A comparison of the McGrath videolaryngoscope with direct laryngoscopy for rapid sequence intubation in the operating theatre: a multicentre randomised controlled trial.

Aspiration of gastric contents is a recognised complication during all phases of anaesthesia. The risk of this event becomes more likely with repeated attempts at tracheal intubation. There is a lack of clinical data on the effectiveness of videolaryngoscopy relative to direct laryngoscopy rapid sequence intubation in the operating theatre. We hypothesised that the use of a videolaryngoscope during rapid sequence intubation would be associated with a higher first pass tracheal intubation success rate than conventional direct laryngoscopy. In this multicentre randomised controlled trial, 1000 adult patients requiring tracheal intubation for elective, urgent or emergency surgery were allocated randomly to airway management using a McGrath™ MAC videolaryngoscope (Medtronic, Minneapolis, MN, USA) or direct laryngoscopy. Both techniques used a Macintosh blade. First-pass tracheal intubation success was higher in patients allocated to the McGrath group (470/500, 94%) compared with those allocated to the direct laryngoscopy group (358/500, 71.6%), odds ratio (95%CI) 1.31 (1.23-1.39); p < 0.001. This advantage was observed in both trainees and consultants. Cormack and Lehane grade ≥ 3 view occurred less frequently in patients allocated to the McGrath group compared with those allocated to the direct laryngoscopy group (5/500, 1% vs. 94/500, 19%, respectively; p < 0.001). Tracheal intubation with a McGrath videolaryngoscope was associated with a lower rate of adverse events compared with direct laryngoscopy (13/500, 2.6% vs. 61/500, 12.2%, respectively; p < 0.001). These findings suggest that the McGrath videolaryngoscope is superior to a conventional direct laryngoscope for rapid sequence intubation in the operating theatre.

A multicentre randomised controlled trial of the McGrath™ Mac videolaryngoscope versus conventional laryngoscopy.

Before completion of this study, there was insufficient evidence demonstrating the superiority of videolaryngoscopy compared with direct laryngoscopy for elective tracheal intubation. We hypothesised that using videolaryngoscopy for routine tracheal intubation would result in higher first-pass tracheal intubation success compared with direct laryngoscopy. In this multicentre randomised trial, 2092 adult patients without predicted difficult airway requiring tracheal intubation for elective surgery were allocated randomly to either videolaryngoscopy with a Macintosh blade (McGrath™) or direct laryngoscopy. First-pass tracheal intubation success was higher with the McGrath (987/1053, 94%), compared with direct laryngoscopy (848/1039, 82%); absolute risk reduction (95%CI) was 12.1% (10.9-13.6%). This resulted in a relative risk (95%CI) of unsuccessful tracheal intubation at first attempt of 0.34 (0.26-0.45; p < 0.001) for McGrath compared with direct laryngoscopy. Cormack and Lehane grade ≥ 3 was observed more frequently with direct laryngoscopy (84/1039, 8%) compared with McGrath (8/1053, 0.7%; p < 0.001) No significant difference in tracheal intubation-associated adverse events was observed between groups. This study demonstrates that using McGrath videolaryngoscopy compared with direct laryngoscopy improves first-pass tracheal intubation success in patients having elective surgery. Practitioners may consider using this device as first choice for tracheal intubation.

Impact of direct laryngoscopy vs. videolaryngoscopy on signal quality of recurrent laryngeal nerve monitoring in thyroid surgery: a randomised parallel group trial.

