxic effects of chemotherapy are a specific concern for the mother and fetus. We wanted to review the existing literature, mainly consisting of case reports, case studies, and retrospective data. RESULTS: Maternal effects Overall, the published data indicate that pregnancy is not an independent risk factor influencing cancer survival. There is no indirect evidence for an increased risk for maternal chemotherapy-related cardiotoxicity. Fetal effects During the first trimester chemotherapy needs to be avoided because of teratogenic risks. The risks of chemotherapy during the second and third trimester are more controversial. It has been associated with intrauterine growth restriction and preterm delivery in some studies, while others did not find the same effect. Cardiotoxic fetal effects have been reported despite the limited transplacental passage of chemotherapy. In most patients this was transient and long-term data are generally reassuring. CONCLUSION: A specific strategy for monitoring fetal and maternal chemotherapy-induced cardiotoxicity is suggested. Prospective data are needed on the long-term effects of chemotherapy in both mother and child.

Advances in the field of adjuvant therapy in breast cancer have led to significant improvements in breast cancer survival. This has resulted in a progressive decline in breast cancer-related mortality, such that in 2010 there were estimated to be 400,000 breast cancer survivors under the age of 40 in the USA. Hence, enquiry into the feasibility of fertility preservation, subsequent pregnancy and breastfeeding is increasingly encountered. Fertility counseling remains suboptimal in breast cancer clinics, and there is a wide perception that pregnancy could worsen the prognosis of young breast cancer survivors, despite the lack of evidence supporting this notion. In addition, fertility preservation by means of embryo or oocyte cryopreservation requires ovarian stimulation, which is associated with a significant rise in estradiol levels and might delay initiation of therapy. All these factors, and others, have influenced the quality of fertility counseling offered to young breast cancer patients. In this article, we will critically analyze the available clinical and biological evidence on the safety and feasibility of pregnancy and breastfeeding following breast cancer. In addition, we will discuss the different fertility-preservation techniques available for these patients., Journal Article, Research Support, Non-U.S. Gov't, Review, SCOPUS: re.j, info:eu-repo/semantics/published

Advances in the field of adjuvant therapy in breast cancer have led to significant improvements in breast cancer survival. This has resulted in a progressive decline in breast cancer-related mortality, such that in 2010 there were estimated to be 400,000 breast cancer survivors under the age of 40 in the USA. Hence, enquiry into the feasibility of fertility preservation, subsequent pregnancy and breastfeeding is increasingly encountered. Fertility counseling remains suboptimal in breast cancer clinics, and there is a wide perception that pregnancy could worsen the prognosis of young breast cancer survivors, despite the lack of evidence supporting this notion. In addition, fertility preservation by means of embryo or oocyte cryopreservation requires ovarian stimulation, which is associated with a significant rise in estradiol levels and might delay initiation of therapy. All these factors, and others, have influenced the quality of fertility counseling offered to young breast cancer patients. In this article, we will critically analyze the available clinical and biological evidence on the safety and feasibility of pregnancy and breastfeeding following breast cancer. In addition, we will discuss the different fertility-preservation techniques available for these patients., Journal Article, Research Support, Non-U.S. Gov't, Review, SCOPUS: re.j, info:eu-repo/semantics/published

Context: Data concerning the safety for pregnancy of cabergoline treatment in hyperprolactinaemic women are still scarce. Objective: To exclude a higher than normal risk for miscarriage and congenital malformation in pregnancies initiated under cabergoline treatment. Design: A retrospective study of 100 pregnancies in 72 hyperprolactinaemic women treated with cabergoline at the time of conception and follow-up of the 88 born children. Methods: Cabergoline was interrupted in 99 pregnancies and continued in one case. Foetal exposure dose to cabergoline was calculated for each pregnancy. Complications of pregnancy and neonatal status were compared to those observed in an age-and delivery time-matched control group of 163 women. Results: The mean foetal exposure dose to cabergoline was 3.6 +/- 4.7 mg. The rate of spontaneous miscarriages was 10%. Three medical terminations of pregnancy were performed for a foetal malformation (3%). Minor to moderate complications were observed in 31% of the pregnancies, a figure similar to that found in the control group. An increase in tumour size (2-8 mm) was observed in 17/37 evaluated cases, needing re-introduction of cabergoline during pregnancy in 5 patients. The 84 deliveries resulted in 88 infants, 3 of them presenting with a malformation (3.4%). Neonatal status was comparable to the control group, where a malformation rate of 6.3% was observed. Postnatal development of the children was normal. Conclusion: Cabergoline treatment at the time of conception appears to be safe for both the pregnancy and the neonate, although more data are still needed on a larger number of pregnancies.

