Impact of Hypertension and Preeclampsia Intervention Trial At Near Term-I (HYPITAT-I) on obstetric management and outcome in The Netherlands.

OBJECTIVE: The Hypertension and Preeclampsia Intervention Trial At near Term-I (HYPITAT-I) randomized controlled trial showed that, in women with gestational hypertension or mild pre-eclampsia at term, induction of labor, compared with expectant management, was associated with improved maternal outcome without compromising neonatal outcome. The aim of the current study was to evaluate the impact of these findings on obstetric management and maternal and perinatal outcomes in The Netherlands. METHODS: We retrieved data for the period 2000-2014 from the Dutch National Perinatal Registry, including 143 749 women with gestational hypertension or pre-eclampsia and a singleton fetus in cephalic presentation, delivered between 36 + 0 and 40 + 6 weeks of gestation (hypertensive disorder of pregnancy (HDP) group). Pregnant women without HDP were used as the reference group (n = 1 649 510). The HYPITAT-I trial was conducted between 2005 and 2008. To study the impact of HYPITAT-I, we compared rate of induction of labor, mode of delivery and maternal and perinatal outcomes in the periods before (2000-2005) and after (2008-2014) the trial. We also differentiated between hospitals that participated in HYPITAT-I and those that did not. RESULTS: In the HDP group, the rate of induction of labor increased from 51.1% before the HYPITAT-I trial to 64.2% after it (relative risk (RR), 1.26; 95% CI, 1.24-1.27). Maternal mortality decreased from 0.022% before the trial to 0.004% after it (RR, 0.20; 95% CI, 0.06-0.70) and perinatal death decreased from 0.49% to 0.27% (RR, 0.54; 95% CI, 0.45-0.65), which was attributable mostly to a decrease in fetal death. Both the increase in induction rate and the reduction in hypertensive complications were more pronounced in hospitals that participated in the HYPITAT-I trial than in those that did not. Following HYPITAT-I, the rate of induction of labor also increased (by 4.6 percentage points) in the reference group; however, the relative increase in the HDP group (13.1 percentage points) was significantly greater (P < 0.001 for the interaction). The reduction in maternal and perinatal deaths did not differ significantly between the HDP and reference groups. There was a decreased incidence of placental abruption in both HDP and reference groups, which was significantly greater in the HDP than in the reference group (P < 0.001 for the interaction). There was also an increased incidence of emergency Cesarean section in both HDP and reference groups; however, this change was significantly greater in the reference than in the HDP group (P < 0.001 for the interaction). CONCLUSION: Following the HYPITAT-I trial, there was a higher rate of induction of labor and improved obstetric outcome in term pregnancies complicated by HDP in The Netherlands. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Maternal mortality due to cardiovascular disease in the Netherlands: a 21-year experience.

OBJECTIVE: Cardiovascular disorders are the leading cause of indirect maternal mortality in Europe. The aim of this study is to present an extensive overview concerning the specific cardiovascular causes of maternal death and to identify avoidable contributing care factors related to these deaths. METHODS: We assessed all cases of maternal death due to cardiovascular disorders collected by a systematic national confidential enquiry of maternal deaths published by the Dutch Maternal Mortality and Morbidity Committee on behalf of the Netherlands Society of Obstetrics and Gynaecology over a 21-year period (1993-2013) in the Netherlands. RESULTS: There were 96 maternal cardiovascular deaths (maternal mortality rate due to cardiovascular diseases 2.4/100,000 liveborn children). Causes were aortic dissection (n = 20, 21%), ischaemic heart disease (n = 17, 18%), cardiomyopathies (including peripartum cardiomyopathy and myocarditis, n = 20, 21%) and (unexplained) sudden death (n = 27, 28%). Fifty-five percent of the deaths occurred postpartum (n = 55, 55%). Care factors that may have contributed to the adverse outcome were identified in 27 cases (28%). These factors were patient-related in 40% (pregnancy against medical advice, underestimation of symptoms) and healthcare-provider-related in 60% (symptoms not recognised, delay in diagnosis, delay in referral). CONCLUSION: The maternal cardiovascular mortality ratio is low in the Netherlands and the main causes of maternal cardiovascular mortality are in line with other European reports. In a minority of cases, care factors that were possibly preventable were identified. Women with cardiovascular disease should be properly counselled about the risks of pregnancy and the symptoms of complications. Education of care providers regarding the incidence, presentation and diagnosis of cardiovascular disease during pregnancy is recommended.