In thyroid surgery, intra-operative neuromonitoring signals of the recurrent laryngeal nerve can be detected by surface electrodes on a tracheal tube positioned at the vocal fold level. The incidence of difficult tracheal intubation in patients undergoing thyroidectomy for nodular goitre ranges from 5.3% to 20.5%. The aim of this study was to compare videolaryngoscopy with conventional direct laryngoscopy as methods for proper placement of the surface electrode to prevent insufficient intra-operative nerve signal quality. In this prospective randomised trial, adult patients requiring tracheal intubation during thyroid surgery were randomly allocated to two groups of C-MAC® (Macintosh style blade) videolaryngoscope or direct laryngoscopy using the Macintosh laryngoscope. Primary outcome was the incidence of insufficient signal electromyogram amplitude level (< 500 µV) after successful tracheal intubation. A total of 260 (130 per group) participants were analysed. An insufficient signal was more frequent with direct laryngoscopy (35/130, 27%), compared with C-MAC (12/130, 9%, p < 0.001). First-pass tracheal intubation success rate was lower with direct laryngoscopy (86/130 (66%)) compared with the C-MAC (125/130 (96%)) (p < 0.0001). Cormack and Lehane grade ≥ 3 was observed more frequently with direct laryngoscopy (16/130 (12%)), compared with the C-MAC (0/130, (0%)) (p < 0.0001). The results suggest that videolaryngoscopy has an impact on the quality of the initial intra-operative neuromonitoring signal in patients undergoing thyroid surgery, and this technique can provide optimised surface electrode positioning.

Non-invasive haemoglobin measurement as an index test to detect pre-operative anaemia in elective surgery patients - a prospective study.

Non-invasive haemoglobin measurement using absolute values lacks the precision to be the sole basis for the treatment of pre-operative anaemia. However, it can possibly serve as a screening test, indexing 'anaemia' with high sensitivity when values remain under prespecified cut-off values. Based on previous data, non-invasive haemoglobin cut-off values (146 g.l-1 for women and 152 g.l-1 for men) detect true anaemia with 99% sensitivity. An index test with these prespecified cut-off values was verified by prospective measurement of non-invasive and invasive haemoglobin pre-operatively in elective surgical patients. In 809 patients, this showed an estimated sensitivity (95%CI) of 98.9% (94.1-99.9%) in women and 96.4% (91.0-99.0%) in men. This saved invasive blood tests in 9% of female and 28% of male patients. In female patients, a lower non-invasive haemoglobin cut-off value (138 g.l-1 ) would save 28% of invasive blood tests with a sensitivity of 95%. The target 99% sensitivity would be reached by non-invasive haemoglobin cut-off values of 152 g.l-1 in female and 162 g.l-1 in male patients, saving 3% and 9% of invasive blood tests, respectively. Bias and limits of agreement between non-invasive and laboratory haemoglobin levels were 2 and - 25 to 28 g.l-1 , respectively. Patient and measurement characteristics did not influence the agreement between non-invasive and laboratory haemoglobin levels. Although sensitivity was very high, the index test using prespecified cut-off values just failed to reach the target sensitivity to detect true anaemia. Nevertheless, with respect to blood-sparing effects, the use of the index test in men may be clinically useful, while an index test with a lower cut-off (132 g.l-1 ) could be more clinically appropriate in women.

[Algorithm for securing an unexpected difficult airway : User analysis on a simulator]. / Algorithmus zur Sicherung des unerwartet schwierigen Atemwegs : Eine Anwenderanalyse am Simulator.

BACKGROUND: Critical incidents in difficult airway management are still a main contributory factor for perioperative morbidity and mortality. Many national associations have developed algorithms for management of these time critical events. For implementation of these algorithms the provision of technical requirements and procedure-related training are essential. Severe airway incidents are rare events and clinical experience of the individual operators is limited; therefore, simulation is an adequate instrument for training and evaluating difficult airway algorithms. OBJECTIVE: The aim of this observational study was to evaluate the application of the institutional difficult airway algorithm among anesthetists. MATERIAL AND METHODS: After ethics committee approval, anesthetists were observed while treating a "cannot intubate" (CI) and a "cannot intubate, cannot ventilate" (CICV) situation in the institutional simulation center. As leader of a supportive team the participants had to deal with an unexpected difficult airway after induction of anesthesia in a patient simulator. The following data were recorded: sequence of the applied airway instruments, time to ventilation after establishing a secured airway using any instrument in the CI situation and time to ventilation via cricothyrotomy in the CICV situation. Conformity to the algorithm was defined by the sequence of the applied instruments. Analysis comprised conformity to the algorithm, non-parametric tests for time to ventilation and differences between junior and senior anesthetists. RESULTS: Out of 50 participants 45 were analyzed in the CI situation. In this situation 93% of the participants acted in conformity with the algorithm. In 62% the airway was secured by flexible intubation endoscopy, in 38% with another device. Data from 46 participants were analyzed in the CICV situation. In this situation 91% acted in conformity with the algorithm. The last device used prior to the decision for cricothyrotomy was flexible intubation endoscopy in 39%, a laryngeal mask in 22% and other instruments in 39%. Of the 50 participants 38 had already been institutionally trained in difficult airway management during the previous 2 years. For cricothyrotomy the participants needed a median time of 63 s and there was no difference between junior and senior anesthetists (p = 0.46). The cricothyrotomy was performed faster using a surgical approach than a transtracheal puncture approach using a Melker emergency cricothyrotomy set (52 s vs. 73 s, p = 0.014). CONCLUSION: The conformity to the algorithm of over 90% indicates a good training level of the participants concerning the difficult airway algorithm. In the observed sample flexible intubation endoscopy tended to be of high significance even in the unanticipated difficult airway. Cricothyrotomy was performed faster surgically than by the use of the transtracheal puncture approach, while no differences between junior and senior anesthetists were observed. For the successful management of an unexpected difficult airway, specific training of these special and rare events is crucial. A standardized provision of special airway instruments stored in a special trolley and frequent application of this trolley in the clinical routine is recommended.

