Geertruida H. de Bock

Safety of laparoscopy versus laparotomy in early-stage endometrial cancer : a randomised trial

BACKGROUND The standard surgery for early-stage endometrial cancer is total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy, which is associated with substantial morbidity. Total laparoscopic hysterectomy (TLH) and bilateral salpingo-oophorectomy is less invasive and is assumed to be associated with lower morbidity, particularly in obese women. This study investigated the complication rate of TLH versus TAH in women with early-stage endometrial cancer. METHODS This randomised trial was done in 21 hospitals in The Netherlands, and 26 gynaecologists with proven sufficient skills in TLH participated. 283 patients with stage I endometrioid adenocarcinoma or complex atypical hyperplasia were randomly allocated (2:1) to the intervention group (TLH, n=187) or control group (TAH, n=96). Randomisation by sequential number generation was done centrally in alternate blocks of six and three participants, with stratification by trial centre. After assignment, the study coordinators, patients, gynaecologists, and members of the panel were not masked to intervention. The primary outcome was major complication rate, assessed by an independent panel. Data were analysed by a modified intention-to-treat analysis, since two patients in both groups were excluded from the main analysis. This trial is registered with the Dutch trial registry, number NTR821. FINDINGS The proportion of major complications was 14.6% (27 of 185) in the TLH group versus 14.9% (14 of 94) in the TAH group, with a difference of -0.3% (95% CI -9.1 to 8.5; p=0.95). The proportion of patients with an intraoperative major complication (nine of 279 [3.2%]) was lower than the proportion with a postoperative major complication (32 of 279 [11.5%]) and did not differ between TLH (five of 185 [2.7%]) and TAH (four of 94 [4.3%]; p=0.49). The proportion of patients with a minor complication was 13.0% (24 of 185) in the TLH group and 11.7% (11 of 94) in the TAH group (p=0.76). Conversion to laparotomy occurred in 10.8% (20 of 185) of the laparoscopic procedures. TLH was associated with significantly less blood loss (p<0.0001), less use of pain medication (p<0.0001), a shorter hospital stay (p<0.0001), and a faster recovery (p=0.002), but the procedure took longer than TAH (p<0.0001). INTERPRETATION Our results showed no evidence of a benefit for TLH over TAH in terms of major complications, but TLH (done by skilled surgeons) was beneficial in terms of a shorter hospital stay, less pain, and quicker resumption of daily activities. FUNDING The Dutch Organization for Health Research and Development (ZonMw), programme efficacy.

Saline contrast hysterosonography in abnormal uterine bleeding: a systematic review and meta-analysis

Objective To assess the diagnostic accuracy of saline contrast hysterosonography in the evaluation of the uterine cavity in women complaining of abnormal uterine bleeding.

Time to stop ovarian cancer screening in BRCA1/2 mutation carriers?

Women at high risk of ovarian cancer due to a genetic predisposition may opt for either surveillance or prophylactic bilateral salpingo‐oophorectomy (pBSO). Main objective of our study was to determine the effectiveness of ovarian cancer screening in women with a BRCA1/2 mutation. We evaluated 241 consecutive women with a BRCA1 or BRCA2 mutation who were enrolled in the surveillance program for hereditary ovarian cancer from September 1995 until May 2006 at the University Medical Center Groningen (UMCG), The Netherlands. The ovarian cancer screening included annual pelvic examination, transvaginal ultrasound (TVU) and serum CA125 measurement. To evaluate the effectiveness of screening in diagnosing (early stage) ovarian cancer sensitivity, specificity, positive and negative predictive values (PPV and NPV) of pelvic examination, TVU and CA125 were calculated. Three ovarian cancers were detected during the surveillance period; 1 prevalent cancer, 1 interval cancer and 1 screen‐detected cancer, all in an advanced stage (FIGO stage IIIc). A PPV of 20% was achieved for pelvic examination, 33% for TVU and 6% for CA125 estimation alone. The NPV were 99.4% for pelvic examination, 99.5% for TVU and 99.4% for CA125. All detected ovarian cancers were in an advanced stage, and sensitivities and positive predictive values of the screening modalities are low. Restricting the analyses to incident contacts that contained all 3 screening modalities did not substantially change the outcomes. Annual gynecological screening of women with a BRCA1/2 mutation to prevent advanced stage ovarian cancer is not effective.

As good as it gets? A meta-analysis and systematic review of methodological quality of heart rate variability studies in functional somatic disorders

Autonomic nervous system (ANS) dysfunction is a potential mechanism connecting psychosocial stress to functional somatic disorders (FSD), such as chronic fatigue syndrome, fibromyalgia and irritable bowel syndrome. We present the first meta-analysis and systematic review of methodological study quality on the association between cardiac ANS dysfunction, measured as parasympathetic nervous system (PNS) activity using heart rate variability (HRV), and FSD. Literature search revealed 23 available studies including data on 533 FSD patients. Meta-analysis on a subgroup of 14 studies with suitable outcome measures indicated lower PNS activity in FSD patients compared to controls (weighted standardized mean difference (SMD)=-0.32, 95% CI -0.63 to -0.01, p=0.04). The reliability of this summary estimate was, however, significantly limited by unexplained heterogeneity in the effect sizes and potential publication bias (weighted SMD after correction for funnel plot asymmetry=0.01, 95% CI -0.34 to 0.36, p=0.95). The systematic review of overall methodological quality of HRV studies in FSD demonstrates that there is substantial room for improvement, especially in selection of healthy control subjects, blinding of researchers performing HRV measurements, report of adequate HRV outcomes, and assessment of and adjustment for potential confounders. Methodological study quality was, however, not a significant predictor of study findings. We conclude that current available evidence is not adequate to firmly reject or accept a role of ANS dysfunction in FSD. Quality criteria and recommendations to improve future research on HRV in FSD are provided.