A randomised phase II trial of the Polo-like kinase inhibitor BI 2536 in chemo-naïve patients with unresectable exocrine adenocarcinoma of the pancreas - a study within the Central European Society Anticancer Drug Research (CESAR) collaborative network.

BACKGROUND: BI 2536, a novel Polo-like kinase 1 inhibitor, was assessed in patients with unresectable advanced exocrine adenocarcinoma of the pancreas. METHODS: The study employed a two-stage design. Randomised first-line patients received BI 2536 200 mg on day 1 (n=43) or 60 mg on days 1-3 (n=43) every 21 days. Recruitment of second-line patients was planned for a second stage dependent on an interim analysis demonstrating ≥ 2 responses in the first 18 evaluable patients following 12 weeks of treatment and/or tumour control ≥ 12 weeks in 5 patients per schedule. Primary end point was objective response rate (ORR). RESULTS: By independent review, ORR was 2.3% (all partial) and 24.4% had stable disease as confirmed best response. The second stage was not initiated. Median overall and progression-free survivals were 149 (95% confidence interval (CI), 91-307) and 46 days (95% CI, 44-56). Most common drug-related adverse events were neutropenia (37.2%), leukopenia (29.1%), fatigue (29.1%) and nausea (22.1%); most common grade 3/4-related events were neutropenia (36.0%), leukopenia (27.9%) and thrombocytopenia (8.1%). CONCLUSION: Given the low ORR and poor survival, further development of BI 2536 monotherapy is not warranted in this population.

Fatal meningitis during pregnancy in the Netherlands: a nationwide confidential enquiry.

OBJECTIVE: To determine the incidence of maternal deaths attributable to meningitis in the Netherlands, and to assess clinical features and risk factors. DESIGN: Confidential enquiry into the causes of maternal deaths. SETTING: Nationwide in the Netherlands. POPULATION: A total of 4 784 408 live births. METHODS: Analysis of all maternal deaths due to meningitis in pregnancy and puerperium from 1983 up to and including 2007 reported to the Maternal Mortality Committee of the Dutch Society of Obstetrics and Gynaecology. MAIN OUTCOME MEASURES: Incidence, clinical features and risk factors. RESULTS: Fifteen maternal deaths occurred due to meningitis, representing 4.4% of all maternal deaths. Twelve women (80%) presented with meningitis during pregnancy, 8 (66%) of them in the third trimester. Presenting symptoms were altered mental status (11; 73%), fever (9; 60%), nuchal rigidity (5; 33%) and headache (13; 87%). Nine women (60%) had otolaryngological infection at presentation or in the previous days or weeks. Twelve women (80%) underwent radiological examination, of which 5 (33%) showed distinct abnormalities. Cerebrospinal fluid (CSF) examination showed infected CSF in 8 (53%) women. In ten women (67%) Streptococcus pneumoniae was isolated. Substandard care was identified in 4 (27%) women. CONCLUSION: Pregnant or puerperal women presenting with classical symptoms of meningitis, particularly those with a history of otolaryngological infection or headache, should undergo thorough investigation and radiological and CSF examinations. Early diagnosis and immediate antibiotic treatment are imperative because of rapid deterioration in pregnant women. In case of doubt, the threshold for antibiotic treatment should be low and close monitoring is warranted.

Regional differences in Dutch maternal mortality.