The novel video-assisted intubating laryngeal mask Totaltrack compared to the intubating laryngeal mask Fastrach - a controlled randomized manikin study.

BACKGROUND: The novel Totaltrack combines a supraglottic airway device with video laryngoscopic tracheal intubation. The intubation laryngeal mask Fastrach is an established device without visual control of intubation. We hypothesized that supraglottic ventilation success with Totaltrack would be similar to Fastrach, but intubation would be performed faster due to visual control of the procedure. METHODS: Fifty-five anaesthesiologists were randomized into one of two study arms: Fastrach Totaltrack. After a standardized introduction, six consecutive attempts of supraglottic ventilation and intubation attempts with each of one of the devices were performed on an airway manikin. The combined primary outcome was: time to supraglottic ventilation and time to ventilation after intubation. Additionally, success rate and learning curves were evaluated. RESULTS: Supraglottic time to ventilation was shorter when using the Fastrach compared to the Totaltrack (median: 7.8 s [confidence interval [CI]: 7.0-8.6 s] vs. 11 s [CI: 7.8-14.2 s], P < 0.001). Intubation was faster using the Fastrach compared to Totaltrack (median: 12.5 s, [CI: 10.1-14.9 s] vs. 23.3 s [CI: 21.5-25.1 s], P < 0.001). Success rate for supraglottic ventilation was comparable between Fastrach and Totaltrack (86-96%). Successful intubation via the device was 100% in Fastrach and ranged from 61% to 93% in Totaltrack, with a higher probability of successful intubation after four applications. CONCLUSION: In this manikin-based study the novel Totaltrack did not prove superior to Fastrach despite a similar design. Video laryngoscopic control of supraglottic ventilation and endotracheal intubation was prolonged using the Totaltrack. Clinical trials are mandatory to evaluate the role of the Totaltrack in airway management.

Survival and contralateral breast cancer in CHEK2 1100delC breast cancer patients: impact of adjuvant chemotherapy.

BACKGROUND: We assessed the sensitivity to adjuvant chemotherapy in cell cycle checkpoint kinase 2 (CHEK2) vs non-CHEK2 breast cancer patients by comparing the contralateral breast cancer incidence and distant disease-free and breast cancer-specific survival between both groups, stratified for adjuvant chemotherapy. METHODS: One Dutch hereditary non-BRCA1/2 breast cancer patient cohort (n=1220) and two Dutch cohorts unselected for family history (n=1014 and n=2488, respectively) were genotyped for CHEK2 1100delC. Hazard ratios for contralateral breast cancer, distant disease-free and breast cancer-specific death for mutation carriers vs noncarriers were calculated using the Cox proportional hazard method, stratified for adjuvant chemotherapy. RESULTS: The CHEK2 mutation carriers (n=193) had an increased incidence of contralateral breast cancer (multivariate hazard ratio 3.97, 95% confidence interval 2.59-6.07). Distant disease-free and breast cancer-specific survival were similar in the first 6 years in mutation carriers compared with noncarriers, but diverted as of 6 years after breast cancer diagnosis (multivariate hazard ratios and 95% confidence intervals 2.65 (1.79-3.93) and 2.05 (1.41-2.99), respectively). No significant interaction between CHEK2 and adjuvant chemotherapy was observed. CONCLUSIONS: The CHEK2 1100delC-associated breast cancer is associated with a higher contralateral breast cancer rate as well as worse survival measures beyond 6 years after diagnosis. No differential sensitivity to adjuvant chemotherapy was observed in CHEK2 patients.