Differences and similarities in breast cancer risk assessment models in clinical practice: which model to choose?

Abstract To show differences and similarities between risk estimation models for breast cancer in healthy women from BRCA1/2-negative or untested families. After a systematic literature search seven models were selected: Gail-2, Claus Model, Claus Tables, BOADICEA, Jonker Model, Claus-Extended Formula, and Tyrer–Cuzick. Life-time risks (LTRs) for developing breast cancer were estimated for two healthy counsellees, aged 40, with a variety in family histories and personal risk factors. Comparisons were made with guideline thresholds for individual screening. Without a clinically significant family history LTRs varied from 6.7% (Gail-2 Model) to 12.8% (Tyrer–Cuzick Model). Adding more information on personal risk factors increased the LTRs and yearly mammography will be advised in most situations. Older models (i.e. Gail-2 and Claus) are likely to underestimate the LTR for developing breast cancer as their baseline risk for women is too low. When models include personal risk factors, surveillance thresholds have to be reformulated. For current clinical practice, the Tyrer–Cuzick Model and the BOADICEA Model seem good choices.

Support of the ‘fallopian tube hypothesis’ in a prospective series of risk-reducing salpingo-oophorectomy specimens

OBJECTIVE To determine the prevalence, localisation and type of occult (non)invasive cancer in risk-reducing salpingo-oophorectomy (RRSO) specimens in BRCA-mutation carriers and high-risk women from BRCA-negative families. METHODS A consecutive series of RRSO specimens of asymptomatic, screen-negative high-risk women were prospectively collected in our tertiary multidisciplinary cancer clinic from January 2000 until March 2012. All high-risk women in this study underwent genetic testing on BRCA-mutations. The surgico-pathological protocol comprised complete resection of ovaries and fallopian tubes, transverse sectioning at 2-3 mm (sectioning and extensively examining the fimbrial end [SEE-FIM] protocol from 2006) and double independent pathology review of morphologically deviant sections. RESULTS Three hundred and sixty RRSOs were performed in 188 BRCA1-carriers, 115 BRCA2-carriers and 57 BRCA-negative women at a median age of 44.0 years. Four occult invasive cancers were detected in BRCA-carriers (1.3%, 95%-confidence interval (CI) 0.03-2.61), all in BRCA1-carriers >40 years of age. All cancers, of which two tubal and two ovarian cancers, were FIGO-stage I/II. Three non-invasive serous intraepithelial carcinomas (STICs) were detected in BRCA-carriers (1.0%, 95%-CI 0.00-2.10). In BRCA-negative women one STIC was found (1.8%, 95%-CI 0.00-5.16), however she carried an unclassified variant in BRCA2. Total follow-up after RRSO was 1691 woman-years, in which one BRCA1-carrier developed peritoneal cancer (0.3%, 95%-CI 0.00-0.82). CONCLUSIONS A low prevalence of occult invasive cancer (1.1%) was found in young asymptomatic, screen-negative women at increased ovarian cancer risk undergoing RRSO. This study adds to the advice to perform RRSO in BRCA1-carriers before the age of 40. Our findings support the hypothesis of the fallopian tube as the primary site of origin of pelvic high-grade serous cancer.

Costs and Effects of Abdominal versus Laparoscopic Hysterectomy: Systematic Review of Controlled Trials

Objective Comparative evaluation of costs and effects of laparoscopic hysterectomy (LH) and abdominal hysterectomy (AH). Data sources Controlled trials from Cochrane Central register of controlled trials, Medline, Embase and prospective trial registers. Selection of studies Twelve (randomized) controlled studies including the search terms costs, laparoscopy, laparotomy and hysterectomy were identified. Methods The type of cost analysis, perspective of cost analyses and separate cost components were assessed. The direct and indirect costs were extracted from the original studies. For the cost estimation, hospital stay and procedure costs were selected as most important cost drivers. As main outcome the major complication rate was taken. Findings Analysis was performed on 2226 patients, of which 1013 (45.5%) in the LH group and 1213 (54.5%) in the AH group. Five studies scored ≥10 points (out of 19) for methodological quality. The reported total direct costs in the LH group (

Amplicon Mapping and Expression Profiling Identify the Fas-Associated Death Domain Gene as a New Driver in the 11q13.3 Amplicon in Laryngeal/Pharyngeal Cancer

63,997) were 6.1% higher than the AH group (

Long-Term Cardiovascular Mortality in Patients With Differentiated Thyroid Carcinoma: An Observational Study

60,114). The reported total indirect costs of the LH group (

Involvement of the TGF-beta and beta-Catenin Pathways in Pelvic Lymph Node Metastasis in Early-Stage Cervical Cancer

1,609) were half of the total indirect in the AH group (