OBJECTIVE: To study regional differences in maternal mortality in the Netherlands. DESIGN: Confidential inquiry into the causes of maternal mortality. SETTING: Nationwide. POPULATION: A total of 3 108 235 live births and 337 maternal deaths. METHODS: Data analysis of all maternal deaths in the period 1993-2008. MAIN OUTCOME MEASURE: Maternal mortality. RESULTS: The overall national maternal mortality ratio was 10.8 per 100 000 live births. In the 12 provinces of the Netherlands, the maternal mortality ratio ranged from 6.2 in Noord Brabant to 16.3 per 100 000 live births in Zeeland. In the four largest cities, maternal mortality varied from 9.3 in Amsterdam to 21.0 in Rotterdam. At a national level, the most frequent direct cause was pre-eclampsia. Increased risks for maternal mortality were found for women living in deprived neighbourhoods (RR 1.41), women from non-Western origin (RR 1.59), and women who were 35 years or older (RR 1.61). CONCLUSION: There are significant variations in maternal mortality ratios in the Netherlands between cities, provinces, and neighbourhoods. In addition, higher maternal mortality was observed in women of non-Western origin and in women who were 35 years of age or older.

Maternal mortality attributable to vascular dissection and rupture in the Netherlands: a nationwide confidential enquiry.

OBJECTIVE: To determine the incidence of maternal deaths attributable to vascular dissection and rupture in the Netherlands, and to assess clinical features, risk factors and the frequency of substandard care in the cases identified. DESIGN: Confidential enquiry into the causes of maternal deaths. SETTING: Nationwide in the Netherlands. POPULATION: A total of 3,108,235 live births. METHODS: Data analysis of all cases of maternal death from vascular dissection and rupture in the period 1993-2008. A literature review was also performed. MAIN OUTCOME MEASURES: Incidence, clinical features, risk factors and frequency of substandard care. RESULTS: A total of 23 maternal deaths attributable to vascular dissection and rupture were reported. In most cases the location was aortic (n=13), followed by coronary (n=4) and splenic (n=3) arteries. Clinical features were various, but most women presented with sudden unexplainable pain. Risk factors were present in 14 cases (61%), with hypertension being most frequently reported in ten cases (43%). Substandard care was determined to have been received in 13 cases (56%), inadequate assessment of complaints and a delay in diagnosis being the most frequent problems identified. CONCLUSIONS: Vascular dissection and rupture in pregnancy, although rare, carry a high risk of maternal and fetal morbidity and mortality. Because of the rarity of this condition and its variety in presentation, diagnosis is easily missed. A high index of suspicion when a woman presents with suggestive complaints, leading to an early diagnosis, may improve the prognosis for the woman and her child.

Lessons learned during implementation of MR-guided High-Intensity Focused Ultrasound treatment of uterine fibroids.

BACKGROUND: Although promising results have been reported for Magnetic Resonance image-guided High-Intensity Focused Ultrasound (MR-HIFU) treatment of uterine fibroids, this treatment is not yet widely implemented in clinical practice. During the implementation of a new technology, lessons are learned and an institutional learning-curve often has to be completed. The primary aim of our prospective cohort study was to characterize our learning-curve based on our clinical outcomes. Secondary aims included identifying our lessons learned during implementation of MR-HIFU on a technical, patient selection, patient counseling, medical specialists and organizational level. RESULTS: Our first seventy patients showed significant symptom reduction and improvement of quality of life at 3, 6 and 12 months after MR-HIFU treatment compared to baseline. After the first 25 cases, a clear plateau phase was reached in terms of failed treatments. The median non-perfused volume percentage of these first 25 treatments was 44.6% (range: 0-99.7), compared to a median of 74.7% (range: 0-120.6) for the subsequent treatments. CONCLUSIONS: Our findings describe the learning-curve during the implementation of MR-HIFU and include straightforward suggestions to shorten learning-curves for future users. Moreover, the lessons we learned on technique, patient selection, patient counseling, medical specialists and organization, together with the provided supplements, may be of benefit to other institutions aiming to implement MR-HIFU treatment of uterine fibroids. Trial registration ISRCTN14634593. Registered January 12, 2021-Retrospectively registered, https://www.isrctn.com/ISRCTN14634593 .

An open-label expanded access study of lapatinib and capecitabine in patients with HER2-overexpressing locally advanced or metastatic breast cancer.