German guidelines for airway management 2023.

The German airway management guidelines are intended to serve as an orientation and decision-making aid and thus contribute to the optimal care of patients undergoing anesthesiologic- and intensive medical care. As part of the pre-anesthesiologic evaluation, anatomical and physiological indications for difficult mask ventilation and intubation shall be evaluated. This includes the assessment of mouth opening, dental status, mandibular protrusion, cervical spine mobility and existing pathologies. The airway shall be secured while maintaining spontaneous breathing if there are predictors or anamnestic indications of difficult or impossible mask ventilation and/or endotracheal intubation. Various techniques can be used here. If there is an unexpectedly difficult airway, a video laryngoscope is recommended after unsuccessful direct laryngoscopy, consequently a video laryngoscope must be available at every anesthesiology workplace. The airway shall primarily be secured with a video laryngoscope in critically ill- and patients at risk of aspiration. Securing the airway using translaryngeal and transtracheal techniques is the "ultima ratio" in airway management. The performance or supervision of airway management in the intensive care unit is the responsibility of experienced physicians and nursing staff. Appropriate education and regular training are essential. Clear communication and interaction between team members are mandatory before every airway management procedure. Once the airway has been secured, the correct position of the endotracheal tube must be verified using capnography.

Outcome of BRCA1- compared with BRCA2-associated ovarian cancer: a nationwide study in the Netherlands.

BACKGROUND: Recent studies suggested an improved overall survival (OS) for BRCA2- versus BRCA1-associated epithelial ovarian cancer (EOC), whereas the impact of chemotherapy is not yet clear. In a nationwide cohort, we examined the results of primary treatment, progression-free survival (PFS), treatment-free interval (TFI), and OS of BRCA1 versus BRCA2 EOC patients. METHODS: Two hundred and forty-five BRCA1- and 99 BRCA2-associated EOC patients were identified through all Dutch university hospitals. Analyses were carried out with the Pearson's Chi-square test, Kaplan-Meier, and Cox regression methods. RESULTS: BRCA1 patients were younger at EOC diagnosis than BRCA2 patients (51 versus 55 years; P < 0.001), without differences regarding histology, tumor grade, and International Federation of Gynecology and Obstetrics (FIGO) stage. Complete response rates after primary treatment, including chemotherapy, did not differ between BRCA1 (86%) and BRCA2 patients (90%). BRCA1 versus BRCA2 patients had a shorter PFS (median 2.2 versus 3.9 years, respectively; P = 0.006), TFI (median 1.7 versus 2.8 years; P = 0.009), and OS (median 6.0 versus 9.7 years; P = 0.04). Differences could not be explained by age at diagnosis, FIGO stage or type of treatment. CONCLUSIONS: PFS and OS were substantially longer in BRCA2- than in BRCA1-associated EOC patients. While response rates after primary treatment were similarly high in both groups, TFI, as surrogate for chemosensitivity, was significantly longer in BRCA2 patients.

Chemosensitivity and outcome of BRCA1- and BRCA2-associated ovarian cancer patients after first-line chemotherapy compared with sporadic ovarian cancer patients.