PURPOSE: The aim of this study was to assess the management and the obstetrical and neonatal outcomes of pregnancies complicated by cancer. PATIENTS AND METHODS: In an international collaborative setting, patients with invasive cancer diagnosed during pregnancy between 1998 and 2008 were identified. Clinical data regarding the cancer diagnosis and treatment and the obstetric and neonatal outcomes were collected and analyzed. RESULTS: Of 215 patients, five (2.3%) had a pregnancy that ended in a spontaneous miscarriage and 30 (14.0%) pregnancies were interrupted. Treatment was initiated during pregnancy in 122 (56.7%) patients and postpartum in 58 (27.0%) patients. The most frequently encountered cancer types were breast cancer (46%), hematologic malignancies (18%), and dermatologic malignancies (10%). The mean gestational age at delivery was 36.3 +/- 2.9 weeks. Delivery was induced in 71.7% of pregnancies, and 54.2% of children were born preterm. In the group of patients prenatally exposed to cytotoxic treatment, the prevalence of preterm labor was increased (11.8%; P = .012). Furthermore, in this group a higher proportion of small-for-gestational-age children (birth weight below 10th percentile) was observed (24.2%; P = .001). Of all neonates, 51.2% were admitted to a neonatal intensive care unit, mainly (85.2%) because of prematurity. There was no increased incidence of congenital malformations. CONCLUSION: Pregnant cancer patients should be treated in a multidisciplinary setting with access to maternal and neonatal intensive care units. Prevention of iatrogenic prematurity appears to be an important part of the treatment strategy.

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Von Hippel-Lindau (VHL) disease is a dominant autosomal disorder inducing the development of many tumors, such as hemangioblastomas in the central nervous system and retina, cysts or tumors (benign or malignant) in the kidneys and/or the pancreas. We report the case of a pregnant woman who presented with a voluminous hemorrhagic cyst of the right kidney with an exophytic lesion detected in the lower median part of the cyst wall. As an anamnestic inquiry resulted in a familial history of VHL disease, a screening imaging was performed and detected three medullary hemangioblastomas. Considering the active bleeding of the renal cyst and its potential malignancy, a unilateral nephrectomy was carried out after pregnancy interruption. Histological analysis confirmed a multilocular clear cell renal carcinoma. This case underlines the importance of screening procedures such as abdominal ultrasonography and medullary magnetic resonance imaging in all pregnant women with a familial history of VHL disease., Case Reports, Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

Von Hippel-Lindau (VHL) disease is a dominant autosomal disorder inducing the development of many tumors, such as hemangioblastomas in the central nervous system and retina, cysts or tumors (benign or malignant) in the kidneys and/or the pancreas. We report the case of a pregnant woman who presented with a voluminous hemorrhagic cyst of the right kidney with an exophytic lesion detected in the lower median part of the cyst wall. As an anamnestic inquiry resulted in a familial history of VHL disease, a screening imaging was performed and detected three medullary hemangioblastomas. Considering the active bleeding of the renal cyst and its potential malignancy, a unilateral nephrectomy was carried out after pregnancy interruption. Histological analysis confirmed a multilocular clear cell renal carcinoma. This case underlines the importance of screening procedures such as abdominal ultrasonography and medullary magnetic resonance imaging in all pregnant women with a familial history of VHL disease., Case Reports, Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