BACKGROUND: The Lapatinib Expanded Access Program (LEAP) was designed to provide access to lapatinib plus capecitabine for HER2-positive metastatic breast cancer patients who previously received an anthracycline, a taxane, and a trastuzumab and had no other treatment options. PATIENTS AND METHODS: LEAP opened globally and enrollment continued until lapatinib received regulatory approval in each participating country. Patients were assessed for progression-free survival (PFS) and overall survival (OS) and monitored for serious adverse events (SAEs). RESULTS: As of 30 September 2008, 4283 patients from 45 countries enrolled in LEAP. The median treatment duration was 24.7 weeks. The most common drug-related SAEs were diarrhea (9.7%), vomiting (4.3%), and nausea (2.4%) and were mainly grade 3 or higher. The incidences of special interest SAEs were decreased left ventricle ejection fraction (0.5%), interstitial lung disease/pneumonitis (0.2%), and serious hepatobiliary events (0.4%). This safety profile is consistent with the overall lapatinib program. The median PFS and OS were 21.1 [95% confidence interval (CI) = 20.1-22.3] and 39.6 (95% CI = 37.7-40.7) weeks, respectively (n = 4006). Subgroup analysis showed longer PFS and OS in patients who had not received prior capecitabine. CONCLUSIONS: These results demonstrate the safety and efficacy of lapatinib in a broader patient population compared with a clinical trial.

Maternal death related to IVF in the Netherlands 1984-2008.

BACKGROUND: We assessed all deaths in the Netherlands that might have been related to IVF or to an IVF pregnancy in order to investigate this most serious complication. METHODS: All deaths related to IVF, within 1 year after IVF, from 1984 to 2008 were collected by sending a letter to all gynaecologists, and by retrieving data from a large cohort study examining the late effects of ovarian stimulation (OMEGA) and from the Dutch Maternal Mortality Committee. RESULTS: Six deaths were directly related to IVF (6/100,000), 17 deaths were directly related to the IVF pregnancy (42.5/100,000) and eight deaths were neither related to the IVF nor to the IVF-related pregnancy. The overall mortality in patients undergoing IVF procedures was lower than in the general population, whereas the overall mortality related to IVF pregnancies was higher than the maternal mortality in the general population. CONCLUSION: The decreased mortality is probably the result of a 'healthy female effect' in women undergoing IVF. The high maternal mortality in IVF pregnancies is probably related to the high number of multiple pregnancies and to the fact that (donor egg) IVF is successfully used in women who are older. The fact that only a few deaths directly related to IVF are reported in the literature whereas we observed six in the Netherlands indicates worldwide under-reporting of IVF-related mortality. We underline the importance of reporting all lethal cases to the European Society of Human Reproduction and Embryology Committee 'Safety and Quality after IVF'.

Cardiac arrest in pregnancy: increasing use of perimortem caesarean section due to emergency skills training?

OBJECTIVE: Management of cardiac arrest in pregnancy is recommended to include perimortem caesarean section (PMCS) in the Managing Obstetric Emergencies and Trauma (MOET) course. In this study, we aimed to assess maternal and neonatal outcome of all cases of PMCS in the Netherlands performed in the last 15 years, and to test the hypothesis that PMCS was used more often since the introduction of the MOET-course in 2004. DESIGN: Retrospective cohort study. SETTING: Nationwide assessment of all cases of PMCS inside or outside hospitals. POPULATION: All known cases of PMCS in the Netherlands from 1993 to 2008. METHODS: Data collection through contacting all Dutch obstetricians and all MOET and Advanced Trauma Life Support instructors. All cases of cardiac arrest during pregnancy were collected by cross-checking with data from the Dutch Maternal Mortality Committee and a nationwide severe maternal morbidity study. MAIN OUTCOME MEASURES: Incidence and case fatality rate of PMCS. Incidence of PMCS before and after introduction of the MOET course. Maternal and neonatal outcome and the process of the PMCS were analysed. RESULTS: During the study period, 55 women had a cardiac arrest, 12 of whom underwent a PMCS. Before the introduction of the MOET course, four PMCSs were performed (0.36/year), compared with eight cases after its introduction (1.6/year, P = 0.01). No PMCS was performed within the recommended 5 minutes after starting resuscitation. Eight of the twelve women (67%) regained cardiac output after PMCS, with two maternal and five neonatal survivors. Maternal case fatality rate was 83%. Neonatal case fatality rate was 58%. CONCLUSIONS: Since the introduction of the MOET course, the use of PMCS has increased. Outcome, however, was still poor. An important factor to improve outcome is more timely application of this potentially life-saving procedure.