BACKGROUND: Because it is insufficiently clear whether BRCA-associated epithelial ovarian cancer (EOC) is more chemosensitive than sporadic EOC, we examined response to chemotherapy, progression-free survival (PFS) and overall survival (OS) in BRCA1- and BRCA2-associated versus sporadic EOC patients. METHODS: Data about patient characteristics, response to and outcome after primary therapy, including chemotherapy, were collected from 99 BRCA1, 13 BRCA2 and 222 sporadic patients. Analyses were carried out using a chi-square test and Kaplan-Meier and Cox regression methods. RESULTS: Complete response (CR) or no evidence of disease (NED) was observed in 87% of the BRCA1 patients, progressive disease (PD) in 2%, being 71% and 15%, respectively, in sporadic EOC patients (P = 0.002). In BRCA2 patients, 92% had CR/NED, and none PD (P = 0.27). Median PFS in BRCA1, BRCA2 and sporadic patients was 2.1 [95% confidence interval (CI) 1.9-2.5] years (P = 0.006), 5.6 (95% CI 0.0-11.5) years (P = 0.008) and 1.3 (95% CI 1.1-1.5) years, respectively. Median OS in the three groups was 5.9 (95% CI 4.7-7.0) years (P < 0.001), >10 years (P = 0.008), and 2.9 (95% CI 2.2-3.5) years, respectively. A trend for a longer PFS and OS in BRCA2 compared with BRCA1 patients was observed. CONCLUSION: Compared with sporadic EOC patients, both BRCA1- and BRCA2-associated patients have improved outcomes after primary therapy, including chemotherapy.

Tumour characteristics, survival and prognostic factors of hereditary breast cancer from BRCA2-, BRCA1- and non-BRCA1/2 families as compared to sporadic breast cancer cases.

AIM OF THE STUDY: Results on tumour characteristics and survival of hereditary breast cancer (BC), especially on BRCA2-associated BC, are inconclusive. The prognostic impact of the classical tumour and treatment factors in hereditary BC is insufficiently known. METHODS: We selected 103 BRCA2-, 223 BRCA1- and 311 non-BRCA1/2 BC patients (diagnosis 1980-2004) from the Rotterdam Family Cancer Clinic. To correct for longevity bias, analyses were also performed while excluding index patients undergoing DNA testing 2 years after BC diagnosis. As a comparison group, 759 sporadic BC patients of comparable age at and year of diagnosis were selected. We compared tumour characteristics, the occurrence of ipsilateral recurrence (LRR) and contralateral BC (CBC) as well as distant disease-free (DDFS), BC-specific (BCSS) and overall survival (OS) between these groups. By multivariate modelling, the prognostic impact of tumour and treatment factors was investigated separately in hereditary BC. RESULTS: We confirmed the presence of the particular BRCA1-phenotype. In contrast, tumour characteristics of BRCA2-associated BC were similar to those of non-BRCA1/2 and sporadic BC, with the exception of a high risk of CBC (3.1% per year) and oestrogen-receptor (ER)-positivity (83%). No significant differences between BRCA2-associated BC and other BC subgroups were found with respect to LRR, DDFS, BCSS and OS. Independent prognostic factors for BC-specific survival in hereditary BC (combining the three subgroups) were tumour stage, adjuvant chemotherapy, histologic grade, ER status and a prophylactic (salpingo-)oophorectomy. CONCLUSIONS: Apart from the frequent occurrence of contralateral BC and a positive ER-status, BRCA2-associated BC did not markedly differ from other hereditary or sporadic BC. Our observation that tumour size and nodal status are prognostic factors also in hereditary BC implies that the strategy to use these factors as a proxy for ultimate mortality appears to be valid also in this specific group of patients.

Mammography: interobserver variability in breast density assessment.

Our objective was to determine the interobserver variability of breast density assessment according to the Breast Imaging Reporting and Data System (BI-RADS) and to examine potential associations between breast density and risk factors for breast cancer. Four experienced breast radiologists received instructions regarding the use of BI-RADS and they assessed 57 mammograms into BI-RADS density categories of 1-4. The weighted kappa values for breast density between pairs of observers were 0.84 (A, B) (almost perfect agreement); 0.75 (A, C), 0.74 (A, D), 0.71 (B, C), 0.77 (B, D), 0.65 (C, D) (substantial agreement). The weighted overall kappa, measured by the intraclass correlation coefficient (ICC), was 0.77 (95% CI: 0.69-0.85). Body mass index was inversely associated with high breast density. In conclusion, overall interobserver agreement in mammographic interpretation of breast density is substantial and therefore, the BI-RADS classification for breast density is useful for standardization in a multicentre study.

[Comparison of GlideScope® Cobalt and McGrath® Series 5 video laryngoscopes with direct laryngoscopy in a simulated regurgitation/aspiration scenario]. / Vergleich der Videolaryngoskope GlideScope® Cobalt und McGrath® Series 5 mit konventioneller Laryngoskopie bei simulierter Regurgitation/Aspiration.