Insulinomas are rare neuroendocrine tumors with an incidence of 4 per 1,000,000 person-years, being even rarer during pregnancy. During pregnancy most cases are recognized or become symptomatic during the first trimester. A 29-year-old woman, primigravida, was hospitalized in the 38th gestational week due to slurred speech, weakness and slow reaction patterns. An electroencephalogram and computed tomography scan of the brain and blood samples were normal. Blood pressure was 170-145/110-95 mmHg, albuminuria was moderate and there was moderate edema of the ankles. Labor started spontaneously the third day, 62 h after of hospitalization, and the patient gave birth to a healthy girl with no neonatal problems. Fourteen hours after delivery, the patient became comatose and developed universal clonic seizures. At the same time plasma glucose was

Insulinomas are rare neuroendocrine tumors with an incidence of 4 per 1,000,000 person-years, being even rarer during pregnancy. During pregnancy most cases are recognized or become symptomatic during the first trimester. A 29-year-old woman, primigravida, was hospitalized in the 38th gestational week due to slurred speech, weakness and slow reaction patterns. An electroencephalogram and computed tomography scan of the brain and blood samples were normal. Blood pressure was 170-145/110-95 mmHg, albuminuria was moderate and there was moderate edema of the ankles. Labor started spontaneously the third day, 62 h after of hospitalization, and the patient gave birth to a healthy girl with no neonatal problems. Fourteen hours after delivery, the patient became comatose and developed universal clonic seizures. At the same time plasma glucose was

The risk of developing lymphoma is greatly increased in HIV infection. Musculoskeletal manifestations of the human immunodeficiency virus (HIV) are common and are sometimes the initial presentation of the disease. Muscle, bone, and joints are involved by septic arthritis, myopathies and neoplasms. HIV-related neoplastic processes that affect the musculoskeletal system include Kaposi's sarcoma and non-Hodgkin's lymphoma, the latter being mainly localized at lower extremities, spine and skull.

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To assess the clinical relevance of adnexal masses in pregnancy and the usefulness of ultrasound in their management.

The pregnancy-associated breast cancer seems to have become increasingly common with a high frequency of advanced breast cancer with axillary node metastases and so associated with poor prognosis., English Abstract, Journal Article, Review, SCOPUS: re.j, info:eu-repo/semantics/published

The pregnancy-associated breast cancer seems to have become increasingly common with a high frequency of advanced breast cancer with axillary node metastases and so associated with poor prognosis., English Abstract, Journal Article, Review, SCOPUS: re.j, info:eu-repo/semantics/published

The use of less radical procedures for the treatment of early cervical cancers is gaining interest among physicians and young patients. Some authors have described surgical procedures aimed at reducing the surgical aggressiveness but the safety of such procedures remains debated. After a polypectomy, a young patient had a diagnosis of stage Ia2 cervical adenosquamous carcinoma in 1995. As she wished to preserve her fertility, she underwent a cone biopsy and pelvic lymphadenectomy, without evidence of tumor spread. In 1998, at the 13th week of gestation, she had a diagnosis of a pelvic mass. The mass was a recurrence of carcinoma involving the myometrium, just underneath the peritoneum. She underwent a radical hysterectomy with bilateral oophorectomy. An ovarian metastasis was also detected at pathological exam. She received chemotherapy postoperatively and remains alive without evidence of disease. The recurrence of cervical cancer is traditionally regarded as an issue concerning the cervix, the parametria, or the lymph nodes. When the uterus is preserved we must also consider the possibility of a recurrence involving the corpus. With wider acceptance of limited therapeutic approaches we must be prepared for the detection of previously unknown patterns of recurrence and the follow-up modalities must be consequently adapted. (C) 2000 Academic Press

For patients who are planning to have chemotherapy, radiotherapy or to undergo bilateral oophorectomy, loss of ovarian function will result in premature ovarian menopause and loss of fertility. For these women, although there is no successful method for the cryopreservation of human oocytes, ovarian tissue cryobanking is proposed with a view to its autotransplantation at a later date or the isolation and in-vitro maturation of oocytes. Embryo preservation is indeed not an option for single women and even for married women because delaying treatment for at least 2 months of in-vitro fertilization cycles is inappropriate and life-threatening. Following the success of animal experiments, there have been reports of ovarian cryopreservation for women having to receive chemotherapy and/or radiotherapy. We present four case reports of ovarian tissue cryobanking and review the consequences of chemotherapy and radiotherapy on gonadal function, as well as the indications for freezing ovarian tissue.