Rise in maternal mortality in the Netherlands.

OBJECTIVE: To assess causes, trends and substandard care factors in maternal mortality in the Netherlands. Design Confidential enquiry into the causes of maternal mortality. SETTING: Nationwide in the Netherlands. POPULATION: 2,557,208 live births. METHODS: Data analysis of all maternal deaths in the period 1993-2005. MAIN OUTCOME MEASURES: Maternal mortality. RESULTS: The overall maternal mortality ratio was 12.1 per 100 000 live births, which was a statistically significant rise compared with the maternal mortality ratio of 9.7 in the period 1983-1992 (OR 1.2, 95% CI 1.0-1.5). The most frequent direct causes were (pre-)eclampsia, thromboembolism, sudden death in pregnancy, sepsis, obstetric haemorrhage and amniotic fluid embolism. The number of indirect deaths also increased, mainly caused by an increase in cardiovascular disorders (OR 2.5, 95% CI 1.4-4.6). Women younger than 20 years and older than 45 years, those with high parity or from nonwestern immigrant populations were at higher risk. Most substandard care was found in women with pre-eclampsia (91%) and in immigrant populations (62%). CONCLUSIONS: Maternal mortality in the Netherlands has increased since 1983-1992. Pre-eclampsia remains the number one cause. Groups at higher risk for complications during pregnancy should be better identified early in pregnancy or before conception, in order to receive preconception advice and more frequent antenatal visits. There is an urgent need for the better education of women and professionals concerning the danger signs, and for the training of professionals in order to improve maternal health care.

Maternal mortality and serious maternal morbidity in Jehovah's witnesses in The Netherlands.

OBJECTIVE: To determine the risk of maternal mortality and serious maternal morbidity because of major obstetric haemorrhage in Jehovah's witnesses in The Netherlands. DESIGN: A retrospective study of case notes. SETTING: All tertiary care centres, general teaching hospitals and other general hospitals in The Netherlands. SAMPLE: All cases of maternal mortality in The Netherlands between 1983 and 2006 and all cases of serious maternal morbidity in The Netherlands between 2004 and 2006. METHODS: Study of case notes using two different nationwide enquiries over two different time periods. MAIN OUTCOME MEASURES: Maternal mortality ratio (MMR) and risk of serious maternal mortality. RESULTS: The MMR for Jehovah's witnesses was 68 per 100,000 live births. We found a risk of 14 per 1000 for Jehovah's witnesses to experience serious maternal morbidity because of obstetric haemorrhage while the risk for the total pregnant population was 4.5 per 1000. CONCLUSIONS: Women who are Jehovah's witnesses are at a six times increased risk for maternal death, at a 130 times increased risk for maternal death because of major obstetric haemorrhage and at a 3.1 times increased risk for serious maternal morbidity because of obstetric haemorrhage, compared to the general Dutch population.

Substandard care in maternal mortality due to hypertensive disease in pregnancy in the Netherlands.