BACKGROUND: Video laryngoscopy has become increasingly important in airway management in the pre- and intrahospital settings. However, using video laryngoscopes in the presence of body fluids can make visualization of the airway difficult. A simulated regurgitation model was used to compare two video laryngoscopes (VL) with direct laryngoscopy. MATERIALS AND METHODS: A total of 72 physicians participated in this randomized trial. The hypopharynx from an Airway Management Trainer was filled with artificially warmed turbid liquid. In addition, the cervical spine of the manikin was immobilized. The VL GlideScope® (GS) and McGrath® Series 5 (McG) were examined with the laryngoscope with Macintoshspatel (DL). Fogging of the camera optics in percent (0 %= clear view, 100 %= no view), the visibility of the glottis by Cormack and Lehane classification (C&L), and the POGO Score (percentage of glottic opening), the time until the endotracheal tube placement, and the success rate were evaluated. RESULTS: No fogging (median 0 %) was present using the GS (interquartile range [IQR]: 0-4), in contrast 45 % fogging was found in the McG group (IQR: 30-60; p < 0.001). Glottic visualization using C&L was better using VL (p < 0.001). A similar result was observed using the POGO Scale: GS 90 % (IQR: 76-100), McG 80 % (IQR: 70-90), and DL 20 % (IQR: 0-50). The time for correct placement was in the DL with 27.6 s (IQR: 22.5-35) faster (p < 0.001), with the GS 48.5 s (IQR: 34.3-65.1) and the McG 66.3 s (IQR: 45.4-90). Successful placement was possible with GS in all cases (72/72), with DL in 71/72 cases, and with the McG in 70/72 cases. CONCLUSION: Using a video laryngsocope with an "anti-fogging" system improved visualization in a simulated aspiration model. In this scenario, VL showed no advantage to direct laryngoscopy in terms of success rate and speed of intubation.

Timing of risk reducing mastectomy in breast cancer patients carrying a BRCA1/2 mutation: retrospective data from the Dutch HEBON study.

It is expected that rapid genetic counseling and testing (RGCT) will lead to increasing numbers of breast cancer (BC) patients knowing their BRCA1/2 carrier status before primary surgery. Considering the potential impact of knowing one's status on uptake and timing of risk-reducing contralateral mastectomy (RRCM), we aimed to evaluate trends over time in RRCM, and differences between carriers identified either before (predictively) or after (diagnostically) diagnosis. We collected data from female BRCA1/2 mutation carriers diagnosed with BC between 1995 and 2009 from four Dutch university hospitals. We compared the timing of genetic testing and RRCM in relation to diagnosis in 1995-2000 versus 2001-2009 for all patients, and predictively and diagnostically tested patients separately. Of 287 patients, 219 (76%) had a diagnostic BRCA1/2 test. In this cohort, the median time from diagnosis to DNA testing decreased from 28 months for those diagnosed between 1995 and 2000 to 14 months for those diagnosed between 2001 and 2009 (p < 0.001). Similarly, over time women in this cohort underwent RRCM sooner after diagnosis (median of 77 vs. 27 months, p = 0.05). Predictively tested women who subsequently developed BC underwent an immediate RRCM significantly more often than women who had a diagnostic test (21/61, 34%, vs. 13/170, 7.6 %, p < 0.001). Knowledge of carrying a BRCA1/2 mutation when diagnosed with BC influenced decisions concerning primary surgery. Additionally, in more recent years, women who had not undergone predictive testing were more likely to undergo diagnostic DNA testing and RRCM sooner after diagnosis. This suggests the need for RGCT to guide treatment decisions.

MRI screening for breast cancer in women with familial or genetic predisposition: design of the Dutch National Study (MRISC).