The present study deals with the characterization of hormone-sensitivity in pregnancy-associated breast cancers (PBCs). This characterization was carried out in 22 PBCs as opposed to 88 non-pregnancy-associated breast cancers (NPBCs). For this study, we used the digital cell image analysis of Feulgen-stained nuclei to assess the type of hormone-sensitivity. In a previous study it was demonstrated that the chromatin pattern in breast cancers is related to the amounts of estrogen receptors they contain. Our results demonstrated that the quantitative description of the chromatin pattern by means of 15 parameters (relating to morphometric, densitometric, and textural features) made it possible to identify typical cell nuclei populations in the PBC and NPBC groups. The use of specific statistical analyses (principal-components and discriminant) made it possible to quantify the proportion of each cell nucleus type in the PBCs. Furthermore, of the 22 PBCs under study, 13 contained a large majority of cell nuclei whose chromatin pattern was characteristic of hormone-sensitive cells, while 5 cases contained a large majority of typically hormone-insensitive ones. The remaining 4 cases contained a relatively similar proportion of typically hormone-sensitive and insensitive cell nuclei. The quantitative chromatin pattern description thus made it possible to characterize the hormone-sensitivity level in PBCs, whereas DNA ploidy level determination did not enable any such characterization to be carried out. The chromatin pattern assay described here, which enables hormone-sensitive pregnancy-associated breast cancers to be identified from hormone-insensitive ones independently from biochemical assays, should help the physician regarding therapy adaptation., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

The present study deals with the characterization of hormone-sensitivity in pregnancy-associated breast cancers (PBCs). This characterization was carried out in 22 PBCs as opposed to 88 non-pregnancy-associated breast cancers (NPBCs). For this study, we used the digital cell image analysis of Feulgen-stained nuclei to assess the type of hormone-sensitivity. In a previous study it was demonstrated that the chromatin pattern in breast cancers is related to the amounts of estrogen receptors they contain. Our results demonstrated that the quantitative description of the chromatin pattern by means of 15 parameters (relating to morphometric, densitometric, and textural features) made it possible to identify typical cell nuclei populations in the PBC and NPBC groups. The use of specific statistical analyses (principal-components and discriminant) made it possible to quantify the proportion of each cell nucleus type in the PBCs. Furthermore, of the 22 PBCs under study, 13 contained a large majority of cell nuclei whose chromatin pattern was characteristic of hormone-sensitive cells, while 5 cases contained a large majority of typically hormone-insensitive ones. The remaining 4 cases contained a relatively similar proportion of typically hormone-sensitive and insensitive cell nuclei. The quantitative chromatin pattern description thus made it possible to characterize the hormone-sensitivity level in PBCs, whereas DNA ploidy level determination did not enable any such characterization to be carried out. The chromatin pattern assay described here, which enables hormone-sensitive pregnancy-associated breast cancers to be identified from hormone-insensitive ones independently from biochemical assays, should help the physician regarding therapy adaptation., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

To evaluate the clinical significance of the presence, location, size, and number of uterine leiomyomas in pregnancy, a retrospective cohort study in which pregnancy complications and outcome of pregnant women with uterine myomas was undertaken by routine second trimester ultrasound examination. The case group consisted of 183 consecutive women with uterine myomas detected and followed during the years 1983-1989; the control group was made up of all pregnancies diagnosed and followed at the obstetric clinic during the period 1985-1987. The incidences of preterm delivery (less than 37 weeks), preterm premature rupture of membranes, in utero growth retardation (less than 5th percentile), placental abruptio, placenta previa, postpartum hemorrhage (more than 500 cc), and retained placenta were not significantly increased in the group of women with myomas compared with the general population. However, cesarean sections were more common in women with myomas (23 vs 12%; P < 0.001). Within the group of women with myomas, the incidence of cesarean section was not different in cases with multiple rather than solitary myomas, but it was significantly higher in cases of lower uterine segment compared with fundal myomas (39 vs 18%; P < 0.01) and when the mean diameter of the myoma was greater than 5 cm (35 vs 17%; P = 0.01). Stepwise logistic regression analysis showed that both myoma location and size were independent predictors of the odds of cesarean section.