OBJECTIVES: To review the standard of care in cases of maternal mortality due to hypertensive diseases in pregnancy and to make recommendations for its improvement. DESIGN: Care given to women with hypertensive disease in pregnancy was audited and substandard care factors identified. SETTING: Confidential enquiry by the Dutch Maternal Mortality Committee (MMC) from the Netherlands Society of Obstetrics and Gynaecology. POPULATION: All maternal deaths reported to the MMC due to hypertensive disease in pregnancy in the Netherlands during the years 2000-04. METHODS: Assessment for substandard care factors using a checklist based on the Dutch guideline of 'Hypertensive Disorders in Pregnancy'. MAIN OUTCOME MEASURES: Substandard care in cases of maternal mortality due to hypertensive diseases in pregnancy. RESULTS: A total of 27 cases of maternal death due to hypertensive disease in pregnancy were reported to the committee in the study period. In 26 cases (96%), substandard care factors were present, of which in 17 cases (63%), these were for more than five different items. In community midwifery care, the most frequent substandard care factor was no testing for proteinuria when clearly indicated (41%). In hospital care, the most frequent substandard care was related to insufficient diagnostic testing when indicated (41%), insufficient management of hypertension by obstetricians (85%), no use or inadequate use of magnesium sulphate (67%), inadequate stabilisation before transport to tertiary care centres and/or delivery (52%) and failure to consider timely delivery (44%). CONCLUSIONS: Education of pregnant women concerning danger signs of hypertensive disease should be improved. Training of midwives and obstetricians should be improved in the following areas: performing basic diagnostic tests, adequate management of hypertension and eclampsia, with more attention to treatment of systolic blood pressure. This training should be guided by clear local protocols. Delivery should not be delayed in serious cases of hypertensive disease in pregnancy, not only after 32-34 weeks but also in early-onset pre-eclampsia as maternal risks often outweigh possible fetal benefits of temporising management.

Somatostatin receptor scintigraphy in advanced renal cell carcinoma. Results of a phase II-trial of somatostatine analogue therapy in patients with advanced RCC.

AIMS: Objective of this prospective study was to evaluate the role of somatostatin receptor scintigraphy (SRS) in advanced renal cell carcinoma (RCC) with respect to potential therapy with somatostatin analogue (SST-A) and to assess the response rate under therapy with SST-A. PATIENTS, METHODS: 16 patients with documented progression of histologically confirmed advanced RCC were included. Planar whole-body SRS was performed 4, 24 and 48 h post i.v. injection of 175-200 MBq 111In-pentetreoide. 5 and 25 h p.i. SPECT of thorax and abdomen were performed. Documentation of somatostatin receptor expression via SRS in >50% of known tumour lesions was the criteria for treatment start with SST-A (Sandostatin LAR-Depot 30 mg i.m. every four weeks). RESULTS: In 9/16 of the patients SRS showed at least one metastasis with moderate (n = 5) or intense (n = 4) tracer uptake. Lesion-based SRS evaluation showed only 12.1% (20/165) of all metastases. Most false-negative lesions were located in the lungs. In two patients, the majority of the known metastases was SRS positive and these patients received SST-A therapy. The first radiographic evaluation after a two-month interval showed progressive disease in both patients. CONCLUSIONS: We conclude that SRS is of limited value in staging of advanced RCC. In our patients SST-A did not result in a growth control of RCC. Consequently, the use of SST-A in advanced RCC seems to be no relevant therapeutic option.

[Mortality in pregnant and newly delivered women due to psychiatric disorders]. / Sterfte bij zwangeren en kraamvrouwen door psychiatrische stoornissen.

Two women, aged 28 and 37 years, both suffering from a psychiatric disorder i.e. puerperal psychosis and mood-disorder respectively, violently ended their lives at 12 days and 5 months after delivery. Early identification of risk factors in a multidisciplinary setting can lead to effective early management of psychiatric disorders during pregnancy and the puerperium. Negative outcomes such as suicide and even infanticide may consequently be prevented. The most common risk factors for suicide during pregnancy and the puerperium are: a history of psychiatric disorders, a family history of psychiatric disorders and current psychiatric symptomatology. Important recommendations to reduce maternal mortality due to psychiatric disorders include improvement of communication between health professionals and systematic registration of maternal mortality.

[Trisomy 18: how lethal is 'lethal'?] / Trisomie 18: hoe lethaal is 'lethaal'?