Mammography screening of women aged 50-70 years for breast cancer has proven to be effective in reducing breast cancer mortality. There is no consensus about the value of breast cancer screening in women aged 40-49 years. Five to ten per cent of all breast cancers are hereditary. One of the options to reduce the risk of breast cancer mortality for women with a familial or genetic predisposition is intensive surveillance. However, the effectiveness of mammography screening for breast cancer in these women, who are mainly younger than 50 years, is unproven. MRI might increase the effectiveness of screening in women with a familial or genetic predisposition. This paper describes the design of the Dutch national study for Magnetic Resonance Imaging (MRI) screening in women with a familial or genetic predisposition. The aims of this study are to investigate: the value of regular surveillance in women with a familial or genetic predisposition for breast cancer, the efficacy of MRI as compared to mammography, cost-effectiveness of regular screening and quality of life during surveillance. Included are women with a lifetime risk of familial breast cancer of 15% or more or BRCA1/2 mutation carriers, who visit one of the Dutch family cancer clinics. The aim is to include 2,500 women. The study started on 1 November 1999. On 1 January 2002, more than 1,700 women, including 210 proven carriers of a BRCA1 or BRCA2 mutation, were included in the study.

Tumor characteristics and detection method in the MRISC screening program for the early detection of hereditary breast cancer.

In the MRISC study, women with an inherited risk for breast cancer were screened by a 6-month clinical breast examination (CBE) and yearly MRI and mammography. We found that the MRISC screening scheme could facilitate early breast cancer diagnosis and that MRI was a more sensitive screening method than mammography, but less specific. In the current study we investigated the contribution of MRI in the early detection of breast cancer in relation to tumor characteristics. From November 1999 to October 2003, 1909 women were included and 50 breast cancers were detected, of which 45 were evaluable and included in the current study. We compared the characteristics of tumors detected by MRI-only with those of all other (non-palpable) screen-detected tumors. Further, we compared the sensitivity of mammography and MRI within subgroups according to different tumor characteristics. Twenty-two (49%) of the 45 breast cancers were detected by MRI and not visible at mammography, of which 20 (44%) were also not palpable (MRI-only detected tumors). MRI-only detected tumors were more often node-negative than other screen-detected cancers (94 vs. 59%; P=0.02) and tended to be more often

Survival and prognostic factors in BRCA1-associated breast cancer.

BACKGROUND: Studies comparing survival in BRCA1-associated and sporadic breast cancer (BC) report inconsistent results and frequently concern small sample sizes. Further, the prognostic impact of the classical tumour and treatment factors is unclear in BRCA1-associated BC. PATIENTS AND METHODS: We selected 223 BC patients diagnosed between 1980 and 2001 within families with a deleterious germline BRCA1-mutation ascertained at the Rotterdam Family Cancer Clinic. To correct for ascertainment bias, the group of index patients undergoing DNA testing more than 2 years after BC diagnosis (n = 53) was separated from the other BRCA1-patients (n = 170). All BRCA1-associated patients were matched in a 1:2 ratio for age and year of diagnosis to sporadic BC patients. We compared the occurrence of ipsi- and contralateral BC (CBC) as well as distant disease-free (DDFS), BC-specific (BCSS) and overall survival (OS). By multivariate modelling, the prognostic impact of tumour and treatment factors was investigated separately in BRCA1-associated and sporadic breast cancers. RESULTS: For the total group of 669 cases, the median follow-up was 5.1 years, the median age at diagnosis 39 years. We confirmed the existence of the typical BRCA1-associated tumour type and the high CBC incidence. No significant differences between BRCA1-associated and sporadic tumours were found with respect to ipsilateral BC recurrence (HR(mult) 0.7; P = 0.24), DDFS (HR(mult) 1.2; P = 0.37) or BC-specific survival (HR(mult) 1.3; P = 0.23). A trend towards a worse survival was found for BRCA1-associated ductal BC (HR(mult) 1.5, P = 0.07). Prognostic factors for BRCA1-associated BC were age at diagnosis, tumour size and morphology, and nodal status. Further, survival was non-significantly improved by systemic treatment and a bilateral salpingo-oophorectomy. No effect on survival of a contralateral prophylactic mastectomy was seen. CONCLUSIONS: BRCA1-associated BC is characterised by specific tumour characteristics, a high incidence of CBC and a trend towards a worse survival for the ductal tumour type. Our observation that tumour size and nodal status are also prognostic factors for BRCA1-associated BC implies that the strategy to use these factors as a proxy for ultimate mortality, for instance in BC screening programmes or the consideration of (contralateral) preventive mastectomy, appears to be valid in this specific group of patients.