Should active treatment be available for children with trisomy 18? In the Netherlands, trisomy 18 is described as a lethal condition leading to death during or immediately after birth. The Dutch course of action for trisomy 18 is termination of pregnancy, almost without exception, or passive treatment without medical interventions. But that approach might be outdated. We present a case that inspired physicians and parents to rethink the perception of trisomy 18.

Fertility and obstetric outcomes after curettage versus expectant management in randomised and non-randomised women with an incomplete evacuation of the uterus after misoprostol treatment for miscarriage.

OBJECTIVE: To assess fertility and obstetric outcomes in women treated with curettage or undergoing expectant management for an incomplete miscarriage after misoprostol treatment. STUDY DESIGN: Between June 2012 and July 2014, we conducted a multicentre randomised clinical trial (RCT) with a parallel cohort study for non-randomised women, treated according to their preference. In the RCT 30 women were allocated curettage and 29 expectant management. In the cohort 197 women participated; 65 underwent curettage and 132 women underwent expectant management. Primary outcome was curation, defined as either an empty uterus on sonography at six weeks or an uneventful clinical follow-up. We used questionnaires to assess fertility and obstetric outcome of the first new pregnancy subsequent to study enrolment. RESULTS: Curation was seen in 91/95 women treated with curettage (95.8%) versus 134/161 women managed expectantly (83.2%) (p=0.003). The response rate was 211/255 (82%). In 198 women pursuing a new pregnancy, conception rates were 92% (67/73) in the curettage group versus 96% (120/125) in the expectant management group (OR 0.96, 95% CI 0.89;1.03, p=0.34), with ongoing pregnancy rates of 87% (58/67) versus 78% (94/120), respectively (OR 1.12, 95% CI 0.99;1.28, p=0.226). Preterm birth rates were 1/46 in the curettage group versus 8/81 in the expectant management group (OR 0.22, 95% CI 0.03;1.71 P=0.15). Caesarean section rates were 23% and 24% for women in the curettage group and expectant management group respectively. CONCLUSION: In women with an incomplete evacuation of the uterus after misoprostol treatment, curettage and expectant management does not lead to different fertility and pregnancy outcomes, as compared to expectant management.

Novel tumor suppressor locus in human chromosome region 3p14.2.

BACKGROUND: Alterations of chromosome region 3p14 are observed in numerous human malignancies. Because the pattern of allelic losses suggests the existence of at least one tumor suppressor gene within this region, we established a library of yeast artificial chromosomes (YACs) containing contiguous human 3p14 sequences to permit a search for tumor suppressor loci within the 3p14 region by use of functional complementation. METHODS: YACs specific for human chromosome region 3p14 were transduced by spheroplast fusion into cells of the human nonpapillary renal carcinoma cell line RCC-1, which shows a cytogenetically detectable 3p deletion and is tumorigenic in nude mice. RESULTS: We identified a 3p14.2-specific YAC clone, located in the vicinity of the fragile histidine triad (FHIT) gene (but toward the telomere), that is capable of inducing sustained suppression of tumorigenicity in nude mice and of activating cellular senescence in vitro. Among 23 mice given injections of RCC-1 cells containing this YAC, 16 (70%) remained tumor free for at least 6 months, whereas tumor formation occurred after a median of 6 weeks in control mice given injections of either RCC-1 parental cells or a revertant cell line (in which the YAC had lost all human sequences) or RCC-1 parental cells containing other, unrelated YACs. Similar results were obtained following microcell-mediated transfer of the entire human chromosome 3. CONCLUSION: These data provide strong evidence for the existence of a novel tumor suppressor locus adjacent to the previously identified candidate tumor suppressor gene, FHIT, in 3p14.2. Positional cloning of the novel suppressor element within the 3p14.2-specific YAC and the sequence's molecular and functional characterization should add to the understanding of the pathogenesis of renal cell carcinoma and other human tumors that exhibit 3p14 aberrations.

[Diagnosis image (258). A women with a 'bullet' in the abdomen]. / Diagnose in beeld (258). Een vrouw met een 'kogel' in het abdomen.

A 48-year-old woman had 17 years after hysterosalpingography a collection of contrast fluid, suggesting a bullet, in the abdomen.